affected sib-pair asp: Topics by Science.gov

Sample records for affected sib-pair asp

Linkage analysis in nuclear families. 2: Relationship between affected sib-pair tests and lod score analysis.

PubMed

Knapp, M; Seuchter, S A; Baur, M P

1994-01-01

It is believed that the main advantage of affected sib-pair tests is that their application requires no information about the underlying genetic mechanism of the disease. However, here it is proved that the mean test, which can be considered the most prominent of the affected sib-pair tests, is equivalent to lod score analysis for an assumed recessive mode of inheritance, irrespective of the true mode of the disease. Further relationships of certain sib-pair tests and lod score analysis under specific assumed genetic modes are investigated.
Exploiting excess sharing: a more powerful test of linkage for affected sib pairs than the transmission/disequilibrium test.

PubMed Central

Wicks, J

2000-01-01

The transmission/disequilibrium test (TDT) is a popular, simple, and powerful test of linkage, which can be used to analyze data consisting of transmissions to the affected members of families with any kind pedigree structure, including affected sib pairs (ASPs). Although it is based on the preferential transmission of a particular marker allele across families, it is not a valid test of association for ASPs. Martin et al. devised a similar statistic for ASPs, Tsp, which is also based on preferential transmission of a marker allele but which is a valid test of both linkage and association for ASPs. It is, however, less powerful than the TDT as a test of linkage for ASPs. What I show is that the differences between the TDT and Tsp are due to the fact that, although both statistics are based on preferential transmission of a marker allele, the TDT also exploits excess sharing in identity-by-descent transmissions to ASPs. Furthermore, I show that both of these statistics are members of a family of "TDT-like" statistics for ASPs. The statistics in this family are based on preferential transmission but also, to varying extents, exploit excess sharing. From this family of statistics, we see that, although the TDT exploits excess sharing to some extent, it is possible to do so to a greater extent-and thus produce a more powerful test of linkage, for ASPs, than is provided by the TDT. Power simulations conducted under a number of disease models are used to verify that the most powerful member of this family of TDT-like statistics is more powerful than the TDT for ASPs. PMID:10788332
Exploiting excess sharing: a more powerful test of linkage for affected sib pairs than the transmission/disequilibrium test.

PubMed

Wicks, J

2000-06-01

The transmission/disequilibrium test (TDT) is a popular, simple, and powerful test of linkage, which can be used to analyze data consisting of transmissions to the affected members of families with any kind pedigree structure, including affected sib pairs (ASPs). Although it is based on the preferential transmission of a particular marker allele across families, it is not a valid test of association for ASPs. Martin et al. devised a similar statistic for ASPs, Tsp, which is also based on preferential transmission of a marker allele but which is a valid test of both linkage and association for ASPs. It is, however, less powerful than the TDT as a test of linkage for ASPs. What I show is that the differences between the TDT and Tsp are due to the fact that, although both statistics are based on preferential transmission of a marker allele, the TDT also exploits excess sharing in identity-by-descent transmissions to ASPs. Furthermore, I show that both of these statistics are members of a family of "TDT-like" statistics for ASPs. The statistics in this family are based on preferential transmission but also, to varying extents, exploit excess sharing. From this family of statistics, we see that, although the TDT exploits excess sharing to some extent, it is possible to do so to a greater extent-and thus produce a more powerful test of linkage, for ASPs, than is provided by the TDT. Power simulations conducted under a number of disease models are used to verify that the most powerful member of this family of TDT-like statistics is more powerful than the TDT for ASPs.
Affected sib pair tests in inbred populations.

PubMed

Liu, W; Weir, B S

2004-11-01

The affected-sib-pair (ASP) method for detecting linkage between a disease locus and marker loci was first established 50 years ago, and since then numerous modifications have been made. We modify two identity-by-state (IBS) test statistics of Lange (Lange, 1986a, 1986b) to allow for inbreeding in the population. We evaluate the power and false positive rates of the modified tests under three disease models, using simulated data. Before estimating false positive rates, we demonstrate that IBS tests are tests of both linkage and linkage disequilibrium between marker and disease loci. Therefore, the null hypothesis of IBS tests should be no linkage and no LD. When the population inbreeding coefficient is large, the false positive rates of Lange's tests become much larger than the nominal value, while those of our modified tests remain close to the nominal value. To estimate power with a controlled false positive rate, we choose the cutoff values based on simulated datasets under the null hypothesis, so that both Lange's tests and the modified tests generate same false positive rate. The powers of Lange's z-test and our modified z-test are very close and do not change much with increasing inbreeding. The power of the modified chi-square test also stays stable when the inbreeding coefficient increases. However, the power of Lange's chi-square test increases with increasing inbreeding, and is larger than that of our modified chi-square test for large inbreeding coefficients. The power is high under a recessive disease model for both Lange's tests and the modified tests, though the power is low for additive and dominant disease models. Allowing for inbreeding is therefore appropriate, at least for diseases known to be recessive.
Two-locus diseas models with two marker loci: The power of affected-sib-pair tests

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

Knapp, M.; Seuchter, S.A.; Bauer, M.P.

1994-11-01

Recently, Schork et al. found that two-trait-locus, two-marker-locus (parametric) linkage analysis can provide substantially more linkage information than can standard one-trait-locus, one-marker-locus methods. However, because of the increased burden of computation, Schork et al. do not expect that their approach will be applied in an initial genome scan. Further, the specification of a suitable two-locus segregation model can be crucial. Affected-sib-pair tests are computationally simple and do not require an explicit specification of the disease model. In the past, however, these tests mainly have been applied to data with a single marker locus. Here, we consider sib-pair tests that makemore » it possible to analyze simultaneously two marker loci. The power of these tests is investigated for different (epistatic and heterogeneous) two-trait-locus models, each trait locus being linked to one of the marker loci. We compare these tests both with the test that is optimal for a certain model and with the strategy that analyzes each marker locus separately. The results indicate that a straightforward extension of the well-known mean test for two marker loci can be much more powerful than single-marker-locus analysis and that its power is only slightly inferior to the power of the optimal test. 21 refs., 5 figs., 2 tabs.« less
A combined analysis of D22S278 marker alleles in affected sib-pairs: Support for a susceptibility locus for schizophrenia at chromosome 22q12

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

Gill, M.; Vallada, H.; Collier, D.

1996-02-16

Several groups have reported weak evidence for linkage between schizophrenia and genetic markers located on chromosome 22q using the lod score method of analysis. However these findings involved different genetic markers and methods of analysis, and so were not directly comparable. To resolve this issue we have performed a combined analysis of genotypic data from the marker D22S278 in multiply affected schizophrenic families derived from 11 independent research groups worldwide. This marker was chosen because it showed maximum evidence for linkage in three independent datasets. Using the affected sib-pair method as implemented by the program ESPA, the combined dataset showedmore » 252 alleles shared compared with 188 alleles not shared (chi-square 9.31, 1df, P = 0.001) where parental genotype data was completely known. When sib-pairs for whom parental data was assigned according to probability were included the number of alleles shared was 514.1 compared with 437.8 not shared (chi-square 6.12, 1df, P = 0.006). Similar results were obtained when a likelihood ratio method for sib-pair analysis was used. These results indicate that there may be a susceptibility locus for schizophrenia at 22q12. 27 refs., 3 tabs.« less
Homozygous parent affected sib pair method for detecting disease predisposing variants: application to insulin dependent diabetes mellitus.

PubMed

Robinson, W P; Barbosa, J; Rich, S S; Thomson, G

1993-01-01

For complex genetic diseases involving incomplete penetrance, genetic heterogeneity, and multiple disease genes, it is often difficult to determine the molecular variant(s) responsible for the disease pathogenesis. Linkage and association studies may help identify genetic regions and molecular variants suspected of being directly responsible for disease predisposition or protection, but, especially for complex diseases, they are less useful for determining when a predisposing molecular variant has been identified. In this paper, we expand upon the simple concept that if a genetic factor predisposing to disease has been fully identified, then a parent homozygous for this factor should transmit either of his/her copies at random to any affected children. Closely linked markers are used to determine identity by descent values in affected sib pairs from a parent homozygous for a putative disease predisposing factor. The expected deviation of haplotype sharing from 50%, when not all haplotypes carrying this factor are in fact equally predisposing, has been algebraically determined for a single locus general disease model. Equations to determine expected sharing for multiple disease alleles or multiple disease locus models have been formulated. The recessive case is in practice limiting and therefore can be used to estimate the maximum proportion of putative susceptibility haplotypes which are in fact predisposing to disease when the mode of inheritance of a disease is unknown. This method has been applied to 27 DR3/DR3 parents and 50 DR4/DR4 parents who have at least 2 children affected with insulin dependent diabetes mellitus (IDDM). The transmission of both DR3 and DR4 haplotypes is statistically different from 50% (P < 0.05 and P < 0.001, respectively). An upper estimate for the proportion of DR3 haplotypes associated with a high IDDM susceptibility is 49%, and for DR4 haplotypes 38%. Our results show that the joint presence of non-Asp at DQ beta position 57 and Arg
Impact of parental relationships in maximum lod score affected sib-pair method.

PubMed

Leutenegger, Anne-Louise; Génin, Emmanuelle; Thompson, Elizabeth A; Clerget-Darpoux, Françoise

2002-11-01

Many studies are done in small isolated populations and populations where marriages between relatives are encouraged. In this paper, we point out some problems with applying the maximum lod score (MLS) method (Risch, [1990] Am. J. Hum. Genet. 46:242-253) in these populations where relationships exist between the two parents of the affected sib-pairs. Characterizing the parental relationships by the kinship coefficient between the parents (f), the maternal inbreeding coefficient (alpha(m), and the paternal inbreeding coefficient (alpha(p)), we explored the relationship between the identity by descent (IBD) vector expected under the null hypothesis of no linkage and these quantities. We find that the expected IBD vector is no longer (0.25, 0.5, 0.25) when f, alpha(m), and alpha(p) differ from zero. In addition, the expected IBD vector does not always follow the triangle constraints recommended by Holmans ([1993] Am. J. Hum. Genet. 52:362-374). So the classically used MLS statistic needs to be adapted to the presence of parental relationships. We modified the software GENEHUNTER (Kruglyak et al. [1996] Am. J. Hum. Genet. 58: 1347-1363) to do so. Indeed, the current version of the software does not compute the likelihood properly under the null hypothesis. We studied the adapted statistic by simulating data on three different family structures: (1) parents are double first cousins (f=0.125, alpha(m)=alpha(p)=0), (2) each parent is the offspring of first cousins (f=0, alpha(m)=alpha(p)=0.0625), and (3) parents are related as in the pedigree from Goddard et al. ([1996] Am. J. Hum. Genet. 58:1286-1302) (f=0.109, alpha(m)=alpha(p)=0.0625). The appropriate threshold needs to be derived for each case in order to get the correct type I error. And using the classical statistic in the presence of both parental kinship and parental inbreeding almost always leads to false conclusions. Copyright 2002 Wiley-Liss, Inc.
Transmission-Ratio Distortion and Allele Sharing in Affected Sib Pairs: A New Linkage Statistic with Reduced Bias, with Application to Chromosome 6q25.3

PubMed Central

Lemire, Mathieu; Roslin, Nicole M.; Laprise, Catherine; Hudson, Thomas J.; Morgan, Kenneth

2004-01-01

We studied the effect of transmission-ratio distortion (TRD) on tests of linkage based on allele sharing in affected sib pairs. We developed and implemented a discrete-trait allele-sharing test statistic, Sad, analogous to the Spairs test statistic of Whittemore and Halpern, that evaluates an excess sharing of alleles at autosomal loci in pairs of affected siblings, as well as a lack of sharing in phenotypically discordant relative pairs, where available. Under the null hypothesis of no linkage, nuclear families with at least two affected siblings and one unaffected sibling have a contribution to Sad that is unbiased, with respect to the effects of TRD independent of the disease under study. If more distantly related unaffected individuals are studied, the bias of Sad is generally reduced compared with that of Spairs, but not completely. Moreover, Sad has higher power, in some circumstances, because of the availability of unaffected relatives, who are ignored in affected-only analyses. We discuss situations in which it may be an efficient use of resources to genotype unaffected relatives, which would give insights for promising study designs. The method is applied to a sample of pedigrees ascertained for asthma in a chromosomal region in which TRD has been reported. Results are consistent with the presence of transmission distortion in that region. PMID:15322985
Pseudoautosomal region in schizophrenia: linkage analysis of seven loci by sib-pair and lod-score methods.

PubMed

d'Amato, T; Waksman, G; Martinez, M; Laurent, C; Gorwood, P; Campion, D; Jay, M; Petit, C; Savoye, C; Bastard, C

1994-05-01

In a previous study, we reported a nonrandom segregation between schizophrenia and the pseudoautosomal locus DXYS14 in a sample of 33 sibships. That study has been extended by the addition of 16 new sibships from 16 different families. Data from six other loci of the pseudoautosomal region and of the immediately adjacent part of the X specific region have also been analyzed. Two methods of linkage analysis were used: the affected sibling pair (ASP) method and the lod-score method. Lod-score analyses were performed on the basis of three different models--A, B, and C--all shown to be consistent with the epidemiological data on schizophrenia. No clear evidence for linkage was obtained with any of these models. However, whatever the genetic model and the disease classification, maximum lod scores were positive with most of the markers, with the highest scores generally being obtained for the DXYS14 locus. When the ASP method was used, the earlier finding of nonrandom segregation between schizophrenia and the DXYS14 locus was still supported in this larger data set, at an increased level of statistical significance. Findings of ASP analyses were not significant for the other loci. Thus, findings obtained from analyses using the ASP method, but not the lod-score method, were consistent with the pseudoautosomal hypothesis for schizophrenia.
Novel homozygous missense variant of GRIN1 in two sibs with intellectual disability and autistic features without epilepsy.

PubMed

Rossi, Massimiliano; Chatron, Nicolas; Labalme, Audrey; Ville, Dorothée; Carneiro, Maryline; Edery, Patrick; des Portes, Vincent; Lemke, Johannes R; Sanlaville, Damien; Lesca, Gaetan

2017-02-01

We report on two consanguineous sibs affected with severe intellectual disability and autistic features due to a homozygous missense variant of GRIN1. Massive parallel sequencing was performed using a gene panel including 450 genes related to intellectual disability and autism spectrum disorders. We found a homozygous missense variation of GRIN1 (c.679G>C; p.(Asp227His)) in the two affected sibs, which was inherited from both unaffected heterozygous parents. Heterozygous variants of GRIN1, encoding the GluN1 subunit of the NMDA receptor, have been reported in patients with neurodevelopmental disorders including epileptic encephalopathy, severe intellectual disability, and movement disorders. The p.(Asp227His) variant is located in the same aminoterminal protein domain as the recently published p.(Arg217Trp), which was found at the homozygous state in two patients with a similar phenotype of severe intellectual disability and autistic features but without epilepsy. In silico predictions were consistent with a deleterious effect. The present findings further expand the clinical spectrum of GRIN1 variants and support the existence of hypomorphic variants causing severe neurodevelopmental impairment with autosomal recessive inheritance.
Helical peptides with three pairs of Asp-Arg and Glu-Arg residues in different orientations and spacings.

PubMed Central

Huyghues-Despointes, B. M.; Scholtz, J. M.; Baldwin, R. L.

1993-01-01

The helix-stabilizing effects of repeating pairs of Asp-Arg and Glu-Arg residues have been characterized using a peptide system of the same design used earlier to study Glu-Lys (Marqusee, S. & Baldwin, R.L., 1987, Proc. Natl. Acad. Sci. USA 84, 8898-8902) and Asp-Lys ion pairs (Marqusee, S. & Baldwin, R.L., 1990, In Protein Folding [Gierasch, L.M. & King, J., Eds.], pp. 85-94, AAAS, Washington, D.C.). The consequences of breaking ion pair and charge-helix dipole interactions by titration to pH 2 have been compared with the results of screening these interactions with NaCl at pH 7.0 and pH 2.5. The four peptides in each set contain three pairs of acidic (A) and basic (B) residues spaced either i, i + 4 or i, i + 3 apart. In one peptide of each kind the pairwise order of residues is AB, with the charges oriented favorably to the helix macrodipole, and in the other peptide the order is BA. The results are as follows: (1) Remarkably, both Asp-Arg and Glu-Arg peptides show the same pattern of helix stabilization at pH 7.0 found earlier for Glu-Lys and Asp-Lys peptides: i + 4 AB > i + 4 BA approximately i + 3 AB > i + 3 BA. (2) The ion pairs and charge-helix dipole interactions cannot be cleanly separated, but the results suggest that both interactions make important contributions to helix stability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8443591
Association study of 25 type 2 diabetes related Loci with measures of obesity in Indian sib pairs.

PubMed

Gupta, Vipin; Vinay, Donipadi Guru; Sovio, Ulla; Rafiq, Sajjad; Kranthi Kumar, Madamchetty Venkata; Janipalli, Charles Spurgeon; Evans, David; Mani, Kulathu Radha; Sandeep, Madana Narasimha; Taylor, Amy; Kinra, Sanjay; Sullivan, Ruth; Bowen, Liza; Timpson, Nicholas; Smith, George Davey; Dudbridge, Frank; Prabhakaran, Dorairaj; Ben-Shlomo, Yoav; Reddy, Kolli Srinath; Ebrahim, Shah; Chandak, Giriraj Ratan

2013-01-01

Obesity is an established risk factor for type 2 diabetes (T2D) and they are metabolically related through the mechanism of insulin resistance. In order to explore how common genetic variants associated with T2D correlate with body mass index (BMI), we examined the influence of 25 T2D associated loci on obesity risk. We used 5056 individuals (2528 sib-pairs) recruited in Indian Migration Study and conducted within sib-pair analysis for six obesity phenotypes. We found associations of variants in CXCR4 (rs932206) and HHEX (rs5015480) with higher body mass index (BMI) (β=0.13, p=0.001) and (β=0.09, p=0.002), respectively and weight (β=0.13, p=0.001) and (β=0.09, p=0.001), respectively. CXCR4 variant was also strongly associated with body fat (β=0.10, p=0.0004). In addition, we demonstrated associations of CXCR4 and HHEX with overweight/obesity (OR=1.6, p=0.003) and (OR=1.4, p=0.002), respectively, in 1333 sib-pairs (2666 individuals). We observed marginal evidence of associations between variants at six loci (TCF7L2, NGN3, FOXA2, LOC646279, FLJ39370 and THADA) and waist hip ratio (WHR), BMI and/or overweight which needs to be validated in larger set of samples. All the above findings were independent of daily energy consumption and physical activity level. The risk score estimates based on eight significant loci (including nominal associations) showed associations with WHR and body fat which were independent of BMI. In summary, we establish the role of T2D associated loci in influencing the measures of obesity in Indian population, suggesting common underlying pathophysiology across populations.
Association Study of 25 Type 2 Diabetes Related Loci with Measures of Obesity in Indian Sib Pairs

PubMed Central

Gupta, Vipin; Vinay, Donipadi Guru; Sovio, Ulla; Rafiq, Sajjad; Kranthi Kumar, Madamchetty Venkata; Janipalli, Charles Spurgeon; Evans, David; Mani, Kulathu Radha; Sandeep, Madana Narasimha; Taylor, Amy; Kinra, Sanjay; Sullivan, Ruth; Bowen, Liza; Timpson, Nicholas; Smith, George Davey; Dudbridge, Frank; Prabhakaran, Dorairaj; Ben-Shlomo, Yoav; Reddy, Kolli Srinath; Ebrahim, Shah; Chandak, Giriraj Ratan

2013-01-01

Obesity is an established risk factor for type 2 diabetes (T2D) and they are metabolically related through the mechanism of insulin resistance. In order to explore how common genetic variants associated with T2D correlate with body mass index (BMI), we examined the influence of 25 T2D associated loci on obesity risk. We used 5056 individuals (2528 sib-pairs) recruited in Indian Migration Study and conducted within sib-pair analysis for six obesity phenotypes. We found associations of variants in CXCR4 (rs932206) and HHEX (rs5015480) with higher body mass index (BMI) (β = 0.13, p = 0.001) and (β = 0.09, p = 0.002), respectively and weight (β = 0.13, p = 0.001) and (β = 0.09, p = 0.001), respectively. CXCR4 variant was also strongly associated with body fat (β = 0.10, p = 0.0004). In addition, we demonstrated associations of CXCR4 and HHEX with overweight/obesity (OR = 1.6, p = 0.003) and (OR = 1.4, p = 0.002), respectively, in 1333 sib-pairs (2666 individuals). We observed marginal evidence of associations between variants at six loci (TCF7L2, NGN3, FOXA2, LOC646279, FLJ3970 and THADA) and waist hip ratio (WHR), BMI and/or overweight which needs to be validated in larger set of samples. All the above findings were independent of daily energy consumption and physical activity level. The risk score estimates based on eight significant loci (including nominal associations) showed associations with WHR and body fat which were independent of BMI. In summary, we establish the role of T2D associated loci in influencing the measures of obesity in Indian population, suggesting common underlying pathophysiology across populations. PMID:23349771
Testing association and linkage using affected-sib-parent study designs.

PubMed

Millstein, Joshua; Siegmund, Kimberly D; Conti, David V; Gauderman, W James

2005-11-01

We have developed a method for jointly testing linkage and association using data from affected sib pairs and their parents. We specify a conditional logistic regression model with two covariates, one that quantifies association (either direct association or indirect association via linkage disequilibrium), and a second that quantifies linkage. The latter covariate is computed based on expected identity-by-descend (ibd) sharing of marker alleles between siblings. In addition to a joint test of linkage and association, our general framework can be used to obtain a linkage test comparable to the mean test (Blackwelder and Elston [1985] Genet. Epidemiol. 2:85-97), and an association test comparable to the Family-Based Association Test (FBAT; Rabinowitz and Laird [2000] Hum. Hered. 50:211-223). We present simulation results demonstrating that our joint test can be more powerful than some standard tests of linkage or association. For example, with a relative risk of 2.7 per variant allele at a disease locus, the estimated power to detect a nearby marker with a modest level of LD was 58.1% by the mean test (linkage only), 69.8% by FBAT, and 82.5% by our joint test of linkage and association. Our model can also be used to obtain tests of linkage conditional on association and association conditional on linkage, which can be helpful in fine mapping. Copyright 2005 Wiley-Liss, Inc.
Maximum likelihood estimation of linkage disequilibrium in half-sib families.

PubMed

Gomez-Raya, L

2012-05-01

Maximum likelihood methods for the estimation of linkage disequilibrium between biallelic DNA-markers in half-sib families (half-sib method) are developed for single and multifamily situations. Monte Carlo computer simulations were carried out for a variety of scenarios regarding sire genotypes, linkage disequilibrium, recombination fraction, family size, and number of families. A double heterozygote sire was simulated with recombination fraction of 0.00, linkage disequilibrium among dams of δ=0.10, and alleles at both markers segregating at intermediate frequencies for a family size of 500. The average estimates of δ were 0.17, 0.25, and 0.10 for Excoffier and Slatkin (1995), maternal informative haplotypes, and the half-sib method, respectively. A multifamily EM algorithm was tested at intermediate frequencies by computer simulation. The range of the absolute difference between estimated and simulated δ was between 0.000 and 0.008. A cattle half-sib family was genotyped with the Illumina 50K BeadChip. There were 314,730 SNP pairs for which the sire was a homo-heterozygote with average estimates of r2 of 0.115, 0.067, and 0.111 for half-sib, Excoffier and Slatkin (1995), and maternal informative haplotypes methods, respectively. There were 208,872 SNP pairs for which the sire was double heterozygote with average estimates of r2 across the genome of 0.100, 0.267, and 0.925 for half-sib, Excoffier and Slatkin (1995), and maternal informative haplotypes methods, respectively. Genome analyses for all possible sire genotypes with 829,042 tests showed that ignoring half-sib family structure leads to upward biased estimates of linkage disequilibrium. Published inferences on population structure and evolution of cattle should be revisited after accommodating existing half-sib family structure in the estimation of linkage disequilibrium.
Maximum Likelihood Estimation of Linkage Disequilibrium in Half-Sib Families

PubMed Central

Gomez-Raya, L.

2012-01-01

Maximum likelihood methods for the estimation of linkage disequilibrium between biallelic DNA-markers in half-sib families (half-sib method) are developed for single and multifamily situations. Monte Carlo computer simulations were carried out for a variety of scenarios regarding sire genotypes, linkage disequilibrium, recombination fraction, family size, and number of families. A double heterozygote sire was simulated with recombination fraction of 0.00, linkage disequilibrium among dams of δ = 0.10, and alleles at both markers segregating at intermediate frequencies for a family size of 500. The average estimates of δ were 0.17, 0.25, and 0.10 for Excoffier and Slatkin (1995), maternal informative haplotypes, and the half-sib method, respectively. A multifamily EM algorithm was tested at intermediate frequencies by computer simulation. The range of the absolute difference between estimated and simulated δ was between 0.000 and 0.008. A cattle half-sib family was genotyped with the Illumina 50K BeadChip. There were 314,730 SNP pairs for which the sire was a homo-heterozygote with average estimates of r2 of 0.115, 0.067, and 0.111 for half-sib, Excoffier and Slatkin (1995), and maternal informative haplotypes methods, respectively. There were 208,872 SNP pairs for which the sire was double heterozygote with average estimates of r2 across the genome of 0.100, 0.267, and 0.925 for half-sib, Excoffier and Slatkin (1995), and maternal informative haplotypes methods, respectively. Genome analyses for all possible sire genotypes with 829,042 tests showed that ignoring half-sib family structure leads to upward biased estimates of linkage disequilibrium. Published inferences on population structure and evolution of cattle should be revisited after accommodating existing half-sib family structure in the estimation of linkage disequilibrium. PMID:22377635
Childhood trauma as a risk factor for psychosis: A sib-pair study.

PubMed

Barrigón, María Luisa; Diaz, Francisco J; Gurpegui, Manuel; Ferrin, Maite; Salcedo, María Dolores; Moreno-Granados, Josefa; Cervilla, Jorge A; Ruiz-Veguilla, Miguel

2015-11-01

Childhood trauma, cannabis use and certain personality traits have been related to the development of psychosis. This study uses a sib-pair design to examine the association between childhood trauma and psychosis controlling for cannabis use and neuroticism. We evaluated 60 patient-sibling pairs, conformed by patients with functional psychosis in the first five years of their illness matched with a non-psychotic sibling. In univariate analyses, patients and siblings were compared with McNemar tests and paired-sample t tests. A conditional logistic regression model of the risk of developing psychosis was built. The dependent variable of this model was the patient-sibling status (patient = 1, sibling = 0). After controlling for cannabis use and neuroticism, the odds of suffering psychosis for subjects who experienced a childhood trauma were 7.3 times higher than the odds for subjects who did not experience a childhood trauma [95% CI, (1.06-50.01); P = 0.04]. Also, after controlling for experiencing childhood trauma and neuroticism, subjects who were heavy cannabis users had odds of suffering psychosis that were 6.4 times higher than the odds of the remaining subjects [95% CI, (1.2-35.2); P = 0.03]. Both childhood trauma and cannabis use were significantly associated with an increased risk of suffering functional psychosis. A neurotic personality also contributed independently to this risk. These findings might help improve the prevention of psychosis and the development of specific treatment strategies on this specific population. Copyright © 2015 Elsevier Ltd. All rights reserved.
Substitution of Asp-309 by Asn in the Arg-Asp-Pro (RDP) motif of Acetobacter diazotrophicus levansucrase affects sucrose hydrolysis, but not enzyme specificity.

PubMed Central

Batista, F R; Hernández, L; Fernández, J R; Arrieta, J; Menéndez, C; Gómez, R; Támbara, Y; Pons, T

1999-01-01

beta-Fructofuranosidases share a conserved aspartic acid-containing motif (Arg-Asp-Pro; RDP) which is absent from alpha-glucopyranosidases. The role of Asp-309 located in the RDP motif of levansucrase (EC 2.4.1.10) from Acetobacter diazotrophicus SRT4 was studied by site-directed mutagenesis. Substitution of Asp-309 by Asn did not affect enzyme secretion. The kcat of the mutant levansucrase was reduced 75-fold, but its Km was similar to that of the wild-type enzyme, indicating that Asp-309 plays a major role in catalysis. The two levansucrases showed optimal activity at pH 5.0 and yielded similar product profiles. Thus the mutation D309N affected the efficiency of sucrose hydrolysis, but not the enzyme specificity. Since the RDP motif is present in a conserved position in fructosyltransferases, invertases, levanases, inulinases and sucrose-6-phosphate hydrolases, it is likely to have a common functional role in beta-fructofuranosidases. PMID:9895294
Microcephalic osteodysplastic primordial dwarfism type I/III in sibs.

PubMed

Meinecke, P; Passarge, E

1991-11-01

The clinical and radiological findings in a pair of sibs with microcephalic osteodysplastic primordial dwarfism (MOPD) are described, a boy who survived for 5 1/2 years and his more severely affected younger sister, who died at the age of 6 months. Neuropathological studies in this girl showed marked micrencephaly with severely hypoplastic, poorly gyrated frontal lobes and absent corpus callosum. Our observation supports the hypothesis that types I and III MOPD probably constitute a spectrum of one and the same entity and published data together with this report are consistent with autosomal recessive inheritance. The pathogenesis of this condition is as yet unknown, but its characteristics indicate a basic defect affecting cell proliferation and tissue differentiation.

Microcephalic osteodysplastic primordial dwarfism type I/III in sibs.

PubMed Central

Meinecke, P; Passarge, E

1991-01-01

The clinical and radiological findings in a pair of sibs with microcephalic osteodysplastic primordial dwarfism (MOPD) are described, a boy who survived for 5 1/2 years and his more severely affected younger sister, who died at the age of 6 months. Neuropathological studies in this girl showed marked micrencephaly with severely hypoplastic, poorly gyrated frontal lobes and absent corpus callosum. Our observation supports the hypothesis that types I and III MOPD probably constitute a spectrum of one and the same entity and published data together with this report are consistent with autosomal recessive inheritance. The pathogenesis of this condition is as yet unknown, but its characteristics indicate a basic defect affecting cell proliferation and tissue differentiation. Images PMID:1770539
Association analysis of 31 common polymorphisms with type 2 diabetes and its related traits in Indian sib pairs.

PubMed

Gupta, V; Vinay, D G; Rafiq, S; Kranthikumar, M V; Janipalli, C S; Giambartolomei, C; Evans, D M; Mani, K R; Sandeep, M N; Taylor, A E; Kinra, S; Sullivan, R M; Bowen, L; Timpson, N J; Smith, G D; Dudbridge, F; Prabhakaran, D; Ben-Shlomo, Y; Reddy, K S; Ebrahim, S; Chandak, G R

2012-02-01

Evaluation of the association of 31 common single nucleotide polymorphisms (SNPs) with fasting glucose, fasting insulin, HOMA-beta cell function (HOMA-β), HOMA-insulin resistance (HOMA-IR) and type 2 diabetes in the Indian population. We genotyped 3,089 sib pairs recruited in the Indian Migration Study from four cities in India (Lucknow, Nagpur, Hyderabad and Bangalore) for 31 SNPs in 24 genes previously associated with type 2 diabetes in European populations. We conducted within-sib-pair analysis for type 2 diabetes and its related quantitative traits. The risk-allele frequencies of all the SNPs were comparable with those reported in western populations. We demonstrated significant associations of CXCR4 (rs932206), CDKAL1 (rs7756992) and TCF7L2 (rs7903146, rs12255372) with fasting glucose, with β values of 0.007 (p = 0.05), 0.01 (p = 0.01), 0.007 (p = 0.05), 0.01 (p = 0.003) and 0.08 (p = 0.01), respectively. Variants in NOTCH2 (rs10923931), TCF-2 (also known as HNF1B) (rs757210), ADAM30 (rs2641348) and CDKN2A/B (rs10811661) significantly predicted fasting insulin, with β values of -0.06 (p = 0.04), 0.05 (p = 0.05), -0.08 (p = 0.01) and -0.08 (p = 0.02), respectively. For HOMA-IR, we detected associations with TCF-2, ADAM30 and CDKN2A/B, with β values of 0.05 (p = 0.04), -0.07 (p = 0.03) and -0.08 (p = 0.02), respectively. We also found significant associations of ADAM30 (β = -0.05; p = 0.01) and CDKN2A/B (β = -0.05; p = 0.03) with HOMA-β. THADA variant (rs7578597) was associated with type 2 diabetes (OR 1.5; 95% CI 1.04, 2.22; p = 0.03). We validated the association of seven established loci with intermediate traits related to type 2 diabetes in an Indian population using a design resistant to population stratification.
Statistics on continuous IBD data: Exact distribution evaluation for a pair of full(half)-sibs and a pair of a (great-) grandchild with a (great-) grandparent

PubMed Central

Stefanov, Valeri T

2002-01-01

Background Pairs of related individuals are widely used in linkage analysis. Most of the tests for linkage analysis are based on statistics associated with identity by descent (IBD) data. The current biotechnology provides data on very densely packed loci, and therefore, it may provide almost continuous IBD data for pairs of closely related individuals. Therefore, the distribution theory for statistics on continuous IBD data is of interest. In particular, distributional results which allow the evaluation of p-values for relevant tests are of importance. Results A technology is provided for numerical evaluation, with any given accuracy, of the cumulative probabilities of some statistics on continuous genome data for pairs of closely related individuals. In the case of a pair of full-sibs, the following statistics are considered: (i) the proportion of genome with 2 (at least 1) haplotypes shared identical-by-descent (IBD) on a chromosomal segment, (ii) the number of distinct pieces (subsegments) of a chromosomal segment, on each of which exactly 2 (at least 1) haplotypes are shared IBD. The natural counterparts of these statistics for the other relationships are also considered. Relevant Maple codes are provided for a rapid evaluation of the cumulative probabilities of such statistics. The genomic continuum model, with Haldane's model for the crossover process, is assumed. Conclusions A technology, together with relevant software codes for its automated implementation, are provided for exact evaluation of the distributions of relevant statistics associated with continuous genome data on closely related individuals. PMID:11996673
Achondroplasia in sibs of normal parents.

PubMed Central

Philip, N; Auger, M; Mattei, J F; Giraud, F

1988-01-01

A new case of recurrent achondroplasia in sibs of normal parents is reported. Two sisters and a half sister were affected. Various mechanisms can be postulated to account for unexpected recurrence of achondroplasia in the same sibship. Germinal mosaicism and unstable premutation are discussed here. Images PMID:3236371
Searching susceptibility loci for bipolar disorder: a sib pair study on chromosome 12.

PubMed

Lorenzi, Cristina; Delmonte, Dario; Pirovano, Adele; Marino, Elena; Bongiorno, Fanny; Catalano, Marco; Colombo, Cristina; Bramanti, Placido; Smeraldi, Enrico

2010-01-01

Several linkage studies demonstrated that different chromosomal regions are involved in the susceptibility to bipolar disorder. In particular, some genome scans evidenced the role of chromosome 12. For this reason, our group chose this chromosome for a preliminary genome scan on a sample of 137 Italian sib pairs, including at least 1 bipolar subject. The analyses were carried out by means of DNA extracted from whole blood. DNA samples were genotyped by 19 simple tandem repeat markers (microsatellites). Starting from the genetic data, we performed two- and multipoint linkage analyses (both parametric and nonparametric) by means of Easy Linkage plus package (version 5.05). The multipoint linkage analyses pointed out a region suggestive of linkage between the markers D12S310 and D12S364, at locus 12p12. In particular, we reached the best evidence of linkage performing multipoint analyses and assuming a recessive model, under the hypothesis of genetic heterogeneity (heterogeneity LOD score = 2.01 and alpha = 0.77). It is interesting to notice that the region at the marker D12S364 is located inside the gene coding for the glutamatergic receptor GRIN2B. Therefore, our finding not only confirmed the role of genetics in determining liability to bipolar disorder, but suggested glutamatergic transmission impairment as a possible cause. Nevertheless, we acknowledge that our study is heavily underpowered. Therefore, independent replication is needed. (c) 2009 S. Karger AG, Basel.
Repression of small toxic protein synthesis by the Sib and OhsC small RNAs.

PubMed

Fozo, Elizabeth M; Kawano, Mitsuoki; Fontaine, Fanette; Kaya, Yusuf; Mendieta, Kathy S; Jones, Kristi L; Ocampo, Alejandro; Rudd, Kenneth E; Storz, Gisela

2008-12-01

The sequences encoding the QUAD1 RNAs were initially identified as four repeats in Escherichia coli. These repeats, herein renamed SIB, are conserved in closely related bacteria, although the number of repeats varies. All five Sib RNAs in E. coli MG1655 are expressed, and no phenotype was observed for a five-sib deletion strain. However, a phenotype reminiscent of plasmid addiction was observed for overexpression of the Sib RNAs, and further examination of the SIB repeat sequences revealed conserved open reading frames encoding highly hydrophobic 18- to 19-amino-acid proteins (Ibs) opposite each sib gene. The Ibs proteins were found to be toxic when overexpressed and this toxicity could be prevented by coexpression of the corresponding Sib RNA. Two other RNAs encoded divergently in the yfhL-acpS intergenic region were similarly found to encode a small hydrophobic protein (ShoB) and an antisense RNA regulator (OhsC). Overexpression of both IbsC and ShoB led to immediate changes in membrane potential suggesting both proteins affect the cell envelope. Whole genome expression analysis showed that overexpression of IbsC and ShoB, as well as the small hydrophobic LdrD and TisB proteins, has both overlapping and unique consequences for the cell.
Repression of small toxic protein synthesis by the Sib and OhsC small RNAs

PubMed Central

Fozo, Elizabeth M.; Kawano, Mitsuoki; Fontaine, Fanette; Kaya, Yusuf; Mendieta, Kathy S.; Jones, Kristi L.; Ocampo, Alejandro; Rudd, Kenneth E.; Storz, Gisela

2008-01-01

Summary The sequences encoding the QUAD1 RNAs were initially identified as four repeats in Escherichia coli. These repeats, herein renamed SIB, are conserved in closely related bacteria, though the number of repeats varies. All five Sib RNAs in E. coli MG1655 are expressed, and no phenotype was observed for a five sib deletion strain. However, a phenotype reminiscent of plasmid addiction was observed for overexpression of the Sib RNAs, and further examination of the SIB repeat sequences revealed conserved open reading frames encoding highly hydrophobic 18–19 amino acid proteins (Ibs) opposite each sib gene. The Ibs proteins were found to be toxic when overexpressed and this toxicity could be prevented by co-expression of the corresponding Sib RNA. Two other RNAs encoded divergently in the yfhL-acpS intergenic region were similarly found to encode a small hydrophobic protein (ShoB) and an antisense RNA regulator (OhsC). Overexpression of both IbsC and ShoB led to immediate changes in membrane potential suggesting both proteins affect the cell envelope. Whole genome expression analysis showed that overexpression of IbsC and ShoB, as well as the small hydrophobic LdrD and TisB proteins, has both overlapping and unique consequences for the cell. PMID:18710431
The distribution of genome shared identical by descent for a pair of full sibs by means of the continuous time Markov chain

NASA Astrophysics Data System (ADS)

Julie, Hongki; Pasaribu, Udjianna S.; Pancoro, Adi

2015-12-01

This paper will allow Markov Chain's application in genome shared identical by descent by two individual at full sibs model. The full sibs model was a continuous time Markov Chain with three state. In the full sibs model, we look for the cumulative distribution function of the number of sub segment which have 2 IBD haplotypes from a segment of the chromosome which the length is t Morgan and the cumulative distribution function of the number of sub segment which have at least 1 IBD haplotypes from a segment of the chromosome which the length is t Morgan. This cumulative distribution function will be developed by the moment generating function.
How the extra methylene group affects the ligation properties of Glu vs. Asp and Gln vs. Asn amino acids: a DFT/PCM study.

PubMed

Dudev, Todor; Doudeva, Lyudmila

2017-02-01

The effect of the extra methylene group on the ligation properties of glutamic (Glu) vs. aspartic (Asp) acid, and glutamine (Gln) vs. asparagine (Asn) amino acids-two pairs of protein building blocks differing by the length of their side chains-has been studied by employing DFT calculations combined with polarizable continuum model (PCM) computations. Complexes of the nominal species with partner ligands of various structures, charge states, and degree of solvent exposure have been examined. The results obtained reveal that the difference in the alkyl chain length of these amino acid residues does not affect the mode of their binding. This, however, influences the thermodynamics of the ligand-ligand and ligand-metal recognition thus bestowing unique ligation characteristics on the competing entities. The calculations reveal that the competition between the longer-chain and shorter-chain analogs is entropy driven and that the differential electronic effects are of minor importance for the process. Thus, the outcome of the rivalry between Asp and Glu, and Asn and Gln is almost unaffected by the nature of the partner ligand, its charge state and, in most cases, the dielectric properties of the binding site. The longer-chain Glu, as opposed to its shorter-chain Asp counterpart, is the preferred partner ligand in various protein binding sites. Contrariwise, the shorter-chain Asn binds more favorably to the respective binding sites than its longer-chain Gln analog. The results obtained shed additional light on the intimate mechanism of the ligand-ligand and ligand-metal recognition in proteins and could be employed as guidelines in protein engineering and design.
A sib-pair study of the Temperament and Character Inventory scales in major depression.

PubMed

Farmer, Anne; Mahmood, Arshad; Redman, Kate; Harris, Tanya; Sadler, Stephanie; McGuffin, Peter

2003-05-01

Certain aspects of the personality may be associated with the vulnerability to develop depression. A sib-pair method has been used to examine the familiality of the 7 scales of the Temperament and Character Inventory (TCI) and whether this could be related to the genetic vulnerability to develop depression. Probands with depression and their nearest-aged siblings from Wales were compared with healthy control probands and their nearest-aged siblings on the TCI and measures of depressed mood. All 7 scales of the TCI were familial, and scores on 6 of the scales were similar to US population scores. However, the Welsh subjects' scores on the self-transcendence scale were markedly lower than the US mean, suggesting strong cultural or national influences on this measure. Harm avoidance scores were substantially influenced by current and past depression, but this scale also showed stable traitlike characteristics that are likely related to the genetic vulnerability to depression. Novelty seeking and self-directedness were also partly state-dependent and were negatively correlated with low mood; high scorers may be resilient to the development of depression. High reward dependence may also protect against the development of depression and is unrelated to mood state. The cooperativeness, persistence, and self-transcendence scales appear to have a limited relationship with the development of depression. Harm avoidance, reward dependence, novelty seeking, and self-directedness have traitlike characteristics that are related to the familiality of depression. Cooperativeness, self-transcendence, and persistence are also familial, but this appears to be unrelated to depression.
Conserved Asp-137 imparts flexibility to tropomyosin and affects function.

PubMed

Sumida, John P; Wu, Eleanor; Lehrer, Sherwin S

2008-03-14

Tropomyosin (Tm) is an alpha-helical coiled-coil that controls muscle contraction by sterically regulating the myosin-actin interaction. Tm moves between three states on F-actin as either a uniform or a non-uniform semi-flexible rod. Tm is stabilized by hydrophobic residues in the "a" and "d" positions of the heptad repeat. The highly conserved Asp-137 is unusual in that it introduces a negative charge on each chain in a position typically occupied by hydrophobic residues. The occurrence of two charged residues in the hydrophobic region is expected to destabilize the region and impart flexibility. To determine whether this region is unstable, we have substituted hydrophobic Leu for Asp-137 and studied changes in Tm susceptibility to limited proteolysis by trypsin and changes in regulation. We found that native and Tm controls that contain Asp-137 were readily cleaved at Arg-133 with t 1/2 of 5 min. In contrast, the Leu-137 mutant was not cleaved under the same conditions. Actin stabilized Tm, causing a 10-fold reduction in the rate of cleavage at Arg-133. The actin-myosin subfragment S1 ATPase activity was greater for the Leu mutant compared with controls in the absence of troponin and in the presence of troponin and Ca2+. We conclude that the highly conserved Asp-137 destabilizes the middle of Tm, resulting in a more flexible region that is important for the cooperative activation of the thin filament by myosin. We thus have shown a link between the dynamic properties of Tm and its function.
Evaluation of seven common lipid associated loci in a large Indian sib pair study.

PubMed

Rafiq, Sajjad; Venkata, Kranthi Kumar M; Gupta, Vipin; Vinay, D G; Spurgeon, Charles J; Parameshwaran, Smitha; Madana, Sandeep N; Kinra, Sanjay; Bowen, Liza; Timpson, Nicholas J; Smith, George Davey; Dudbridge, Frank; Prabhakaran, Dorairaj; Ben-Shlomo, Yoav; Reddy, K Srinath; Ebrahim, Shah; Chandak, Giriraj R

2012-11-14

Genome wide association studies (GWAS), mostly in Europeans have identified several common variants as associated with key lipid traits. Replication of these genetic effects in South Asian populations is important since it would suggest wider relevance for these findings. Given the rising prevalence of metabolic disorders and heart disease in the Indian sub-continent, these studies could be of future clinical relevance. We studied seven common variants associated with a variety of lipid traits in previous GWASs. The study sample comprised of 3178 sib-pairs recruited as participants for the Indian Migration Study (IMS). Associations with various lipid parameters and quantitative traits were analyzed using the Fulker genetic association model. We replicated five of the 7 main effect associations with p-values ranging from 0.03 to 1.97x10(-7). We identified particularly strong association signals at rs662799 in APOA5 (beta=0.18 s.d, p=1.97 x 10(-7)), rs10503669 in LPL (beta =-0.18 s.d, p=1.0 x 10(-4)) and rs780094 in GCKR (beta=0.11 s.d, p=0.001) loci in relation to triglycerides. In addition, the GCKR variant was also associated with total cholesterol (beta=0.11 s.d, p=3.9x10(-4)). We also replicated the association of rs562338 in APOB (p=0.03) and rs4775041 in LIPC (p=0.007) with LDL-cholesterol and HDL-cholesterol respectively. We report associations of five loci with various lipid traits with the effect size consistent with the same reported in Europeans. These results indicate an overlap of genetic effects pertaining to lipid traits across the European and Indian populations.
A tonoplast Glu/Asp/GABA exchanger that affects tomato fruit amino acid composition.

PubMed

Snowden, Christopher J; Thomas, Benjamin; Baxter, Charles J; Smith, J Andrew C; Sweetlove, Lee J

2015-03-01

Vacuolar accumulation of acidic metabolites is an important aspect of tomato fruit flavour and nutritional quality. The amino acids Asp and Glu accumulate to high concentrations during ripening, while γ-aminobutyrate (GABA) shows an approximately stoichiometric decline. Given that GABA can be catabolised to form Glu and subsequently Asp, and the requirement for the fruit to maintain osmotic homeostasis during ripening, we hypothesised the existence of a tonoplast transporter that exports GABA from the vacuole in exchange for import of either Asp or Glu. We show here that the tomato vacuolar membrane possesses such a transport property: transport of Glu across isolated tonoplast vesicle membranes was trans-stimulated in counterexchange mode by GABA, Glu and Asp. We identified SlCAT9 as a candidate protein for this exchanger using quantitative proteomics of a tonoplast-enriched membrane fraction. Transient expression of a SlCAT9-YFP fusion in tobacco confirmed a tonoplast localisation. The function of the protein was examined by overexpression of SlCAT9 in transgenic tomato plants. Tonoplast vesicles isolated from transgenic plants showed higher rates of Glu and GABA transport than wild-type (WT) only when assayed in counterexchange mode with Glu, Asp, or GABA. Moreover, there were substantial increases in the content of all three cognate amino acids in ripe fruit from the transgenic plants. We conclude that SlCAT9 is a tonoplast Glu/Asp/GABA exchanger that strongly influences the accumulation of these amino acids during fruit development. © 2015 The Authors The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.
Aeromonas sobria serine protease (ASP): a subtilisin family endopeptidase with multiple virulence activities.

PubMed

Imamura, Takahisa; Murakami, Yoji; Nitta, Hidetoshi

2017-09-26

Aeromonas sobria serine protease (ASP) is secreted from Aeromonas sobria, a pathogen causing gastroenteritis and sepsis. ASP resembles Saccharomyces cerevisiae Kex2, a member of the subtilisin family, and preferentially cleaves peptide bonds at the C-terminal side of paired basic amino acid residues; also accepting unpaired arginine at the P1 site. Unlike Kex2, however, ASP lacks an intramolecular chaperone N-terminal propeptide, instead utilizes the external chaperone ORF2 for proper folding, therefore, ASP and its homologues constitute a new subfamily in the subtilisin family. Through activation of the kallikrein/kinin system, ASP induces vascular leakage, and presumably causes edema and septic shock. ASP accelerates plasma clotting by α-thrombin generation from prothrombin, whereas it impairs plasma clottability by fibrinogen degradation, together bringing about blood coagulation disorder that occurs in disseminated intravascular coagulation, a major complication of sepsis. From complement C5 ASP liberates C5a that induces neutrophil recruitment and superoxide release, and mast cell degranulation, which are associated with pus formation, tissue injury and diarrhea, respectively. Nicked two-chain ASP also secreted from A. sobria is more resistant to inactivation by α2-macroglobulin than single-chain ASP, thereby raising virulence activities. Thus, ASP is a potent virulence factor and may participate in the pathogenesis of A. sobria infection.
Substitution of amino acids Asp-85, Asp-212, and Arg-82 in bacteriorhodopsin affects the proton release phase of the pump and the pK of the Schiff base.

PubMed

Otto, H; Marti, T; Holz, M; Mogi, T; Stern, L J; Engel, F; Khorana, H G; Heyn, M P

1990-02-01

Photocycle and flash-induced proton release and uptake were investigated for bacteriorhodopsin mutants in which Asp-85 was replaced by Ala, Asn, or Glu; Asp-212 was replaced by Asn or Glu; Asp-115 was replaced by Ala, Asn, or Glu; Asp-96 was replaced by Ala, Asn, or Glu; and Arg-82 was replaced by Ala or Gln in dimyristoylphosphatidylcholine/3-[(3-cholamidopropyl)dimethylammonio]-1- propanesulfonate micelles at pH 7.3. In the Asp-85----Ala and Asp-85----Asn mutants, the absence of the charged carboxyl group leads to a blue chromophore at 600 and 595 nm, respectively, and lowers the pK of the Schiff base deprotonation to 8.2 and 7, respectively, suggesting a role for Asp-85 as counterion to the Schiff base. The early part of the photocycles of the Asp-85----Ala and Asp-85----Asn mutants is strongly perturbed; the formation of a weak M-like intermediate is slowed down about 100-fold over wild type. In both mutants, proton release is also slower but clearly precedes the rise of M. The amplitude of the early (less than 0.2 microseconds) reversed photovoltage component in the Asp-85----Asn mutant is very large, and the net charge displacement is close to zero, indicating proton release and uptake on the cytoplasmic side of the membrane. The data suggest an obligatory role for Asp-85 in the efficient deprotonation of the Schiff base and in the proton release phase, probably as proton acceptor. In the Asp-212----Asn mutant, the rise of the absorbance change at 410 nm is slowed down to 220 microsecond, its amplitude is small, and the release of protons is delayed to 1.9 ms. The absorbance changes at 650 nm indicate perturbations in the early time range with a slow K intermediate. Thus Asp-212 also participates in the early events of charge translocation and deprotonation of the Schiff base. In the Arg-82----Gln mutant, no net transient proton release was observed, whereas, in the Arg-82----Ala mutant, uptake and release were reversed. The pK shift of the purple
Dansylated octapeptide Dns-Glu-Asp-Asp-Ser-Asp-Glu-Glu-Asn inhibits the proliferation rate of HL-60 cells.

PubMed

Marsili, V; Nardicchi, V; Lupidi, G; Brozzetti, A; Gianfranceschi, G L

1996-12-01

Small acidic phosphorylated chromatin peptides show regulatory activity on gene expression. The peptide pyroGlu-Asp-Asp-Ser-Asp-Glu-Glu-Asn, synthesized on the basis of structural and biochemical studies, shows functional properties in vitro (phosphorylation by casein kinase II, control of DNA transcription by RNA polymerase II, inhibition of proliferation and promotion of differentiation in some cell lines) very similar to those of native chromatin peptides. In this report we show that the dansylated octapeptide Dns-Glu-Asp-Asp-Ser-Asp-Glu-Glu-Asn remarkably inhibits cell growth of the HL-60 cell line. The biological effect of the peptide seems to be considerably higher than that shown by the nondansylated peptide, and it cannot be attributed to a toxic effect of the Dns group. The measurement of uptake of 3H-labelled Glu-Asp-Asp-Ser-Asp-Glu-Glu-Asn demonstrates that it is unable to pass through the HL-60 cell membrane. It is our considered opinion that the addition of hydrophobic groups to the peptide N-terminus should increase the biological activity by improving its transport through the cellular membrane.
Cleavage of the actin-capping protein alpha -adducin at Asp-Asp-Ser-Asp633-Ala by caspase-3 is preceded by its phosphorylation on serine 726 in cisplatin-induced apoptosis of renal epithelial cells.

PubMed

van de Water, B; Tijdens, I B; Verbrugge, A; Huigsloot, M; Dihal, A A; Stevens, J L; Jaken, S; Mulder, G J

2000-08-18

Decreased phosphorylation of focal adhesion kinase and paxillin is associated with loss of focal adhesions and stress fibers and precedes the onset of apoptosis (van de Water, B., Nagelkerke, J. F., and Stevens, J. L. (1999) J. Biol. Chem. 274, 13328-13337). The cortical actin cytoskeletal network is also lost during apoptosis, yet little is known about the temporal relationship between altered phosphorylation of proteins that are critical in the regulation of this network and their potential cleavage by caspases during apoptosis. Adducins are central in the cortical actin network organization. Cisplatin caused apoptosis of renal proximal tubular epithelial cells, which was associated with the cleavage of alpha-adducin into a 74-kDa fragment; this was blocked by a general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD-fmk). Hemagglutinin-tagged human alpha-adducin was cleaved into a similar 74-kDa fragment by caspase-3 in vitro but not by caspase-6 or -7. Asp-Arg-Val-Asp(29)-Glu, Asp-Ile-Val-Asp(208)-Arg, and Asp-Asp-Ser-Asp(633)-Ala were identified as the principal caspase-3 cleavage sites; Asp-Asp-Ser-Asp(633)-Ala was key in the formation of the 74-kDa fragment. Cisplatin also caused an increased phosphorylation of alpha-adducin and gamma-adducin in the MARCKS domain that preceded alpha-adducin cleavage and was associated with loss of adducins from adherens junctions; this was not affected by z-VAD-fmk. In conclusion, the data support a model in which increased phosphorylation of alpha-adducin due to cisplatin leads to dissociation from the cytoskeleton, a situation rendered irreversible by caspase-3-mediated cleavage of alpha-adducin at Asp-Asp-Ser-Asp(633)-Ala.
Evaluation of seven common lipid associated loci in a large Indian sib pair study

PubMed Central

2012-01-01

Background Genome wide association studies (GWAS), mostly in Europeans have identified several common variants as associated with key lipid traits. Replication of these genetic effects in South Asian populations is important since it would suggest wider relevance for these findings. Given the rising prevalence of metabolic disorders and heart disease in the Indian sub-continent, these studies could be of future clinical relevance. Methods We studied seven common variants associated with a variety of lipid traits in previous GWASs. The study sample comprised of 3178 sib-pairs recruited as participants for the Indian Migration Study (IMS). Associations with various lipid parameters and quantitative traits were analyzed using the Fulker genetic association model. Results We replicated five of the 7 main effect associations with p-values ranging from 0.03 to 1.97x10-7. We identified particularly strong association signals at rs662799 in APOA5 (beta=0.18 s.d, p=1.97 x 10-7), rs10503669 in LPL (beta =−0.18 s.d, p=1.0 x 10-4) and rs780094 in GCKR (beta=0.11 s.d, p=0.001) loci in relation to triglycerides. In addition, the GCKR variant was also associated with total cholesterol (beta=0.11 s.d, p=3.9x10-4). We also replicated the association of rs562338 in APOB (p=0.03) and rs4775041 in LIPC (p=0.007) with LDL-cholesterol and HDL-cholesterol respectively. Conclusions We report associations of five loci with various lipid traits with the effect size consistent with the same reported in Europeans. These results indicate an overlap of genetic effects pertaining to lipid traits across the European and Indian populations. PMID:23150898
Power analysis of QTL detection in half-sib families using selective DNA pooling

PubMed Central

Baro, Jesús Á; Carleos, Carlos; Corral, Norberto; López, Teresa; Cañón, Javier

2001-01-01

Individual loci of economic importance (QTL) can be detected by comparing the inheritance of a trait and the inheritance of loci with alleles readily identifiable by laboratory methods (genetic markers). Data on allele segregation at the individual level are costly and alternatives have been proposed that make use of allele frequencies among progeny, rather than individual genotypes. Among the factors that may affect the power of the set up, the most important are those intrinsic to the QTL: the additive effect of the QTL, and its dominance, and distance between markers and QTL. Other factors are relative to the choice of animals and markers, such as the frequency of the QTL and marker alleles among dams and sires. Data collection may affect the detection power through the size of half-sib families, selection rate within families, and the technical error incurred when estimating genetic frequencies. We present results for a sensitivity analysis for QTL detection using pools of DNA from selected half-sibs. Simulations showed that conclusive detection may be achieved with families of at least 500 half-sibs if sires are chosen on the criteria that most of their marker alleles are either both missing, or one is fixed, among dams. PMID:11403746
SIB-DOTA: a trifunctional prosthetic group potentially amenable for multi-modal labeling that enhances tumor uptake of internalizing monoclonal antibodies.

PubMed

Vaidyanathan, G; White, B J; Affleck, D J; Zhao, X G; Welsh, P C; McDougald, D; Choi, J; Zalutsky, M R

2012-12-15

A major drawback of internalizing monoclonal antibodies (mAbs) radioiodinated with direct electrophilic approaches is that tumor retention of radioactivity is compromised by the rapid washout of iodo-tyrosine, the primary labeled catabolite for mAbs labeled via this strategy. In our continuing efforts to develop more versatile residualizing labels that could overcome this problem, we have designed SIB-DOTA, a prosthetic labeling template that combines the features of the prototypical, dehalogenation-resistant N-succinimidyl 3-iodobenzoate (SIB) with DOTA, a useful macrocyclic chelator for labeling with radiometals. Herein we describe the synthesis of the unlabeled standard of this prosthetic moiety, its protected tin precursor, and radioiodinated SIB-DOTA. An anti-EGFRvIII-reactive mAb, L8A4 was radiolabeled with [(131)I]SIB-DOTA in 27.1±6.2% (n=2) conjugation yields and its targeting properties to the same mAb labeled with [(125)I]SGMIB both in vitro and in vivo using U87MG·ΔEGFR cells and xenografts were compared. In vitro paired-label internalization assays showed that the intracellular radioactivity from [(131)I]SIB-DOTA-L8A4 was 21.4±0.5% and 26.2±1.1% of initially bound radioactivity at 16 and 24h, respectively. In comparison, these values for [(125)I]SGMIB-L8A4 were 16.7±0.5% and 14.9±1.1%. Similarly, the SIB-DOTA prosthetic group provided better tumor targeting in vivo than SGMIB over 8 d period. These results suggest that SIB-DOTA warrants further evaluation as a residualizing agent for labeling internalizing mAbs including those targeted to EGFRvIII. Copyright © 2012 Elsevier Ltd. All rights reserved.

Familiality of factor analysis-derived YBOCS dimensions in OCD-affected sibling pairs from the OCD Collaborative Genetics Study.

PubMed

Hasler, Gregor; Pinto, Anthony; Greenberg, Benjamin D; Samuels, Jack; Fyer, Abby J; Pauls, David; Knowles, James A; McCracken, James T; Piacentini, John; Riddle, Mark A; Rauch, Scott L; Rasmussen, Steven A; Willour, Virginia L; Grados, Marco A; Cullen, Bernadette; Bienvenu, O Joseph; Shugart, Yin-Yao; Liang, Kung-Yee; Hoehn-Saric, Rudolf; Wang, Ying; Ronquillo, Jonne; Nestadt, Gerald; Murphy, Dennis L

2007-03-01

Identification of familial, more homogenous characteristics of obsessive-compulsive disorder (OCD) may help to define relevant subtypes and increase the power of genetic and neurobiological studies of OCD. While factor-analytic studies have found consistent, clinically meaningful OCD symptom dimensions, there have been only limited attempts to evaluate the familiality and potential genetic basis of such dimensions. Four hundred eighteen sibling pairs with OCD were evaluated using the Structured Clinical Interview for DSM-IV and the Yale-Brown Obsessive Compulsive Scale (YBOCS) Symptom Checklist and Severity scales. After controlling for sex, age, and age of onset, robust sib-sib intraclass correlations were found for two of the four YBOCS factors: Factor IV (hoarding obsessions and compulsions (p = .001) and Factor I (aggressive, sexual, and religious obsessions, and checking compulsions; p = .002). Smaller, but still significant, familiality was found for Factor III (contamination/cleaning; p = .02) and Factor II (symmetry/ordering/arranging; p = .04). Limiting the sample to female subjects more than doubled the familiality estimates for Factor II (p = .003). Among potentially relevant comorbid conditions for genetic studies, bipolar I/II and major depressive disorder were strongly associated with Factor I (p < .001), whereas ADHD, alcohol dependence, and bulimia were associated with Factor II (p < .01). Factor-analyzed OCD symptom dimensions in sibling pairs with OCD are familial with some gender-dependence, exhibit relatively specific relationships to comorbid psychiatric disorders and thus may be useful as refined phenotypes for molecular genetic studies of OCD.
Identifying involvement of Lys251/Asp252 pair in electron transfer and associated proton transfer at the quinone reduction site of Rhodobacter capsulatus cytochrome bc1.

PubMed

Kuleta, Patryk; Sarewicz, Marcin; Postila, Pekka; Róg, Tomasz; Osyczka, Artur

2016-10-01

Describing dynamics of proton transfers in proteins is challenging, but crucial for understanding processes which use them for biological functions. In cytochrome bc1, one of the key enzymes of respiration or photosynthesis, proton transfers engage in oxidation of quinol (QH2) and reduction of quinone (Q) taking place at two distinct catalytic sites. Here we evaluated by site-directed mutagenesis the contribution of Lys251/Asp252 pair (bacterial numbering) in electron transfers and associated with it proton uptake to the quinone reduction site (Qi site). We showed that the absence of protonable group at position 251 or 252 significantly changes the equilibrium levels of electronic reactions including the Qi-site mediated oxidation of heme bH, reverse reduction of heme bH by quinol and heme bH/Qi semiquinone equilibrium. This implicates the role of H-bonding network in binding of quinone/semiquinone and defining thermodynamic properties of Q/SQ/QH2 triad. The Lys251/Asp252 proton path is disabled only when both protonable groups are removed. With just one protonable residue from this pair, the entrance of protons to the catalytic site is sustained, albeit at lower rates, indicating that protons can travel through parallel routes, possibly involving water molecules. This shows that proton paths display engineering tolerance for change as long as all the elements available for functional cooperation secure efficient proton delivery to the catalytic site. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
In search of susceptibility genes for type 2 diabetes in West Africa: the design and results of the first phase of the AADM study.

PubMed

Rotimi, C N; Dunston, G M; Berg, K; Akinsete, O; Amoah, A; Owusu, S; Acheampong, J; Boateng, K; Oli, J; Okafor, G; Onyenekwe, B; Osotimehin, B; Abbiyesuku, F; Johnson, T; Fasanmade, O; Furbert-Harris, P; Kittles, R; Vekich, M; Adegoke, O; Bonney, G; Collins, F

2001-01-01

The purpose of this study is to map type 2 diabetes susceptibility genes in West African ancestral populations of African-Americans, through an international collaboration between West African and US investigators. Affected sib-pairs (ASP) along with unaffected spouse controls are being enrolled and examined in West Africa, with two sites established in Ghana (Accra and Kumasi) and three in Nigeria (Enugu, Ibadan, and Lagos). Eligible participants are invited to study clinics to obtain detailed epidemiologic, family, and medical history information. Blood samples are drawn from each participant to measure glucose, insulin, C-peptide, total cholesterol, LDL, HDL, triglycerides, albumin, creatinine, urea, uric acid, total calcium and to detect autoantibodies to glutamic acid decarboxylase (GAD). DNA is isolated from frozen white blood cells obtained from 20 ml of EDTA whole blood samples. With full informed consent, 162 individuals from 78 families have been enrolled and examined since the Africa America Diabetes Mellitus (AADM) study began in June of 1997. Logistics of field examinations and specimen shipping have been successfully established. At the end of the third year of field activity (September 2000) the AADM study will have enrolled and performed comprehensive examination on 400 ASP with type 2 diabetes, for a minimum of 800 cases and 200 controls from Ghana and Nigeria. At the current participation rate, the goal of 400 sib-pairs and 200 controls will be met before the scheduled closing date. The AADM study will create a comprehensive epidemiologic and genetic resource that will facilitate a powerful genome-wide search for West African susceptibility genes to type 2 diabetes.
Somatic Incompatibility in Diakaryotic-monokaryotic and Dikaryotic Pairings of Echinodontium tinctorium

Treesearch

A. Dan Wilson

1991-01-01

Somatic incompatibility in dikaryotic-monokaryotic (di-mon) and dikaryotic pairings of Echinodontium tinctorium was investigated in vitro on 4.5% malt agar. Antagonistic reactions of varying intensity occurred in all pairings between 12 allopatric dikaryons from Idaho and Arizona, between 14 sib-composed dikaryons from two Idaho sites, and in over...
Site-directed mutagenesis of the conserved Asp-443 and Asp-498 carboxy-terminal residues of HIV-1 reverse transcriptase.

PubMed Central

Mizrahi, V; Usdin, M T; Harington, A; Dudding, L R

1990-01-01

Substitution of the conserved Asp-443 residue of HIV-1 reverse transcriptase by asparagine specifically suppressed the ribonuclease H activity of the enzyme without affecting the reverse transcriptase activity, suggesting involvement of this ionizable residue at the ribonuclease H active site. An analogous asparagine substitution of the Asp-498 residue yielded an unstable enzyme that was difficult to enzymatically characterize. However, the instability caused by the Asn-498 mutation was relieved by the introduction of a second distal Asn-443 substitution, yielding an enzyme with wild type reverse transcriptase activity, but lacking ribonuclease H activity. Images PMID:1699202
Performance of full-sib families of Douglas-fir in pure-family and mixed-family deployments

Treesearch

Peter J. Gould; J. Bradley St.Clair; Paul D. Anderson

2011-01-01

A major objective of tree improvement programs is to identify genotypes that will perform well in operational deployments. Relatively little is known, however, about how the competitive environment affects performance in different types of deployments. We tested whether the genetic composition and density of deployments affect the performance of full-sib families of...
Characterization of the functional role of Asp141, Asp194, and Asp464 residues in the Mn2+-L-malate binding of pigeon liver malic enzyme.

PubMed

Chou, W Y; Chang, H P; Huang, C H; Kuo, C C; Tong, L; Chang, G G

2000-02-01

Pigeon liver malic enzyme was inactivated and cleaved at Asp141, Asp194, and Asp464 by the Cu2+-ascorbate system in acidic environment. Site-specific mutagenesis was performed at these putative metal-binding sites. Three point mutants, D141N, D194N, and D464N; three double mutants, D(141,194)N, D(194,464)N, and D(141,464)N; and a triple mutant, D(141,194,464)N; as well as the wild-type malic enzyme (WT) were successfully cloned and expressed in Escherichia coli cells. All recombinant enzymes, except the triple mutant, were purified to apparent homogeneity by successive Q-Sepharose and adenosine-2',5'-bisphosphate-agarose columns. The mutants showed similar apparent Km,NADP values to that of the WT. The Km,Mal value was increased in the D141N and D194N mutants. The Km,Mn value, on the other hand, was increased only in the D141N mutant by 14-fold, corresponding to approximately 1.6 kcal/mol for the Asp141-Mn2+ binding energy. Substrate inhibition by L-malate was only observed in WT, D464N, and D(141,464)N. Initial velocity experiments were performed to derive the various kinetic parameters. The possible interactions between Asp141, Asp194, and Asp464 were analyzed by the double-mutation cycles and triple-mutation box. There are synergistic weakening interactions between Asp141 and Asp194 in the metal binding that impel the D(141,194)N double mutant to an overall specificity constant [k(cat)/(Kd,Mn Km,Mal Km,NADP)] at least four orders of magnitude smaller than the WT value. This difference corresponds to an increase of 6.38 kcal/mol energy barrier for the catalytic efficiency. Mutation at Asp464, on the other hand, has partial additivity on the mutations at Asp141 and Asp194. The overall specificity constants for the double mutants D(194,464)N and D(141,464)N or the triple mutant D(141,194,464)N were decreased by only 10- to 100-fold compared to the WT. These results strongly suggest the involvement of Asp141 in the Mn2+-L-malate binding for the pigeon liver malic
The Future of the ASP Conference Series

NASA Astrophysics Data System (ADS)

Jensen, Joseph B.; Barnes, Jonathan; Moody, J. Ward; Szkody, Paula

The Astronomical Society of the Pacific (ASP) has been publishing the proceedings of conferences in astronomy and astrophysics for more than 20 years. The ASP Conference Series (ASPCS) is widely known for its affordable and high quality printed volumes. The ASPCS is adapting to the changing market by making electronically published volumes available to subscribers around the world, including papers in the Astrophysics Data System (ADS) database, and allowing authors to post papers on e-print archives. We discuss the role of the printed book in our future plans, and how electronic publishing affects the types of products and services we offer. Recently there has been increasing pressure in the academic world for open access (electronic copies of scholarly publications made freely-available immediately after publication), and we discuss how the ASPCS is responding to the needs of the professional astronomical community, the ASP, and humanity at large. While we cannot yet provide full open access and stay in business, we are actively pursuing several initiatives to improve the quality of our product and the impact of the papers we publish.
FURTHER ANALYSIS OF SUBTYPES OF AUTOMATICALLY REINFORCED SIB: A REPLICATION AND QUANTITATIVE ANALYSIS OF PUBLISHED DATASETS

PubMed Central

Hagopian, Louis P.; Rooker, Griffin W.; Zarcone, Jennifer R.; Bonner, Andrew C.; Arevalo, Alexander R.

2017-01-01

Hagopian, Rooker, and Zarcone (2015) evaluated a model for subtyping automatically reinforced self-injurious behavior (SIB) based on its sensitivity to changes in functional analysis conditions and the presence of self-restraint. The current study tested the generality of the model by applying it to all datasets of automatically reinforced SIB published from 1982 to 2015. We identified 49 datasets that included sufficient data to permit subtyping. Similar to the original study, Subtype-1 SIB was generally amenable to treatment using reinforcement alone, whereas Subtype-2 SIB was not. Conclusions could not be drawn about Subtype-3 SIB due to the small number of datasets. Nevertheless, the findings support the generality of the model and suggest that sensitivity of SIB to disruption by alternative reinforcement is an important dimension of automatically reinforced SIB. Findings also suggest that automatically reinforced SIB should no longer be considered a single category and that additional research is needed to better understand and treat Subtype-2 SIB. PMID:28032344
ASP archiving solution of regional HUSpacs.

PubMed

Pohjonen, Hanna; Kauppinen, Tomi; Ahovuo, Juhani

2004-09-01

The application service provider (ASP) model is not novel, but widely used in several non-health care-related business areas. In this article, ASP is described as a potential solution for long-term and back-up archiving of the picture archiving and communication system (PACS) of the Hospital District of Helsinki and Uusimaa (HUS). HUSpacs is a regional PACS for 21 HUS hospitals serving altogether 1.4 million citizens. The ultimate goal of this study was to define the specifications for the ASP archiving service and to compare different commercial options for archiving solutions (costs derived by unofficial requests for proposal): in-house PACS components, the regional ASP concept and the hospital-based ASP concept. In conclusion, the large scale of the HUS installation enables a cost-effective regional ASP archiving, resulting in a four to five times more economical solution than hospital-based ASP.
Occurrence of the Cys311 DRD2 variant in a pedigree multiply affected with panic disorder

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

Crawford, F.; Hoyne, J.; Diaz, P.

1995-08-14

Following the detection of the rare DRD2 codon 311 variant (Ser{yields}Cys) in an affected member from a large, multiply affected panic disorder family, we investigated the occurrence of this variant in other family members. The variant occurred in both affected and unaffected individuals. Further screening in panic disorder sib pairs unrelated to this family failed to detect the Cys311 variant. Our data suggests that this variant has no pathogenic role in panic disorder. 18 refs., 1 fig.
Barriers to carrier testing for adult cystic fibrosis sibs: the importance of not knowing.

PubMed

Fanos, J H; Johnson, J P

1995-10-23

Early experience in centers offering population screening for cystic fibrosis (CF) has shown that few of the public are taking advantage of the offer [Miller, 1993: New Scientist 139:6]. There is similar low utilization among adult CF sibs [Fanos and Johnson, 1993: Am J Hum Genet 53:A51]. The purpose of this study was to identify factors motivating or interfering with the pursuit of carrier testing in adult CF sibs. Eighty-four adult CF sibs and their spouses, drawn from Children's Hospital, Oakland, CA, and Children's Hospital, Boston, MA, were interviewed for about an hour, and qualitative material was coded on various themes. Structural and psychological barriers to the transmission of genetic information were identified: 1) sibs encountered difficulty in obtaining information concerning availability of testing; 2) parental guilt and blame prevents parents from discussing genetic issues with the sib; 3) sibs rarely discuss testing with each other; 4) the CF patient or parent often has difficulty with the implications of the sib seeking carrier testing; 5) family and individual myths about carrier status influence the sib's decision to seek testing; 6) statistical odds have lost meaning in families where the rare has already occurred; 7) the sib fears loss of interpersonal desirability; and 8) carrier status can serve an important function in binding guilt. Remaining unaware of their carrier status may serve significant psychological functions for individuals at risk.
Compound Heterozygous Inheritance of Mutations in Coenzyme Q8A Results in Autosomal Recessive Cerebellar Ataxia and Coenzyme Q10 Deficiency in a Female Sib-Pair.

PubMed

Jacobsen, Jessie C; Whitford, Whitney; Swan, Brendan; Taylor, Juliet; Love, Donald R; Hill, Rosamund; Molyneux, Sarah; George, Peter M; Mackay, Richard; Robertson, Stephen P; Snell, Russell G; Lehnert, Klaus

2017-11-21

Autosomal recessive ataxias are characterised by a fundamental loss in coordination of gait with associated atrophy of the cerebellum. There is significant clinical and genetic heterogeneity amongst inherited ataxias; however, an early molecular diagnosis is essential with low-risk treatments available for some of these conditions. We describe two female siblings who presented early in life with unsteady gait and cerebellar atrophy. Whole exome sequencing revealed compound heterozygous inheritance of two pathogenic mutations (p.Leu277Pro, c.1506+1G>A) in the coenzyme Q8A gene (COQ8A), a gene central to biosynthesis of coenzyme Q (CoQ). The paternally derived p.Leu277Pro mutation is predicted to disrupt a conserved motif in the substrate-binding pocket of the protein, resulting in inhibition of CoQ 10 production. The maternal c.1506+1G>A mutation destroys a canonical splice donor site in exon 12 affecting transcript processing and subsequent protein translation. Mutations in this gene can result in primary coenzyme Q 10 deficiency type 4, which is characterized by childhood onset of cerebellar ataxia and exercise intolerance, both of which were observed in this sib-pair. Muscle biopsies revealed unequivocally low levels of CoQ 10, and the siblings were subsequently established on a therapeutic dose of CoQ 10 with distinct clinical evidence of improvement after 1 year of treatment. This case emphasises the importance of an early and accurate molecular diagnosis for suspected inherited ataxias, particularly given the availability of approved treatments for some subtypes.
Absorption kinetics and action profiles of subcutaneously administered insulin analogues (AspB9GluB27, AspB10, AspB28) in healthy subjects.

PubMed

Kang, S; Brange, J; Burch, A; Vølund, A; Owens, D R

1991-11-01

The subcutaneous absorption and resulting changes in plasma insulin or analogue, glucose, C-peptide, and blood intermediary metabolite concentrations after subcutaneous bolus injection of three soluble human insulin analogues (AspB9GluB27, monomeric; AspB28, mixture of monomers and dimers; and AspB10, dimeric) and soluble human insulin were evaluated. Fasting healthy male volunteers (n = 7) were studied on five occasions 1 wk apart randomly receiving 0.6 nmol.kg-1 s.c. 125I-labeled AspB10 or soluble human insulin (Novolin R, Novo, Copenhagen); 1st study and 0.6 nmol.kg-1 s.c. 125I-labeled AspB28, AspB9GluB27 or soluble human insulin (2nd study). Residual radioactivity at the injection site was measured over 8 h with frequent venous sampling for plasma immunoreactive insulin or analogue, glucose, C-peptide, and blood intermediary metabolite concentrations. The three analogues were absorbed 2-3 times faster than human insulin. The mean +/- SE time to 50% residual radioactivity was 94 +/- 6 min for AspB10 compared with 184 +/- 10 min for human insulin (P less than 0.001), 83 +/- 8 min for AspB28 (P less than 0.005), and 63 +/- 9 min for AspB9GluB27 (P less than 0.001) compared with 182 +/- 21 min for human insulin. delta Peak plasma insulin analogue levels were significantly higher after each analogue than after human insulin (P less than 0.005). With all three analogues, the mean hypoglycemic nadir occurred earlier at 61-65 min postinjection compared with 201-210 min for the reference human insulins (P less than 0.005). The magnitude of the hypoglycemic nadir was greater after AspB9GluB27 (P less than 0.05) and AspB28 (P less than 0.001) compared with human insulin. There was a significantly faster onset and offset of responses in C-peptide and intermediary metabolite levels after the analogues than after human insulin (P less than 0.05). The rapid absorption and biological actions of these analogues offer potential therapeutic advantages over the current short
Analysis of Factors Affecting System Performance in the ASpIRE Challenge

DTIC Science & Technology

2015-12-13

performance in the ASpIRE (Automatic Speech recognition In Reverberant Environments) challenge. In particular, overall word error rate (WER) of the solver...systems is analyzed as a function of room, distance between talker and microphone, and microphone type. We also analyze speech activity detection...analysis will inform the design of future challenges and provide insight into the efficacy of current solutions addressing noisy reverberant speech
[Comparison of SIB-IMRT treatment plans for upper esophageal carcinoma].

PubMed

Fu, Wei-hua; Wang, Lv-hua; Zhou, Zong-mei; Dai, Jian-rong; Hu, Yi-min

2003-06-01

To implement simultaneous integrated boost intensity-modulated radiotherapy(SIB-IMRT) plans for upper esophageal carcinoma and investigate the dose profiles of tumor and electively treated region and the dose to organs at risk (OARs). SIB-IMRT plans were designed for two patients with upper esophageal carcinoma. Two target volumes were predefined: PTV1, the target volume of the primary lesion, which was given to 67.2 Gy, and PTV2, the target volume of electively treated region, which was given to 50.4 Gy. With the same dose-volume constraints, but different beams arrangements (3, 5, 7, or 9 equispaced coplanar beams), four plans were generated. Indices, including dose distribution, dose volume histogram (DVH) and conformity index, were used for comparison of these plans. The plan with three intensity-modulated beams could produce good dose distribution for the two target volumes. The dose conformity to targets and the dose to OARs were improved as the beam number increased. The dose distributions in targets changed little when the beam number increased from 7 to 9. Five to seven intensity-modulated beams can produce desirable dose distributions for simultaneous integrated boost (SIB) treatment for upper esophageal carcinoma. The primary tumor can get higher equivalent dose by SIB treatments. It is easier and more efficient to design plans with equispaced coplanar beams. The efficacy of SIB-IMRT remains to be determined by the clinical outcome.
Filamentous fungal-specific septin AspE is phosphorylated in vivo and interacts with actin, tubulin and other septins in the human pathogen Aspergillus fumigatus

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

Juvvadi, Praveen Rao; Belina, Detti; Soderblom, Erik J.

2013-02-15

Highlights: ► In vivo interactions of the novel septin AspE were identified by GFP-Trap® affinity purification. ► Septins AspA, AspB, AspC and AspD interacted with AspE in vivo. ► Actin and tubulin interacted with AspE in vivo. ► AspE is phosphorylated at six serine residues in vivo. -- Abstract: We previously analyzed the differential localization patterns of five septins (AspA–E), including a filamentous fungal-specific septin, AspE, in the human pathogen Aspergillus fumigatus. Here we utilized the A. fumigatus strain expressing an AspE–EGFP fusion protein and show that this novel septin with a tubular localization pattern in hyphae is phosphorylated inmore » vivo and interacts with the other septins, AspA, AspB, AspC and AspD. The other major proteins interacting with AspE included the cytoskeletal proteins, actin and tubulin, which may be involved in the organization and transport of the septins. This is the first report analyzing the phosphorylation of AspE and localizing the sites of phosphorylation, and opens opportunities for further analysis on the role of post-translational modifications in the assembly and organization of A. fumigatus septins. This study also describes the previously unknown interaction of AspE with the actin-microtubule network. Furthermore, the novel GFP-Trap® affinity purification method used here complements widely-used GFP localization studies in fungal systems.« less
Evidence for Linkage of Bipolar Disorder to Chromosome 18 with a Parent-of-Origin Effect

PubMed Central

Stine, O. Colin; Xu, Jianfeng; Koskela, Rebecca; McMahon, Francis J.; Gschwend, Michele; Friddle, Carl; Clark, Chris D.; McInnis, Melvin G.; Simpson, Sylvia G.; Breschel, Theresa S.; Vishio, Eva; Riskin, Kelly; Feilotter, Harriet; Chen, Eugene; Shen, Susan; Folstein, Susan; Meyers, Deborah A.; Botstein, David; Marr, Thomas G.; DePaulo, J. Raymond

1995-01-01

A susceptibility gene on chromosome 18 and a parent-of-origin effect have been suggested for bipolar affective disorder (BPAD). We have studied 28 nuclear families selected for apparent unilineal transmission of the BPAD phenotype, by using 31 polymorphic markers spanning chromosome 18. Evidence for linkage was tested with affected-sib-pair and LOD score methods under two definitions of the affected phenotype. The affected-sib-pair analyses indicated excess allele sharing for markers on 18p within the region reported previously. The greatest sharing was at D18S37: 64% in bipolar and recurrent unipolar (RUP) sib pairs (P = .0006). In addition, excess sharing of the paternally, but not maternally, transmitted alleles was observed at three markers on 18q: at D18S41, 51 bipolar and RUP sib pairs were concordant for paternally transmitted alleles, and 21 pairs were discordant (P = .0004). The evidence for linkage to loci on both 18p and 18q was strongest in the 11 paternal pedigrees, i.e., those in which the father or one of the father's sibs is affected. In these pedigrees, the greatest allele sharing (81%; P = .00002) and the highest LOD score (3.51; θ = 0.0) were observed at D18S41. Our results provide further support for linkage of BPAD to chromosome 18 and the first molecular evidence for a parent-of-origin effect operating in this disorder. The number of loci involved, and their precise location, require further study. PMID:8533768
eNOS Glu298Asp polymorphism and hypertension in a cohort study in Japanese.

PubMed

Kishimoto, Takuji; Misawa, Yumiko; Kaetu, Akihiko; Nagai, Maria; Osaki, Yoneatsu; Okamoto, Mikizoh; Yoshida, Soiti; Kurosawa, Yoichi; Fukumoto, Soji

2004-11-01

Some recent case-control association studies have suggested negative and positive relationship between Glu298Asp (the substitution of aspartic acid for glutamic acid at amino acid position 298) polymorphism of the endothelial nitric oxide synthase (eNOS) gene and hypertension. To investigate whether the Glu298Asp polymorphism of the eNOS gene affects the incidence of hypertension, a retrospective cohort study was performed. The baseline data among Japanese workers in Shimane Prefecture, Japan, were obtained at regular health examination in 1992, and a retrospective cohort study was performed to analyze the influence of Glu298Asp polymorphism on the incidence of hypertension in 1998. The incidences of Glu298Glu, Glu298Asp, and Asp298Asp genotypes in the subjects were 86.4%, 12.6% and 1.1%, respectively. The risk ratios of Glu298Asp and Asp298Asp against Glu298Glu for the incidence of hypertension by single variance analysis were 0.830 in total subjects [95% confidence interval (CI) 0.474-1.452], 0.596 in subjects 20-39 years old (95% CI; 0.207-1.717), and 0.915 in subjects 40-59 years old (95% CI; 0.464-1.805). The risk ratios of Glu298Asp and Asp298Asp against Glu298Glu for the incidence of hypertension by multiple variance analysis adjusted for sex, BMI, serum total cholesterol, serum high-density lipoprotein (HDL) cholesterol, fasting glucose, cigarette smoking, drinking habits, eating habits, and exercise in 1992 were 0.750 in total subjects (95% CI; 0.421-1.335), 0.505 in subjects 20-39 years old (95% CI; 0.170-1.496), and 0.873 in subjects 40-59 years old (95% CI; 0.434-1.757). These results suggested no association between the Glu298Asp gene polymorphism and the incidence of hypertension in this selected population.
The score statistic of the LD-lod analysis: detecting linkage adaptive to linkage disequilibrium.

PubMed

Huang, J; Jiang, Y

2001-01-01

We study the properties of a modified lod score method for testing linkage that incorporates linkage disequilibrium (LD-lod). By examination of its score statistic, we show that the LD-lod score method adaptively combines two sources of information: (a) the IBD sharing score which is informative for linkage regardless of the existence of LD and (b) the contrast between allele-specific IBD sharing scores which is informative for linkage only in the presence of LD. We also consider the connection between the LD-lod score method and the transmission-disequilibrium test (TDT) for triad data and the mean test for affected sib pair (ASP) data. We show that, for triad data, the recessive LD-lod test is asymptotically equivalent to the TDT; and for ASP data, it is an adaptive combination of the TDT and the ASP mean test. We demonstrate that the LD-lod score method has relatively good statistical efficiency in comparison with the ASP mean test and the TDT for a broad range of LD and the genetic models considered in this report. Therefore, the LD-lod score method is an interesting approach for detecting linkage when the extent of LD is unknown, such as in a genome-wide screen with a dense set of genetic markers. Copyright 2001 S. Karger AG, Basel

ASP-G: an ASP-based method for finding attractors in genetic regulatory networks

PubMed Central

Mushthofa, Mushthofa; Torres, Gustavo; Van de Peer, Yves; Marchal, Kathleen; De Cock, Martine

2014-01-01

Motivation: Boolean network models are suitable to simulate GRNs in the absence of detailed kinetic information. However, reducing the biological reality implies making assumptions on how genes interact (interaction rules) and how their state is updated during the simulation (update scheme). The exact choice of the assumptions largely determines the outcome of the simulations. In most cases, however, the biologically correct assumptions are unknown. An ideal simulation thus implies testing different rules and schemes to determine those that best capture an observed biological phenomenon. This is not trivial because most current methods to simulate Boolean network models of GRNs and to compute their attractors impose specific assumptions that cannot be easily altered, as they are built into the system. Results: To allow for a more flexible simulation framework, we developed ASP-G. We show the correctness of ASP-G in simulating Boolean network models and obtaining attractors under different assumptions by successfully recapitulating the detection of attractors of previously published studies. We also provide an example of how performing simulation of network models under different settings help determine the assumptions under which a certain conclusion holds. The main added value of ASP-G is in its modularity and declarativity, making it more flexible and less error-prone than traditional approaches. The declarative nature of ASP-G comes at the expense of being slower than the more dedicated systems but still achieves a good efficiency with respect to computational time. Availability and implementation: The source code of ASP-G is available at http://bioinformatics.intec.ugent.be/kmarchal/Supplementary_Information_Musthofa_2014/asp-g.zip. Contact: Kathleen.Marchal@UGent.be or Martine.DeCock@UGent.be Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25028722
Supporting NEESPI with Data Services - The SIB-ESS-C e-Infrastructure

NASA Astrophysics Data System (ADS)

Gerlach, R.; Schmullius, C.; Frotscher, K.

2009-04-01

Data discovery and retrieval is commonly among the first steps performed for any Earth science study. The way scientific data is searched and accessed has changed significantly over the past two decades. Especially the development of the World Wide Web and the technologies that evolved along shortened the data discovery and data exchange process. On the other hand the amount of data collected and distributed by earth scientists has increased exponentially requiring new concepts for data management and sharing. One such concept to meet the demand is to build up Spatial Data Infrastructures (SDI) or e-Infrastructures. These infrastructures usually contain components for data discovery allowing users (or other systems) to query a catalogue or registry and retrieve metadata information on available data holdings and services. Data access is typically granted using FTP/HTTP protocols or, more advanced, through Web Services. A Service Oriented Architecture (SOA) approach based on standardized services enables users to benefit from interoperability among different systems and to integrate distributed services into their application. The Siberian Earth System Science Cluster (SIB-ESS-C) being established at the University of Jena (Germany) is such a spatial data infrastructure following these principles and implementing standards published by the Open Geospatial Consortium (OGC) and the International Organization for Standardization (ISO). The prime objective is to provide researchers with focus on Siberia with the technical means for data discovery, data access, data publication and data analysis. The region of interest covers the entire Asian part of the Russian Federation from the Ural to the Pacific Ocean including the Ob-, Lena- and Yenissey river catchments. The aim of SIB-ESS-C is to provide a comprehensive set of data products for Earth system science in this region. Although SIB-ESS-C will be equipped with processing capabilities for in-house data generation
Assembly of the Type II Secretion System such as Found in Vibrio cholerae Depends on the Novel Pilotin AspS

PubMed Central

Dunstan, Rhys A.; Heinz, Eva; Wijeyewickrema, Lakshmi C.; Pike, Robert N.; Purcell, Anthony W.; Evans, Timothy J.; Praszkier, Judyta; Robins-Browne, Roy M.; Strugnell, Richard A.; Korotkov, Konstantin V.; Lithgow, Trevor

2013-01-01

The Type II Secretion System (T2SS) is a molecular machine that drives the secretion of fully-folded protein substrates across the bacterial outer membrane. A key element in the machinery is the secretin: an integral, multimeric outer membrane protein that forms the secretion pore. We show that three distinct forms of T2SSs can be distinguished based on the sequence characteristics of their secretin pores. Detailed comparative analysis of two of these, the Klebsiella-type and Vibrio-type, showed them to be further distinguished by the pilotin that mediates their transport and assembly into the outer membrane. We have determined the crystal structure of the novel pilotin AspS from Vibrio cholerae, demonstrating convergent evolution wherein AspS is functionally equivalent and yet structurally unrelated to the pilotins found in Klebsiella and other bacteria. AspS binds to a specific targeting sequence in the Vibrio-type secretins, enhances the kinetics of secretin assembly, and homologs of AspS are found in all species of Vibrio as well those few strains of Escherichia and Shigella that have acquired a Vibrio-type T2SS. PMID:23326233
A Cyclic Nucleotide-Gated Channel Mutation Associated with Canine Daylight Blindness Provides Insight into a Role for the S2 Segment Tri-Asp motif in Channel Biogenesis

PubMed Central

Tanaka, Naoto; Delemotte, Lucie; Klein, Michael L.; Komáromy, András M.; Tanaka, Jacqueline C.

2014-01-01

Cone cyclic nucleotide-gated channels are tetramers formed by CNGA3 and CNGB3 subunits; CNGA3 subunits function as homotetrameric channels but CNGB3 exhibits channel function only when co-expressed with CNGA3. An aspartatic acid (Asp) to asparagine (Asn) missense mutation at position 262 in the canine CNGB3 (D262N) subunit results in loss of cone function (daylight blindness), suggesting an important role for this aspartic acid residue in channel biogenesis and/or function. Asp 262 is located in a conserved region of the second transmembrane segment containing three Asp residues designated the Tri-Asp motif. This motif is conserved in all CNG channels. Here we examine mutations in canine CNGA3 homomeric channels using a combination of experimental and computational approaches. Mutations of these conserved Asp residues result in the absence of nucleotide-activated currents in heterologous expression. A fluorescent tag on CNGA3 shows mislocalization of mutant channels. Co-expressing CNGB3 Tri-Asp mutants with wild type CNGA3 results in some functional channels, however, their electrophysiological characterization matches the properties of homomeric CNGA3 channels. This failure to record heteromeric currents suggests that Asp/Asn mutations affect heteromeric subunit assembly. A homology model of S1–S6 of the CNGA3 channel was generated and relaxed in a membrane using molecular dynamics simulations. The model predicts that the Tri-Asp motif is involved in non-specific salt bridge pairings with positive residues of S3/S4. We propose that the D262N mutation in dogs with CNGB3-day blindness results in the loss of these inter-helical interactions altering the electrostatic equilibrium within in the S1–S4 bundle. Because residues analogous to Tri-Asp in the voltage-gated Shaker potassium channel family were implicated in monomer folding, we hypothesize that destabilizing these electrostatic interactions impairs the monomer folding state in D262N mutant CNG channels
Conformational Change in the Active Site of Streptococcal Unsaturated Glucuronyl Hydrolase Through Site-Directed Mutagenesis at Asp-115.

PubMed

Nakamichi, Yusuke; Oiki, Sayoko; Mikami, Bunzo; Murata, Kousaku; Hashimoto, Wataru

2016-08-01

Bacterial unsaturated glucuronyl hydrolase (UGL) degrades unsaturated disaccharides generated from mammalian extracellular matrices, glycosaminoglycans, by polysaccharide lyases. Two Asp residues, Asp-115 and Asp-175 of Streptococcus agalactiae UGL (SagUGL), are completely conserved in other bacterial UGLs, one of which (Asp-175 of SagUGL) acts as a general acid and base catalyst. The other Asp (Asp-115 of SagUGL) also affects the enzyme activity, although its role in the enzyme reaction has not been well understood. Here, we show substitution of Asp-115 in SagUGL with Asn caused a conformational change in the active site. Tertiary structures of SagUGL mutants D115N and D115N/K370S with negligible enzyme activity were determined at 2.00 and 1.79 Å resolution, respectively, by X-ray crystallography. The side chain of Asn-115 is drastically shifted in both mutants owing to the interaction with several residues, including Asp-175, by formation of hydrogen bonds. This interaction between Asn-115 and Asp-175 probably prevents the mutants from triggering the enzyme reaction using Asp-175 as an acid catalyst.
ExPASy: SIB bioinformatics resource portal.

PubMed

Artimo, Panu; Jonnalagedda, Manohar; Arnold, Konstantin; Baratin, Delphine; Csardi, Gabor; de Castro, Edouard; Duvaud, Séverine; Flegel, Volker; Fortier, Arnaud; Gasteiger, Elisabeth; Grosdidier, Aurélien; Hernandez, Céline; Ioannidis, Vassilios; Kuznetsov, Dmitry; Liechti, Robin; Moretti, Sébastien; Mostaguir, Khaled; Redaschi, Nicole; Rossier, Grégoire; Xenarios, Ioannis; Stockinger, Heinz

2012-07-01

ExPASy (http://www.expasy.org) has worldwide reputation as one of the main bioinformatics resources for proteomics. It has now evolved, becoming an extensible and integrative portal accessing many scientific resources, databases and software tools in different areas of life sciences. Scientists can henceforth access seamlessly a wide range of resources in many different domains, such as proteomics, genomics, phylogeny/evolution, systems biology, population genetics, transcriptomics, etc. The individual resources (databases, web-based and downloadable software tools) are hosted in a 'decentralized' way by different groups of the SIB Swiss Institute of Bioinformatics and partner institutions. Specifically, a single web portal provides a common entry point to a wide range of resources developed and operated by different SIB groups and external institutions. The portal features a search function across 'selected' resources. Additionally, the availability and usage of resources are monitored. The portal is aimed for both expert users and people who are not familiar with a specific domain in life sciences. The new web interface provides, in particular, visual guidance for newcomers to ExPASy.
Comparison of subcutaneous soluble human insulin and insulin analogues (AspB9, GluB27; AspB10; AspB28) on meal-related plasma glucose excursions in type I diabetic subjects.

PubMed

Kang, S; Creagh, F M; Peters, J R; Brange, J; Vølund, A; Owens, D R

1991-07-01

To compare postprandial glucose excursions and plasma free insulin-analogue levels after subcutaneous injection of three novel human insulin analogues (AspB10; AspB9, GluB27; and AspB28) with those after injection of soluble human insulin (Actrapid HM U-100). Six male subjects with insulin-dependent diabetes, at least 1 wk apart and after an overnight fast and basal insulin infusion, received 72 nmol (approximately 12 U) s.c. of soluble human insulin 30 min before, or 72 nmol of each of the three analogues immediately before, a standard 500-kcal meal. Mean basal glucoses were similar on the 4 study days. Compared to human insulin (6.3 +/- 0.8 mM), mean +/- SE peak incremental glucose rises were similar after analogues AspB10 (5.4 +/- 0.8 mM) and AspB9, GluB27 (5.4 +/- 0.7 mM) and significantly lower after analogue AspB28 (3.6 +/- 1.2 mM, P less than 0.02). Relative to soluble human insulin (100% +/- SE21), incremental areas under the glucose curve between 0 and 240 min were 79% +/- 34 (AspB10, NS), 70% +/- 29 (AspB9, GluB27, NS), and 43% +/- 23 (AspB28, P less than 0.02). Basal plasma free insulin levels were similar on the 4 study days. Plasma free insulin-analogue levels rose rapidly to peak 30 min after injection at 308 +/- 44 pM (AspB10); 1231 +/- 190 pM (AspB9, GluB27) and 414 +/- 42 pM (AspB28) and were significantly higher than corresponding (i.e., 30 min postmeal) plasma free insulin levels of 157 +/- 15 pM (P less than 0.02 in each case). Plasma profiles of the insulin analogues were more physiological than that of human insulin after subcutaneous injection. All three analogues given immediately before the meal are at least as effective as soluble human insulin given 30 min earlier. These analogues are promising potential candidates for short-acting insulins of the future.
Familial Clustering of Executive Functioning in Affected Sibling Pair Families with ADHD

ERIC Educational Resources Information Center

Slaats-Willemse, Dorine; Swaab-Barneveld, Hanna; De Sonneville, Leo; Buitelaar, Jan

2005-01-01

Objective: To investigate familial clustering of executive functioning (i.e., response inhibition, fine visuomotor functioning, and attentional control) in attention-deficit/hyperactivity disorder (ADHD)-affected sibling pairs. Method: Fifty-two affected sibling pairs aged 6 to 18 years and diagnosed with ADHD according to DSM-IV performed the…
New technique for fertilizing eggs of burbot, asp and ide under hatchery conditions.

PubMed

Kucharczyk, Dariusz; Nowosad, Joanna; Łuczyński, Marek J; Targońska, Katarzyna

2016-09-01

The development of a new protocol for egg fertilization may increase embryo survival and benefit the aquaculture process. In the present study, a new technique of partially adding sperm to activated eggs in the artificial fertilization of burbot (Lota lota), ide (Leuciscus idus) and asp (Aspius aspius) eggs was evaluated. If the same volume of sperm was divided into two or three parts and added to eggs in 30-60s intervals, it significantly improved embryo survival at the eyed-egg-stage of development. In the present study, the periodic addition of spermatozoa to eggs affected fertilization (ide and asp) and embryo survival rates (ide, asp and burbot) and might be successfully applied under hatchery conditions. Copyright © 2016 Elsevier B.V. All rights reserved.
ASP Strategies and Appropriate Antibiotic Use

PubMed Central

Lee, Brian R; Tribble, Alison; Handy, Lori; Gerber, Jeffrey S; Hersh, Adam L; Kronman, Matthew; Terrill, Cindy; Newland, Jason

2017-01-01

Abstract Background The Infectious Diseases Society of America (IDSA) recommends hospitals implement antimicrobial stewardship programs (ASP) in order to decrease inappropriate antibiotic use due to the rise in antibiotic-resistant infections. Data are limited on the extent to which different ASP strategies influence appropriate antibiotic use. Methods We conducted an online survey in 2016 of U.S. Children’s Hospitals to collect hospital-level information on dedicated ASP effort, ASP monitoring activities, use of audit-feedback, formulary restrictions, rapid diagnostics, etc. During the same period the ASP teams at these hospitals completed 3 point prevalence surveys that documented details on all admitted patients 0–17 years receiving any antibiotics, determined what ASP modifications could be made, and if the antibiotic was appropriate. We employed hierarchical, multivariable logit models to examine which ASP-related, hospital-level strategies were associated with appropriate antibiotic use. Results Thirty hospitals participated. A total of 6,921 patients were included, representing 10,068 total antibiotics. Of these orders, 8,554 (85.0%) were categorized as appropriate, though this varied across sites (range: 68-92%). Additionally, 78.2% of antibiotics did not have recommended modifications. Appropriate antibiotic use was significantly higher for hospitals that relied on rapid diagnostics (aOR: 1.6; P < 0.001) or monitored their days of therapy (DOT) rate (aOR: 1.4; P < 0.001), whereas the presence of either audit-feedback (aOR: 1.04; P = 0.75) or formulary restrictions (aOR: 0.83; P = 0.059) were not associated. Having annual education for all prescribers had increased likelihood of antibiotics having no modification recommendations (aOR: 1.45; P = 0.037). Total ASP FTE was not correlated with hospital-level percent appropriate use (corr: −0.05; P = 0.79) or antibiotic modification recommendations (corr: −0.08; P = 0.67). Conclusion Routine
SibRank: Signed bipartite network analysis for neighbor-based collaborative ranking

NASA Astrophysics Data System (ADS)

Shams, Bita; Haratizadeh, Saman

2016-09-01

Collaborative ranking is an emerging field of recommender systems that utilizes users' preference data rather than rating values. Unfortunately, neighbor-based collaborative ranking has gained little attention despite its more flexibility and justifiability. This paper proposes a novel framework, called SibRank that seeks to improve the state of the art neighbor-based collaborative ranking methods. SibRank represents users' preferences as a signed bipartite network, and finds similar users, through a novel personalized ranking algorithm in signed networks.
Pseudoautosomal linkage of Hodgkin disease.

PubMed

Horwitz, M; Wiernik, P H

1999-11-01

Heritable factors appear to account for much of the risk for Hodgkin disease (HD). There is evidence for an HLA-linked gene, but other predisposing loci remain unaccounted for. The observation of a family coinheriting both HD and Leri-Weill dyschondrosteosis (LWD) suggests that a gene conferring risk for HD resides adjacent to the LWD locus. The gene responsible for LWD, SHOX, localizes to the short-arm pseudoautosomal region (PAR) of the X and Y chromosomes. A unique segregation pattern for PAR-linked genes has been predicted-that affected sibs will tend to be same sex. An excess of sex-concordant affected sib pairs with HD has been noted but has been attributed to an environmental etiology. These two observations-sex concordance in sib pairs with HD and cosegregation of HD and LWD-impelled a test of the hypothesis that there is a PAR-localized gene for HD. By first scoring recombinations dissociating sex from phenotype in individuals from pedigrees with LWD, we determined a male maximum recombination frequency (thetamax) of.405. This places SHOX near the short-arm telomeres of the sex chromosome and supports the prediction that PAR recombination is obligatory for spermatogenesis. By inferring recombinations between HD and sexual phenotype in sib pairs, we predict, for the postulated HD gene, a male thetamax as high as .254, which places it in proximity to SHOX. Morton's nonparametric affected-sib-pair "beta" model was used in the evaluation of linkage between HD and phenotypic sex and gave a LOD score of 2.41. Using this approach, we reevaluated evidence for HLA linkage in HD in haplotyped sib pairs and found a LOD score of 2.00. The resulting beta values indicate that the putative PAR- and HLA-linked loci account for 29% and 40%, respectively, of the heritability of HD in an American population.
Further evidence for the increased power of LOD scores compared with nonparametric methods.

PubMed

Durner, M; Vieland, V J; Greenberg, D A

1999-01-01

In genetic analysis of diseases in which the underlying model is unknown, "model free" methods-such as affected sib pair (ASP) tests-are often preferred over LOD-score methods, although LOD-score methods under the correct or even approximately correct model are more powerful than ASP tests. However, there might be circumstances in which nonparametric methods will outperform LOD-score methods. Recently, Dizier et al. reported that, in some complex two-locus (2L) models, LOD-score methods with segregation analysis-derived parameters had less power to detect linkage than ASP tests. We investigated whether these particular models, in fact, represent a situation that ASP tests are more powerful than LOD scores. We simulated data according to the parameters specified by Dizier et al. and analyzed the data by using a (a) single locus (SL) LOD-score analysis performed twice, under a simple dominant and a recessive mode of inheritance (MOI), (b) ASP methods, and (c) nonparametric linkage (NPL) analysis. We show that SL analysis performed twice and corrected for the type I-error increase due to multiple testing yields almost as much linkage information as does an analysis under the correct 2L model and is more powerful than either the ASP method or the NPL method. We demonstrate that, even for complex genetic models, the most important condition for linkage analysis is that the assumed MOI at the disease locus being tested is approximately correct, not that the inheritance of the disease per se is correctly specified. In the analysis by Dizier et al., segregation analysis led to estimates of dominance parameters that were grossly misspecified for the locus tested in those models in which ASP tests appeared to be more powerful than LOD-score analyses.
Paradigm Diagnostics Salmonella Indicator Broth (PDX-SIB) for detection of Salmonella on selected environmental surfaces.

PubMed

Olstein, Alan; Griffith, Leena; Feirtag, Joellen; Pearson, Nicole

2013-01-01

The Paradigm Diagnostics Salmonella Indicator Broth (PDX-SIB) is intended as a single-step selective enrichment indicator broth to be used as a simple screening test for the presence of Salmonella spp. in environmental samples. This method permits the end user to avoid multistep sample processing to identify presumptively positive samples, as exemplified by standard U.S. reference methods. PDX-SIB permits the outgrowth of Salmonella while inhibiting the growth of competitive Gram-negative and -positive microflora. Growth of Salmonella-positive cultures results in a visual color change of the medium from purple to yellow when the sample is grown at 37 +/- 1 degree C. Performance of PDX-SIB has been evaluated in five different categories: inclusivity-exclusivity, methods comparison, ruggedness, lot-to-lot variability, and shelf stability. The inclusivity panel included 100 different Salmonella serovars, 98 of which were SIB-positive during the 30 to 48 h incubation period. The exclusivity panel included 33 different non-Salmonella microorganisms, 31 of which were SIB-negative during the incubation period. Methods comparison studies included four different surfaces: S. Newport on plastic, S. Anatum on sealed concrete, S. Abaetetuba on ceramic tile, and S. Typhimurium in the presence of 1 log excess of Citrobacter freundii. Results of the methods comparison studies demonstrated no statistical difference between the SIB method and the U.S. Food and Drug Administration-Bacteriological Analytical Manual reference method, as measured by the Mantel-Haenszel Chi-square test. Ruggedness studies demonstrated little variation in test results when SIB incubation temperatures were varied over a 34-40 degrees C range. Lot-to-lot consistency results suggest no detectable differences in manufactured goods using two reference Salmonella serovars and one non-Salmonella microorganism.
Field performance of shortleaf pine half-sib families though 10 years in the Ouachita Mountains of Arkansas

Treesearch

John C. Brissette; James P. Barnett

2003-01-01

Shortleaf pine (Pinus echinata Mill.) seeds collected from six half-sib families were grown as both bareroot and container stock and outplanted on two sites in the Ouachita Mountains of Arkansas. Survival and growth were measured at years 1, 3, 5, and 10 afier planting. Stock-type and family interacted to affect height at year 1 on one site. There...
Impact of maternal obesity on inhaled corticosteroid use in childhood: a registry based analysis of first born children and a sibling pair analysis.

PubMed

Lowe, Adrian J; Ekeus, Cecilia; Bråbäck, Lennart; Rajaleid, Kristiina; Forsberg, Bertil; Hjern, Anders

2013-01-01

It has been proposed that maternal obesity during pregnancy may increase the risk that the child develops allergic disease and asthma, although the mechanisms underpinning this relationship are currently unclear. We sought to assess if this association may be due to confounding by genetic or environmental risk factors that are common to maternal obesity and childhood asthma, using a sibling pair analysis. The study population comprised a Swedish national cohort of term children born between 1992 and 2008 to native Swedish parents. Maternal body mass index (BMI) was measured at 8-10 weeks gestation. Unconditional logistic regression models were used to determine if maternal obesity was associated with increased risk of inhaled corticosteroid (ICS) in 431,718 first-born children, while adjusting for potential confounders. An age-matched discordant sib-pair analysis was performed, taking into account shared genetic and environmental risk factors. Maternal over-weight and obesity were associated with increased risk that the child would require ICS (for BMI≥35 kg/m(2), aOR = 1.30, 95%CI = 1.10-1.52 compared with normal weight mothers) in children aged 6-12 years. Similar effects were seen in younger children, but in children aged 13-16 years, maternal obesity (BMI≥30) was related to increased risk of ICS use in girls (aOR = 1.28, 95%CI = 1.07-1.53) but not boys (OR = 1.05, 95%CI = 0.87-1.26). The sib-pair analysis, which included 2,034 sib-pairs older than six years who were discordant for both ICS use and maternal BMI category, failed to find any evidence that increasing maternal weight was related to increased risk of ICS use. Maternal obesity is associated with increased risk of childhood ICS use up to approximately 12 years of age, but only in girls after this age. These effects could not be confirmed in a sib pair analysis, suggesting either limited statistical power, or the effects of maternal BMI may be due to shared genetic or
Psychometric appraisal of the Scale for Interpersonal Behavior (SIB) in France.

PubMed

Bouvard, M; Arrindell, W A; Guérin, J; Bouchard, C; Rion, A C; Ducottet, E; Séchaud, M; Mollard, E; Grillet, P R; Dang, C; Cottraux, J

1999-08-01

The present study was carried out in France to evaluate the reliability and validity of the Scale for Interpersonal Behavior (SIB), a multidimensional measure of difficulty and distress in assertiveness that was originally developed in The Netherlands. This appraisal was conducted with a clinical sample (N = 166) and a general population sample (N = 150). The clinical series comprised 115 patients with social phobia and 51 patients with personality disorder, 28 of whom were of the avoidant type. Support was found for internal consistency and test-retest reliability of the French SIB. Compared to controls, both social phobics and patients with an avoidant personality disorder had significantly lower mean scores on all performance scales and significantly higher ones on all distress scales, with the social phobics occupying a position in between. Findings in relation to convergent and divergent validity were quite satisfactory. Sensitivity of the French SIB for detecting change was demonstrated in a subgroup of the clinical Ss who had undergone 15 sessions of cognitive-behavioral group therapy for underassertiveness.
A DRD1 haplotype is associated with risk for autism spectrum disorders in male-only affected sib-pair families.

PubMed

Hettinger, Joe A; Liu, Xudong; Schwartz, Charles E; Michaelis, Ron C; Holden, Jeanette J A

2008-07-05

Individuals with autism spectrum disorders (ASDs) have impairments in executive function and social cognition, with males generally being more severely affected in these areas than females. Because the dopamine D1 receptor (encoded by DRD1) is integral to the neural circuitry mediating these processes, we examined the DRD1 gene for its role in susceptibility to ASDs by performing single marker and haplotype case-control comparisons, family-based association tests, and genotype-phenotype assessments (quantitative transmission disequilibrium tests: QTDT) using three DRD1 polymorphisms, rs265981C/T, rs4532A/G, and rs686T/C. Our previous findings suggested that the dopaminergic system may be more integrally involved in families with affected males only than in other families. We therefore restricted our study to families with two or more affected males (N = 112). There was over-transmission of rs265981-C and rs4532-A in these families (P = 0.040, P = 0.038), with haplotype TDT analysis showing over-transmission of the C-A-T haplotype (P = 0.022) from mothers to affected sons (P = 0.013). In addition, haplotype case-control comparisons revealed an increase of this putative risk haplotype in affected individuals relative to a comparison group (P = 0.004). QTDT analyses showed associations of the rs265981-C, rs4532-A, rs686-T alleles, and the C-A-T haplotype with more severe problems in social interaction, greater difficulties with nonverbal communication and increased stereotypies compared to individuals with other haplotypes. Preferential haplotype transmission of markers at the DRD1 locus and an increased frequency of a specific haplotype support the DRD1 gene as a risk gene for core symptoms of ASD in families having only affected males. Copyright 2008 Wiley-Liss, Inc.
Structural elucidation of the DFG-Asp in and DFG-Asp out states of TAM kinases and insight into the selectivity of their inhibitors.

PubMed

Messoussi, Abdellah; Peyronnet, Lucile; Feneyrolles, Clémence; Chevé, Gwénaël; Bougrin, Khalid; Yasri, Aziz

2014-10-10

Structural elucidation of the active (DFG-Asp in) and inactive (DFG-Asp out) states of the TAM family of receptor tyrosine kinases is required for future development of TAM inhibitors as drugs. Herein we report a computational study on each of the three TAM members Tyro-3, Axl and Mer. DFG-Asp in and DFG-Asp out homology models of each one were built based on the X-ray structure of c-Met kinase, an enzyme with a closely related sequence. Structural validation and in silico screening enabled identification of critical amino acids for ligand binding within the active site of each DFG-Asp in and DFG-Asp out model. The position and nature of amino acids that differ among Tyro-3, Axl and Mer, and the potential role of these residues in the design of selective TAM ligands, are discussed.
Severe myopia with unusual retinal anomalies and Dandy-Walker sequence in two sibs. A distinct new neuro-ocular disorder.

PubMed

de Crecchio, Giuseppe; Cennamo, Gilda; de Leeuw, Nicole; Ventruto, Maria Luisa; Lonardo, Maria Concetta; Friso, Patrizia; Ventruto, Valerio

2013-12-01

We have observed a male and a female, sibs of non-consanguineous parents, affected by severe myopia with characteristic retinal defects and Dandy-Walker variant. The peculiarity of the retinopathy consists of pathological myopia with anomalous vitreal fenestrated membranes in the retinal periphery. We suppose that these associations may configure a new genetic syndrome.

Quantitative determination of free D-Asp, L-Asp and N-methyl-D-aspartate in mouse brain tissues by chiral separation and Multiple Reaction Monitoring tandem mass spectrometry.

PubMed

Fontanarosa, Carolina; Pane, Francesca; Sepe, Nunzio; Pinto, Gabriella; Trifuoggi, Marco; Squillace, Marta; Errico, Francesco; Usiello, Alessandro; Pucci, Piero; Amoresano, Angela

2017-01-01

Several studies have suggested that free d-Asp has a crucial role in N-methyl d-Asp receptor-mediated neurotransmission playing very important functions in physiological and pathological processes. This paper describes the development of an analytical procedure for the direct and simultaneous determination of free d-Asp, l-Asp and N-methyl d-Asp in specimens of different mouse brain tissues using chiral LC-MS/MS in Multiple Reaction Monitoring scan mode. After comparing three procedures and different buffers and extraction solvents, a simple preparation procedure was selected the analytes of extraction. The method was validated by analyzing l-Asp, d-Asp and N-methyl d-Asp recovery at different spiked concentrations (50, 100 and 200 pg/μl) yielding satisfactory recoveries (75-110%), and good repeatability. Limits of detection (LOD) resulted to be 0.52 pg/μl for d-Asp, 0.46 pg/μl for l-Asp and 0.54 pg/μl for NMDA, respectively. Limits of quantification (LOQ) were 1.57 pg/μl for d-Asp, 1.41 pg/μl for l-Asp and 1.64 pg/μl for NMDA, respectively. Different concentration levels were used for constructing the calibration curves which showed good linearity. The validated method was then successfully applied to the simultaneous detection of d-Asp, l-Asp and NMDA in mouse brain tissues. The concurrent, sensitive, fast, and reproducible measurement of these metabolites in brain tissues will be useful to correlate the amount of free d-Asp with relevant neurological processes, making the LC-MS/MS MRM method well suited, not only for research work but also for clinical analyses.
Characterization of yields for Pinus taeda genotypes at the half-sib, full-sib, and varietal levels of genetic improvement at two planting densities at age 5 in the upper coastal plain of Georgia

Treesearch

Derek Dougherty; Michael Kane; Robert Teskey; Richard Daniels; Jeff Wright

2012-01-01

Seedling deployment options for the establishment of operational Pinus taeda plantations in the Southeastern U.S. now include half-sib families, full-sib crosses, and varietals. In 2005, a study to evaluate the effects of genotype and density on yield and quality was established on a moderately well-drained upland site in the Upper Coastal Plain in...
Olfactory attractants and parity affect prenatal androgens and territoriality of coyote breeding pairs.

PubMed

Schell, Christopher J; Young, Julie K; Lonsdorf, Elizabeth V; Mateo, Jill M; Santymire, Rachel M

2016-10-15

Hormones are fundamental mediators of personality traits intimately linked with reproductive success. Hence, alterations to endocrine factors may dramatically affect individual behavior that has subsequent fitness consequences. Yet it is unclear how hormonal or behavioral traits change with environmental stressors or over multiple reproductive opportunities, particularly for biparental fauna. To simulate an environmental stressor, we exposed captive coyote (Canis latrans) pairs to novel coyote odor attractants (i.e. commercial scent lures) mid-gestation to influence territorial behaviors, fecal glucocorticoid (FGMs) and fecal androgen metabolites (FAMs). In addition, we observed coyote pairs as first-time and experienced breeders to assess the influence of parity on our measures. Treatment pairs received the odors four times over a 20-day period, while control pairs received water. Odor-treated pairs scent-marked (e.g. urinated, ground scratched) and investigated odors more frequently than control pairs, and had higher FAMs when odors were provided. Pairs had higher FAMs as first-time versus experienced breeders, indicating that parity also affected androgen production during gestation. Moreover, repeatability in scent-marking behaviors corresponded with FGMs and FAMs, implying that coyote territoriality during gestation is underpinned by individually-specific hormone profiles. Our results suggest coyote androgens during gestation are sensitive to conspecific olfactory stimuli and prior breeding experience. Consequently, fluctuations in social or other environmental stimuli as well as increasing parity may acutely affect coyote traits essential to reproductive success. Copyright © 2016 Elsevier Inc. All rights reserved.
SCAMP and the ASP

NASA Astrophysics Data System (ADS)

Idehara, H.; Carbon, D. F.

2004-12-01

We present two new, publicly available tools to support the examination and interpretation of spectra. SCAMP is a specialized graphical user interface for MATLAB. It allows researchers to rapidly intercompare sets of observational, theoretical, and/or laboratory spectra. Users have extensive control over the colors and placement of individual spectra, and over spectrum normalization from one spectral region to another. Spectra can be interactively assigned to user-defined groups and the groupings recalled at a later time. The user can measure/record positions and intensities of spectral features, interactively spline-fit spectra, and normalize spectra by fitted splines. User-defined wavelengths can be automatically highlighted in SCAMP plots. The user can save/print annotated graphical output suitable for a scientific notebook depicting the work at any point. The ASP is a WWW portal that provides interactive access to two spectrum data sets: a library of synthetic stellar spectra and a library of laboratory PAH spectra. The synthetic stellar spectra in the ASP are appropriate to the giant branch with an assortment of compositions. Each spectrum spans the full range from 2 to 600 microns at a variety of resolutions. The ASP is designed to allow users to quickly identify individual features at any resolution that arise from any of the included isotopic species. The user may also retrieve the depth of formation of individual features at any resolution. PAH spectra accessible through the ASP are drawn from the extensive library of spectra measured by the NASA Ames Astrochemistry Laboratory. The user may interactively choose any subset of PAHs in the data set, combine them with user-defined weights and temperatures, and view/download the resultant spectrum at any user-defined resolution. This work was funded by the NASA Advanced Supercomputing Division, NASA Ames Research Center.
Pseudoautosomal Linkage of Hodgkin Disease

PubMed Central

Horwitz, Marshall; Wiernik2, Peter H.

1999-01-01

Summary Heritable factors appear to account for much of the risk for Hodgkin disease (HD). There is evidence for an HLA-linked gene, but other predisposing loci remain unaccounted for. The observation of a family coinheriting both HD and Leri-Weill dyschondrosteosis (LWD) suggests that a gene conferring risk for HD resides adjacent to the LWD locus. The gene responsible for LWD, SHOX, localizes to the short-arm pseudoautosomal region (PAR) of the X and Y chromosomes. A unique segregation pattern for PAR-linked genes has been predicted—that affected sibs will tend to be same sex. An excess of sex-concordant affected sib pairs with HD has been noted but has been attributed to an environmental etiology. These two observations—sex concordance in sib pairs with HD and cosegregation of HD and LWD—impelled a test of the hypothesis that there is a PAR-localized gene for HD. By first scoring recombinations dissociating sex from phenotype in individuals from pedigrees with LWD, we determined a male maximum recombination frequency (θmax) of .405. This places SHOX near the short-arm telomeres of the sex chromosome and supports the prediction that PAR recombination is obligatory for spermatogenesis. By inferring recombinations between HD and sexual phenotype in sib pairs, we predict, for the postulated HD gene, a male θmax as high as .254, which places it in proximity to SHOX. Morton's nonparametric affected-sib-pair “β” model was used in the evaluation of linkage between HD and phenotypic sex and gave a LOD score of 2.41. Using this approach, we reevaluated evidence for HLA linkage in HD in haplotyped sib pairs and found a LOD score of 2.00. The resulting β values indicate that the putative PAR- and HLA-linked loci account for 29% and 40%, respectively, of the heritability of HD in an American population. PMID:10521308
Intelligence quotient profile in myotonic dystrophy, intergenerational deficit, and correlation with CTG amplification.

PubMed Central

Turnpenny, P; Clark, C; Kelly, K

1994-01-01

An abbreviated Wechsler Adult Intelligence Scale Revised (WAIS-R) was used to assess verbal and arithmetical cognitive performance in 55 subjects with myotonic dystrophy (DM), covering all grades of disease severity, and 31 controls at 50% risk of inheriting DM. Scaled scores from the assessment were converted into an intelligence quotient (IQ) estimation on each person. Significant IQ differences were found between: (1) all 55 DM subjects (mean 90.2, SD 16.1) and 31 controls (102.6, SD 9.4), with no sex differences in either group; (2) 15 affected parents (99.3, SD 12.2) and their affected children (88.1, SD 17.2), where significance was dependent on parental sex being female; and (3) 15 pairs of affected sibs (89.6, SD 13.2) and their normal sibs (100.2, SD 7.6). IQ steadily declined as (1) the age of onset of signs and symptoms decreased, and (2) the CTG expansion size increased. The correlation appeared to be more linear with age of onset. The correlation of IQ difference and CTG expansion difference in both the DM parent-child pairs and normal sib-affected sib pairs was poor, indicating that CTG expansion is not a reliable predictor of IQ either in individual persons or families. Further analysis of cognitive function in DM is required to clarify specific deficits characteristic of this patient group. PMID:8071955
New support for an old hypothesis: density affects extra-pair paternity

PubMed Central

Mayer, Christian; Pasinelli, Gilberto

2013-01-01

Density has been suggested to affect variation in extra-pair paternity (EPP) in avian mating systems, because increasing density promotes encounter rates and thus mating opportunities. However, the significance of density affecting EPP variation in intra- and interspecific comparisons has remained controversial, with more support from intraspecific comparisons. Neither experimental nor empirical studies have consistently provided support for the density hypothesis. Testing the density hypothesis is challenging because density measures may not necessarily reflect extra-pair mating opportunities, mate guarding efforts may covary with density, populations studied may differ in migratory behavior and/or climatic conditions, and variation in density may be insufficient. Accounting for these potentially confounding factors, we tested whether EPP rates within and among subpopulations of the reed bunting (Emberiza schoeniclus) were related to density. Our analyses were based on data from 13 subpopulations studied over 4 years. Overall, 56.4% of totally 181 broods contained at least one extra-pair young (EPY) and 37.1% of totally 669 young were of extra-pair origin. Roughly 90% of the extra-pair fathers were from the adjacent territory or from the territory after the next one. Within subpopulations, the proportion of EPY in broods was positively related to local breeding density. Similarly, among subpopulations, proportion of EPY was positively associated with population density. EPP was absent in subpopulations consisting of single breeding pairs, that is, without extra-pair mating opportunities. Our study confirms that density is an important biological factor, which significantly influences the amount of EPP within and among subpopulations, but also suggests that other mechanisms influence EPP beyond the variation explained by density. PMID:23533071
Full-Sibs in Cohorts of Newly Settled Coral Reef Fishes

PubMed Central

Bernardi, Giacomo; Beldade, Ricardo; Holbrook, Sally J.; Schmitt, Russell J.

2012-01-01

Reef fishes exhibit a bipartite life cycle where a benthic adult stage is preceded by a pelagic dispersal phase during which larvae are presumed to be mixed and transported by oceanic currents. Genetic analyses based on twelve microsatellite loci of 181 three-spot dascyllus (Dascyllus trimaculatus) that settled concurrently on a small reef in French Polynesia revealed 11 groups of siblings (1 full sibs and 10 half-sibs). This is the first evidence that fish siblings can journey together throughout their entire planktonic dispersal phase (nearly a month long for three-spot dascyllus). Our findings have critical implications for the dynamics and genetic structure of fish populations, as well as for the design of marine protected areas and management of fisheries. PMID:23028700
Inferring relationships between pairs of individuals from locus heterozygosities

PubMed Central

Presciuttini, Silvano; Toni, Chiara; Tempestini, Elena; Verdiani, Simonetta; Casarino, Lucia; Spinetti, Isabella; Stefano, Francesco De; Domenici, Ranieri; Bailey-Wilson, Joan E

2002-01-01

Background The traditional exact method for inferring relationships between individuals from genetic data is not easily applicable in all situations that may be encountered in several fields of applied genetics. This study describes an approach that gives affordable results and is easily applicable; it is based on the probabilities that two individuals share 0, 1 or both alleles at a locus identical by state. Results We show that these probabilities (zi) depend on locus heterozygosity (H), and are scarcely affected by variation of the distribution of allele frequencies. This allows us to obtain empirical curves relating zi's to H for a series of common relationships, so that the likelihood ratio of a pair of relationships between any two individuals, given their genotypes at a locus, is a function of a single parameter, H. Application to large samples of mother-child and full-sib pairs shows that the statistical power of this method to infer the correct relationship is not much lower than the exact method. Analysis of a large database of STR data proves that locus heterozygosity does not vary significantly among Caucasian populations, apart from special cases, so that the likelihood ratio of the more common relationships between pairs of individuals may be obtained by looking at tabulated zi values. Conclusions A simple method is provided, which may be used by any scientist with the help of a calculator or a spreadsheet to compute the likelihood ratios of common alternative relationships between pairs of individuals. PMID:12441003
Female bluethroats enhance offspring immunocompetence through extra-pair copulations.

PubMed

Johnsen, A; Andersen, V; Sunding, C; Lifjeld, J T

2000-07-20

Female birds frequently copulate with extra-pair males, but the adaptive value of this behaviour is poorly understood. Some studies have suggested that 'good genes' may be involved, where females seek to have their eggs fertilized by high-quality males without receiving any material benefits from them. Nevertheless, it remains to be shown that a genetic benefit is passed on to offspring. Here we report that nestling bluethroats, Luscinia svecica, sired by extra-pair males had a higher T-cell-mediated immune response than their maternal half-siblings raised in the same nest. The difference could not be attributed to nestling body mass, sex or hatching order, but may be an effect of paternal genotype. Extra-pair young were also more immunocompetent than their paternal half-sibs raised in the genetic father's own nest, which indicates an additional effect of maternal genotype. Our results are consistent with the idea that females engage in extra-pair copulations to obtain compatible viability genes, rather than 'good genes' per se.
Aspergillus fumigatus proteases, Asp f 5 and Asp f 13, are essential for airway inflammation and remodelling in a murine inhalation model.

PubMed

Namvar, S; Warn, P; Farnell, E; Bromley, M; Fraczek, M; Bowyer, P; Herrick, S

2015-05-01

In susceptible individuals, exposure to Aspergillus fumigatus can lead to the development of atopic lung diseases such as allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS). Protease allergens including Asp f 5 and Asp f 13 from Aspergillus fumigatus are thought to be important for initiation and progression of allergic asthma. To assess the importance of secreted protease allergens Asp f 5 (matrix metalloprotease) and Asp f 13 (serine protease) in Aspergillus fumigatus-induced inflammation, airway hyperactivity, atopy and airway wall remodelling in a murine model following chronic exposure to secreted allergens. BALB/c mice were repeatedly intranasally dosed over the course of 5 weeks with culture filtrate from wild-type (WT), Asp f 5 null (∆5) or Asp f 13 null (∆13) strains of Aspergillus fumigatus. Airway hyper-reactivity was measured by non-invasive whole-body plethysmography, Th2 response and airway inflammation by ELISA and cell counts, whilst airway remodelling was assessed by histological analysis. Parent WT and ∆5 culture filtrates showed high protease activity, whilst protease activity in ∆13 culture filtrate was low. Chronic intranasal exposure to the three different filtrates led to comparable airway hyper-reactivity and Th2 response. However, protease allergen deleted strains, in particular ∆13 culture filtrate, induced significantly less airway inflammation and remodelling compared to WT culture filtrate. Aspergillus fumigatus-secreted allergen proteases, Asp f 5 and Asp f 13, are important for recruitment of inflammatory cells and remodelling of the airways in this murine model. However, deletion of a single allergen protease fails to alleviate airway hyper-reactivity and allergic immune response. Targeting protease activity of Aspergillus fumigatus in conditions such as SAFS or ABPA may have beneficial effects in preventing key aspects of airway pathology. © 2014 John Wiley & Sons Ltd.
Influence of Glu/Arg, Asp/Arg, and Glu/Lys Salt Bridges on α-Helical Stability and Folding Kinetics.

PubMed

Meuzelaar, Heleen; Vreede, Jocelyne; Woutersen, Sander

2016-06-07

Using a combination of ultraviolet circular dichroism, temperature-jump transient-infrared spectroscopy, and molecular dynamics simulations, we investigate the effect of salt bridges between different types of charged amino-acid residue pairs on α-helix folding. We determine the stability and the folding and unfolding rates of 12 alanine-based α-helical peptides, each of which has a nearly identical composition containing three pairs of positively and negatively charged residues (either Glu(-)/Arg(+), Asp(-)/Arg(+), or Glu(-)/Lys(+)). Within each set of peptides, the distance and order of the oppositely charged residues in the peptide sequence differ, such that they have different capabilities of forming salt bridges. Our results indicate that stabilizing salt bridges (in which the interacting residues are spaced and ordered such that they favor helix formation) speed up α-helix formation by up to 50% and slow down the unfolding of the α-helix, whereas salt bridges with an unfavorable geometry have the opposite effect. Comparing the peptides with different types of charge pairs, we observe that salt bridges between side chains of Glu(-) and Arg(+) are most favorable for the speed of folding, probably because of the larger conformational space of the salt-bridging Glu(-)/Arg(+) rotamer pairs compared to Asp(-)/Arg(+) and Glu(-)/Lys(+). We speculate that the observed impact of salt bridges on the folding kinetics might explain why some proteins contain salt bridges that do not stabilize the final, folded conformation. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.
A Survey of Aspartate Phenylalanine and Glutamate Phenylalanine Interactions in the Protein Data Bank: Searching for Anion Pairs

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

Philip, Vivek M; Harris, Jason B; Adams, Rachel M

Protein structures are stabilized using noncovalent interactions. In addition to the traditional noncovalent interactions, newer types of interactions are thought to be present in proteins. One such interaction, an anion pair, in which the positively charged edge of an aromatic ring interacts with an anion, forming a favorable anion quadrupole interaction, has been previously proposed [Jackson, M. R., et al. (2007) J. Phys. Chem. B111, 8242 8249]. To study the role of anion interactions in stabilizing protein structure, we analyzed pairwise interactions between phenylalanine (Phe) and the anionic amino acids, aspartate (Asp) and glutamate (Glu). Particular emphasis was focused onmore » identification of Phe Asp or Glu pairs separated by less than 7 in the high-resolution, nonredundant Protein Data Bank. Simplifying Phe to benzene and Asp or Glu to formate molecules facilitated in silico analysis of the pairs. Kitaura Morokuma energy calculations were performed on roughly 19000 benzene formate pairs and the resulting energies analyzed as a function of distance and angle. Edgewise interactions typically produced strongly stabilizing interaction energies (2 to 7.3 kcal/mol), while interactions involving the ring face resulted in weakly stabilizing to repulsive interaction energies. The strongest, most stabilizing interactions were identified as preferentially occurring in buried residues. Anion pairs are found throughout protein structures, in helices as well as strands. Numerous pairs also had nearby cation interactions as well as potential stacking. While more than 1000 structures did not contain an anion pair, the 3134 remaining structures contained approximately 2.6 anion pairs per protein, suggesting it is a reasonably common motif that could contribute to the overall structural stability of a protein.« less
The ASP: Programs to Inspire Educators

NASA Astrophysics Data System (ADS)

Hurst, Anna; Gurton, S.; Bennett, M.; Berendson, M.; Gibbs, M.

2006-12-01

The Astronomical Society of the Pacific (ASP) provides educators with new approaches to hands-on astronomy and space science. Through interactive educational programs, our goal is to help more people understand, appreciate, and enjoy astronomy and science. Over the past several years, the ASP has re-dedicated itself to achieving this mission through an ever-expanding portfolio of programs. Our astronomy and education programs target educators of all descriptions classroom teachers, informal science educators (in science museums, planetariums, nature centers, etc.), college astronomy teachers, and amateur astronomers providing them with materials and training to capture the attention of their students and audiences and to introduce them to science via an initial engagement in astronomy. In this poster we provide an overview of current programs that include partnerships with the National Optical Astronomy Observatory, the Association of Science-Technology Centers, TERC, the Astronomical League, NASA, and the SETI Institute to address this broad range of formal and informal educators. Additionally, the poster will provide a summary of recently conducted research by the ASP regarding the Project ASTRO program, done in cooperation with our national partners, to gauge whether the program, as perceived by the teachers participating in Project ASTRO, a) assists in correcting common misconceptions in astronomy or science and b) improve students' attitudes towards science. Additional information regarding the ASP's educational programs can be found at: www.astrosociety.org/education.html
The Absolute Spectrum Polarimeter (ASP)

NASA Technical Reports Server (NTRS)

Kogut, A. J.

2010-01-01

The Absolute Spectrum Polarimeter (ASP) is an Explorer-class mission to map the absolute intensity and linear polarization of the cosmic microwave background and diffuse astrophysical foregrounds over the full sky from 30 GHz to 5 THz. The principal science goal is the detection and characterization of linear polarization from an inflationary epoch in the early universe, with tensor-to-scalar ratio r much greater than 1O(raised to the power of { -3}) and Compton distortion y < 10 (raised to the power of{-6}). We describe the ASP instrument and mission architecture needed to detect the signature of an inflationary epoch in the early universe using only 4 semiconductor bolometers.
TM9/Phg1 and SadA proteins control surface expression and stability of SibA adhesion molecules in Dictyostelium.

PubMed

Froquet, Romain; le Coadic, Marion; Perrin, Jackie; Cherix, Nathalie; Cornillon, Sophie; Cosson, Pierre

2012-02-01

TM9 proteins form a family of conserved proteins with nine transmembrane domains essential for cellular adhesion in many biological systems, but their exact role in this process remains unknown. In this study, we found that genetic inactivation of the TM9 protein Phg1A dramatically decreases the surface levels of the SibA adhesion molecule in Dictyostelium amoebae. This is due to a decrease in sibA mRNA levels, in SibA protein stability, and in SibA targeting to the cell surface. A similar phenotype was observed in cells devoid of SadA, a protein that does not belong to the TM9 family but also exhibits nine transmembrane domains and is essential for cellular adhesion. A contact site A (csA)-SibA chimeric protein comprising only the transmembrane and cytosolic domains of SibA and the extracellular domain of the Dictyostelium surface protein csA also showed reduced stability and relocalization to endocytic compartments in phg1A knockout cells. These results indicate that TM9 proteins participate in cell adhesion by controlling the levels of adhesion proteins present at the cell surface.
Role of C-Terminal Cysteine Residues of Aspergillus fumigatus Allergen Asp f 4 in Immunoglobulin E Binding

PubMed Central

Ramachandran, Harikrishnan; Banerjee, Banani; Greenberger, Paul A.; Kelly, Kevin J.; Fink, Jordan N.; Kurup, Viswanath P.

2004-01-01

Among the several allergens cloned and expressed from Aspergillus fumigatus, Asp f 4 is a major one associated with allergic bronchopulmonary aspergillosis (ABPA). The structure-function relationship of allergens is important in understanding the immunopathogenesis, diagnosis, and treatment of allergic diseases. These include the epitopes, conformational or linear, deletion of the N or C terminus or both N and C termini, and glycosylation or nonglycosylation, all of which affect immune responses. Similarly, the role of cysteine residues present in allergens may yield useful information regarding the conformational structure of allergens and the immunoglobulin E (IgE) epitope interaction. Such information may help in developing new strategies towards immunotherapy. In order to define the role of cysteine in the interaction of the antibody with Asp f 4, we have constructed mutants by selectively deleting cysteine residues from the C-terminal region of the Asp f 4. Immunological evaluation of these engineered recombinant constructs was conducted by using sera from patients with ABPA, Aspergillus skin test-positive asthmatics, and healthy controls. The results demonstrate strong IgE binding with Asp f 4 and two truncated mutants, Asp f 41-234 (amino acids [aa] 1 to 234) and Asp f 41-241 (aa 1 to 241), while another mutant, Asp f 41-196 (aa 1 to 196), showed reactivity with fewer patients. The result suggests that deletion of cysteines and the alteration of IgE epitopes at the C-terminal end resulted in conformational changes, which may have a potential role in the immunomodulation of the disease. PMID:15013973
Two sibs who are double heterozygotes for achondroplasia and pseudoachondroplastic dysplasia.

PubMed Central

Woods, C G; Rogers, J G; Mayne, V

1994-01-01

We report a family in which two sibs have both achondroplasia and pseudoachondroplastic dysplasia. The mother has achondroplasia and the father has pseudoachondroplastic dysplasia, which he had inherited from his father. Both children appeared typical of achondroplasia at birth. By 1 1/2 years they had developed a fixed lumbar kyphosis with gibbus and had additional x ray changes unusual for just achondroplasia and suggestive of pseudoachondroplastic dysplasia. Subsequently both children have shown characteristic features of both conditions and have grown less well than expected for achondroplasia. Radiographs show the striking synergistic effects of the two conditions. MRI in both sibs confirmed brain stem compression at the foramen magnum. This may be an important complication and should be actively sought in any double heterozygote. Images PMID:7966194
Large-scale linkage analysis of 1302 affected relative pairs with rheumatoid arthritis

PubMed Central

Hamshere, Marian L; Segurado, Ricardo; Moskvina, Valentina; Nikolov, Ivan; Glaser, Beate; Holmans, Peter A

2007-01-01

Rheumatoid arthritis is the most common systematic autoimmune disease and its etiology is believed to have both strong genetic and environmental components. We demonstrate the utility of including genetic and clinical phenotypes as covariates within a linkage analysis framework to search for rheumatoid arthritis susceptibility loci. The raw genotypes of 1302 affected relative pairs were combined from four large family-based samples (North American Rheumatoid Arthritis Consortium, United Kingdom, European Consortium on Rheumatoid Arthritis Families, and Canada). The familiality of the clinical phenotypes was assessed. The affected relative pairs were subjected to autosomal multipoint affected relative-pair linkage analysis. Covariates were included in the linkage analysis to take account of heterogeneity within the sample. Evidence of familiality was observed with age at onset (p << 0.001) and rheumatoid factor (RF) IgM (p << 0.001), but not definite erosions (p = 0.21). Genome-wide significant evidence for linkage was observed on chromosome 6. Genome-wide suggestive evidence for linkage was observed on chromosomes 13 and 20 when conditioning on age at onset, chromosome 15 conditional on gender, and chromosome 19 conditional on RF IgM after allowing for multiple testing of covariates. PMID:18466440
Improved ASP I/O performance. [For 370/195

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

Engert, D.E.

1975-11-01

An improvement to the I/0 routines of ASP is described, which can save 25% of the EXCPs issued by ASP. Unused buffers in the buffer pool are used to retain parts of the single track table, and only two modules are changed. 4 figures (auth)

Glu298Asp eNOS gene polymorphism causes attenuation in nonexercising muscle vasodilatation.

PubMed

Dias, Rodrigo G; Alves, Maria-Janieire N N; Pereira, Alexandre C; Rondon, Maria Urbana P B; Dos Santos, Marcelo R; Krieger, José E; Krieger, Marta H; Negrão, Carlos E

2009-04-10

The influence of Glu298Asp endothelial nitric oxide synthase (eNOS) polymorphism in exercise-induced reflex muscle vasodilatation is unknown. We hypothesized that nonexercising forearm blood flow (FBF) responses during handgrip isometric exercise would be attenuated in individuals carrying the Asp298 allele. In addition, these responses would be mediated by reduced eNOS function and NO-mediated vasodilatation or sympathetic vasoconstriction. From 287 volunteers previously genotyped, we selected 33 healthy individuals to represent three genotypes: Glu/Glu [n = 15, age 43 +/- 3 yr, body mass index (BMI) 22.9 +/- 0.3 kg/m(2)], Glu/Asp (n = 9, age 41 +/- 3 yr, BMI 23.7 +/- 1.0 kg/m(2)), and Asp/Asp (n = 9, age 40 +/- 4 yr, BMI 23.5 +/- 0.9 kg/m(2)). Heart rate (HR), mean blood pressure (MBP), and FBF (plethysmography) were recorded for 3 min at baseline and 3 min during isometric handgrip exercise. Baseline HR, MBP, FBF, and forearm vascular conductance (FVC) were similar among genotypes. FVC responses to exercise were significantly lower in Asp/Asp when compared with Glu/Asp and Glu/Glu (Delta = 0.07 +/- 0.14 vs. 0.64 +/- 0.20 and 0.57 +/- 0.09 units, respectively; P = 0.002). Further studies showed that intra-arterial infusion of NG-monomethyl-L-arginine (L-NMMA) did not change FVC responses to exercise in Asp/Asp, but significantly reduced FVC in Glu/Glu (Delta = 0.79 +/- 0.14 vs. 0.14 +/- 0.09 units). Thus the differences between Glu/Glu and Asp/Asp were no longer observed (P = 0.62). l-NMMA + phentolamine increased similarly FVC responses to exercise in Glu/Glu and Asp/Asp (P = 0.43). MBP and muscle sympathetic nerve activity increased significant and similarly throughout experimental protocols in Glu/Glu and Asp/Asp. Individuals who are homozygous for the Asp298 allele of the eNOS enzyme have attenuated nonexercising muscle vasodilatation in response to exercise. This genotype difference is due to reduced eNOS function and NO-mediated vasodilatation, but not
Effect of peptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly on the morphology of the thymus in hypophysectomized young and old birds.

PubMed

Pateyk, A V; Baranchugova, L M; Rusaeva, N S; Obydenko, V I; Kuznik, B I

2013-03-01

Investigations were carried out on chicks of different age. It was found that the most pronounced changes in the morphology of the thymus occurred after neonatal hypophysectomy. These changes are least pronounced in old chicks. Peptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly synthesized on the basis of amino acid composition of peptide complexes of the anterior and posterior pituitary lobes administered to hypophysectomized birds regardless of age promoted recovery of the morphological structures of the thymus. The anterior pituitary peptide (Lys-Glu-Asp-Gly) had more pronounced effect on the recovery of thymic structure than posterior pituitary peptide (Ala-Glu-Asp-Gly).
Image-Word Pairing-Congruity Effect on Affective Responses

NASA Astrophysics Data System (ADS)

Sanabria Z., Jorge C.; Cho, Youngil; Sambai, Ami; Yamanaka, Toshimasa

The present study explores the effects of familiarity on affective responses (pleasure and arousal) to Japanese ad elements, based on the schema incongruity theory. Print ads showing natural scenes (landscapes) were used to create the stimuli (images and words). An empirical study was conducted to measure subjects' affective responses to image-word combinations that varied in terms of incongruity. The level of incongruity was based on familiarity levels, and was statistically determined by a variable called ‘pairing-congruity status’. The tested hypothesis proposed that even highly familiar image-word combinations, when combined incongruously, would elicit strong affective responses. Subjects assessed the stimuli using bipolar scales. The study was effective in tracing interactions between familiarity, pleasure and arousal, although the incongruous image-word combinations did not elicit the predicted strong effects on pleasure and arousal. The results suggest a need for further research incorporating kansei (i.e., creativity) into the process of stimuli selection.
Modeling Surface Climate in US Cities Using Simple Biosphere Model Sib2

NASA Technical Reports Server (NTRS)

Zhang, Ping; Bounoua, Lahouari; Thome, Kurtis; Wolfe, Robert; Imhoff, Marc

2015-01-01

We combine Landsat- and the Moderate Resolution Imaging Spectroradiometer (MODIS)-based products in the Simple Biosphere model (SiB2) to assess the effects of urbanized land on the continental US (CONUS) surface climate. Using National Land Cover Database (NLCD) Impervious Surface Area (ISA), we define more than 300 urban settlements and their surrounding suburban and rural areas over the CONUS. The SiB2 modeled Gross Primary Production (GPP) over the CONUS of 7.10 PgC (1 PgC= 10(exp 15) grams of Carbon) is comparable to the MODIS improved GPP of 6.29 PgC. At state level, SiB2 GPP is highly correlated with MODIS GPP with a correlation coefficient of 0.94. An increasing horizontal GPP gradient is shown from the urban out to the rural area, with, on average, rural areas fixing 30% more GPP than urbans. Cities built in forested biomes have stronger UHI magnitude than those built in short vegetation with low biomass. Mediterranean climate cities have a stronger UHI in wet season than dry season. Our results also show that for urban areas built within forests, 39% of the precipitation is discharged as surface runoff during summer versus 23% in rural areas.
Asymmetric membranes for destabilization of oil droplets in produced water from alkaline-surfactant-polymer (ASP) flooding

NASA Astrophysics Data System (ADS)

Ramlee, Azierah; Chiam, Chel-Ken; Sarbatly, Rosalam

2018-05-01

This work presents a study of destabilization of oil droplets in the produced water from alkaline-surfactant-polymer (ASP) flooding by using four types of laboratory-fabricated polyvinylidene fluoride (PVDF) membranes. The PVDF membranes were fabricated via immersion precipitation method with ethanol (0 - 30 %, v/v) as the coagulant. The membranes with the effective area of 17.35 cm2 were tested with synthesized ASP solution as the feed in cross-flow microfiltration process. The ASP feed solution initially contained the oil droplets with radius ranged from 40 to 100 nm and the mean radius was 61 nm. Results have shown that the concentration of the ethanol in the coagulation bath affects the formation of the membrane structure and the corresponding porosity, while no significance influence on the membrane thickness. Coalescence of the oil droplets was occurred when the ASP solution permeated through the asymmetric PVDF membranes. Through the coalescence process, the oil droplets were destabilized where the radius of the oil droplets in the permeates increased to 1.5-4 µm with the corresponding mean radius ranged from 2.4 to 2.7 µm.
Multinational Consensus: Insulin Initiation with Insulin Degludec/Aspart (IDegAsp).

PubMed

Kalra, Sanjay; Atkin, Stephen; Cervera, Antonio; Das, Ashok Kumar; Demir, Ozgur; Demir, Tevfik; Fariduddin, Md; Vo, Khoa Tuan; Ku, Bon Jeong; Kumar, Ajay; Latif, Zafar A; Malek, Rachid; Matawaran, Bien J; Mehta, Roopa; Tran, Nam Quang; Panelo, Araceli; Ruder, Sundeep; Saldana, Joel Rodriquez; Shaikh, Khalid A; Shakya, Amit; Shrestha, Dina; Unnikrishnan, A G

2018-05-23

Insulin degludec/aspart (IDegAsp) is the first soluble insulin co-formulation, combining a long-acting insulin degludec (IDeg) and rapid-acting insulin aspart (IAsp). In type 2 diabetes patients with oral antidiabetes agent (OAD) inadequacy, insulin initiation with IDegAsp once daily provides superior long-term glycemic control compared to insulin glargine, with similar fasting plasma glucose (FPG) and insulin doses, and numerically lower rates of overall and nocturnal hypoglycemia. Furthermore, in patients with uncontrolled type 2 diabetes previously treated with insulins, IDegAsp twice daily effectively improves glycated hemoglobin and FPG, with fewer hypoglycemic episodes versus premix insulins and basal bolus therapy. In patients with type 1 diabetes mellitus, IDegAsp once daily with two doses of IAsp is a convenient, yet effective, regimen as compared to the conventional 4-5 injection-based basal bolus therapy. IDegAsp is an appropriate and reasonable option for initiation of insulin therapy in both type 1 and type 2 diabetes.
[Effects of Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly peptides on hormonal activity and thyroid morphology in hypophysectomized mature and old birds].

PubMed

Kuznik, B I; Pateiuk, A V; Rusaeva, N S; Baranchugova, L M; Obydenko, V I

2011-01-01

The aim of the paper was to investigate effects of Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly peptides which were designed and synthesized on the basis of amino acid study of the hypophyseal anterior and posterior lobe peptides on the thyroid morphology and hormonal activity in mature chicken and old birds. Hypophysectomy was established to produce atrophic changes in the thyroid gland and development of secondary hypothyrosis. Administration of Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly tetrapeptides significantly prevented these impairments by increasing the levels of the thyroid-stimulating hormone (TSH) as well as T3 and T4. Restoration of the thyroid functions and morphology was registered to be greater in one-year-old chicken as compared to five-year-old ones.
A survey of aspartate-phenylalanine and glutamate-phenylalanine interactions in the protein data bank: searching for anion-π pairs.

PubMed

Philip, Vivek; Harris, Jason; Adams, Rachel; Nguyen, Don; Spiers, Jeremy; Baudry, Jerome; Howell, Elizabeth E; Hinde, Robert J

2011-04-12

Protein structures are stabilized using noncovalent interactions. In addition to the traditional noncovalent interactions, newer types of interactions are thought to be present in proteins. One such interaction, an anion-π pair, in which the positively charged edge of an aromatic ring interacts with an anion, forming a favorable anion-quadrupole interaction, has been previously proposed [Jackson, M. R., et al. (2007) J. Phys. Chem. B111, 8242-8249]. To study the role of anion-π interactions in stabilizing protein structure, we analyzed pairwise interactions between phenylalanine (Phe) and the anionic amino acids, aspartate (Asp) and glutamate (Glu). Particular emphasis was focused on identification of Phe-Asp or -Glu pairs separated by less than 7 Å in the high-resolution, nonredundant Protein Data Bank. Simplifying Phe to benzene and Asp or Glu to formate molecules facilitated in silico analysis of the pairs. Kitaura-Morokuma energy calculations were performed on roughly 19000 benzene-formate pairs and the resulting energies analyzed as a function of distance and angle. Edgewise interactions typically produced strongly stabilizing interaction energies (-2 to -7.3 kcal/mol), while interactions involving the ring face resulted in weakly stabilizing to repulsive interaction energies. The strongest, most stabilizing interactions were identified as preferentially occurring in buried residues. Anion-π pairs are found throughout protein structures, in helices as well as β strands. Numerous pairs also had nearby cation-π interactions as well as potential π-π stacking. While more than 1000 structures did not contain an anion-π pair, the 3134 remaining structures contained approximately 2.6 anion-π pairs per protein, suggesting it is a reasonably common motif that could contribute to the overall structural stability of a protein.
A Survey of Aspartate-Phenylalanine and Glutamate-Phenylalanine Interactions in the Protein Data Bank: Searching for Anion-pi Pairs

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

Philip, Vivek M; Harris, Jason B; Adams, Rachel M

Protein structures are stabilized using noncovalent interactions. In addition to the traditional noncovalent interactions, newer types of interactions are thought to be present in proteins. One such interaction, an anion-{pi} pair, in which the positively charged edge of an aromatic ring interacts with an anion, forming a favorable anion-quadrupole interaction, has been previously proposed [Jackson, M. R., et al. (2007) J. Phys. Chem. B111, 8242-8249]. To study the role of anion-{pi} interactions in stabilizing protein structure, we analyzed pairwise interactions between phenylalanine (Phe) and the anionic amino acids, aspartate (Asp) and glutamate (Glu). Particular emphasis was focused on identification ofmore » Phe-Asp or -Glu pairs separated by less than 7 {angstrom} in the high-resolution, nonredundant Protein Data Bank. Simplifying Phe to benzene and Asp or Glu to formate molecules facilitated in silico analysis of the pairs. Kitaura-Morokuma energy calculations were performed on roughly 19000 benzene-formate pairs and the resulting energies analyzed as a function of distance and angle. Edgewise interactions typically produced strongly stabilizing interaction energies (-2 to -7.3 kcal/mol), while interactions involving the ring face resulted in weakly stabilizing to repulsive interaction energies. The strongest, most stabilizing interactions were identified as preferentially occurring in buried residues. Anion-{pi} pairs are found throughout protein structures, in helices as well as {beta} strands. Numerous pairs also had nearby cation-{pi} interactions as well as potential {pi}-{pi} stacking. While more than 1000 structures did not contain an anion-{pi} pair, the 3134 remaining structures contained approximately 2.6 anion-{pi} pairs per protein, suggesting it is a reasonably common motif that could contribute to the overall structural stability of a protein.« less
Classification of pseudo pairs between nucleotide bases and amino acids by analysis of nucleotide-protein complexes.

PubMed

Kondo, Jiro; Westhof, Eric

2011-10-01

Nucleotide bases are recognized by amino acid residues in a variety of DNA/RNA binding and nucleotide binding proteins. In this study, a total of 446 crystal structures of nucleotide-protein complexes are analyzed manually and pseudo pairs together with single and bifurcated hydrogen bonds observed between bases and amino acids are classified and annotated. Only 5 of the 20 usual amino acid residues, Asn, Gln, Asp, Glu and Arg, are able to orient in a coplanar fashion in order to form pseudo pairs with nucleotide bases through two hydrogen bonds. The peptide backbone can also form pseudo pairs with nucleotide bases and presents a strong bias for binding to the adenine base. The Watson-Crick side of the nucleotide bases is the major interaction edge participating in such pseudo pairs. Pseudo pairs between the Watson-Crick edge of guanine and Asp are frequently observed. The Hoogsteen edge of the purine bases is a good discriminatory element in recognition of nucleotide bases by protein side chains through the pseudo pairing: the Hoogsteen edge of adenine is recognized by various amino acids while the Hoogsteen edge of guanine is only recognized by Arg. The sugar edge is rarely recognized by either the side-chain or peptide backbone of amino acid residues.
Classification of pseudo pairs between nucleotide bases and amino acids by analysis of nucleotide–protein complexes

PubMed Central

Kondo, Jiro; Westhof, Eric

2011-01-01

Nucleotide bases are recognized by amino acid residues in a variety of DNA/RNA binding and nucleotide binding proteins. In this study, a total of 446 crystal structures of nucleotide–protein complexes are analyzed manually and pseudo pairs together with single and bifurcated hydrogen bonds observed between bases and amino acids are classified and annotated. Only 5 of the 20 usual amino acid residues, Asn, Gln, Asp, Glu and Arg, are able to orient in a coplanar fashion in order to form pseudo pairs with nucleotide bases through two hydrogen bonds. The peptide backbone can also form pseudo pairs with nucleotide bases and presents a strong bias for binding to the adenine base. The Watson–Crick side of the nucleotide bases is the major interaction edge participating in such pseudo pairs. Pseudo pairs between the Watson–Crick edge of guanine and Asp are frequently observed. The Hoogsteen edge of the purine bases is a good discriminatory element in recognition of nucleotide bases by protein side chains through the pseudo pairing: the Hoogsteen edge of adenine is recognized by various amino acids while the Hoogsteen edge of guanine is only recognized by Arg. The sugar edge is rarely recognized by either the side-chain or peptide backbone of amino acid residues. PMID:21737431
A new plan quality index for nasopharyngeal cancer SIB IMRT.

PubMed

Jin, X; Yi, J; Zhou, Y; Yan, H; Han, C; Xie, C

2014-02-01

A new plan quality index integrating dosimetric and radiobiological indices was proposed to facilitate the evaluation and comparison of simultaneous integrated boost (SIB) intensity modulated radiotherapy (IMRT) plans for nasopharyngeal cancer (NPC) patients. Ten NPC patients treated by SIB-IMRT were enrolled in the study. Custom software was developed to read dose-volume histogram (DVH) curves from the treatment planning system (TPS). A plan filtering matrix was introduced to filter plans that fail to satisfy treatment protocol. Target plan quality indices and organ at risk (OAR) plan quality indices were calculated for qualified plans. A unique composite plan quality index (CPQI) was proposed based on the relative weight of these indices to evaluate and compare competing plans. Plan ranking results were compared with detailed statistical analysis, radiation oncology quality system (ROQS) scoring results and physician's evaluation results to verify the accuracy of this new plan quality index. The average CPQI values for plans with OAR priority of low, normal, high, and PTV only were 0.22 ± 0.08, 0.49 ± 0.077, 0.71 ± 0.062, and -0.21 ± 0.16, respectively. There were significant differences among these plan quality indices (One-way ANOVA test, p < 0.01). This was consistent with statistical analysis, ROQS results and physician's ranking results in which 90% OAR high plans were selected. Plan filtering matrix was able to speed up the plan evaluation process. The new matrix plan quality index CPQI showed good consistence with physician ranking results. It is a promising index for NPC SIB-IMRT plan evaluation. Copyright © 2013 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
Fine mapping of the chromosome 12 late-onset Alzheimer disease locus: potential genetic and phenotypic heterogeneity.

PubMed

Scott, W K; Grubber, J M; Conneally, P M; Small, G W; Hulette, C M; Rosenberg, C K; Saunders, A M; Roses, A D; Haines, J L; Pericak-Vance, M A

2000-03-01

Apolipoprotein E (APOE) is the only confirmed susceptibility gene for late-onset Alzheimer disease (AD). In a recent genomic screen of 54 families with late-onset AD, we detected significant evidence for a second late-onset AD locus located on chromosome 12 between D12S373 and D12S390. Linkage to this region was strongest in 27 large families with at least one affected individual without an APOE-4 allele, suggesting that APOE and the chromosome 12 locus might have independent effects. We have since genotyped several additional markers across the region, to refine the linkage results. In analyzing these additional data, we have addressed the issue of heterogeneity in the data set by weighting results by clinical and neuropathologic features, sibship size, and APOE genotype. When considering all possible affected sib pairs (ASPs) per nuclear family, we obtained a peak maximum LOD score between D12S1057 and D12S1042. The magnitude and location of the maximum LOD score changed when different weighting schemes were used to control for the number of ASPs contributed by each nuclear family. Using the affected-relative-pair method implemented in GENEHUNTER-PLUS, we obtained a maximum LOD score between D12S398 and D12S1632, 25 cM from the original maximum LOD score. These results indicate that family size influences the location estimate for the chromosome 12 AD gene. The results of conditional linkage analysis by use of GENEHUNTER-PLUS indicated that evidence for linkage to chromosome 12 was stronger in families with affected individuals lacking an APOE-4 allele; much of this evidence came from families with affected individuals with neuropathologic diagnosis of dementia with Lewy bodies (DLB). Taken together, these results indicate that the chromosome 12 locus acts independently of APOE to increase the risk of late-onset familial AD and that it may be associated with the DLB variant of AD.
The Annular Suspension and Pointing System /ASPS/

NASA Technical Reports Server (NTRS)

Anderson, W. W.; Woolley, C. T.

1978-01-01

The Annular Suspension and Pointing System (ASPS) may be attached to a carrier vehicle for orientation, mechanical isolation, and fine pointing purposes applicable to space experiments. It has subassemblies for both coarse and vernier pointing. A fourteen-degree-of-freedom simulation of the ASPS mounted on a Space Shuttle has yielded initial performance data. The simulation describes: the magnetic actuators, payload sensors, coarse gimbal assemblies, control algorithms, rigid body dynamic models of the payload and Shuttle, and a control system firing model.
Caspofungin exposure alters the core septin AspB interactome of Aspergillus fumigatus.

PubMed

Vargas-Muñiz, José M; Renshaw, Hilary; Waitt, Greg; Soderblom, Erik J; Moseley, M Arthur; Palmer, Jonathan M; Juvvadi, Praveen R; Keller, Nancy P; Steinbach, William J

2017-04-01

Aspergillus fumigatus, the main etiological agent of invasive aspergillosis, is a leading cause of death in immunocompromised patients. Septins, a conserved family of GTP-binding proteins, serve as scaffolding proteins to recruit enzymes and key regulators to different cellular compartments. Deletion of the A. fumigatus septin aspB increases susceptibility to the echinocandin antifungal caspofungin. However, how AspB mediates this response to caspofungin is unknown. Here, we characterized the AspB interactome under basal conditions and after exposure to a clinically relevant concentration of caspofungin. While A. fumigatus AspB interacted with 334 proteins, including kinases, cell cycle regulators, and cell wall synthesis-related proteins under basal growth conditions, caspofungin exposure altered AspB interactions. A total of 69 of the basal interactants did not interact with AspB after exposure to caspofungin, and 54 new interactants were identified following caspofungin exposure. We generated A. fumigatus deletion strains for 3 proteins (ArpB, Cyp4, and PpoA) that only interacted with AspB following exposure to caspofungin that were previously annotated as induced after exposure to antifungal agents, yet only PpoA was implicated in the response to caspofungin. Taken together, we defined how the septin AspB interactome is altered in the presence of a clinically relevant antifungal. Copyright © 2017 Elsevier Inc. All rights reserved.
Failure to find linkage between a functional polymorphism in the dopamine D4 receptor gene and schizophrenia

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

Shaikh, S.; Gill, M.; Collier, D.A.

1994-03-15

We report the results of a linkage study in 24 families multiply affected with schizophrenia using a polymorphic DNA sequence encoding the third cytoplasmic loop of the dopamine D4 receptor. Two-point LOD score analyses with a range of single gene models ranging from near dominant to near recessive revealed no evidence for linkage. In addition, we examined the data by non-parametric sib-pair analysis and found no excess sharing of alleles between affected sib-pairs. We therefore conclude that mutations within the dopamine D4 receptor gene do not have a major aetiological role in schizophrenia in our collection of pedigrees. 20 refs.,more » 2 tabs.« less
ASP Programs and IYA

NASA Astrophysics Data System (ADS)

Manning, James G.

2009-01-01

At the forefront of sharing the excitement of the exploration of the universe for 120 years, the Astronomical Society of the Pacific is poised to use its networks and services to implement education and outreach programs for the 2009 International Year of Astronomy (IYA2009). The ASP is partnering with NASA, the AAS and other astronomy and education organizations on IYA2009 projects, and is developing signature programs for implementation-with the overarching goal of bringing together scientists, educators and amateur astronomers in efforts to improve science education and science literacy through astronomy. The presentation will outline five major thrusts designed to serve the amateur astronomy community, formal educators, informal educators, the online community, and these communities in combination through IYA-related professional development, resources, and the facilitation of connections. The use of the proceedings of the IYA2009 Symposium in St. Louis in June, 2008 as an IYA2009 resource will be mentioned, and the ASP will encourage partners to work with the Society to help reach mutual goals and objectives for IYA2009 and beyond.
Array Simulations Platform (ASP) predicts NASA Data Link Module (NDLM) performance

NASA Technical Reports Server (NTRS)

Snook, Allen David

1993-01-01

Through a variety of imbedded theoretical and actual antenna patterns, the array simulation platform (ASP) enhanced analysis of the array antenna pattern effects for the KTx (Ku-Band Transmit) service of the NDLM (NASA Data Link Module). The ASP utilizes internally stored models of the NDLM antennas and can develop the overall pattern of antenna arrays through common array calculation techniques. ASP expertly assisted in the diagnosing of element phase shifter errors during KTx testing and was able to accurately predict the overall array pattern from combinations of the four internally held element patterns. This paper provides an overview of the use of the ASP software in the solving of array mis-phasing problems.
Effects of mutations of thermolysin, as N116 to asp and asp150 to glu, on salt-induced activation and stabilization.

PubMed

Menach, Evans; Yasukawa, Kiyoshi; Inouye, Kuniyo

2013-01-01

Neutral salts activate and stabilize thermolysin. We previously found that two single mutations, Asn116→Asp and Asp150→Glu, increase the activity of thermolysin. In the present study, we examined their effects on NaCl-induced activation and stabilization. In the hydrolysis of N-[3-(2-furyl)acryloyl]-glycyl-L-leucine amide, the relative activities (the ratios of the specificity constant, kcat/Km, at x M NaCl to that at 0 M NaCl) at 0.5-4.0 M NaCl of D150E and N116D/D150E were lower than those of wild-type thermolysin (WT) and N116D, respectively. In thermal inactivation at 70 °C, the relative stabilities (the ratios of the first-order rate constant, kobs, at 0 M NaCl to that at x M NaCl) at 0.5-4.0 M NaCl of D150E and N116D/D150E were lower than those of WT and N116D, respectively. These results indicate that unlike Asn116→Asp, Asp150→Glu reduced NaCl-induced activation and stabilization, suggesting that the binding of ions with certain residues of thermolysin is involved in the activation and stabilization.
Regulation of the sodium bicarbonate cotransporter kNBC1 function: role of Asp(986), Asp(988) and kNBC1-carbonic anhydrase II binding.

PubMed

Gross, Eitan; Pushkin, Alexander; Abuladze, Natalia; Fedotoff, Olga; Kurtz, Ira

2002-11-01

The HCO(3)(-) : Na(+) cotransport stoichiometry of the electrogenic sodium bicarbonate cotransporter kNBC1 determines the reversal potential (E(rev)) and thus the net direction of transport of these ions through the cotransporter. Previously, we showed that phosphorylation of kNBC1-Ser(982) in the carboxy-terminus of kNBC1 (kNBC1-Ct), by cAMP-protein kinase A (PKA), shifts the stoichiometry from 3 : 1 to 2 : 1 and that binding of bicarbonate to the cotransporter is electrostaticaly modulated. These results raise the possibility that phosphorylated kNBC1-Ser(982), or other nearby negatively charged residues shift the stoichiometry by blocking a bicarbonate-binding site. In the current study, we examined the role of the negative charge on Ser(982)-phosphate and three aspartate residues in a D986NDD custer in altering the stoichiometry of kNBC1. mPCT cells expressing kNBC1 mutants were grown on filters and mounted in an Ussing chamber for electrophysiological studies. Enhanced green fluorescence protein (EGFP)-tagged mutant constructs expressed in the same cells were used to determine the phosphorylation status of kNBC1-Ser(982). The data indicate that both kNBC1-Asp(986) and kNBC1-Asp(988), but not kNBC1-Asp(989), are required for the phosphorylation-induced shift in stoichiometry. A homologous motif (D887ADD) in the carboxy-terminus of the anion exchanger AE1 binds to carbonic anhydrase II (CAII). In isothermal titration calorimetry experiments, CAII was found to bind to kNBC1-Ct with a K(D) of 160 +/- 10 nM. Acetazolamide inhibited the short-circuit current through the cotransporter by 65 % when the latter operated in the 3 : 1 mode, but had no effect on the current in the 2 : 1 mode. Acetazolamide did not affect the cotransport stoichiometry or the ability of 8-Br-cAMP to shift the stoichiometry. Although CAII does not affect the transport stoichiometry, it may play an important role in enhancing the flux through the transporter when kNBC1-Ser(982) is

The ASP3 locus in Saccharomyces cerevisiae originated by horizontal gene transfer from Wickerhamomyces.

PubMed

League, Garrett P; Slot, Jason C; Rokas, Antonis

2012-11-01

The asparagine degradation pathway in the S288c laboratory strain of Saccharomyces cerevisiae is comprised of genes located at two separate loci. ASP1 is located on chromosome IV and encodes for cytosolic l-asparaginase I, whereas ASP3 contains a gene cluster located on chromosome XII comprised of four identical genes, ASP3-1, ASP3-2, ASP3-3, and ASP3-4, which encode for cell wall-associated l-asparaginase II. Interestingly, the ASP3 locus appears to be only present, in variable copy number, in S. cerevisiae strains isolated from laboratory or industrial environments and is completely absent from the genomes of 128 diverse fungal species. Investigation of the evolutionary history of ASP3 across these 128 genomes as well as across the genomes of 43 S. cerevisiae strains shows that ASP3 likely arose in a S. cerevisiae strain via horizontal gene transfer (HGT) from, or a close relative of, the wine yeast Wickerhamomyces anomalus, which co-occurs with S. cerevisiae in several biotechnological processes. Thus, because the ASP3 present in the S288c laboratory strain of S. cerevisiae is induced in response to nitrogen starvation, its acquisition may have aided yeast adaptation to artificial environments. Our finding that the ASP3 locus in S. cerevisiae originated via HGT further highlights the importance of gene sharing between yeasts in the evolution of their remarkable metabolic diversity. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
Cognitive Efficacy (SIB) of 13.3 Versus 4.6 mg/24 h Rivastigmine Patch in Severe Alzheimer's Disease.

PubMed

Isaacson, Richard S; Ferris, Steven; Velting, Drew M; Meng, Xiangyi

2016-05-01

Severe Impairment Battery (SIB) data from the 24-week, randomized, double-blind ACTivities of daily living and cognitION (ACTION) study suggest that patients with severe Alzheimer's disease (AD) benefit from treatment with 13.3 versus 4.6 mg/24 h rivastigmine patch. The objective of this retrospective analysis was to further examine the cognitive efficacy of 13.3 versus 4.6 mg/24 h rivastigmine patch on individual SIB items, and SIB domains derived using factor analysis of these items. Change from baseline at Week 24 on 9 new factor-defined domains and individual items was calculated and compared using effect sizes (Cohen's d). Numerically less decline was observed with 13.3 versus 4.6 mg/24 h patch on all domains and the majority of individual items. Largest least squares mean treatment differences were observed on "visuospatial reasoning," "object naming," "recognition," "design copying," "social agency," "ideational praxis," and "comprehension" domains. These findings suggest 13.3 mg/24 h rivastigmine patch demonstrates broad cognitive efficacy across a range of SIB items and domains in patients with severe AD. © The Author(s) 2015.
Clinical experiences with an ASP model backup archive for PACS images

NASA Astrophysics Data System (ADS)

Liu, Brent J.; Cao, Fei; Documet, Luis; Huang, H. K.; Muldoon, Jean

2003-05-01

Last year we presented a Fault-Tolerant Backup Archive using an Application Service Provider (ASP) model for disaster recovery. The purpose of this paper is to update and provide clinical experiences related towards implementing the ASP model archive solution for short-term backup of clinical PACS image data as well as possible applications other than disaster recovery. The ASP backup archive provides instantaneous, automatic backup of acquired PACS image data and instantaneous recovery of stored PACS image data all at a low operational cost and with little human intervention. This solution can be used for a variety of scheduled and unscheduled downtimes that occur on the main PACS archive. A backup archive server with hierarchical storage was implemented offsite from the main PACS archive location. Clinical data from a hospital PACS is sent to this ASP storage server in parallel to the exams being archived in the main server. Initially, connectivity between the main archive and the ASP storage server is established via a T-1 connection. In the future, other more cost-effective means of connectivity will be researched such as the Internet 2. We have integrated the ASP model backup archive with a clinical PACS at Saint John's Health Center and has been operational for over 6 months. Pitfalls encountered during integration with a live clinical PACS and the impact to clinical workflow will be discussed. In addition, estimations of the cost of establishing such a solution as well as the cost charged to the users will be included. Clinical downtime scenarios, such as a scheduled mandatory downtime and an unscheduled downtime due to a disaster event to the main archive, were simulated and the PACS exams were sent successfully from the offsite ASP storage server back to the hospital PACS in less than 1 day. The ASP backup archive was able to recover PACS image data for comparison studies with no complex operational procedures. Furthermore, no image data loss was
Testing the Simple Biosphere model (SiB) using point micrometeorological and biophysical data

NASA Technical Reports Server (NTRS)

Sellers, P. J.; Dorman, J. L.

1987-01-01

The suitability of the Simple Biosphere (SiB) model of Sellers et al. (1986) for calculation of the surface fluxes for use within general circulation models is assessed. The structure of the SiB model is described, and its performance is evaluated in terms of its ability to realistically and accurately simulate biophysical processes over a number of test sites, including Ruthe (Germany), South Carolina (U.S.), and Central Wales (UK), for which point biophysical and micrometeorological data were available. The model produced simulations of the energy balances of barley, wheat, maize, and Norway Spruce sites over periods ranging from 1 to 40 days. Generally, it was found that the model reproduced time series of latent, sensible, and ground-heat fluxes and surface radiative temperature comparable with the available data.
Family losses following truncation selection in populations of half-sib families

Treesearch

J. H. Roberds; G. Namkoong; H. Kang

1980-01-01

Family losses during truncation selection may be sizable in populations of half-sib families. Substantial losses may occur even in populations containing little or no variation among families. Heavier losses will occur, however, under conditions of high heritability where there is considerable family variation. Standard deviations and therefore variances of family loss...
Establishment of a nested-ASP-PCR method to determine the clarithromycin resistance of Helicobacter pylori.

PubMed

Luo, Xiao-Feng; Jiao, Jian-Hua; Zhang, Wen-Yue; Pu, Han-Ming; Qu, Bao-Jin; Yang, Bing-Ya; Hou, Min; Ji, Min-Jun

2016-07-07

To investigate clarithromycin resistance positions 2142, 2143 and 2144 of the 23SrRNA gene in Helicobacter pylori (H. pylori) by nested-allele specific primer-polymerase chain reaction (nested-ASP-PCR). The gastric tissue and saliva samples from 99 patients with positive results of the rapid urease test (RUT) were collected. The nested-ASP-PCR method was carried out with the external primers and inner allele-specific primers corresponding to the reference strain and clinical strains. Thirty gastric tissue and saliva samples were tested to determine the sensitivity of nested-ASP-PCR and ASP-PCR methods. Then, clarithromycin resistance was detected for 99 clinical samples by using different methods, including nested-ASP-PCR, bacterial culture and disk diffusion. The nested-ASP-PCR method was successfully established to test the resistance mutation points 2142, 2143 and 2144 of the 23SrRNA gene of H. pylori. Among 30 samples of gastric tissue and saliva, the H. pylori detection rate of nested-ASP-PCR was 90% and 83.33%, while the detection rate of ASP-PCR was just 63% and 56.67%. Especially in the saliva samples, nested-ASP-PCR showed much higher sensitivity in H. pylori detection and resistance mutation rates than ASP-PCR. In the 99 RUT-positive gastric tissue and saliva samples, the H. pylori-positive detection rate by nested-ASP-PCR was 87 (87.88%) and 67 (67.68%), in which there were 30 wild-type and 57 mutated strains in gastric tissue and 22 wild-type and 45 mutated strains in saliva. Genotype analysis showed that three-points mixed mutations were quite common, but different resistant strains were present in gastric mucosa and saliva. Compared to the high sensitivity shown by nested-ASP-PCR, the positive detection of bacterial culture with gastric tissue samples was 50 cases, in which only 26 drug-resistant strains were found through analyzing minimum inhibitory zone of clarithromycin. The nested-ASP-PCR assay showed higher detection sensitivity than ASP-PCR and
The modeling and design of the Annular Suspension and Pointing System /ASPS/. [for Space Shuttle

NASA Technical Reports Server (NTRS)

Kuo, B. C.; Lin, W. C. W.

1979-01-01

The Annular Suspension and Pointing System (ASPS) is a payload auxiliary pointing device of the Space Shuttle. The ASPS is comprised of two major subassemblies, a vernier and a coarse pointing subsystem. The three functions provided by the ASPS are related to the pointing of the payload, centering the payload in the magnetic actuator assembly, and tracking the payload mounting plate and shuttle motions by the coarse gimbals. The equations of motion of a simplified planar model of the ASPS are derived. Attention is given to a state diagram of the dynamics of the ASPS with position-plus-rate controller, the nonlinear spring characteristic for the wire-cable torque of the ASPS, the design of the analog ASPS through decoupling and pole placement, and the time response of different components of the continuous control system.
Phosphate-Catalyzed Succinimide Formation from Asp Residues: A Computational Study of the Mechanism.

PubMed

Kirikoshi, Ryota; Manabe, Noriyoshi; Takahashi, Ohgi

2018-02-24

Aspartic acid (Asp) residues in proteins and peptides are prone to the non-enzymatic reactions that give biologically uncommon l-β-Asp, d-Asp, and d-β-Asp residues via the cyclic succinimide intermediate (aminosuccinyl residue, Suc). These abnormal Asp residues are known to have relevance to aging and pathologies. Despite being non-enzymatic, the Suc formation is thought to require a catalyst under physiological conditions. In this study, we computationally investigated the mechanism of the Suc formation from Asp residues that were catalyzed by the dihydrogen phosphate ion, H₂PO₄ - . We used Ac-l-Asp-NHMe (Ac = acetyl, NHMe = methylamino) as a model compound. The H₂PO₄ - ion (as a catalyst) and two explicit water molecules (as solvent molecules stabilizing the negative charge) were included in the calculations. All of the calculations were performed by density functional theory with the B3LYP functional. We revealed a phosphate-catalyzed two-step mechanism (cyclization-dehydration) of the Suc formation, where the first step is predicted to be rate-determining. In both steps, the reaction involved a proton relay mediated by the H₂PO₄ - ion. The calculated activation barrier for this mechanism (100.3 kJ mol -1 ) is in reasonable agreement with an experimental activation energy (107 kJ mol -1 ) for the Suc formation from an Asp-containing peptide in a phosphate buffer, supporting the catalytic mechanism of the H₂PO₄ - ion that is revealed in this study.
Screening for Multiple Genes Influencing Dyslexia.

ERIC Educational Resources Information Center

Smith, Shelley D.; And Others

1991-01-01

Examines the "sib pair" method of linkage analysis designed to locate genes influencing dyslexia, which has several advantages over the "LOD" score method. Notes that the sib pair analysis was able to detect the same linkages as the LOD method, plus a possible third region. Confirms that the sib pair method is an effective means of screening. (RS)
Does time after pair bond disruption affect subsequent reproduction in the socially monogamous woodland vole (Microtus pinetorum)?

PubMed Central

Renfro, Caroline A.; Pesek, Daniel W.; Bobeck, Kelly; Solomon, Nancy G.

2010-01-01

Disruption of the pair bond between socially monogamous animals leads to changes in behavior, which may have reproductive consequences. There are two alternative hypotheses to explain the effect of the length of time since pair bond disruption on subsequent reproduction. One hypothesis predicts that voles housed immediately with a new opposite-sex conspecific will be as likely to produce litters and will produce them as quickly as voles separated from their initial mate for longer. Alternatively, if attachment between mates is enduring, we expect that more voles separated longer from their previous mates will produce litters and produce them sooner than voles re-paired immediately after separation from their initial mates. Woodland voles, paired with opposite-sex conspecifics, remained together until parturition. Mates were then separated for zero, seven, or fourteen days until re-pairing with an opposite-sex conspecific. Pair bond disruption did not prevent males and females from mating subsequently, which was consistent with data from our breeding colony. In addition, the length of time an individual remained alone after pair bond disruption did not affect the latency to produce a litter. Our results show that having been paired previously does not affect subsequent reproduction in this socially monogamous vole. PMID:19429197
Mechanism research on starting residual oil migration in ASP flooding with different Alkali concentration

NASA Astrophysics Data System (ADS)

Xia, Huifen; Pan, Junliang; Niu, Lijuan; Xu, Tianhan

2018-02-01

The results illustrate that under the condition of the same viscosity of ASP system, oil displacement efficiency is different while the ASP system with different alkali concentration has the same order of magnitude as the interfacial tension of oil. In this paper, the microscopic simulation visual model is used to study the mechanism of starting migration of residual oil by doing ASP flooding experiments with different alkali concentration. The results indicate that the migration of residual oil is different from that in the ASP systems with different alkali concentration. ASP system with high alkali concentration can start the migration by means of emulsifying residual oil into oil droplets and oil threads, on this account, increasing the alkali concentration can make the recovery degree of ASP system higher, which will finally be beneficial to the oil recovery.
Effect of tetrapeptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly on the structure and function of the thyroid gland in neonatally hypophysectomized chickens.

PubMed

Kuznik, B I; Pateyuk, A V; Rusaeva, N S

2008-01-01

Tetrapeptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly were synthesized on the basis of amino acid composition of pituitary cytomedins. Administration of these tetrapeptides to hypophysectomized chickens for 40 days was followed by an increase in the concentrations of thyrotropic hormone and thyroid hormones and recovery of thyroid gland structure.
Height and seasonal growth pattern of jack pine full-sib families

Treesearch

Don E. Riemenschneider

1981-01-01

Total tree height, seasonal shoot elongation, dates of growth initiation and cessation, and mean daily growth rate were measured and analyzed for a population of jack pine full-sib families derived from inter-provenance crosses. Parental provenance had no effect on these variables although this may have been due to small sample size. Progenies differed significantly...
Establishment of a nested-ASP-PCR method to determine the clarithromycin resistance of Helicobacter pylori

PubMed Central

Luo, Xiao-Feng; Jiao, Jian-Hua; Zhang, Wen-Yue; Pu, Han-Ming; Qu, Bao-Jin; Yang, Bing-Ya; Hou, Min; Ji, Min-Jun

2016-01-01

AIM: To investigate clarithromycin resistance positions 2142, 2143 and 2144 of the 23SrRNA gene in Helicobacter pylori (H. pylori) by nested-allele specific primer-polymerase chain reaction (nested-ASP-PCR). METHODS: The gastric tissue and saliva samples from 99 patients with positive results of the rapid urease test (RUT) were collected. The nested-ASP-PCR method was carried out with the external primers and inner allele-specific primers corresponding to the reference strain and clinical strains. Thirty gastric tissue and saliva samples were tested to determine the sensitivity of nested-ASP-PCR and ASP-PCR methods. Then, clarithromycin resistance was detected for 99 clinical samples by using different methods, including nested-ASP-PCR, bacterial culture and disk diffusion. RESULTS: The nested-ASP-PCR method was successfully established to test the resistance mutation points 2142, 2143 and 2144 of the 23SrRNA gene of H. pylori. Among 30 samples of gastric tissue and saliva, the H. pylori detection rate of nested-ASP-PCR was 90% and 83.33%, while the detection rate of ASP-PCR was just 63% and 56.67%. Especially in the saliva samples, nested-ASP-PCR showed much higher sensitivity in H. pylori detection and resistance mutation rates than ASP-PCR. In the 99 RUT-positive gastric tissue and saliva samples, the H. pylori-positive detection rate by nested-ASP-PCR was 87 (87.88%) and 67 (67.68%), in which there were 30 wild-type and 57 mutated strains in gastric tissue and 22 wild-type and 45 mutated strains in saliva. Genotype analysis showed that three-points mixed mutations were quite common, but different resistant strains were present in gastric mucosa and saliva. Compared to the high sensitivity shown by nested-ASP-PCR, the positive detection of bacterial culture with gastric tissue samples was 50 cases, in which only 26 drug-resistant strains were found through analyzing minimum inhibitory zone of clarithromycin. CONCLUSION: The nested-ASP-PCR assay showed higher
Application service provider (ASP) financial models for off-site PACS archiving

NASA Astrophysics Data System (ADS)

Ratib, Osman M.; Liu, Brent J.; McCoy, J. Michael; Enzmann, Dieter R.

2003-05-01

For the replacement of its legacy Picture Archiving and Communication Systems (approx. annual workload of 300,000 procedures), UCLA Medical Center has evaluated and adopted an off-site data-warehousing solution based on an ASP financial with a one-time single payment per study archived. Different financial models for long-term data archive services were compared to the traditional capital/operational costs of on-site digital archives. Total cost of ownership (TCO), including direct and indirect expenses and savings, were compared for each model. Financial parameters were considered: logistic/operational advantages and disadvantages of ASP models versus traditional archiving systems. Our initial analysis demonstrated that the traditional linear ASP business model for data storage was unsuitable for large institutions. The overall cost markedly exceeds the TCO of an in-house archive infrastructure (when support and maintenance costs are included.) We demonstrated, however, that non-linear ASP pricing models can be cost-effective alternatives for large-scale data storage, particularly if they are based on a scalable off-site data-warehousing service and the prices are adapted to the specific size of a given institution. The added value of ASP is that it does not require iterative data migrations from legacy media to new storage media at regular intervals.
Use of computer decision support in an antimicrobial stewardship program (ASP).

PubMed

Evans, R S; Olson, J A; Stenehjem, E; Buckel, W R; Thorell, E A; Howe, S; Wu, X; Jones, P S; Lloyd, J F

2015-01-01

Document information needs, gaps within the current electronic applications and reports, and workflow interruptions requiring manual information searches that decreased the ability of our antimicrobial stewardship program (ASP) at Intermountain Healthcare (IH) to prospectively audit and provide feedback to clinicians to improve antimicrobial use. A framework was used to provide access to patient information contained in the electronic medical record, the enterprise-wide data warehouse, the data-driven alert file and the enterprise-wide encounter file to generate alerts and reports via pagers, emails and through the Centers for Diseases and Control's National Healthcare Surveillance Network. Four new applications were developed and used by ASPs at Intermountain Medical Center (IMC) and Primary Children's Hospital (PCH) based on the design and input from the pharmacists and infectious diseases physicians and the new Center for Diseases Control and Prevention/National Healthcare Safety Network (NHSN) antibiotic utilization specifications. Data from IMC and PCH now show a general decrease in the use of drugs initially targeted by the ASP at both facilities. To be effective, ASPs need an enormous amount of "timely" information. Members of the ASP at IH report these new applications help them improve antibiotic use by allowing efficient, timely review and effective prioritization of patients receiving antimicrobials in order to optimize patient care.
C3 Polymorphism Influences Circulating Levels of C3, ASP and Lipids in Schizophrenic Patients.

PubMed

Nsaiba, Mohamed Jalloul; Lapointe, Marc; Mabrouk, Hajer; Douki, Wahiba; Gaha, Lotfi; Pérusse, Louis; Bouchard, Claude; Jrad, Besma Bel Hadj; Cianflone, Katherine

2015-05-01

Excessive activation of complement is associated with many diseases including schizophrenia. Investigation of C3 polymorphisms, circulating C3, cleavage product ASP/C3adesArg, and lipid metabolism. Cross-sectional analysis. C3 genotyping (CC vs GG for R102L) was performed on 434 Tunisian people consisting of 272 schizophrenic (SZ) patients and 162 control subjects. In a age- and gender-matched subgroups of the three genotypes (131 SZ and 112 NOR), plasma triglycerides, total cholesterol (C), LDL-C, HDL-C, ASP, and complement C3 were measured. C3 gene polymorphism influences BMI and plasma C3, ASP, triglyceride, total cholesterol, LDL-C and HDL-C among SZ patients (p < 0.05-0.0001), with increasing values demonstrated from CC (common form) to CG (heterozygote form) to GG (rare homozygote) forms. Significant correlations between plasma C3 and BMI, triglyceride, HDL-C and ASP (p < 0.05-0.0001) were observed, while ASP correlated with BMI and LDL-C (p = 0.005, p = 0.001, respectively) in SZ patients. Further, proportional conversion of C3 to ASP (%ASP/C3) also increased (p < 0.0001, GG>CG>CC). C3 polymorphisms and plasma C3, ASP and %ASP/C3 correlated with lipid parameters in this SZ population, suggesting that factors predisposing patients to schizophrenia are permissive for complement pathway activation and dyslipidemic influences.
Genetic dissection of powdery mildew resistance in interspecific half-sib grapevine families using SNP-based maps.

PubMed

Teh, Soon Li; Fresnedo-Ramírez, Jonathan; Clark, Matthew D; Gadoury, David M; Sun, Qi; Cadle-Davidson, Lance; Luby, James J

2017-01-01

Quantitative trait locus (QTL) identification in perennial fruit crops is impeded largely by their lengthy generation time, resulting in costly and labor-intensive maintenance of breeding programs. In a grapevine (genus Vitis ) breeding program, although experimental families are typically unreplicated, the genetic backgrounds may contain similar progenitors previously selected due to their contribution of favorable alleles. In this study, we investigated the utility of joint QTL identification provided by analyzing half-sib families. The genetic control of powdery mildew was studied using two half-sib F 1 families, namely GE0711/1009 (MN1264 × MN1214; N = 147) and GE1025 (MN1264 × MN1246; N = 125) with multiple species in their ancestry. Maternal genetic maps consisting of 1077 and 1641 single nucleotide polymorphism (SNP) markers, respectively, were constructed using a pseudo-testcross strategy. Ratings of field resistance to powdery mildew were obtained based on whole-plant evaluation of disease severity. This 2-year analysis uncovered two QTLs that were validated on a consensus map in these half-sib families with improved precision relative to the parental maps. Examination of haplotype combinations based on the two QTL regions identified strong association of haplotypes inherited from 'Seyval blanc', through MN1264, with powdery mildew resistance. This investigation also encompassed the use of microsatellite markers to establish a correlation between 206-bp (UDV-015b) and 357-bp (VViv67) fragment sizes with resistance-carrying haplotypes. Our work is one of the first reports in grapevine demonstrating the use of SNP-based maps and haplotypes for QTL identification and tagging of powdery mildew resistance in half-sib families.
Effects of sib-mating and wind pollination on nursery seedling size, growth components, and phenology of Douglas-fir seed-orchard progenies.

Treesearch

Frank C. Sorensen

1997-01-01

Polymix outcross (X), full-sib (FS), and wind-pollination (WP) families were produced on 25 seed trees and 10 half-sib families on 10 of the same trees in a Pseudotsuga menziesii (Mirb.) Franco var. menziesii seedling seed orchard. Seedlings were raised at two sowing densities for 2 years in the nursery, and inbreeding depression in seedling size...
Schizophrenia: A genome scan targets chromosomes 3p and 8p as potential sites of susceptibility genes

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

Pulver, A.E.; Lasseter, V.K.; Kasch, L.

Using a systematically ascertained sample of 57 families, each having 2 or more members with a consensus diagnosis of schizophrenia (DSM-III-R criteria), we have carried out linkage studies of 520 loci, covering approximately 70% of the genome for susceptibility loci for schizophrenia. A two-stage strategy based on lod score thresholds from simulation studies of our sample identified regions for further exploration. In each region, a dense map of highly informative dinucleotide repeat polymorphisms (heterozygosity greater than .70) was analyzed using dominant, recessive, and {open_quotes}affected only{close_quotes} models and nonparametric sib pair identity-by-descent methods. For one region, 8p22-p21, affected sib-pair analyses gavemore » a P value = .0001, corresponding to a lod score approximately equal to 3.00. For 8p22-p21, the maximum two-point lod score occurred using the {open_quotes}affected only{close_quotes} recessive model (Z{sub max} = 2.35; {theta}{sub M} = {theta}{sub F}); allowing for a constant sex difference in recombination fractions found in reference pedigrees, Z{sub max} = 2.78 ({theta}{sub M}/{theta}{sub F} = 3). For a second region, 3p26-p24, the maximum two-point lod score was 2.34 ({open_quotes}affected only{close_quotes} dominant model), and the affected sib-pair P value was .01. These two regions are worthy of further exploration as potential sites of susceptibility genes for schizophrenia. 59 refs., 2 figs., 4 tabs.« less

Determination of ASPS performance for large payloads in the shuttle orbiter disturbance environment. [digital simulation

NASA Technical Reports Server (NTRS)

Keckler, C. R.; Kibler, K. S.; Powell, L. F.

1979-01-01

A high fidelity simulation of the annular suspension and pointing system (ASPS), its payload, and the shuttle orbiter was used to define the worst case orientations of the ASPS and its payload for the various vehicle disturbances, and to determine the performance capability of the ASPS under these conditions. The most demanding and largest proposed payload, the Solar Optical Telescope was selected for study. It was found that, in all cases, the ASPS more than satisfied the payload's requirements. It is concluded that, to satisfy facility class payload requirements, the ASPS or a shuttle orbiter free-drift mode (control system off) should be utilized.
NOS3 Glu298Asp genotype and blood pressure response to endurance training: the HERITAGE family study.

PubMed

Rankinen, T; Rice, T; Pérusse, L; Chagnon, Y C; Gagnon, J; Leon, A S; Skinner, J S; Wilmore, J H; Rao, D C; Bouchard, C

2000-11-01

Endothelium-dependent vasodilation is a mechanism that may affect blood pressure response to endurance training. Because NO plays a central role in this process, the endothelial NO synthase gene is a good candidate for the regulation of exercise blood pressure. We investigated the associations between an endothelial NO synthase gene polymorphism (Glu298Asp) and endurance training-induced changes in resting and submaximal exercise blood pressure in 471 white subjects of the HERITAGE Family Study. Two submaximal exercise tests at 50 W were conducted both before and after a 20-week endurance training program. Steady-state exercise blood pressure was measured twice in each test with an automated unit. The Glu298Asp polymorphism was typed with a PCR-based method and digestion with BAN:II. Both systolic and diastolic blood pressure at 50 W decreased in response to the training program, whereas resting blood pressure remained unchanged. The decrease in diastolic blood pressure at 50 W was greater (P=0.0005, adjusted for age, gender, baseline body mass index, and baseline diastolic blood pressure at 50 W) in the Glu/Glu homozygotes (4.4 [SEM 0.4] mm Hg, n=187) than in the heterozygotes (3.1 [0.4] mm Hg, n=213) and the Asp/Asp homozygotes (1.3 [0.7] mm Hg, n=71). The genotype accounted for 2.3% of the variance in diastolic blood pressure at 50 W training response. Both the Glu298 homozygotes and the heterozygotes had a greater (P=0.013) training-induced reduction in rate-pressure product at 50 W than the Asp298 homozygotes. These data suggest that DNA sequence variation in the endothelial NO synthase gene locus is associated with the endurance training-induced decreases in submaximal exercise diastolic blood pressure and rate-pressure product in sedentary normotensive white subjects.
Evidence for association of a common variant of the endothelial nitric oxide synthase gene (Glu298→Asp polymorphism) to the presence, extent, and severity of coronary artery disease

PubMed Central

Colombo, M G; Andreassi, M G; Paradossi, U; Botto, N; Manfredi, S; Masetti, S; Rossi, G; Clerico, A; Biagini, A

2002-01-01

Background: Genetic variants of endothelial nitric oxide synthase (eNOS) could influence individual susceptibility to coronary artery disease. Objective: To assess whether Glu298→Asp polymorphism of the eNOS gene is associated with the occurrence and severity of angiographically defined coronary artery disease in the Italian population. Methods: Polymerase chain reaction/restriction fragment length polymorphism analysis was done to detect the Glu298→Asp variant of the eNOS gene in 201 patients with coronary artery disease and 114 controls. The severity of coronary artery disease was expressed by the number of affected vessels and by the Duke scoring system. Results: The frequencies of the eNOS Glu/Glu, Glu/Asp, and Asp/Asp genotypes in the coronary artery disease group were significantly different from those of controls (45.3%, 38.8%, and 15.9% v 42.1%, 51.8%, and 6.1%, respectively; χ2 = 8.589, p = 0.0136). In comparison with subjects who had a Glu298 allele in the eNOS gene, the risk of coronary artery disease was increased among Asp/Asp carriers (odds ratio 2.9, 95% confidence interval 1.2 to 6.8, p = 0.01) and was independent of the other common risk factors (p = 0.04). There was a significant association between the eNOS Glu298→Asp variant and both the number of stenosed vessels (mean (SEM), 2.3 (0.1) for Asp/Asp v 1.9 (0.1) and 1.8 (0.1) for Glu/Glu and Glu/Asp, respectively; p = 0.01) and the Duke score (56.1 (3.1) for Asp/Asp v 46.7 (2.0) and 46.1 (1.9) for Glu/Glu and Glu/Asp, respectively; p = 0.02). Conclusions: Glu298→Asp polymorphism of the eNOS gene appears to be associated with the presence, extent, and severity of angiographically assessed coronary artery disease. PMID:12010932
The Gly-54-->Asp allelic form of human mannose-binding protein (MBP) fails to bind MBP-associated serine protease.

PubMed Central

Matsushita, M; Ezekowitz, R A; Fujita, T

1995-01-01

The human mannose-binding protein (MBP) is a pattern recognition molecule that appears to play a role in initial host defence. MBP activates the complement cascade and it may act as an opsonin both in the absence and in the presence of complement. A number of distinct MBP allelic forms exist in different population groups. An allele that occurs in 5-7% of Caucasians was identified by an inability to activate the complement system. A homozygous mutation at base pair 230 of the MBP gene results in a Gly-to-Asp substitution at the fifth collagen repeat. It appears that the resultant protein, MBPD, is able to form high-order multimers that bind bacteria but do not support complement activation. Recently a novel serine protease, the MBP-associated serine protease (MASP), has been described. MBP-MASP complexes circulate in serum and result in the direct activation of a novel complement pathway (lectin pathway) in the absence of the first complement components. In this study we demonstrate that MASP and its proenzyme proMASP are unable to bind to recombinant (r)MBPD. This lack of a MASP-rMBPD association corresponds to a failure of the Gly-54-->Asp form of MBP to activate complement. Our results provide a biochemical basis for the functional deficit in the Gly-54-->Asp allelic form of MBP and suggest that the proMASP/MASP binding site maps to the fifth collagen repeat of MBP. Images Figure 1 PMID:7487919
Resistance mutations of Pro197, Asp376 and Trp574 in the acetohydroxyacid synthase (AHAS) affect pigments, growths, and competitiveness of Descurainia sophia L.

PubMed

Zhang, Yongzhi; Xu, Yufang; Wang, Shipeng; Li, Xuefeng; Zheng, Mingqi

2017-11-27

D. Sophia is one of the most problematic weed species infesting winter wheat in China, and has evolved high resistance to tribenuron-methyl. Amino acid substitutions at site of Pro197, Asp376 and Trp574 in acetohydroxyacid synthase (AHAS) were mainly responsible for D. sophia resistance to tribenuron-methyl. In this study, D. sophia plant individually homozygous for specific AHAS mutation (Pro197Leu, Pro197His, Pro197Ser, Pro197Thr, Asp376Glu and Trp574Leu) were generated. In addition, the effects of resistance mutations on pigments, growths and competitiveness of susceptible (S) and resistant (R) plants of D. sophia were investigated. The results indicated the R plants carrying Pro197Leu or Pro197His or Asp376Glu or Trp574Leu displayed stronger competitiveness than S plants. The adverse effects on R plants aggravated with the increase of R plants proportion, which made the R plants against domination the weed community in absent of herbicide selection. Therefore, these resistance mutation have no obvious adverse effects on the pigments (chlorophyll a, chlorophyll b and carotenoid), relative growth rates (RGR), leaf area ratio (LAR) and net assimilation rate (NAR) of R plants.
Genetic Difference in Height Growth and Survival of Cottonwood Full-Sib Families

Treesearch

D. T. Cooper; W. K. Randall

1973-01-01

Sixteen full-sib families from crosses between four fast-growing female and four fast-growing male clones of cottonwood (Populus deltoides Bartr.) were clonally evaluated for 1 year in a replicated field test. Seedling size had no effect on clonal performance. Approximately 70 percent of the genetic variance for height and 20 percent of that for...
77 FR 16113 - ASP Ventures Corp., Order of Suspension of Trading

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-19

... SECURITIES AND EXCHANGE COMMISSION [File No. 500-1] ASP Ventures Corp., Order of Suspension of Trading March 15, 2012. It appears to the Securities and Exchange Commission that there is a lack of current and accurate information concerning the securities of ASP Ventures Corp. because it has not filed any periodic reports since the period ended...
Annular Suspension and Pointing System (ASPS) magnetic rotary joint

NASA Technical Reports Server (NTRS)

Smith, W. E.; Quach, W.; Thomas, W.

1993-01-01

The Annular Suspension and Pointing System (ASPS) is a prototype of flight hardware for a high-accuracy space payload pointing mount. The long term project objective is to perform modifications and implement improvements to the existing ASPS in hopes of recommission. Also, new applications will be investigated for this technology. This report will focus on the first aspect of this overall goal, to establish operation of a single bearing station. Presented is an overview of the system history and bearing operation followed by the processes, results, and status of the single bearing study.
Evaluation of Ga-DOTA-(D-Asp)n as bone imaging agents: D-aspartic acid peptides as carriers to bone.

PubMed

Ogawa, Kazuma; Ishizaki, Atsushi; Takai, Kenichiro; Kitamura, Yoji; Makino, Akira; Kozaka, Takashi; Kiyono, Yasushi; Shiba, Kazuhiro; Odani, Akira

2017-10-25

67 Ga-DOTA-(L-Asp) 11 and 67 Ga-DOTA-(L-Asp) 14 , which have been developed as bone imaging agents, showed a high accumulation in bone and a rapid blood clearance in mice. However, peptides composed of D-amino acids are more stable in vivo than those composed of their L-equivalents. In this study, 67 Ga-DOTA-(D-Asp) n (n = 2, 5, 8, 11, or 14) were synthesized using the Fmoc-based solid-phase methodology and evaluated. In hydroxyapatite binding assay, binding of 67 Ga-DOTA-(D-Asp) n tended to increase with increasing length of the amino acid chain. 67 Ga-DOTA-(D-Asp) 11 and 67 Ga-DOTA-(D-Asp) 14 caused a high accumulation of radioactivity in the bones of the mice. However, the results for 67 Ga-DOTA-(D-Asp) n and 67 Ga-DOTA-(L-Asp) n were comparable. In urine analyses, the proportion of intact complex after injection of 67 Ga-DOTA-(D-Asp) 14 was significantly higher than that of 67 Ga-DOTA-(L-Asp) 14 . Although 67 Ga-DOTA-(D-Asp) 14 was more stable than 67 Ga-DOTA-(L-Asp) 14 , the properties of 67 Ga-DOTA-(D-Asp) n and 67 Ga-DOTA-(L-Asp) n as bone imaging agents may be comparable.
A high-density SNP linkage scan with 142 combined subtype ADHD sib pairs identifies linkage regions on chromosomes 9 and 16.

PubMed

Asherson, P; Zhou, K; Anney, R J L; Franke, B; Buitelaar, J; Ebstein, R; Gill, M; Altink, M; Arnold, R; Boer, F; Brookes, K; Buschgens, C; Butler, L; Cambell, D; Chen, W; Christiansen, H; Feldman, L; Fleischman, K; Fliers, E; Howe-Forbes, R; Goldfarb, A; Heise, A; Gabriëls, I; Johansson, L; Lubetzki, I; Marco, R; Medad, S; Minderaa, R; Mulas, F; Müller, U; Mulligan, A; Neale, B; Rijsdijk, F; Rabin, K; Rommelse, N; Sethna, V; Sorohan, J; Uebel, H; Psychogiou, L; Weeks, A; Barrett, R; Xu, X; Banaschewski, T; Sonuga-Barke, E; Eisenberg, J; Manor, I; Miranda, A; Oades, R D; Roeyers, H; Rothenberger, A; Sergeant, J; Steinhausen, H-C; Taylor, E; Thompson, M; Faraone, S V

2008-05-01

As part of the International Multi-centre ADHD Genetics project we completed an affected sibling pair study of 142 narrowly defined Diagnostic and Statistical Manual of Mental Disorders, fourth edition combined type attention deficit hyperactivity disorder (ADHD) proband-sibling pairs. No linkage was observed on the most established ADHD-linked genomic regions of 5p and 17p. We found suggestive linkage signals on chromosomes 9 and 16, respectively, with the highest multipoint nonparametric linkage signal on chromosome 16q23 at 99 cM (log of the odds, LOD=3.1) overlapping data published from the previous UCLA (University of California, Los Angeles) (LOD>1, approximately 95 cM) and Dutch (LOD>1, approximately 100 cM) studies. The second highest peak in this study was on chromosome 9q22 at 90 cM (LOD=2.13); both the previous UCLA and German studies also found some evidence of linkage at almost the same location (UCLA LOD=1.45 at 93 cM; German LOD=0.68 at 100 cM). The overlap of these two main peaks with previous findings suggests that loci linked to ADHD may lie within these regions. Meta-analysis or reanalysis of the raw data of all the available ADHD linkage scan data may help to clarify whether these represent true linked loci.
Effects of protonation state of Asp181 and position of active site water molecules on the conformation of PTP1B.

PubMed

Ozcan, Ahmet; Olmez, Elif Ozkirimli; Alakent, Burak

2013-05-01

In protein tyrosine phosphatase 1B (PTP1B), the flexible WPD loop adopts a closed conformation (WPDclosed ) in the active state of PTP1B, bringing the catalytic Asp181 close to the active site pocket, while WPD loop is in an open conformation (WPDopen ) in the inactive state. Previous studies showed that Asp181 may be protonated at physiological pH, and ordered water molecules exist in the active site. In the current study, molecular dynamics simulations are employed at different Asp181 protonation states and initial positions of active site water molecules, and compared with the existing crystallographic data of PTP1B. In WPDclosed conformation, the active site is found to maintain its conformation only in the protonated state of Asp181 in both free and liganded states, while Asp181 is likely to be deprotonated in WPDopen conformation. When the active site water molecule network that is a part of the free WPDclosed crystal structure is disrupted, intermediate WPD loop conformations, similar to that in the PTPRR crystal structure, are sampled in the MD simulations. In liganded PTP1B, one active site water molecule is found to be important for facilitating the orientation of Cys215 and the phosphate ion, thus may play a role in the reaction. In conclusion, conformational stability of WPD loop, and possibly catalytic activity of PTP1B, is significantly affected by the protonation state of Asp181 and position of active site water molecules, showing that these aspects should be taken into consideration both in MD simulations and inhibitor design. Copyright © 2013 Wiley Periodicals, Inc.
Thigmomorphogenesis: anatomical, morphological and mechanical analysis of genetically different sibs of Pinus taeda in response to mechanical perturbation.

PubMed

Telewski, F W; Jaffe, M J

1986-01-01

Twenty-three open pollinated families (half-sibs) and four controlled pollinated families (full-sibs) of Pinus taeda L. (loblolly pine) were grown in a greenhouse and analyzed for changes induced by mechanical perturbation (MP). These changes included inhibition of stem and needle elongation, bracing of branch nodes, and increased radial growth in the direction of the MP. Inhibition of stem elongation was the least variable feature measured. Leaf extension and stem diameter were highly variable between half-sibs. MP induced increased drag in greenhouse grown P. taeda in wind-tunnel tests. In P. taeda, MP induced decreased flexibility and increased elasticity and plasticity of the stem. The increased radial growth of the stems overrode the increase in elasticity, resulting in an overall decrease in flexibility. MP trees had a higher rupture point than non-MP controls. Increased radial growth is a result of more rapid cell divisions of the vascular cambium, resulting in increased numbers of tracheids. The decreased leader growth is partly due to a decreased tracheid length in response to MP.
Thigmomorphogenesis: anatomical, morphological and mechanical analysis of genetically different sibs of Pinus taeda in response to mechanical perturbation

NASA Technical Reports Server (NTRS)

Telewski, F. W.; Jaffe, M. J.

1986-01-01

Twenty-three open pollinated families (half-sibs) and four controlled pollinated families (full-sibs) of Pinus taeda L. (loblolly pine) were grown in a greenhouse and analyzed for changes induced by mechanical perturbation (MP). These changes included inhibition of stem and needle elongation, bracing of branch nodes, and increased radial growth in the direction of the MP. Inhibition of stem elongation was the least variable feature measured. Leaf extension and stem diameter were highly variable between half-sibs. MP induced increased drag in greenhouse grown P. taeda in wind-tunnel tests. In P. taeda, MP induced decreased flexibility and increased elasticity and plasticity of the stem. The increased radial growth of the stems overrode the increase in elasticity, resulting in an overall decrease in flexibility. MP trees had a higher rupture point than non-MP controls. Increased radial growth is a result of more rapid cell divisions of the vascular cambium, resulting in increased numbers of tracheids. The decreased leader growth is partly due to a decreased tracheid length in response to MP.
[Carcinogenesis and its mechanism of mutant-type[12Asp]K-ras4B gene].

PubMed

Gui, Li-ming; Wei, Li-hui; Zhang, Ying-mei; Wang, Jian-liu; Wang, Ying; Chen, Ying; Ma, Da-long

2002-01-01

Ras gene plays an important role in the extra- and intra-cellular signal transduction pathway. It mediates series cascade reactions, and eventually actives transcriptional factors in nucleus. It is unknown on the mechanism of carcinogenesis of Ras gene in endometrial carcinoma, though K-ras mutant is very common in endometrial atypical hyperplasia and carcinoma. On basis of discovering the mutation in 12th codon of K-ras in endometrial carcinoma cell line, HEC-1A, we explored the carcinogenesis and molecular mechanism of mutant-type [12Asp] K-ras4B gene. (1) Full-length [12Asp]K-ras4B cDNA was amplified with RT-PCR, then inserted into pcDI eukaryotic expressive vector. (2) Morphological change, growth kinetics in vitro and tumorigencity in nude mice in vivo after-before transfection were observed. (3) To test the cell growth kinetics by methyl thiazolium tetrazolium (MTT) and [3H]thymidine incorporation method. (1) The authors have successfully constructed eukaryotic expression plasmid pcDI-[12Asp] K-ras4B; (2) To confirm that [12Asp] K-ras4B mutant can trigger the neoplastic transformation of NIH3T3 cells by test in vitro and in vivo. (3) After pMCV-RasN17 plasmid, a Ras mutant were transfected into pcDI-[12Asp] K-ras4B cells, the growth of this cell were restrained significantly in comparison with control group. (4) These findings indicate the expression of RafS621A resulted in remarkable inhibition in proliferation of pcDI-[12Asp]K-ras4B cell (P < 0.05). However, RafCAAX mutant can enhance pcDI-[12Asp]K-ras4B cell growth (P < 0.05). (1) [12Asp]K-ras4B gene alone is able to cause neoplastic transformation in NIH3T3 cells in vitro and in vivo. (2) [12Asp]K-ras4B-induced NIH3T3 cells neoplastic transformation required Raf signaling pathway.
Intercomparison of SOUP, ASP, LPSP, and MDI magnetograms

NASA Astrophysics Data System (ADS)

Berger, T.; Lites, B.; Martinez-Pillet, V.; Tarbell, T.; Title, A.

2001-05-01

We compare simultaneous magnetograms of a solar active region taken by the Advanced Stokes Polarimeter (ASP) and the Solar Optical Universal Polimeter (SOUP) in 1998. In addition we compare magnetograms taken by the La Palma Stokes Polarimeter (LPSP), the Michelson Doppler Imager (MDI) on SOHO, and the SOUP instrument in 2000. The SOUP instrument on the Swedish Vacuum Solar Telescope (SVST) attains the highest spatial resolution but has the least understood calibration; the ASP on the Dunn Solar Telescope (DST) at Sacramento Peak attains the highest magnetic field precision. The goal of the program is to better quantify the SOUP magnetograms and thereby study magnetic element dynamics in the photosphere with higher precision.
ASP Celebrates IYA, One Month at a Time

NASA Astrophysics Data System (ADS)

Gurton, Suzanne; Berendsen, M.; Hurst, A.; White, V.

2008-05-01

Serving three major networks of educators, the ASP, in coordination with NASA and NOAO and others, is building a comprehensive program to celebrate the International Year of Astronomy (IYA) by featuring a different astronomy theme during each month of 2009. We will provide a rich array of themed resources, such as activities, tele-conferences, and news stories, to the variety of educators served by the ASP: amateur astronomers, museum educators and teachers. This poster will present our program of monthly themes, along with associated services and resources, to support the diverse public outreach efforts of the members of the NASA Night Sky Network, participants in Astronomy From the Ground Up, and Project ASTRO partners.
ASP: Gearing Up for the Next 120

NASA Astrophysics Data System (ADS)

Manning, J. G.

2010-08-01

In 2009, the Astronomical Society of the Pacific celebrates 120 years of serving the cause of astronomy, with a membership of professional and amateur astronomers, educators, and interested public; professional and popular publications; and increasingly, a variety of education and professional development programs and dissemination networks serving our various constituencies. As the Society begins a new strategic planning phase and looks forward to the next 120 years of service, with a re-articulated mission ("Advancing science literacy through engagement in astronomy") and a continuing commitment to science, education and outreach, in which direction(s) shall it head? The presenter will offer a few thoughts and conference participants will be surveyed for theirs in their role as continuing or newly minted ASP members. Outcomes: The audience will gain insight into ASP's future planning and will be surveyed for their input in the process.
Open Access and the Future of the ASP Conference Series

NASA Astrophysics Data System (ADS)

Jensen, J. B.; Moody, J. W.; Barnes, J.

2010-10-01

The Astronomical Society of the Pacific (ASP) has been publishing the proceedings of conferences in astronomy and astrophysics for more than twenty years. The ASP Conference Series (ASPCS) is widely known for its affordable and high-quality printed volumes. The ASPCS is adapting to the changing ways astronomers use our proceedings volumes, both electronically and in print. Recently there has been increasing pressure from government agencies and the academic community for "open access" (electronic copies of scholarly publications made freely available immediately after publication), and we discuss how the ASPCS is responding to the needs of the professional astronomical community, the scholarly society that supports us (the ASP), and humanity at large. While we cannot yet provide full open access and stay in business, we are actively pursuing several initiatives to improve the quality of our product and the impact of the papers we publish.
CMAPS_ASPS_DATA-LCM_GTC

EPA Pesticide Factsheets

Total mercury in precipitation collected using ASPS automated wet-only instrument and analyzed by cold vapor atomic fluorescence spectroscopy.This dataset is associated with the following publication:Lynam, M., J.T. Dvonch, J. Barres, M. Landis , and A. Kamal. Investigating the impact of local urban sources on total atmospheric mercury wet deposition in Cleveland, Ohio, USA. ATMOSPHERIC ENVIRONMENT. Elsevier Science Ltd, New York, NY, USA, 127: 262-271, (2016).
Reduced rDNA Copy Number Does Not Affect “Competitive” Chromosome Pairing in XYY Males of Drosophila melanogaster

PubMed Central

Maggert, Keith A.

2014-01-01

The ribosomal DNA (rDNA) arrays are causal agents in X-Y chromosome pairing in meiosis I of Drosophila males. Despite broad variation in X-linked and Y-linked rDNA copy number, polymorphisms in regulatory/spacer sequences between rRNA genes, and variance in copy number of interrupting R1 and R2 retrotransposable elements, there is little evidence that different rDNA arrays affect pairing efficacy. I investigated whether induced rDNA copy number polymorphisms affect chromosome pairing in a “competitive” situation in which complex pairing configurations were possible using males with XYY constitution. Using a common normal X chromosome, one of two different full-length Y chromosomes, and a third chromosome from a series of otherwise-isogenic rDNA deletions, I detected no differences in X-Y or Y-Y pairing or chromosome segregation frequencies that could not be attributed to random variation alone. This work was performed in the context of an undergraduate teaching program at Texas A&M University, and I discuss the pedagogical utility of this and other such experiments. PMID:24449686

Asp 58 modulates lens αA-crystallin oligomer formation and chaperone function.

PubMed

Takata, Takumi; Nakamura-Hirota, Tooru; Inoue, Rintaro; Morishima, Ken; Sato, Nobuhiro; Sugiyama, Masaaki; Fujii, Noriko

2018-06-01

Senile cataract onset is caused by insolubilization of lens proteins. The lens crystallin protein family correctly orders the formation of homo- or hetero-oligomers in lens fiber cells. Because lens fiber cells do not divide, covalent post-translational modifications, such as isomerization of aspartate residues, accumulate with aging. Although many isomerization sites of αA-crystallin have been reported, their structural and functional contributions have never been identified. In this study, αA-crystallin was extracted from aged human lens and separated into each oligomeric state by size exclusion chromatography and electrophoresis. The novel combination methodology of in-solution/gel tryptic digestion with liquid chromatography equipped with mass spectrometry (LC-MS/MS) was used to evaluate the isomerization of Asp 58. The contributions of isomerization to assembly, solubility, and chaperone functions of αA-crystallin were estimated using a series of mutations of Asp 58 in αA-crystallin. The results indicated that the isomerization of Asp 58 depended on the oligomer size and age of the lens. The substitution of Asp 58 for hydrophobic residues increased αA-crystallin oligomer size and decreased solubility. All substitutions decreased the chaperone function of αA-crystallin for aggregates of bovine βL-crystallin and alcohol dehydrogenase. The data indicated that Asp 58 in αA-crystallin was critical for intermolecular interactions in the lens. Our results also suggested that LC-MS/MS-based isomerization analyses of in-gel-digested products could be useful for investigating the isomerization of Asp residues in oligomeric states. This method could also be used to analyze d/l ratios of amino acid residues in soluble protein aggregates. © 2018 Federation of European Biochemical Societies.
Normative studies with the Scale for Interpersonal Behaviour (SIB): II. US students. A cross-cultural comparison with Dutch data.

PubMed

Arrindell, W A; Bridges, K R; van der Ende, J; St Lawrence, J S; Gray-Shellberg, L; Harnish, R; Rogers, R; Sanderman, R

2001-12-01

The Scale for Interpersonal Behaviour (SIB), a multidimensional, self-report measure of state assertiveness, was administered to a nationwide sample of 2375 undergraduates enrolled at 11 colleges and universities across the USA. The SIB was developed in the Netherlands for the independent assessment of both distress associated with self-assertion in a variety of social situations and the likelihood of engaging in a specific assertive response. This is done with four factorially-derived, first-order dimensions: (i) Display of negative feelings (Negative assertion); (ii) Expression of and dealing with personal limitations; (iii) Initiating assertiveness; and (iv) Praising others and the ability to deal with compliments/praise of others (Positive assertion). The present study was designed to determine the cross-national invariance of the original Dutch factors and the construct validity of the corresponding dimensions. It also set out to develop norms for a nationwide sample of US students. The results provide further support for the reliability, factorial and construct validity of the SIB. Compared to their Dutch equivalents, US students had meaningfully higher distress in assertiveness scores on all SIB scales (medium to large effect sizes), whereas differences on the performance scales reflected small effect sizes. The cross-national differences in distress scores were hypothesized to have originated from the American culture being more socially demanding with respect to interpersonal competence than the Dutch, and from the perceived threats and related cognitive appraisals that are associated with such demands.
Tetrapod-type [Asp1] angiotensin is present in a holostean fish, Amia calva.

PubMed

Takei, Y; Itahara, Y; Butler, D G; Watanabe, T X; Oudit, G Y

1998-05-01

The renin-angiotensin system has been identified in various vertebrates, from elasmobranchs to mammals. Tetrapod (amphibians to mammals) angiotensin (ANG) has Asp at the N-terminus, but Asp is replaced by Asn in elasmobranch and teleost fish. ANG I has been isolated from incubates of plasma and kidney extracts of the bowfin Amia calva, a holostean fish, using the eel vasopressor activity as an assay system; its sequence was found to be H-Asp-Arg-Val-Tyr-Val-His-Pro-Phe-Asn-Leu-OH after sequence analysis, mass spectrometry, and comparison with the synthetic peptide. This sequence is identical to bullfrog ANG I. [Asn1] ANG I was not detected. Thus the bowfin is the first fish species which contains only [Asp1] ANG I. The bowfin ANG I and II were no more vasopressor than eel peptides in the bowfin, indicating that bowfin ANG II receptors do not distinguish between [Asp1] and [Asn1] peptides. In the rat, bowfin ANG I and rat [Ile5, His9] ANG I have equipressor activities when examined in different animals, but the vasopressor activity of bowfin ANG I decreased following rat ANG I in the same animals, although the activity of rat ANG I was unaffected after bowfin ANG I. The present study directly demonstrates the presence of the renin-angiotensin system in a holostean fish and showed that its ANG II receptors have not yet fully coevolved with the homologous [Asp1] peptide.
ASP6537, a novel highly selective cyclooxygenase-1 inhibitor, exerts potent antithrombotic effect without "aspirin dilemma".

PubMed

Sakata, Chinatsu; Kawasaki, Tomihisa; Kato, Yasuko; Abe, Masaki; Suzuki, Ken-ichi; Ohmiya, Makoto; Funatsu, Toshiyuki; Morita, Yoshiaki; Okada, Masamichi

2013-07-01

Aspirin inhibits both the cyclooxygenase (COX)-1-dependent production of thromboxane A2 (TXA2) in platelets and COX-2-dependent production of anti-aggregatory prostaglandin I2 (PGI2) in vessel walls, resulting in "aspirin dilemma." Our objective is to investigate whether ASP6537 can overcome aspirin dilemma and exert a potent antithrombotic effect without a concurrent ulcerogenic effect. We evaluated the inhibitory effects of ASP6537 on recombinant human COX-1 (rhCOX-1) and rhCOX-2 activities using a COX-1/2 selectivity test. To determine whether ASP6537 induces aspirin dilemma, we examined the effects of ASP6537 on in vitro TXA2 and PGI2 metabolite production from platelets and isolated aorta of guinea pigs, and on plasma concentrations of TXA2 and PGI2 metabolites in aged rats. Finally, we evaluated the antithrombotic effects and ulcerogenic activity of ASP6537 using an electrically induced carotid arterial thrombosis model and a gastric ulcer model in guinea pigs. The IC50 ratios of rhCOX-2 to rhCOX-1 for ASP6537 and aspirin were >142,000 and 1.63 fold, respectively. ASP6537 inhibited TXA2 production more selectively than aspirin in in vitro and in vivo TXA2/PGI2 production studies. ASP6537 exerted a significant antithrombotic effect at ≥3 mg/kg, while aspirin tended to inhibit thrombosis at 300 mg/kg but it was not statistically significant. Further, ASP6537 did not induce ulcer formation at 100 mg/kg, whereas aspirin exhibited an ulcerogenic effect at doses of ≥100 mg/kg. ASP6537 functions as a highly selective COX-1 inhibitor with a superior ability to aspirin for normalizing TXA2/PGI2 balance, and exerts antithrombotic effect without ulcerogenic effect. Copyright © 2013 Elsevier Ltd. All rights reserved.
Genetic evidence of extra-pair paternity and intraspecific brood parasitism in the monk parakeet

PubMed Central

2013-01-01

Introduction The monk parakeet (Myiopsitta monachus) is a widespread invasive species native to southern South America that has become established in many regions of the world. Monk parakeets breed in a large, fully enclosed structure built from twigs, which consist of one to many individual brooding chambers. The species has been considered to be socially and genetically monogamous. However, genetic relatedness of adults to juveniles in the native area was found to be lower than expected for monogamy. To assess the significance of this discrepancy, we examined individual and population genetic patterns of microsatellite loci at two sites in Córdoba province, Argentina. Results We sampled 154 nestlings and 42 adults in Córdoba, Argentina. Mean value of pairwise relatedness of nestlings within chambers was about 0.40. Contrarily, relatedness of nestlings between chambers was close to zero. We found a considerable degree of variation in nestling pairwise relatedness and parentage within chambers, including chambers with combinations of unrelated, half-sib, and full-sib nestlings. The proportion of sibling relatedness indicated monogamy in 47% and extra pair-paternity in 40% of the chambers. We also found intra-brood parasitism in 3% of the chambers. Conclusions Our results indicate that the monk parakeet is sexually polygamous in its native range in Argentina, which is consistent with the observed mean value of relatedness of adults to juveniles of about 0.4. We also confirm the existence of intra-brood parasitism. High density of monk parakeets may favor occurrence of extra-pair paternity and intra-brood parasitism in the native sites. PMID:24209709
Implementation of an ASP model offsite backup archive for clinical images utilizing Internet 2

NASA Astrophysics Data System (ADS)

Liu, Brent J.; Chao, Sander S.; Documet, Jorge; Lee, Jasper; Lee, Michael; Topic, Ian; Williams, Lanita

2005-04-01

With the development of PACS technology and an increasing demand by medical facilities to become filmless, there is a need for a fast and efficient method of providing data backup for disaster recovery and downtime scenarios. At the Image Processing Informatics Lab (IPI), an ASP Backup Archive was developed using a fault-tolerant server with a T1 connection to serve the PACS at the St. John's Health Center (SJHC) Santa Monica, California. The ASP archive server has been in clinical operation for more than 18 months, and its performance was presented at this SPIE Conference last year. This paper extends the ASP Backup Archive to serve the PACS at the USC Healthcare Consultation Center II (HCC2) utilizing an Internet2 connection. HCC2 is a new outpatient facility that recently opened in April 2004. The Internet2 connectivity between USC's HCC2 and IPI has been established for over one year. There are two novelties of the current ASP model: 1) Use of Internet2 for daily clinical operation, and 2) Modifying the existing backup archive to handle two sites in the ASP model. This paper presents the evaluation of the ASP Backup Archive based on the following two criteria: 1) Reliability and performance of the Internet2 connection between HCC2 and IPI using DICOM image transfer in a clinical environment, and 2) Ability of the ASP Fault-Tolerant backup archive to support two separate clinical PACS sites simultaneously. The performances of using T1 and Internet2 at the two different sites are also compared.
Exploration of genetic architecture through sib-ship reconstruction in advanced breeding population of Eucalyptus nitens.

PubMed

Klápště, Jaroslav; Suontama, Mari; Telfer, Emily; Graham, Natalie; Low, Charlie; Stovold, Toby; McKinley, Russel; Dungey, Heidi

2017-01-01

Accurate inference of relatedness between individuals in breeding population contributes to the precision of genetic parameter estimates, effectiveness of inbreeding management and the amount of genetic progress delivered from breeding programs. Pedigree reconstruction has been proven to be an efficient tool to correct pedigree errors and recover hidden relatedness in open pollinated progeny tests but the method can be limited by the lack of parental genotypes and the high proportion of alien pollen from outside the breeding population. Our study investigates the efficiency of sib-ship reconstruction in an advanced breeding population of Eucalyptus nitens with only partially tracked pedigree. The sib-ship reconstruction allowed the identification of selfs (4% of the sample) and the exploration of their potential effect on inbreeding depression in the traits studied. We detected signs of inbreeding depression in diameter at breast height and growth strain while no indications were observed in wood density, wood stiffness and tangential air-dry shrinkage. After the application of a corrected sib-ship relationship matrix, additive genetic variance and heritability were observed to increase where signs of inbreeding depression were initially detected. Conversely, the same genetic parameters for traits that appeared to be free of inbreeding depression decreased in size. It therefore appeared that greater genetic variance may be due, at least in part, to contributions from inbreeding in these studied populations rather than a removal of inbreeding as is traditionally thought.
ASP Celebrates IYA, One Month at a Time

NASA Astrophysics Data System (ADS)

Gurton, S.; Berendsen, M.; Hurst, A.; White, V.

2008-11-01

Serving three major networks of educators, the ASP is working with NASA, NOAO, ASTC and others to build a comprehensive program to celebrate the International Year of Astronomy (IYA2009). By featuring a different astronomy theme during each month of 2009, we will provide a rich array of themed resources, such as demonstrations and activities, teleconferences, and news stories to the variety of educators served by the ASP. This poster will present our program of monthly themes, along with associated services and resources, to support the diverse public outreach efforts of the members of the NASA Night Sky Network, museum educators in Astronomy From the Ground Up, and teachers in grades K--12 including Project ASTRO National Network partners and subscribers to Universe in the Classroom.
Genetics of cold hardiness in a cloned full-sib family of coastal Douglas-fir

Treesearch

T.S. Anekonda; W.T. Adams; S.N. Aitken; D.B. Neale; K.D. Jermstad; N.C. Wheeler

2000-01-01

Variation in cold-hardiness traits, and their extent of genetic control and interrelationships, were investigated among individuals (clones) within a single large full-sib family of coastal Douglas-fir (Pseudotsuga menziesii var. menziesii (Mirb.) Franco) from Oregon. Cold injury to needle, stem, and bud tissues was evaluated...
Magnetic and structural properties of ferromagnetic Fe 5PB 2 and Fe 5SiB 2 and effects of Co and Mn substitutions

DOE PAGES

McGuire, Michael A.; Parker, David S.

2015-10-22

Crystallographic and magnetic properties of Fe 5PB 2, Fe 4CoPB 2, Fe 4MnPB 2, Fe 5SiB 2, Fe 4CoSiB 2, and Fe 4MnSiB 2 are reported. All adopt the tetragonal Cr 5B 3 structure-type and are ferromagnetic at room temperature with easy axis of magnetization along the c-axis. The spin reorientation in Fe 5SiB 2 is observed as an anomaly in the magnetization near 170 K, and is suppressed by substitution of Co or Mn for Fe. The silicides are found to generally have larger magnetic moments than the phosphides, but the data suggests smaller magnetic anisotropy in the silicides.more » Cobalt substitution reduces the Curie temperatures by more than 100 K and ordered magnetic moments by 16-20%, while manganese substitution has a much smaller effect. This suggests Mn moments align ferromagnetically with the Fe and that Co does not have an ordered moment in these structures. Anisotropic thermal expansion is observed in Fe 5PB 2 and Fe 5SiB 2, with negative thermal expansion seen along the c-axis of Fe 5SiB 2. First principles calculations of the magnetic properties of Fe 5SiB 2 and Fe 4MnSiB 2 are reported. The results, including the magnetic moment and anisotropy, and are in good agreement with experiment.« less
Lattice thermal conductivity of monolayer AsP from first-principles molecular dynamics.

PubMed

Sun, Yajing; Shuai, Zhigang; Wang, Dong

2018-05-23

Few-layered arsenic-phosphorus alloys, AsxP(1-x), with a puckered structure have been recently synthesized and demonstrated with fully tunable band gaps and optical properties. It is predicted that the carrier mobility of monolayer AsP compounds is even higher than that of black phosphorene (b-P). The anisotropic and orthogonal electrical and thermal transport properties of the puckered group VA elements make them intriguing materials for thermoelectric applications. Herein, we investigated the thermal transport properties of AsP based on first-principles molecular dynamics and the Boltzmann transport equation. We reveal that monolayer AsP with three different chemical structures possesses thermal conductivities lower than b-P, but with increased anisotropy. Further, these structures behave profoundly different on heat conduction. This can be attributed to the distinct low-frequency optical modes associated with their bonding nature. Our results highlight the impact of atomic arrangement on the thermal conductivity of AsP, and the structure-property relationship established may guide the fabrication of thermoelectric materials via the engineered alloying method.
Short-term carbon partitioning fertilizer responses vary among two full-sib loblolly pine clones

Treesearch

Jeremy P. Stovall; John R. Seiler; Thomas R. Fox

2012-01-01

We investigated the effects of fertilizer application on the partitioning of gross primary productivity (GPP) between contrasting full-sib clones of Pinus taeda (L.). Our objective was to determine if fertilizer growth responses resulted from similar short-term changes to partitioning. A modeling approach incorporating respiratory carbon (C) fluxes,...
Physiological adjustment of two full-sib families of ponderosa pine to elevated CO2

Treesearch

Nancy Grulke; J.L. Hom; S.W. Roberts

1993-01-01

Seeds from two full-sib families of ponderosa pine (Pinus ponderosa) with known differences in growth rates were germinated and grown in an ambient (350 Âµl l-1) or elevated (700 Âµl I-1) CO2 concentration. Gas exchange at both ambient and elevated CO2...
A dosimetric comparison of 3D-CRT, IMRT, and static tomotherapy with an SIB for large and small breast volumes

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

Michalski, Andrea; Central Coast Cancer Centre, Gosford Hospital, Gosford, New South Wales; Atyeo, John, E-mail: john.atyeo@sydney.edu.au

2014-07-01

Radiation therapy to the breast is a complex task, with many different techniques that can be employed to ensure adequate dose target coverage while minimizing doses to the organs at risk. This study compares the dose planning outcomes of 3 radiation treatment modalities, 3 dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and static tomotherapy, for left-sided whole-breast radiation treatment with a simultaneous integrated boost (SIB). Overall, 20 patients with left-sided breast cancer were separated into 2 cohorts, small and large, based on breast volume. Dose plans were produced for each patient using 3D-CRT, IMRT, and static tomotherapy. Allmore » patients were prescribed a dose of 45 Gy in 20 fractions to the breast with an SIB of 56 Gy in 20 fractions to the tumor bed and normalized so that D{sub 98%} > 95% of the prescription dose. Dosimetric comparisons were made between the 3 modalities and the interaction of patient size. All 3 modalities offered adequate planning target volume (PTV) coverage with D{sub 98%} > 95% and D{sub 2%} < 107%. Static tomotherapy offered significantly improved (p = 0.006) dose homogeneity to the PTV{sub boost} {sub eval} (0.079 ± 0.011) and breast minus the SIB volume (Breast{sub SIB}) (p < 0.001, 0.15 ± 0.03) compared with the PTV{sub boost} {sub eval} (0.085 ± 0.008, 0.088 ± 0.12) and Breast{sub SIB} (0.22 ± 0.05, 0.23 ± 0.03) for IMRT and 3D-CRT, respectively. Static tomotherapy also offered statistically significant reductions (p < 0.001) in doses to the ipsilateral lung mean dose of 6.79 ± 2.11 Gy compared with 7.75 ± 2.54 Gy and 8.29 ± 2.76 Gy for IMRT and 3D-CRT, respectively, and significantly (p < 0.001) reduced heart doses (mean = 2.83 ± 1.26 Gy) compared to both IMRT and 3D-CRT (mean = 3.70 ± 1.44 Gy and 3.91 ± 1.58 Gy). Static tomotherapy is the dosimetrically superior modality for the whole breast with an SIB compared with IMRT and 3D-CRT. IMRT is superior to
Brief cognitive assessment of Alzheimer's disease in advanced stages: Proposal for a Brazilian version of the Short Battery for Severe Impairment (SIB-8).

PubMed

Wajman, José Roberto; Bertolucci, Paulo Henrique Ferreira

2013-01-01

The measurement of cognitive abilities of patients with severe dementia can serve a wide range of methodological and clinical needs. To validate a proposed severe impairment battery SIB-8 for a Brazilian population sample as part of the neuropsychological assessment of patients with Alzheimer's disease (AD) in advanced stages. After a systematic process of translation and back-translation, the SIB-8 was applied to 95 patients with AD at different stages; moderate, moderately severe and severe according to FAST subdivisions (5, 6 and 7), with scores on the Mini-Mental State Examination (MMSE) of between 5 and 15 and followed by the Division of Behavioral Neurology and the Center for Aging Brain of the Federal University of São Paulo - UNIFESP. Inferential data revealed that the SIB-8 instrument behaved differently at each stage of the disease with a statistical value of sensitivity p<0.001, gradually reflecting the expected course of the dementia, inherent with the decline of cognitive functions. Findings indicated that the SIB-8 is a useful tool for the evaluation and prospective comparison of AD patients in advanced stages, retaining its original characteristics in our population.
Glycemic control in familial vs. sporadic type 1 diabetes patients over 5 years.

PubMed

Reddy, Sujana; Reinert, Steven E; Gopalakrishnan, Geetha; Plante, Wendy; Boney, Charlotte M; Quintos, Jose Bernardo

2014-01-01

Studies have shown that familial type 1 diabetes patients (FTID) have less severe metabolic derangement at presentation compared to sporadic patients (ST1D), but data on long-term metabolic control are lacking. (1) FT1D will have less severe presentation and better HbA1c over 5 years compared to ST1D; (2) HbA1c in the offspring will correlate with parent HbA1c in parent-offspring group; and (3) HbA1c of the second affected sibling (SP2) will correlate with the first affected sibling (SP1) in sib-pairs. Cohort of 33 parent-offspring and 19 sib-pairs; controls included 33 sporadic subjects matched by age, sex, ethnicity, puberty, and insulin regimen. Paired t-test and Pearson's correlation were used for statistical analysis. At diagnosis, mean age in FT1D vs. matched ST1D (7.7±4.9 vs. 7.6±4.5 years), mean HbA1c (9.6% vs. 10.7%), HCO3 (21 vs. 18 meq/L), glucose (428 vs. 463 mg/dL) and pH (7.35 vs. 7.36; p=ns) were not different. At 5 years, HbA1c (8.9% vs. 8.8%; p=0.81), clinic visits (12 vs. 12.5, p=0.68) and emergency room visits (0.48 vs. 0.24, p=0.10) were not different. In affected siblings, only HCO3 was different (SP1:18 vs. SP2: 24 meq/L; p<0.01). HbA1c for SP2 correlated positively with SP1 (r=0.67, p<0.01). Offspring HbA1c correlated positively with affected parents (9.3% vs. 8.6%, r=0.57, p=0.18) but was not significant. Metabolic control at diagnosis and at 5 years was similar in FT1D and ST1D. In sib-pairs, the second affected sibling had milder clinical presentation compared to the first affected sibling.
Topology of AspT, the aspartate:alanine antiporter of Tetragenococcus halophilus, determined by site-directed fluorescence labeling.

PubMed

Nanatani, Kei; Fujiki, Takashi; Kanou, Kazuhiko; Takeda-Shitaka, Mayuko; Umeyama, Hideaki; Ye, Liwen; Wang, Xicheng; Nakajima, Tasuku; Uchida, Takafumi; Maloney, Peter C; Abe, Keietsu

2007-10-01

The gram-positive lactic acid bacterium Tetragenococcus halophilus catalyzes the decarboxylation of L-aspartate (Asp) with release of L-alanine (Ala) and CO(2). The decarboxylation reaction consists of two steps: electrogenic exchange of Asp for Ala catalyzed by an aspartate:alanine antiporter (AspT) and intracellular decarboxylation of the transported Asp catalyzed by an L-aspartate-beta-decarboxylase (AspD). AspT belongs to the newly classified aspartate:alanine exchanger family (transporter classification no. 2.A.81) of transporters. In this study, we were interested in the relationship between the structure and function of AspT and thus analyzed the topology by means of the substituted-cysteine accessibility method using the impermeant, fluorescent, thiol-specific probe Oregon Green 488 maleimide (OGM) and the impermeant, nonfluorescent, thiol-specific probe [2-(trimethylammonium)ethyl]methanethiosulfonate bromide. We generated 23 single-cysteine variants from a six-histidine-tagged cysteineless AspT template. A cysteine position was assigned an external location if the corresponding single-cysteine variant reacted with OGM added to intact cells, and a position was assigned an internal location if OGM labeling required cell lysis. The topology analyses revealed that AspT has a unique topology; the protein has 10 transmembrane helices (TMs), a large hydrophilic cytoplasmic loop (about 180 amino acids) between TM5 and TM6, N and C termini that face the periplasm, and a positively charged residue (arginine 76) within TM3. Moreover, the three-dimensional structure constructed by means of the full automatic modeling system indicates that the large hydrophilic cytoplasmic loop of AspT possesses a TrkA_C domain and a TrkA_C-like domain and that the three-dimensional structures of these domains are similar to each other even though their amino acid sequences show low similarity.
Big Sib Students' Perceptions of the Educational Environment at the School of Medical Sciences, Universiti Sains Malaysia, using Dundee Ready Educational Environment Measure (DREEM) Inventory.

PubMed

Arzuman, Hafiza; Yusoff, Muhamad Saiful Bahri; Chit, Som Phong

2010-07-01

A cross-sectional descriptive study was conducted among Big Sib students to explore their perceptions of the educational environment at the School of Medical Sciences, Universiti Sains Malaysia (USM) and its weak areas using the Dundee Ready Educational Environment Measure (DREEM) inventory. The DREEM inventory is a validated global instrument for measuring educational environments in undergraduate medical and health professional education. The English version of the DREEM inventory was administered to all Year 2 Big Sib students (n = 67) at a regular Big Sib session. The purpose of the study as well as confidentiality and ethical issues were explained to the students before the questionnaire was administered. The response rate was 62.7% (42 out of 67 students). The overall DREEM score was 117.9/200 (SD 14.6). The DREEM indicated that the Big Sib students' perception of educational environment of the medical school was more positive than negative. Nevertheless, the study also revealed some problem areas within the educational environment. This pilot study revealed that Big Sib students perceived a positive learning environment at the School of Medical Sciences, USM. It also identified some low-scored areas that require further exploration to pinpoint the exact problems. The relatively small study population selected from a particular group of students was the major limitation of the study. This small sample size also means that the study findings cannot be generalised.
Fault-tolerant back-up archive using an ASP model for disaster recovery

NASA Astrophysics Data System (ADS)

Liu, Brent J.; Huang, H. K.; Cao, Fei; Documet, Luis; Sarti, Dennis A.

2002-05-01

A single point of failure in PACS during a disaster scenario is the main archive storage and server. When a major disaster occurs, it is possible to lose an entire hospital's PACS data. Few current PACS archives feature disaster recovery, but the design is limited at best. These drawbacks include the frequency with which the back-up is physically removed to an offsite facility, the operational costs associated to maintain the back-up, the ease-of-use to perform the backup consistently and efficiently, and the ease-of-use to perform the PACS image data recovery. This paper describes a novel approach towards a fault-tolerant solution for disaster recovery of short-term PACS image data using an Application Service Provider model for service. The ASP back-up archive provides instantaneous, automatic backup of acquired PACS image data and instantaneous recovery of stored PACS image data all at a low operational cost. A back-up archive server and RAID storage device is implemented offsite from the main PACS archive location. In the example of this particular hospital, it was determined that at least 2 months worth of PACS image exams were needed for back-up. Clinical data from a hospital PACS is sent to this ASP storage server in parallel to the exams being archived in the main server. A disaster scenario was simulated and the PACS exams were sent from the offsite ASP storage server back to the hospital PACS. Initially, connectivity between the main archive and the ASP storage server is established via a T-1 connection. In the future, other more cost-effective means of connectivity will be researched such as the Internet 2. A disaster scenario was initiated and the disaster recovery process using the ASP back-up archive server was success in repopulating the clinical PACS within a short period of time. The ASP back-up archive was able to recover two months of PACS image data for comparison studies with no complex operational procedures. Furthermore, no image data loss
First results of registering ionospheric disturbances obtained with SibNet network of GNSS receivers in active space experiments

NASA Astrophysics Data System (ADS)

Ishin, Artem; Perevalova, Natalia; Voeykov, Sergey; Khakhinov, Vitaliy

2017-12-01

Global and regional networks of GNSS receivers have been successfully used for geophysical research for many years; the number of continuous GNSS stations in the world is steadily growing. The article presents the first results of the use of a new regional network of GNSS stations (SibNet) in active space experiments. The Institute of Solar-Terrestrial Physics of Siberian Branch of Russian Academy of Sciences (ISTP SB RAS) has established this network in the South Baikal region. We describe in detail SibNet, characteristics of receivers in use, parameters of antennas and methods of their installation. We also present the general structure of observation site and the plot of coverage of the receiver operating zone at 50-55° latitudes by radio paths. It is shown that the selected location of receivers allows us to detect ionospheric irregularities of various scales. The purpose of the active space experiments was to reveal and record parameters of the ionospheric irregu larities caused by effects from jet streams of Progress cargo spacecraft. The mapping technique enabled us to identify weak, vertically localized ionospheric irregularities and associate them with the Progress spacecraft engine impact. Thus, it has been shown that SibNet deployed in the Southern Baikal region is an effective instrument for monitoring ionospheric conditions.

Effects of Asp-179 mutations in TEMpUC19 beta-lactamase on susceptibility to beta-lactams.

PubMed Central

Vakulenko, S B; Tóth, M; Taibi, P; Mobashery, S; Lerner, S A

1995-01-01

To examine the effect of disruption of the salt bridge (between Arg-164 and Asp-179 [numbering of Ambler et al. (Biochem J. 267:269-272, 1991)]) that anchors the conserved omega-loop in class A beta-lactamases, we obtained mutant enzymes with each of the 19 other amino acid residues replacing Asp-179 in the TEM beta-lactamase encoded by pUC19 and studied the level of resistance to various beta-lactams conferred by each enzyme. All mutations of Asp-179 compromised the level of resistance to ampicillin, but most of them enhanced resistance to ceftazidime. In contrast, mutations of Asp-179 generally impaired the low levels of resistance to cefepime and aztreonam. One might expect to find clinical isolates with mutant TEM beta-lactamases with replacements of Asp-179 that express an expanded spectrum of resistance to beta-lactams including ceftazidime. PMID:7486939
Racemization at the Asp 58 residue in αA-crystallin from the lens of high myopic cataract patients.

PubMed

Zhu, Xiang-Jia; Zhang, Ke-Ke; He, Wen-Wen; Du, Yu; Hooi, Michelle; Lu, Yi

2018-02-01

Post-translational modifications in lens proteins are key causal factors in cataract. As the most abundant post-translational modification in the lens, racemization may be closely related to the pathogenesis of cataract. Racemization of αA-crystallin, a crucial structural and heat shock protein in the human lens, could significantly influence its structure and function. In previous studies, elevated racemization from l-Asp 58 to d-isoAsp58 in αA-crystallin has been found in age-related cataract (ARC) lenses compared to normal aged human lenses. However, the role of racemization in high myopic cataract (HMC), which is characterized by an early onset of nuclear cataract, remains unknown. In the current study, apparently different from ARC, significantly increased racemization from l-Asp 58 to d-Asp 58 in αA-crystallin was identified in HMC lenses. The average racemization rates for each Asp isoform were calculated in ARC and HMC group. In ARC patients, the conversion of l-Asp 58 to d-isoAsp 58, up to 31.89%, accounted for the main proportion in racemization, which was in accordance with the previous studies. However, in HMC lenses, the conversion of l-Asp 58 to d-Asp 58, as high as 35.44%, accounted for the largest proportion of racemization in αA-crystallin. The different trend in the conversion of αA-crystallin by racemization, especially the elevated level of d-Asp 58 in HMC lenses, might prompt early cataractogenesis and a possible explanation of distinct phenotypes of cataract in HMC. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
Additive antithrombotic effect of ASP6537, a selective cyclooxygenase (COX)-1 inhibitor, in combination with clopidogrel in guinea pigs.

PubMed

Sakata, Chinatsu; Suzuki, Ken-Ichi; Morita, Yoshiaki; Kawasaki, Tomihisa

2017-03-05

Clopidogrel (Plavix ® , Sanofi-Aventis), the adenosine diphosphate P2Y 12 receptor antagonist, is reported to be effective in the prevention of cardiovascular events and is often used in combination with aspirin, particularly in high-risk patients. ASP6537 is a reversible cyclooxygenase (COX)-1 inhibitor that is under investigation as an anti-platelet agent. First, we investigated the reversibility of the antiplatelet effect of ASP6537 and its interaction with ibuprofen to compare the usability of ASP6537 with that of aspirin. We then evaluated the antithrombotic effect of ASP6537 in combination with clopidogrel using a FeCl 3 -induced thrombosis model in guinea pigs. ASP6537 exerted reversible antiplatelet activity, and no pharmacodynamic interaction with ibuprofen was noted. When administered as monotherapy, ASP6537 exerted a significant antithrombotic effect at ≥3mg/kg, while aspirin inhibited thrombosis at 100mg/kg. ASP6537 exerted significant additive effects in combination with clopidogrel, and the minimum antithrombotic dose was reduced by concomitant administration of clopidogrel. Our study showed that ASP6537 did not interact with ibuprofen and has clear additive effects in combination with clopidogrel. ASP6537 may therefore represent a promising antiplatelet agent for use in clinical settings in combination with clopidogrel. Copyright © 2017 Elsevier B.V. All rights reserved.
A comparative study of occurrence and fate of endocrine disruptors: diethyl phthalate and dibutyl phthalate in ASP- and SBR-based wastewater treatment plants.

PubMed

Saini, Gita; Pant, Shalini; Singh, Shri Om; Kazmi, A A; Alam, Tanveer

2016-11-01

Phthalates are endocrine-disrupting chemicals which affect endocrine system by bio-accumulation in aquatic organisms and produce adverse health effects in aquatic organisms as well as human beings, when come in contact. Present study focuses on occurrence and removal of two phthalates: diethylphthalate (DEP) and dibutylphthalate (DBP) in two full-scale wastewater treatment plants (WWTPs) i.e. sewage treatment plants (STPs) based on well-adopted technologies, activated sludge process (ASP) and sequencing batch reactor (SBR).Gas chromatography-mass spectrometry (GC-MS) analysis was performed for both wastewater and sludge sample for determination and identification of the concentration of these compounds in both STPs by monitoring the STPs for 9 months. It was observed that the concentration of DEP was less than DBP in the influent of ASP and SBR. Average concentrations of DEP and DBP in sludge sample of ASP were found to be 2.15 and 2.08 ng/g, whereas in SBR plant, these values were observed as 1.71 and 2.01 ng/g, respectively. Concerning the removal efficiency of DEP, SBR and ASP plants were found effective with removal efficiency of 91.51 and 91.03 %, respectively. However, in the case of DBP, SBR showed lower removal efficiency (85.42 %) as compared to ASP (92.67 %). Comparative study of both plants proposed that in ASP plant, DBP reduction was higher than the SBR. Fourier transformation infrared (FTIR) analysis also confirmed the same result of sludge analysis for both STPs. Sludge disposal studied with scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and thermo-gravimetric analysis (TGA) techniques confirmed that sludge of both STPs have high calorific value and can be used as fuel to make fuel-briquettes and bottom ash to make firebricks.
A randomized phase II/III study of adverse events between sequential (SEQ) versus simultaneous integrated boost (SIB) intensity modulated radiation therapy (IMRT) in nasopharyngeal carcinoma; preliminary result on acute adverse events.

PubMed

Songthong, Anussara P; Kannarunimit, Danita; Chakkabat, Chakkapong; Lertbutsayanukul, Chawalit

2015-08-08

To investigate acute and late toxicities comparing sequential (SEQ-IMRT) versus simultaneous integrated boost intensity modulated radiotherapy (SIB-IMRT) in nasopharyngeal carcinoma (NPC) patients. Newly diagnosed stage I-IVB NPC patients were randomized to receive SEQ-IMRT or SIB-IMRT, with or without chemotherapy. SEQ-IMRT consisted of two sequential radiation treatment plans: 2 Gy x 25 fractions to low-risk planning target volume (PTV-LR) followed by 2 Gy x 10 fractions to high-risk planning target volume (PTV-HR). In contrast, SIB-IMRT consisted of only one treatment plan: 2.12 Gy and 1.7 Gy x 33 fractions to PTV-HR and PTV-LR, respectively. Toxicities were evaluated according to CTCAE version 4.0. Between October 2010 and November 2013, 122 eligible patients were randomized between SEQ-IMRT (54 patients) and SIB-IMRT (68 patients). With median follow-up time of 16.8 months, there was no significant difference in toxicities between the two IMRT techniques. During chemoradiation, the most common grade 3-5 acute toxicities were mucositis (15.4% vs 13.6%, SEQ vs SIB, p = 0.788) followed by dysphagia (9.6% vs 9.1%, p = 1.000) and xerostomia (9.6% vs 7.6%, p = 0.748). During the adjuvant chemotherapy period, 25.6% and 32.7% experienced grade 3 weight loss in SEQ-IMRT and SIB-IMRT (p = 0.459). One-year overall survival (OS) and progression-free survival (PFS) were 95.8% and 95.5% in SEQ-IMRT and 98% and 90.2% in SIB-IMRT, respectively (p = 0.472 for OS and 0.069 for PFS). This randomized, phase II/III trial comparing SIB-IMRT versus SEQ-IMRT in NPC showed no statistically significant difference between both IMRT techniques in terms of acute adverse events. Short-term tumor control and survival outcome were promising.
Associations between XPD Asp312Asn Polymorphism and Risk of Head and Neck Cancer: A Meta-Analysis Based on 7,122 Subjects

PubMed Central

Hu, Yuan Yuan; Yuan, Hua; Jiang, Guang Bing; Chen, Ning; Wen, Li; Leng, Wei Dong; Zeng, Xian Tao; Niu, Yu Ming

2012-01-01

Background To investigate the association between XPD Asp312Asn polymorphism and head and neck cancer risk through this meta-analysis. Methods We performed a meta-analysis of 9 published case-control studies including 2,670 patients with head and neck cancer and 4,452 controls. An odds ratio (OR) with a 95% confidence interval (CI) was applied to assess the association between XPD Asp312Asn polymorphism and head and neck cancer risk. Results Overall, no significant association between XPD Asp312Asn polymorphism and head and neck cancer risk was found in this meta-analysis (Asn/Asn vs. Asp/Asp: OR = 0.95, 95%CI = 0.80–1.13, P = 0.550, P heterogeneity = 0.126; Asp/Asn vs. Asp/Asp: OR = 1.11, 95%CI = 0.99–1.24, P = 0.065, P heterogeneity = 0.663; Asn/Asn+Asp/Asn vs. Asp/Asp: OR = 1.07, 95%CI = 0.97–1.19, P = 0.189, P heterogeneity = 0.627; Asn/Asn vs. Asp/Asp+Asp/Asn: OR = 0.87, 95%CI = 0.68–1.10, P = 0.243, P heterogeneity = 0.089). In the subgroup analysis by HWE, ethnicity, and study design, there was still no significant association detected in all genetic models. Conclusions This meta-analysis demonstrates that XPD Asp312Asn polymorphism may not be a risk factor for developing head and neck cancer. PMID:22536360
Lack of association between the APEX1 Asp148Glu polymorphism and sporadic amyotrophic lateral sclerosis.

PubMed

Coppedè, Fabio; Lo Gerfo, Annalisa; Carlesi, Cecilia; Piazza, Selina; Mancuso, Michelangelo; Pasquali, Livia; Murri, Luigi; Migliore, Lucia; Siciliano, Gabriele

2010-02-01

Impairments in DNA repair enzymes have been observed in amyotrophic lateral sclerosis (ALS) tissues, particularly in the activity of the apurinic/apyrimidinic endonuclease 1 (APEX1). Moreover, it was suggested that the common APEX1 Asp148Glu polymorphism might be associated with ALS risk. To further address this question we performed the present study aimed at evaluating the contribution of the APEX1 Asp148Glu polymorphism in sporadic ALS (sALS) risk and clinical presentation, including age and site of onset and disease progression. We screened 134 sALS Italian patients and 129 matched controls for the presence of the APEX1 Asp148Glu polymorphism. No difference in APEX1 Asp148Glu allele and genotype frequencies was found between the groups, nor was the polymorphism associated with age and site of onset or disease progression. Present results do not support a role for the APEX1 Asp148Glu polymorphism in sALS pathogenesis in the Italian population.
Topology of AspT, the Aspartate:Alanine Antiporter of Tetragenococcus halophilus, Determined by Site-Directed Fluorescence Labeling▿ †

PubMed Central

Nanatani, Kei; Fujiki, Takashi; Kanou, Kazuhiko; Takeda-Shitaka, Mayuko; Umeyama, Hideaki; Ye, Liwen; Wang, Xicheng; Nakajima, Tasuku; Uchida, Takafumi; Maloney, Peter C.; Abe, Keietsu

2007-01-01

The gram-positive lactic acid bacterium Tetragenococcus halophilus catalyzes the decarboxylation of l-aspartate (Asp) with release of l-alanine (Ala) and CO2. The decarboxylation reaction consists of two steps: electrogenic exchange of Asp for Ala catalyzed by an aspartate:alanine antiporter (AspT) and intracellular decarboxylation of the transported Asp catalyzed by an l-aspartate-β-decarboxylase (AspD). AspT belongs to the newly classified aspartate:alanine exchanger family (transporter classification no. 2.A.81) of transporters. In this study, we were interested in the relationship between the structure and function of AspT and thus analyzed the topology by means of the substituted-cysteine accessibility method using the impermeant, fluorescent, thiol-specific probe Oregon Green 488 maleimide (OGM) and the impermeant, nonfluorescent, thiol-specific probe [2-(trimethylammonium)ethyl]methanethiosulfonate bromide. We generated 23 single-cysteine variants from a six-histidine-tagged cysteineless AspT template. A cysteine position was assigned an external location if the corresponding single-cysteine variant reacted with OGM added to intact cells, and a position was assigned an internal location if OGM labeling required cell lysis. The topology analyses revealed that AspT has a unique topology; the protein has 10 transmembrane helices (TMs), a large hydrophilic cytoplasmic loop (about 180 amino acids) between TM5 and TM6, N and C termini that face the periplasm, and a positively charged residue (arginine 76) within TM3. Moreover, the three-dimensional structure constructed by means of the full automatic modeling system indicates that the large hydrophilic cytoplasmic loop of AspT possesses a TrkA_C domain and a TrkA_C-like domain and that the three-dimensional structures of these domains are similar to each other even though their amino acid sequences show low similarity. PMID:17660287
GLU298ASP and 4G/5G Polymorphisms and the Risk of Ischemic Stroke in Young Individuals.

PubMed

Esparza-García, Juan Carlos; Santiago-Germán, David; Guadalupe Valades-Mejía, María; Hernández-Juárez, Jesus; Aguilar-Sosa, Eberth; Leaños-Miranda, Alfredo; Alvarado-Moreno, Antonio; Majluf-Cruz, Abraham; Isordia-Salas, Irma

2015-09-01

Polymorphisms in the endothelial nitric oxide synthase (eNOS) and in the plasminogen activator inhibitor -1 (PAI-1) genes have been implicated in stroke pathogenesis but results are still controversial. The aim of this study was to examine the possible contribution of Glu298Asp in the eNOS and 4G/5G in the PAI-1polymorphisms with ischemic stroke in a young Mexican population. In a case-control study, conducted between January 2006 and June 2010, 204 patients ≤45 years of age with ischemic stroke and 204 controls matched by age and gender, were recruited. The Glu298Asp and 4G/5G polymorphisms were determined in all participants by polymerase chain reaction-restriction fragment length polymorphism. There was a significant difference in the Glu298Asp genotype distribution (P=0.001) and allele frequency between the two groups (P=0.001). The 4G/5G genotype distribution (P=0.40) and the allele frequency was similar between groups; (P=0.13). There were independent factors for ischemic stroke: Asp carriage (GluAsp+AspAsp) (P=0.02); smoking (P=0.01); hypertension (P=0.03), and familial history of atherothrombotic disease (P=0.04). The Asp allele from the Gu298Asp gene represents an independent risk factor for ischemic stroke in a young Mexican population. In contrast, the 4G/5G was not associated with an increased risk for this disease in the same group of patients, as previously has been demonstrated in other populations.
Self-Injurious Behavior and Fragile X Syndrome: Findings from the National Fragile X Survey

ERIC Educational Resources Information Center

Symons, Frank J.; Byiers, Breanne J.; Raspa, Melissa; Bishop, Ellen; Bailey, Donald B., Jr.

2010-01-01

We used National Fragile X Survey data in order to examine reported self-injurious behavior (SIB) to (a) generate lifetime and point prevalence estimates, (b) document detailed features of SIB (frequency, types, location, severity) in relation to gender, and (c) compare comorbid conditions between matched pairs (SIB vs. no SIB). Results indicate…
Effects of Childhood and Middle-Adulthood Family Conditions on Later-Life Mortality: Evidence from the Utah Population Database, 1850-2002

PubMed Central

Mineau, Mineau P; Gilda, Garibotti; Kerber, Richard

2014-01-01

We examine how key early family circumstances affect mortality risks decades later. Early life conditions are measured by parental mortality, parental fertility (e.g., offspring sibship size, parental age at offspring birth), religious upbringing, and parental socioeconomic status. Prior to these early life conditions are familial and genetic factors that affect life-span. Accordingly, we consider the role of parental and familial longevity on adult mortality risks. We analyze the large Utah Population Database which contains a vast amount of genealogical and other vital/health data that contain full life histories of individuals and hundreds of their relatives. To control for unobserved heterogeneity, we analyze sib-pair data for 12,000 sib-pairs using frailty models. We found modest effects of key childhood conditions (birth order, sibship size, parental religiosity, parental SES, and parental death in childhood). Our measures of familial aggregation of longevity were large and suggest an alternative view of early life conditions. PMID:19278766
Introduction of the ASP3D Computer Program for Unsteady Aerodynamic and Aeroelastic Analyses

NASA Technical Reports Server (NTRS)

Batina, John T.

2005-01-01

A new computer program has been developed called ASP3D (Advanced Small Perturbation 3D), which solves the small perturbation potential flow equation in an advanced form including mass-consistent surface and trailing wake boundary conditions, and entropy, vorticity, and viscous effects. The purpose of the program is for unsteady aerodynamic and aeroelastic analyses, especially in the nonlinear transonic flight regime. The program exploits the simplicity of stationary Cartesian meshes with the movement or deformation of the configuration under consideration incorporated into the solution algorithm through a planar surface boundary condition. The new ASP3D code is the result of a decade of developmental work on improvements to the small perturbation formulation, performed while the author was employed as a Senior Research Scientist in the Configuration Aerodynamics Branch at the NASA Langley Research Center. The ASP3D code is a significant improvement to the state-of-the-art for transonic aeroelastic analyses over the CAP-TSD code (Computational Aeroelasticity Program Transonic Small Disturbance), which was developed principally by the author in the mid-1980s. The author is in a unique position as the developer of both computer programs to compare, contrast, and ultimately make conclusions regarding the underlying formulations and utility of each code. The paper describes the salient features of the ASP3D code including the rationale for improvements in comparison with CAP-TSD. Numerous results are presented to demonstrate the ASP3D capability. The general conclusion is that the new ASP3D capability is superior to the older CAP-TSD code because of the myriad improvements developed and incorporated.
L-Asp is a useful tool in the purification of the ionotropic glutamate receptor A2 ligand-binding domain.

PubMed

Krintel, Christian; Frydenvang, Karla; Ceravalls de Rabassa, Anna; Kaern, Anne M; Gajhede, Michael; Pickering, Darryl S; Kastrup, Jette S

2014-05-01

In purification of the ionotropic glutamate receptor A2 (GluA2) ligand-binding domain (LBD), L-Glu-supplemented buffers have previously been used for protein stabilization during the procedure. This sometimes hampers structural studies of low-affinity ligands, because L-Glu is difficult to displace, despite extensive dialysis. Here, we show that L-Asp binds to full-length GluA2 with low affinity (Ki = 0.63 mM) and to the GluA2 LBD with even lower affinity (Ki = 2.6 mM), and we use differential scanning fluorimetry to show that L-Asp is able to stabilize the isolated GluA2 LBD. We also show that L-Asp can replace L-Glu during purification, providing both equal yields and purity of the resulting protein sample. Furthermore, we solved three structures of the GluA2 LBD in the presence of 7.5, 50 and 250 mM L-Asp. Surprisingly, with 7.5 mM L-Asp, the GluA2 LBD crystallized as a mixed dimer, with L-Glu being present in one subunit, and neither L-Asp nor L-Glu being present in the other subunit. Thus, residual L-Glu is retained from the expression medium. On the other hand, only L-Asp was found at the binding site when 50 or 250 mM L-Asp was used for crystallization. The binding mode observed for L-Asp at the GluA2 LBD is very similar to that described for L-Glu. Taking our findings together, we have shown that L-Asp can be used instead of L-Glu for ligand-dependent stabilization of the GluA2 LBD during purification. This will enable structural studies of low-affinity ligands for lead optimization in structure-based drug design. Structural data are available in the Protein Data Bank under accession numbers 4O3B (7.5 mM L-Asp), 4O3C (50 mM L-Asp), and 4O3A (250 mM L-Asp). © 2014 FEBS.
The Crystal Structure of Peroxiredoxin Asp f3 Provides Mechanistic Insight into Oxidative Stress Resistance and Virulence of Aspergillus fumigatus.

PubMed

Hillmann, Falk; Bagramyan, Karine; Straßburger, Maria; Heinekamp, Thorsten; Hong, Teresa B; Bzymek, Krzysztof P; Williams, John C; Brakhage, Axel A; Kalkum, Markus

2016-09-14

Invasive aspergillosis and other fungal infections occur in immunocompromised individuals, including patients who received blood-building stem cell transplants, patients with chronic granulomatous disease (CGD), and others. Production of reactive oxygen species (ROS) by immune cells, which incidentally is defective in CGD patients, is considered to be a fundamental process in inflammation and antifungal immune response. Here we show that the peroxiredoxin Asp f3 of Aspergillus fumigatus inactivates ROS. We report the crystal structure and the catalytic mechanism of Asp f3, a two-cysteine type peroxiredoxin. The latter exhibits a thioredoxin fold and a homodimeric structure with two intermolecular disulfide bonds in its oxidized state. Replacement of the Asp f3 cysteines with serine residues retained its dimeric structure, but diminished Asp f3's peroxidase activity, and extended the alpha-helix with the former peroxidatic cysteine residue C61 by six residues. The asp f3 deletion mutant was sensitive to ROS, and this phenotype was rescued by ectopic expression of Asp f3. Furthermore, we showed that deletion of asp f3 rendered A. fumigatus avirulent in a mouse model of pulmonary aspergillosis. The conserved expression of Asp f3 homologs in medically relevant molds and yeasts prompts future evaluation of Asp f3 as a potential therapeutic target.
Laboratory evaluation of the pointing stability of the ASPS Vernier System

NASA Technical Reports Server (NTRS)

1980-01-01

The annular suspension and pointing system (ASPS) is an end-mount experiment pointing system designed for use in the space shuttle. The results of the ASPS Vernier System (AVS) pointing stability tests conducted in a laboratory environment are documented. A simulated zero-G suspension was used to support the test payload in the laboratory. The AVS and the suspension were modelled and incorporated into a simulation of the laboratory test. Error sources were identified and pointing stability sensitivities were determined via simulation. Statistical predictions of laboratory test performance were derived and compared to actual laboratory test results. The predicted mean pointing stability during simulated shuttle disturbances was 1.22 arc seconds; the actual mean laboratory test pointing stability was 1.36 arc seconds. The successful prediction of laboratory test results provides increased confidence in the analytical understanding of the AVS magnetic bearing technology and allows confident prediction of in-flight performance. Computer simulations of ASPS, operating in the shuttle disturbance environment, predict in-flight pointing stability errors less than 0.01 arc seconds.
Biodegradation of phenanthrene in bioaugmented microcosm by consortium ASP developed from coastal sediment of Alang-Sosiya ship breaking yard.

PubMed

Patel, Vilas; Patel, Janki; Madamwar, Datta

2013-09-15

A phenanthrene-degrading bacterial consortium (ASP) was developed using sediment from the Alang-Sosiya shipbreaking yard at Gujarat, India. 16S rRNA gene-based molecular analyses revealed that the bacterial consortium consisted of six bacterial strains: Bacillus sp. ASP1, Pseudomonas sp. ASP2, Stenotrophomonas maltophilia strain ASP3, Staphylococcus sp. ASP4, Geobacillus sp. ASP5 and Alcaligenes sp. ASP6. The consortium was able to degrade 300 ppm of phenanthrene and 1000 ppm of naphthalene within 120 h and 48 h, respectively. Tween 80 showed a positive effect on phenanthrene degradation. The consortium was able to consume maximum phenanthrene at the rate of 46 mg/h/l and degrade phenanthrene in the presence of other petroleum hydrocarbons. A microcosm study was conducted to test the consortium's bioremediation potential. Phenanthrene degradation increased from 61% to 94% in sediment bioaugmented with the consortium. Simultaneously, bacterial counts and dehydrogenase activities also increased in the bioaugmented sediment. These results suggest that microbial consortium bioaugmentation may be a promising technology for bioremediation. Copyright © 2013 Elsevier Ltd. All rights reserved.
Structural effect of the Asp345a insertion in penicillin-binding protein 2 from penicillin-resistant strains of Neisseria gonorrhoeae.

PubMed

Fedarovich, Alena; Cook, Edward; Tomberg, Joshua; Nicholas, Robert A; Davies, Christopher

2014-12-09

A hallmark of penicillin-binding protein 2 (PBP2) from penicillin-resistant strains of Neisseria gonorrhoeae is insertion of an aspartate after position 345. The insertion resides on a loop near the active site and is immediately adjacent to an existing aspartate (Asp346) that forms a functionally important hydrogen bond with Ser363 of the SxN conserved motif. Insertion of other amino acids, including Glu and Asn, can also lower the rate of acylation by penicillin, but these insertions abolish transpeptidase function. Although the kinetic consequences of the Asp insertion are well-established, how it impacts the structure of PBP2 is unknown. Here, we report the 2.2 Å resolution crystal structure of a truncated construct of PBP2 containing all five mutations present in PBP2 from the penicillin-resistant strain 6140, including the Asp insertion. Commensurate with the strict specificity for the Asp insertion over similar amino acids, the insertion does not cause disordering of the structure, but rather induces localized flexibility in the β2c-β2d loop. The crystal structure resolves the ambiguity of whether the insertion is Asp345a or Asp346a (due to the adjacent Asp) because the hydrogen bond between Asp346 and Ser362 is preserved and the insertion is therefore Asp346a. The side chain of Asp346a projects directly toward the β-lactam-binding site near Asn364 of the SxN motif. The Asp insertion may lower the rate of acylation by sterically impeding binding of the antibiotic or by hindering breakage of the β-lactam ring during acylation because of the negative charge of its side chain.
Substrate specificity of the aspartate:alanine antiporter (AspT) of Tetragenococcus halophilus in reconstituted liposomes.

PubMed

Sasahara, Ayako; Nanatani, Kei; Enomoto, Masaru; Kuwahara, Shigefumi; Abe, Keietsu

2011-08-19

The aspartate:alanine antiporter (AspT) of the lactic acid bacterium Tetragenococcus halophilus is a member of the aspartate:alanine exchanger (AAEx) transporter family. T. halophilus AspT catalyzes the electrogenic exchange of L-aspartate(1-) with L-alanine(0). Although physiological functions of AspT were well studied, L-aspartate(1-):L-alanine(0) antiport mechanisms are still unsolved. Here we report that the binding sites of L-aspartate and L-alanine are independently present in AspT by means of the kinetic studies. We purified His(6)-tagged T. halophilus AspT and characterized its kinetic properties when reconstituted in liposomes (K(m) = 0.35 ± 0.03 mm for L-aspartate, K(m) = 0.098 ± 0 mm for D-aspartate, K(m) = 26 ± 2 mm for L-alanine, K(m) = 3.3 ± 0.2 mm for D-alanine). Competitive inhibition by various amino acids of L-aspartate or L-alanine in self-exchange reactions revealed that L-cysteine selectively inhibited L-aspartate self-exchange but only weakly inhibited L-alanine self-exchange. Additionally, L-serine selectively inhibited L-alanine self-exchange but barely inhibited L-aspartate self-exchange. The aspartate analogs L-cysteine sulfinic acid, L-cysteic acid, and D-cysteic acid competitively and strongly inhibited L-aspartate self-exchange compared with L-alanine self-exchange. Taken together, these kinetic data suggest that the putative binding sites of L-aspartate and L-alanine are independently located in the substrate translocation pathway of AspT.
Coordination ability determined transition metal ions substitution of Tb in Tb-Asp fluorescent nanocrystals and a facile ions-detection approach.

PubMed

Duan, Jiazhi; Ma, Baojin; Liu, Feng; Zhang, Shan; Wang, Shicai; Kong, Ying; Du, Min; Han, Lin; Wang, Jianjun; Sang, Yuanhua; Liu, Hong

2018-04-26

Although the synthesis and fluorescent properties of lanthanide-amino acid complex nanostructures have been investigated extensively, limited studies have been reported on metal ions' substitution ability for the lanthanide ions in the complex and their effect on the fluorescent property. In this study, taking biocompatible Tb-aspartic acid (Tb-Asp) complex nanocrystals as a model, the substitution mechanism of metal ions, particularly transition metals, for Tb ions in Tb-Asp nanocrystals and the change in the fluorescent property of the Tb-Asp nanocrystals after substitution were systematically investigated. The experimental results illustrated that metal ions with higher electronegativity, higher valence, and smaller radius possess stronger ability for Tb ions' substitution in Tb-Asp nanocrystals. Based on the effect of substituting ions' concentration on the fluorescent property of Tb-Asp, a facile method for copper ions detection with high sensitivity was proposed by measuring the fluorescent intensity of Tb-Asp nanocrystals' suspensions containing different concentrations of copper ions. The good biocompatibility, great convenience of synthesis and sensitive detection ability make Tb-Asp nanocrystals a very low cost and effective material for metal ions detection, which also opens a new door for practical applications of metal-Asp coordinated nanocrystals.
A DNA Aptamer Recognizes the Asp f 1 Allergen of Aspergillus fumigatus

PubMed Central

Low, Swee Yang; Hill, Jane E.; Peccia, Jordan

2009-01-01

Allergies are caused by the binding of IgE antibodies onto specific sites on allergens. However, in the assessment of exposure to airborne allergens, current techniques such as whole spore counts fail to account for the presence of these allergenic epitopes that trigger allergic reactions. The objective of the research is to develop a DNA aptamer for the Asp f 1 allergen of the pathogenic fungus Aspergillus fumigatus, using an IgE-binding epitope of the allergen as the target for aptamer selection. Through in vitro SELEX, an aptamer has been produced that binds with nanomolar affinity to the Asp f 1 IgE-epitope. The aptamer is also able to recognize the native Asp f 1 allergen, and does not bind to allergenic proteins from non-target mold species such as Alternaria alternata. Production of this aptamer provides proof-of-principle that allergen measurement methods can be developed to indicate the potent fraction, or allergenicity, of allergens. PMID:19545545

Dosimetric comparison of standard three-dimensional conformal radiotherapy followed by intensity-modulated radiotherapy boost schedule (sequential IMRT plan) with simultaneous integrated boost-IMRT (SIB IMRT) treatment plan in patients with localized carcinoma prostate.

PubMed

Bansal, A; Kapoor, R; Singh, S K; Kumar, N; Oinam, A S; Sharma, S C

2012-07-01

DOSIMETERIC AND RADIOBIOLOGICAL COMPARISON OF TWO RADIATION SCHEDULES IN LOCALIZED CARCINOMA PROSTATE: Standard Three-Dimensional Conformal Radiotherapy (3DCRT) followed by Intensity Modulated Radiotherapy (IMRT) boost (sequential-IMRT) with Simultaneous Integrated Boost IMRT (SIB-IMRT). Thirty patients were enrolled. In all, the target consisted of PTV P + SV (Prostate and seminal vesicles) and PTV LN (lymph nodes) where PTV refers to planning target volume and the critical structures included: bladder, rectum and small bowel. All patients were treated with sequential-IMRT plan, but for dosimetric comparison, SIB-IMRT plan was also created. The prescription dose to PTV P + SV was 74 Gy in both strategies but with different dose per fraction, however, the dose to PTV LN was 50 Gy delivered in 25 fractions over 5 weeks for sequential-IMRT and 54 Gy delivered in 27 fractions over 5.5 weeks for SIB-IMRT. The treatment plans were compared in terms of dose-volume histograms. Also, Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) obtained with the two plans were compared. The volume of rectum receiving 70 Gy or more (V > 70 Gy) was reduced to 18.23% with SIB-IMRT from 22.81% with sequential-IMRT. SIB-IMRT reduced the mean doses to both bladder and rectum by 13% and 17%, respectively, as compared to sequential-IMRT. NTCP of 0.86 ± 0.75% and 0.01 ± 0.02% for the bladder, 5.87 ± 2.58% and 4.31 ± 2.61% for the rectum and 8.83 ± 7.08% and 8.25 ± 7.98% for the bowel was seen with sequential-IMRT and SIB-IMRT plans respectively. For equal PTV coverage, SIB-IMRT markedly reduced doses to critical structures, therefore should be considered as the strategy for dose escalation. SIB-IMRT achieves lesser NTCP than sequential-IMRT.
Effects of peptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly on hormonal activity and structure of the thyroid gland in hypophysectomized young chickens and old hens.

PubMed

Kuznik, B I; Pateyuk, A V; Rusaeva, N S; Baranchugova, L M; Obydenko, V I

2011-02-01

Hypophysectomy in 5-days chickens and old hens was followed by hormonal disturbances and structural changes in the thyroid gland. Administration of peptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly synthesized on the basis the amino acid composition of extracts from the anterior and posterior lobes of the pituitary gland, respectively, to hypophysectomized birds for 40 days significantly reduced the degree of these changes. The normalizing effect of synthetic peptides on the concentration of thyrotrophic hormone and thyroid hormones in old hens was less pronounced than in chickens.
Structural Effect of the Asp345a Insertion in Penicillin-Binding Protein 2 from Penicillin-Resistant Strains of Neisseria gonorrhoeae

PubMed Central

2015-01-01

A hallmark of penicillin-binding protein 2 (PBP2) from penicillin-resistant strains of Neisseria gonorrhoeae is insertion of an aspartate after position 345. The insertion resides on a loop near the active site and is immediately adjacent to an existing aspartate (Asp346) that forms a functionally important hydrogen bond with Ser363 of the SxN conserved motif. Insertion of other amino acids, including Glu and Asn, can also lower the rate of acylation by penicillin, but these insertions abolish transpeptidase function. Although the kinetic consequences of the Asp insertion are well-established, how it impacts the structure of PBP2 is unknown. Here, we report the 2.2 Å resolution crystal structure of a truncated construct of PBP2 containing all five mutations present in PBP2 from the penicillin-resistant strain 6140, including the Asp insertion. Commensurate with the strict specificity for the Asp insertion over similar amino acids, the insertion does not cause disordering of the structure, but rather induces localized flexibility in the β2c−β2d loop. The crystal structure resolves the ambiguity of whether the insertion is Asp345a or Asp346a (due to the adjacent Asp) because the hydrogen bond between Asp346 and Ser362 is preserved and the insertion is therefore Asp346a. The side chain of Asp346a projects directly toward the β-lactam-binding site near Asn364 of the SxN motif. The Asp insertion may lower the rate of acylation by sterically impeding binding of the antibiotic or by hindering breakage of the β-lactam ring during acylation because of the negative charge of its side chain. PMID:25403720
[Comparison of the Effectiveness and Safety of Combined Chemotherapy with PEG-Asp for Treatment of ALL and T-NHL Patients].

PubMed

Xu, Yan; Wang, Jin; Yang, Nan; Bai, Ju; Zhang, Peng-Yu; Gu, Liu-Fang; Lei, Bo; Liu, Jie; Wang, Fang-Xia; Huang, Bing-Qiao; Zhang, Wang-Gang; He, Ai-Li; Cao, Xing-Mei; Chen, Yin-Xia; Ma, Xiao-Rong

2016-04-01

To explore the effectiveness and safety of combined chemotherapy with pegasparaginase (PEG-Asp) for treatment of patients with acute lymphoblastic leukemia (ALL) and T cell non-Hodgkin's lymphoma (T-NHL) patients. A total of 62 ALL or T-NHL patients were diagnosed and treated in our department and were enrolled in this study. Among them, 22 patients received the combined chemotherapy with PEG-Asp, while the other 40 patients received the standard chemotherapy with L-asparaginase (L-Asp) as the control. Therapeutic effectiveness, adverse effects, duration and expense of hospitalization, treatment-related mortality and survival were evaluated and compared in 2 different groups. In group of combined chemotherapy with PEG-Asp, the overall response rate was 90.91% (20 cases), among them CR rate and PR rate are 77.27% (17 cases) and 13.64% (3 cases), respectively. In the group of standard chemotherapy with L-Asp, the overall response rate was 87.5% (35 cases), among them CR rate and PR rate were 72.5% (29 cases) and 15% (6 cases), respectively. The difference neither between PEG-Asp and L-Asp chemotherapy groups nor between ALL and T-NHL subgroups was significant (P > 0.05). The 6-month and 12-month overall survival rates were not significantly different between the PEG-Asp and L-Asp chemotherapy groups, respectively (P > 0.05). The adverse effects were identified as degree 1-2 according to the WHO criteria of drug toxicity. Neither the adverse effects identified as degree 3-4 nor the treatment-related death were observed. Expect for allergy and hyperglycaemia, the difference of side-effect incidence between the two groups were not significant (P > 0.05). The treatment for all the patients in PEG-Asp chemotherapy group was completed, while the treatment with L-Asp was completed only in 29 cases. Moreover, both average duration and expense of hospitalization after the combined chemotherapy were less than the control. With higher response rate, lower drug toxicity and
Planning for Multiagent Using ASP-Prolog

NASA Astrophysics Data System (ADS)

Son, Tran Cao; Pontelli, Enrico; Nguyen, Ngoc-Hieu

This paper presents an Answer Set Programming based approach to multiagent planning. The proposed methodology extends the action language \\cal B in [12] to represent and reason about plans with cooperative actions of an individual agent operating in a multiagent environment. This language is used to formalize multiagent planning problems and the notion of a joint plan for multiagent in the presence of cooperative actions. Finally, the paper presents a system for computing joint plans based on the ASP-Prolog system.
Residue frequencies and pairing preferences at protein-protein interfaces.

PubMed

Glaser, F; Steinberg, D M; Vakser, I A; Ben-Tal, N

2001-05-01

We used a nonredundant set of 621 protein-protein interfaces of known high-resolution structure to derive residue composition and residue-residue contact preferences. The residue composition at the interfaces, in entire proteins and in whole genomes correlates well, indicating the statistical strength of the data set. Differences between amino acid distributions were observed for interfaces with buried surface area of less than 1,000 A(2) versus interfaces with area of more than 5,000 A(2). Hydrophobic residues were abundant in large interfaces while polar residues were more abundant in small interfaces. The largest residue-residue preferences at the interface were recorded for interactions between pairs of large hydrophobic residues, such as Trp and Leu, and the smallest preferences for pairs of small residues, such as Gly and Ala. On average, contacts between pairs of hydrophobic and polar residues were unfavorable, and the charged residues tended to pair subject to charge complementarity, in agreement with previous reports. A bootstrap procedure, lacking from previous studies, was used for error estimation. It showed that the statistical errors in the set of pairing preferences are generally small; the average standard error is approximately 0.2, i.e., about 8% of the average value of the pairwise index (2.9). However, for a few pairs (e.g., Ser-Ser and Glu-Asp) the standard error is larger in magnitude than the pairing index, which makes it impossible to tell whether contact formation is favorable or unfavorable. The results are interpreted using physicochemical factors and their implications for the energetics of complex formation and for protein docking are discussed. Proteins 2001;43:89-102. Copyright 2001 Wiley-Liss, Inc.
Active Play in After-school Programmes: development of an intervention and description of a matched-pair cluster-randomised trial assessing physical activity play in after-school programmes.

PubMed

Riiser, Kirsti; Helseth, Sølvi; Ellingsen, Hanna; Fallang, Bjørg; Løndal, Knut

2017-08-04

Interventions delivered in after-school programmes (ASPs) have the potential to become a means of ensuring adequate physical activity among schoolchildren. This requires a motivational climate, allowing for self-determined play. If trained, ASP staff may represent a valuable resource for supporting such play. Increasing knowledge and supportive skills among ASP staff may also potentially increase their motivation for work. The purpose of this article is to describe the development of the 'Active Play in ASP' intervention, which aims to promote physical activity among first graders attending ASP, and to present a protocol for a matched-pair cluster-randomised trial to evaluate the intervention. Informed by experiences from practice, evidence-based knowledge and theory, the intervention was developed in a stepwise process including focus group meetings and a small-scale pilot test. The intervention contains a course programme for ASP staff to increase their skills in how to support physical activity through play. In a cluster randomised controlled trial, the ASPs will be matched and randomly allocated to receive the 7-month intervention or to a control group. Outcomes will be assessed at baseline, after 7 and 19 months. First graders attending the ASPs included are eligible. The primary outcome will be accelerometer-determined minutes in moderate to vigorous physical activity in the ASP. The study uses a mixed methods approach including observations and interviews to provide rich descriptions of the concept of children's physical activity in ASP. Moreover, the trial will assess whether the ASP staff benefits from participation in the intervention in terms of increased work motivation. Lastly, process evaluations of programme fidelity, satisfaction and suggestions on improvement will be performed. The study is approved by the Data Protection Official for Research (reference no 46008). Results will be presented in conferences and peer-reviewed journals. Clinical Trials
Covariance Between Genotypic Effects and its Use for Genomic Inference in Half-Sib Families

PubMed Central

Wittenburg, Dörte; Teuscher, Friedrich; Klosa, Jan; Reinsch, Norbert

2016-01-01

In livestock, current statistical approaches utilize extensive molecular data, e.g., single nucleotide polymorphisms (SNPs), to improve the genetic evaluation of individuals. The number of model parameters increases with the number of SNPs, so the multicollinearity between covariates can affect the results obtained using whole genome regression methods. In this study, dependencies between SNPs due to linkage and linkage disequilibrium among the chromosome segments were explicitly considered in methods used to estimate the effects of SNPs. The population structure affects the extent of such dependencies, so the covariance among SNP genotypes was derived for half-sib families, which are typical in livestock populations. Conditional on the SNP haplotypes of the common parent (sire), the theoretical covariance was determined using the haplotype frequencies of the population from which the individual parent (dam) was derived. The resulting covariance matrix was included in a statistical model for a trait of interest, and this covariance matrix was then used to specify prior assumptions for SNP effects in a Bayesian framework. The approach was applied to one family in simulated scenarios (few and many quantitative trait loci) and using semireal data obtained from dairy cattle to identify genome segments that affect performance traits, as well as to investigate the impact on predictive ability. Compared with a method that does not explicitly consider any of the relationship among predictor variables, the accuracy of genetic value prediction was improved by 10–22%. The results show that the inclusion of dependence is particularly important for genomic inference based on small sample sizes. PMID:27402363
HLA non-class II genes may confer type I diabetes susceptibility in a Mapuche (Amerindian) affected family.

PubMed

Pérez-Bravo, Francisco; Martinez-Laso, Jorge; Martin-Villa, Jose M; Moscoso, Juan; Moreno, Almudena; Serrano-Vela, Juan I; Zamora, Jorge; Asenjo, Silvia; Gleisner, Andrea; Arnaiz-Villena, Antonio

2006-01-01

A rare case of type I diabetes is studied in an Amerindian (Mapuche) family from Chile, analyzing glutamic acid decarboxylase, islet-cell autoantibodies and human leukocyte antigen (HLA) genes. The affected sib is the only one that has one specific HLA haplotype combination that differs from the other sibs only in the HLA class I genes. It is concluded that HLA diabetes susceptibility factors may be placed outside the class II region or even that susceptibility factors do not exist in the HLA region in this Amerindian family.
Human mass balance, metabolite profile and identification of metabolic enzymes of [¹⁴C]ASP015K, a novel oral janus kinase inhibitor.

PubMed

Oda, Kazuo; Cao, Ying J; Sawamoto, Taiji; Nakada, Naoyuki; Fisniku, Ogert; Nagasaka, Yasuhisa; Sohda, Kin-Ya

2015-01-01

1. The human mass balance of (14)C-labelled ASP015K ([(14)C]ASP015K), an orally bioavailable Janus kinase (JAK) inhibitor, was characterized in six healthy male subjects after a single oral dose of [(14)C]ASP015K (100 mg, 3.7 MBq) in solution. [(14)C]ASP015K was rapidly absorbed with tmax of 1.6 and 1.8 h for ASP015K and total radioactivity in plasma, respectively. Mean recovery in urine and feces amounted to 36.8% and 56.6% of the administered dose, respectively. The main components of radioactivity in plasma and urine were ASP015K and M2 (5'-O-sulfo ASP015K). In feces, ASP015K and M4 (7-N-methyl ASP015K) were the main components. 2. In vitro study of ASP015K metabolism showed that the major isozyme contributing to the formation of M2 was human sulfotransferase (SULT) 2A1 and of M4 was nicotinamide N-methyltransferase (NNMT). 3. The in vitro intrinsic clearance (CLint_in vitro) of M4 formation from ASP015K in human liver cytosol (HLC) was 11-fold higher than that of M2. The competitive inhibitory effect of nicotinamide on M4 formation in the human liver was considered the reason for high CLint_in vitro of M4 formation, while each metabolic pathway made a near equal contribution to the in vivo elimination of ASP015K. ASP015K was cleared by multiple mechanisms.
Fast and Reliable Thermodynamic Approach for Determining the Protonation State of the Asp Dyad.

PubMed

Huang, Jinfeng; Sun, Bin; Yao, Yuan; Liu, Junjun

2017-09-25

The protonation state of the asp dyad is significantly important in revealing enzymatic mechanisms and developing drugs. However, it is hard to determine by calculating free energy changes between possible protonation states, because the free energy changes due to protein conformational flexibility are usually much larger than those originating from different locations of protons. Sophisticated and computationally expensive methods such as free energy perturbation, thermodynamic integration (TI), and quantum mechanics/molecular mechanics are therefore usually used for this purpose. In the present study, we have developed a simple thermodynamic approach to effectively eliminating the free energy changes arising from protein conformational flexibility and estimating the free energy changes only originated from the locations of protons, which provides a fast and reliable method for determining the protonation state of asp dyads. The test of this approach on a total of 15 asp dyad systems, including BACE-1 and HIV-1 protease, shows that the predictions from this approach are all consistent with experiments or with the computationally expensive TI calculations. It is clear that our thermodynamic approach could be used to rapidly and reliably determine the protonation state of the asp dyad.
Efficient peptide ligation between allyl-protected Asp and Cys followed by palladium-mediated deprotection.

PubMed

Kamo, Naoki; Hayashi, Gosuke; Okamoto, Akimitsu

2018-04-24

An efficient method for peptide ligation between C-terminal Asp(OAllyl) and N-terminal Cys has been developed. Peptide ligation and removal of the allyl group at the Asp carboxylate side chain proceeded in one pot by adding a small amount of Pd/TPPTS complex. Based on this efficient synthetic method, PEP-19 (61 amino acids), which is highly expressed in Purkinje cells, was synthesized.
Electrospun PLA: PCL composites embedded with unmodified and 3-aminopropyltriethoxysilane (ASP) modified halloysite nanotubes (HNT)

NASA Astrophysics Data System (ADS)

Haroosh, Hazim J.; Dong, Yu; Chaudhary, Deeptangshu S.; Ingram, Gordon D.; Yusa, Shin-ichi

2013-02-01

Electrospinning is a simple and versatile fiber synthesis technique in which a high-voltage electric field is applied to a stream of polymer melt or polymer solution, resulting in the formation of continuous micro/nanofibers. Halloysite nanotubes (HNT) have been found to achieve improved structural and mechanical properties when embedded into various polymer matrices. This research work focuses on blending poly( ɛ-caprolactone) (PCL) (9 and 15 wt%/v) and poly(lactic acid) (PLA) (fixed at 8 wt%/v) solutions with HNT at two different concentrations 1 and 2 wt%/v. Both unmodified HNT and HNT modified with 3-aminopropyltriethoxysilane (ASP) were utilized in this study. Fiber properties have been shown to be strongly related to the solution viscosity and electrical conductivity. The addition of HNT increased the solution viscosity, thus resulting in the production of uniform fibers. For both PCL concentrations, the average fiber diameter increased with the increasing of HNT concentration. The average fiber diameters with HNT-ASP were reduced considerably in comparison to those with unmodified HNT when using 15 wt%/v PCL. Slightly better dispersion was obtained for PLA: PCL composites embedded with HNT-ASP compared to unmodified HNT. Furthermore, the addition of HNT-ASP to the polymeric blends resulted in a moderate decrease in the degree of crystallinity, as well as slight reductions of glass transition temperature of PCL, the crystallization temperature and melting temperature of PLA within composite materials. The infrared spectra of composites confirmed the successful embedding of HNT-ASP into PLA: PCL nanofibers relative to unmodified HNT due to the premodification using ASP to reduce the agglomeration behavior. This study provides a new material system that could be potentially used in drug delivery, and may facilitate good control of the drug release process.
The dipeptide Pro-Asp promotes IGF-1 secretion and expression in hepatocytes by enhancing JAK2/STAT5 signaling pathway.

PubMed

Wang, Songbo; Wang, Guoqing; Zhang, Mengyuan; Zhuang, Lu; Wan, Xiaojuan; Xu, Jingren; Wang, Lina; Zhu, Xiaotong; Gao, Ping; Xi, Qianyun; Zhang, Yongliang; Shu, Gang; Jiang, Qingyan

2016-11-15

It has been implicated that IGF-1 secretion can be regulated by dietary protein. However, whether the dipeptides, one of digested products of dietary protein, have influence on IGF-1 secretion remain largely unknown. Our study aimed to investigate the effects of the dipeptide Pro-Asp on IGF-1 secretion and expression in hepatocytes and to explore the possible underlying mechanisms. Our findings demonstrated that Pro-Asp promoted the secretion and gene expression of IGF-1 in HepG2 cells and primary porcine hepatocytes. Meanwhile, Pro-Asp activated the ERK and Akt signaling pathways, downstream of IGF-1. In addition, Pro-Asp enhanced GH-mediated JAK2/STAT5 signaling pathway, while inhibition of JAK2/STAT5 blocked the promotive effect of Pro-Asp on IGF-1 secretion and expression. Moreover, acute injection of Pro-Asp stimulated IGF-1 expression and activated JAK2/STAT5 signaling pathway in mice liver. Together, these results suggested that the dipeptide Pro-Asp promoted IGF-1 secretion and expression in hepatocytes by enhancing GH-mediated JAK2/STAT5 signaling pathway. Copyright © 2016. Published by Elsevier Ireland Ltd.
Genomewide significant linkage to recurrent, early-onset major depressive disorder on chromosome 15q.

PubMed

Holmans, Peter; Zubenko, George S; Crowe, Raymond R; DePaulo, J Raymond; Scheftner, William A; Weissman, Myrna M; Zubenko, Wendy N; Boutelle, Sandra; Murphy-Eberenz, Kathleen; MacKinnon, Dean; McInnis, Melvin G; Marta, Diana H; Adams, Philip; Knowles, James A; Gladis, Madeleine; Thomas, Jo; Chellis, Jennifer; Miller, Erin; Levinson, Douglas F

2004-06-01

A genome scan was performed on the first phase sample of the Genetics of Recurrent Early-Onset Depression (GenRED) project. The sample consisted of 297 informative families containing 415 independent affected sibling pairs (ASPs), or, counting all possible pairs, 685 informative affected relative pairs (555 ASPs and 130 other pair types). Affected cases had recurrent major depressive disorder (MDD) with onset before age 31 years for probands or age 41 years for other affected relatives; the mean age at onset was 18.5 years, and the mean number of depressive episodes was 7.3. The Center for Inherited Disease Research genotyped 389 microsatellite markers (mean spacing of 9.3 cM). The primary linkage analysis considered allele sharing in all possible affected relative pairs with the use of the Z(lr) statistic computed by the ALLEGRO program. A secondary logistic regression analysis considered the effect of the sex of the pair as a covariate. Genomewide significant linkage was observed on chromosome 15q25.3-26.2 (Zlr=4.14, equivalent LOD = 3.73, empirical genomewide P=.023). The linkage was not sex specific. No other suggestive or significant results were observed in the primary analysis. The secondary analysis produced three regions of suggestive linkage, but these results should be interpreted cautiously because they depended primarily on the small subsample of 42 male-male pairs. Chromosome 15q25.3-26.2 deserves further study as a candidate region for susceptibility to MDD.
Dosimetric comparison of standard three-dimensional conformal radiotherapy followed by intensity-modulated radiotherapy boost schedule (sequential IMRT plan) with simultaneous integrated boost–IMRT (SIB IMRT) treatment plan in patients with localized carcinoma prostate

PubMed Central

Bansal, A.; Kapoor, R.; Singh, S. K.; Kumar, N.; Oinam, A. S.; Sharma, S. C.

2012-01-01

Aims: Dosimeteric and radiobiological comparison of two radiation schedules in localized carcinoma prostate: Standard Three-Dimensional Conformal Radiotherapy (3DCRT) followed by Intensity Modulated Radiotherapy (IMRT) boost (sequential-IMRT) with Simultaneous Integrated Boost IMRT (SIB-IMRT). Material and Methods: Thirty patients were enrolled. In all, the target consisted of PTV P + SV (Prostate and seminal vesicles) and PTV LN (lymph nodes) where PTV refers to planning target volume and the critical structures included: bladder, rectum and small bowel. All patients were treated with sequential-IMRT plan, but for dosimetric comparison, SIB-IMRT plan was also created. The prescription dose to PTV P + SV was 74 Gy in both strategies but with different dose per fraction, however, the dose to PTV LN was 50 Gy delivered in 25 fractions over 5 weeks for sequential-IMRT and 54 Gy delivered in 27 fractions over 5.5 weeks for SIB-IMRT. The treatment plans were compared in terms of dose–volume histograms. Also, Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) obtained with the two plans were compared. Results: The volume of rectum receiving 70 Gy or more (V > 70 Gy) was reduced to 18.23% with SIB-IMRT from 22.81% with sequential-IMRT. SIB-IMRT reduced the mean doses to both bladder and rectum by 13% and 17%, respectively, as compared to sequential-IMRT. NTCP of 0.86 ± 0.75% and 0.01 ± 0.02% for the bladder, 5.87 ± 2.58% and 4.31 ± 2.61% for the rectum and 8.83 ± 7.08% and 8.25 ± 7.98% for the bowel was seen with sequential-IMRT and SIB-IMRT plans respectively. Conclusions: For equal PTV coverage, SIB-IMRT markedly reduced doses to critical structures, therefore should be considered as the strategy for dose escalation. SIB-IMRT achieves lesser NTCP than sequential-IMRT. PMID:23204659
R76 in transmembrane domain 3 of the aspartate:alanine transporter AspT is involved in substrate transport.

PubMed

Suzuki, Satomi; Nanatani, Kei; Abe, Keietsu

2016-01-01

The L-aspartate:L-alanine antiporter of Tetragenococcus halophilus (AspT) possesses an arginine residue (R76) within the GxxxG motif in the central part of transmembrane domain 3 (TM3)-a residue that has been estimated to transport function. In this study, we carried out amino acid substitutions of R76 and used proteoliposome reconstitution for analyzing the transport function of each substitution. Both l-aspartate and l-alanine transport assays showed that R76K has higher activity than the AspT-WT (R76), whereas R76D and R76E have lower activity than the AspT-WT. These results suggest that R76 is involved in AspT substrate transport.
Low temperature effects on nitrification and nitrifier community structure in V-ASP for decentralized wastewater treatment and its improvement by bio-augmentation.

PubMed

Yuan, Jiajia; Dong, Wenyi; Sun, Feiyun; Zhao, Ke

2018-03-01

The vegetation-activated sludge process (V-ASP) has been proved to be an environment-friendly decentralized wastewater treatment system with extra esthetic function and less footprint. However, the effects of low temperature on the treatment performance of V-ASP and related improvement methods are rarely investigated, up to now. In this work, the effect of low temperature on nitrification in V-ASP was comprehensively investigated from overall nitrification performance, substrate utilization kinetics, functional enzymatic activities, and microbial community structure shift by comparison with conventional ASP. Bio-augmentation methods in terms of single-time nitrifier-enriched biomass dosage were employed to improve nitrification efficiency in bench- and full-scale systems. The experiment results demonstrated that the NH 4 + -N removal efficiency in V-ASP system decreased when the operational temperature decreased from 30 to 15 °C, and the decreasing extent was rather smaller compared to ASP, as well as ammonium and nitrite oxidation rates and enzymatic activities, which indicated the V-ASP system possesses high resistance to low temperature. With direct dosage of 1.6 mg nitrifier/gSS sludge, the nitrification efficiency in V-ASP was enhanced dramatically from below 50% to above 90%, implying that bio-augmentation was effective for V-ASP whose enzymatic activities and microbial communities were both also improved. The feasibility and effectiveness of bio-augmentation was further confirmed in a full-scale V-ASP system after a long-term experiment which is instructive for the practical application.
Structural specificity of Rn nuclease I as probed on yeast tRNA(Phe) and tRNA(Asp).

PubMed Central

Przykorska, A; el Adlouni, C; Keith, G; Szarkowski, J W; Dirheimer, G

1992-01-01

A single-strand-specific nuclease from rye germ (Rn nuclease I) was characterized as a tool for secondary and tertiary structure investigation of RNAs. To test the procedure, yeast tRNA(Phe) and tRNA(Asp) for which the tertiary structures are known, as well as the 3'-half of tRNA(Asp) were used as substrates. In tRNA(Phe) the nuclease introduced main primary cuts at positions U33 and A35 of the anticodon loop and G18 and G19 of the D loop. No primary cuts were observed within the double stranded stems. In tRNA(Asp) the main cuts occurred at positions U33, G34, U35, C36 of the anticodon loop and G18 and C20:1 positions in the D loop. No cuts were observed in the T loop in intact tRNA(Asp) but strong primary cleavages occurred at positions psi 55, C56, A57 within that loop in the absence of the tertiary interactions between T and D loops (use of 3'-half tRNA(Asp)). These results show that Rn nuclease I is specific for exposed single-stranded regions. Images PMID:1542562
Design of the annular suspension and pointing system /ASPS/ through decoupling and pole placement. [for Space Shuttle

NASA Technical Reports Server (NTRS)

Kuo, B. C.; Lin, W. C. W.

1980-01-01

A decoupling and pole-placement technique has been developed for the Annular Suspension and Pointing System (ASPS) of the Space Shuttle which uses bandwidths as performance criteria. The dynamics of the continuous-data ASPS allows the three degrees of freedom to be totally decoupled by state feedback through constant gains, so that the bandwidth of each degree of freedom can be independently specified without interaction. Although it is found that the digital ASPS cannot be completely decoupled, the bandwidth requirements are satisfied by pole placement and a trial-and-error method based on approximate decoupling.

Combined use of [TBA][L-ASP] and hydroxypropyl-β-cyclodextrin as selectors for separation of Cinchona alkaloids by capillary electrophoresis.

PubMed

Zhang, Yu; Yu, Haixia; Wu, Yujiao; Zhao, Wenyan; Yang, Min; Jing, Huanwang; Chen, Anjia

2014-10-01

In this paper, a new capillary electrophoresis (CE) separation and detection method was developed for the chiral separation of the four major Cinchona alkaloids (quinine/quinidine and cinchonine/cinchonidine) using hydroxypropyl-β-cyclodextrin (HP-β-CD) and chiral ionic liquid ([TBA][L-ASP]) as selectors. Separation parameters such as buffer concentrations, pH, HP-β-CD and chiral ionic liquid concentrations, capillary temperature, and separation voltage were investigated. After optimization of separation conditions, baseline separation of the three analytes (cinchonidine, quinine, cinchonine) was achieved in fewer than 7 min in ammonium acetate background electrolyte (pH 5.0) with the addition of HP-β-CD in a concentration of 40 mM and [TBA][L-ASP] of 14 mM, while the baseline separation of cinchonine and quinidine was not obtained. Therefore, the first-order derivative electropherogram was applied for resolving overlapping peaks. Regression equations revealed a good linear relationship between peak areas in first-order derivative electropherograms and concentrations of the two diastereomer pairs. The results not only indicated that the first-order derivative electropherogram was effective in determination of a low content component and of those not fully separated from adjacent ones, but also showed that the ionic liquid appeared to be a very promising chiral selector in CE. Copyright © 2014 Elsevier Inc. All rights reserved.
A Substrate-Assisted Mechanism of Nucleophile Activation in a Ser-His-Asp Containing C-C Bond Hydrolase

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

Ruzzini, Antonio C.; Bhowmik, Shiva; Ghosh, Subhangi

The meta-cleavage product (MCP) hydrolases utilize a Ser–His–Asp triad to hydrolyze a carbon–carbon bond. Hydrolysis of the MCP substrate has been proposed to proceed via an enol-to-keto tautomerization followed by a nucleophilic mechanism of catalysis. Ketonization involves an intermediate, ES red, which possesses a remarkable bathochromically shifted absorption spectrum. We investigated the catalytic mechanism of the MCP hydrolases using DxnB2 from Sphingomonas wittichii RW1. Pre-steady-state kinetic and LC ESI/MS evaluation of the DxnB2-mediated hydrolysis of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid to 2-hydroxy-2,4-pentadienoic acid and benzoate support a nucleophilic mechanism catalysis. In DxnB2, the rate of ES red decay and product formation showed amore » solvent kinetic isotope effect of 2.5, indicating that a proton transfer reaction, assigned here to substrate ketonization, limits the rate of acylation. For a series of substituted MCPs, this rate was linearly dependent on MCP pK a2 (β nuc ~ 1). Structural characterization of DxnB2 S105A:MCP complexes revealed that the catalytic histidine is displaced upon substrate-binding. The results provide evidence for enzyme-catalyzed ketonization in which the catalytic His–Asp pair does not play an essential role. The data further suggest that ES red represents a dianionic intermediate that acts as a general base to activate the serine nucleophile. This substrate-assisted mechanism of nucleophilic catalysis distinguishes MCP hydrolases from other serine hydrolases.« less
Ca-asp bound X-ray structure and inhibition of Bacillus anthracis dihydroorotase (DHOase).

PubMed

Rice, Amy J; Lei, Hao; Santarsiero, Bernard D; Lee, Hyun; Johnson, Michael E

2016-10-01

Dihydroorotase (DHOase) is the third enzyme in the de novo pyrimidine synthesis pathway and is responsible for the reversible cyclization of carbamyl-aspartate (Ca-asp) to dihydroorotate (DHO). DHOase is further divided into two classes based on several structural characteristics, one of which is the length of the flexible catalytic loop that interacts with the substrate, Ca-asp, regulating the enzyme activity. Here, we present the crystal structure of Class I Bacillus anthracis DHOase with Ca-asp in the active site, which shows the peptide backbone of glycine in the shorter loop forming the necessary hydrogen bonds with the substrate, in place of the two threonines found in Class II DHOases. Despite the differences in the catalytic loop, the structure confirms that the key interactions between the substrate and active site residues are similar between Class I and Class II DHOase enzymes, which we further validated by mutagenesis studies. B. anthracis DHOase is also a potential antibacterial drug target. In order to identify prospective inhibitors, we performed high-throughput screening against several libraries using a colorimetric enzymatic assay and an orthogonal fluorescence thermal binding assay. Surface plasmon resonance was used for determining binding affinity (KD) and competition analysis with Ca-asp. Our results highlight that the primary difference between Class I and Class II DHOase is the catalytic loop. We also identify several compounds that can potentially be further optimized as potential B. anthracis inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.
Fundamental Roles of the Golgi-Associated Toxoplasma Aspartyl Protease, ASP5, at the Host-Parasite Interface

PubMed Central

Hammoudi, Pierre-Mehdi; Jacot, Damien; Mueller, Christina; Di Cristina, Manlio; Dogga, Sunil Kumar; Marq, Jean-Baptiste; Romano, Julia; Tosetti, Nicolò; Dubrot, Juan; Emre, Yalin; Lunghi, Matteo; Coppens, Isabelle; Yamamoto, Masahiro; Sojka, Daniel; Pino, Paco; Soldati-Favre, Dominique

2015-01-01

Toxoplasma gondii possesses sets of dense granule proteins (GRAs) that either assemble at, or cross the parasitophorous vacuole membrane (PVM) and exhibit motifs resembling the HT/PEXEL previously identified in a repertoire of exported Plasmodium proteins. Within Plasmodium spp., cleavage of the HT/PEXEL motif by the endoplasmic reticulum-resident protease Plasmepsin V precedes trafficking to and export across the PVM of proteins involved in pathogenicity and host cell remodelling. Here, we have functionally characterized the T. gondii aspartyl protease 5 (ASP5), a Golgi-resident protease that is phylogenetically related to Plasmepsin V. We show that deletion of ASP5 causes a significant loss in parasite fitness in vitro and an altered virulence in vivo. Furthermore, we reveal that ASP5 is necessary for the cleavage of GRA16, GRA19 and GRA20 at the PEXEL-like motif. In the absence of ASP5, the intravacuolar nanotubular network disappears and several GRAs fail to localize to the PVM, while GRA16 and GRA24, both known to be targeted to the host cell nucleus, are retained within the vacuolar space. Additionally, hypermigration of dendritic cells and bradyzoite cyst wall formation are impaired, critically impacting on parasite dissemination and persistence. Overall, the absence of ASP5 dramatically compromises the parasite’s ability to modulate host signalling pathways and immune responses. PMID:26473595
Association between Toll-like receptor 4 Asp299Gly polymorphism and coronary heart disease susceptibility.

PubMed

Wu, B W; Zhu, J; Shi, H M; Jin, B; Wen, Z C

2017-08-07

Published data on the association between Toll-like receptor 4 (TLR4) Asp299Gly polymorphism and coronary heart disease (CHD) susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. English-language studies were identified by searching PubMed and Embase databases (up to November 2016). All epidemiological studies were regarding Caucasians because no TLR4 Asp/Gly and Gly/Gly genotypes have been detected in Asians. A total of 20 case-control studies involving 14,416 cases and 10,764 controls were included in the meta-analysis. Overall, no significant associations were found between TLR4 Asp299Gly polymorphism and CHD susceptibility in the dominant model (OR=0.89; 95%CI=0.74 to 1.06; P=0.20) pooled in the meta-analysis. In the subgroup analysis by CHD, non-significant associations were found in cases compared to controls. When stratified by control source, no significantly decreased risk was found in the additive model or dominant model. The present meta-analysis suggests that the TLR4 Asp299Gly polymorphism was not associated with decreased CHD risk in Caucasians.
Determination of the protonation state of the Asp dyad: conventional molecular dynamics versus thermodynamic integration.

PubMed

Huang, Jinfeng; Zhu, Yali; Sun, Bin; Yao, Yuan; Liu, Junjun

2016-03-01

The protonation state of the Asp dyad is important as it can reveal enzymatic mechanisms, and the information this provides can be used in the development of drugs for proteins such as memapsin 2 (BACE-1), HIV-1 protease, and rennin. Conventional molecular dynamics (MD) simulations have been successfully used to determine the preferred protonation state of the Asp dyad. In the present work, we demonstrate that the results obtained from conventional MD simulations can be greatly influenced by the particular force field applied or the values used for control parameters. In principle, free-energy changes between possible protonation states can be used to determine the protonation state. We show that protonation state prediction by the thermodynamic integration (TI) method is insensitive to force field version or to the cutoff for calculating nonbonded interactions (a control parameter). In the present study, the protonation state of the Asp dyad predicted by TI calculations was the same regardless of the force field and cutoff value applied. Contrary to the intuition that conventional MD is more efficient, our results clearly show that the TI method is actually more efficient and more reliable for determining the protonation state of the Asp dyad.
Nonlinear analysis and performance evaluation of the Annular Suspension and Pointing System (ASPS)

NASA Technical Reports Server (NTRS)

Joshi, S. M.

1978-01-01

The Annular Suspension and Pointing System (ASPS) can provide high accurate fine pointing for a variety of solar-, stellar-, and Earth-viewing scientific instruments during space shuttle orbital missions. In this report, a detailed nonlinear mathematical model is developed for the ASPS/Space Shuttle system. The equations are augmented with nonlinear models of components such as magnetic actuators and gimbal torquers. Control systems and payload attitude state estimators are designed in order to obtain satisfactory pointing performance, and statistical pointing performance is predicted in the presence of measurement noise and disturbances.
Purification and characterisation of a novel antistaphylococcal peptide (ASP-1) from Bacillus sp. URID 12.1.

PubMed

Chalasani, Ajay Ghosh; Roy, Utpal; Nema, Sushma

2018-01-01

A strong antistaphylococcal peptide (ASP-1) from Bacillus subtilis URID 12.1 strain that is active against cefoxitin- and methicillin-resistant Staphylococcus aureus clinical isolates was purified to homogeneity by solvent extraction, silica gel-based adsorption chromatography and reversed-phase high-performance liquid chromatography. The peptide sequence of ASP-1 as determined by MALDI-TOF/MS and ESI-FTICR-MS was acetylated Phe-Thr-Ala-Val-Dhb-Phe-Ile/Leu. The peptide was further analysed by alkaline hydrolysis, ESI-Q-TOF-MS and an ion mobility assay, which detected the presence of a lactone ring in the intact peptide and a cyclic nature, subsequently revealing the linearised peptide sequence as acPhe-Leu-Phe-Thr-Val-Ala-Dhb. Based on the molecular mass (804.5 Da), peptide sequence and amino acid composition, ASP-1 was identified as a lactone ring-containing peptide similar to TL-119, a poorly studied cyclic depsipeptide. Circular dichroism spectroscopy revealed its predominantly random structure in aqueous solution and its β-sheet conformation in methanol. Minimum inhibitory concentrations (MICs) of the purified peptide against S. aureus and methicillin-resistant S. aureus (MRSA) ranged from 2 µg/mL to 64 µg/mL. At sub-MICs and 1× MIC, ASP-1 showed a strong antibiofilm characteristic. ASP-1 at a concentration of 128 µg/mL did not show haemolytic activity, and no cytotoxicity was observed against hepatic carcinoma and breast carcinoma cell lines at the same concentration. Peptide ASP-1 with anti-MRSA and antibiofilm abilities and non-haemolytic and non-cytotoxic properties has not been reported previously. These findings suggest that it may serve as a lead molecule for developing alternative topical antibacterial agents. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
Implementing the Simple Biosphere Model (SiB) in a general circulation model: Methodologies and results

NASA Technical Reports Server (NTRS)

Sato, N.; Sellers, P. J.; Randall, D. A.; Schneider, E. K.; Shukla, J.; Kinter, J. L., III; Hou, Y.-T.; Albertazzi, E.

1989-01-01

The Simple Biosphere MOdel (SiB) of Sellers et al., (1986) was designed to simulate the interactions between the Earth's land surface and the atmosphere by treating the vegetation explicitly and relistically, thereby incorporating biophysical controls on the exchanges of radiation, momentum, sensible and latent heat between the two systems. The steps taken to implement SiB in a modified version of the National Meteorological Center's spectral GCM are described. The coupled model (SiB-GCM) was used with a conventional hydrological model (Ctl-GCM) to produce summer and winter simulations. The same GCM was used with a conventional hydrological model (Ctl-GCM) to produce comparable 'control' summer and winter variations. It was found that SiB-GCM produced a more realistic partitioning of energy at the land surface than Ctl-GCM. Generally, SiB-GCM produced more sensible heat flux and less latent heat flux over vegetated land than did Ctl-GCM and this resulted in the development of a much deeper daytime planetary boundary and reduced precipitation rates over the continents in SiB-GCM. In the summer simulation, the 200 mb jet stream and the wind speed at 850 mb were slightly weakened in the SiB-GCM relative to the Ctl-GCM results and equivalent analyses from observations.
Microstructure simulation of rapidly solidified ASP30 high-speed steel particles by gas atomization

NASA Astrophysics Data System (ADS)

Ma, Jie; Wang, Bo; Yang, Zhi-liang; Wu, Guang-xin; Zhang, Jie-yu; Zhao, Shun-li

2016-03-01

In this study, the microstructure evolution of rapidly solidified ASP30 high-speed steel particles was predicted using a simulation method based on the cellular automaton-finite element (CAFE) model. The dendritic growth kinetics, in view of the characteristics of ASP30 steel, were calculated and combined with macro heat transfer calculations by user-defined functions (UDFs) to simulate the microstructure of gas-atomized particles. The relationship among particle diameter, undercooling, and the convection heat transfer coefficient was also investigated to provide cooling conditions for simulations. The simulated results indicated that a columnar grain microstructure was observed in small particles, whereas an equiaxed microstructure was observed in large particles. In addition, the morphologies and microstructures of gas-atomized ASP30 steel particles were also investigated experimentally using scanning electron microscopy (SEM). The experimental results showed that four major types of microstructures were formed: dendritic, equiaxed, mixed, and multi-droplet microstructures. The simulated results and the available experimental data are in good agreement.
Exploring the administrative mechanism of China's Paired Assistance to Disaster Affected Areas programme.

PubMed

Zhong, Kaibin; Lu, Xiaoli

2017-10-31

The Paired Assistance to Disaster Affected Areas (PADAA) programme is a mutual aid initiative with Chinese characteristics, which speeded up the process of restoring and reconstructing regions affected by the Wenchuan earthquake on 12 May 2008. The PADAA is an efficient instrument for catastrophe recovery, yet it remains a mysterious mechanism to many members of disaster management communities. This paper aims to lift the veil on it by assessing its origins and evolution. It draws on the multi-level moderated competition model to explain how the PADAA functions within the Chinese administrative system. The country's top-down political system allows the central authority to mandate provincial and local governments from more economically developed regions to assist devastated areas with post-disaster reconstruction. The practices of local accountability complement vertical control by giving leaders from donor regions strong incentives to accomplish assigned reconstruction tasks, resulting in intense competition between them. © 2017 The Author(s). Disasters © Overseas Development Institute, 2017.
Heterozygous p.Asp50Asn mutation in the GJB2 gene in two Cameroonian patients with keratitis-ichthyosis-deafness (KID) syndrome.

PubMed

Wonkam, Ambroise; Noubiap, Jean Jacques N; Bosch, Jason; Dandara, Collet; Toure, Geneviève Bengono

2013-08-07

Keratitis-Ichthyosis-Deafness (KID) syndrome (OMIM 148210) is a congenital ectodermal defect that consists of an atypical ichthyosiform erythroderma associated with congenital sensorineural deafness. KID appears to be genetically heterogeneous and most cases are caused by GJB2 mutations. Mutations in African patients have been rarely described. We report on two unrelated Cameroonian individuals affected with sporadic KID, presenting with the classic phenotypic triad. The two patients were heterozygous for the most frequent p.Asp50Asn mutation. This first report in patients from sub-Saharan African origin supports the hypothesis that the occurrence of KID due to p.Asp50Asn mutation in GJB2 seems not to be population specific. Our finding has implication in medical genetic practice, specifically in the molecular diagnosis of KID in Africans. These cases also reveal and emphasize the urgent need to develop appropriate policies to care for patients with rare/orphan diseases in Sub-Saharan Africa, as many of these cases become more and more recognizable.
Bacterial communities and enzymatic activities in the vegetation-activated sludge process (V-ASP) and related advantages by comparison with conventional constructed wetland.

PubMed

Yuan, Jiajia; Dong, Wenyi; Sun, Feiyun; Zhao, Ke; Du, Changhang; Shao, Yunxian

2016-11-01

A new-developed vegetation-activated sludge process (V-ASP) was implemented for decentralized domestic wastewater treatment, and studied in lab-scale and full-scale. The main purpose of this work was the investigation of biomass activities and microbial communities in V-ASP by comparison with conventional constructed wetland (CW), to unveil the causations of its consistently higher pollutants removal efficiencies. Compared with CWs, V-ASP has greater vegetation nitrogen and phosphorus uptake rates, higher biomass and enzymatic activities, and more bacteria community diversity. The microbial community structure was comprehensively analyzed by using high-throughput sequencing. It was observed that Proteobacteria was dominated in both CWs and V-ASPs, while their subdivisions distribution was rather different. V-ASPs contained a higher nitrite-oxidizing bacteria (Nitrospira) abundances that resulted in a consistently better nitrogen removal efficiency. Hence, a long-term experiment of full-scale V-ASP displayed stably excellent capability in resistance of influent loading shocks and seasonal temperature effect. Copyright © 2016 Elsevier Ltd. All rights reserved.
Ala397Asp mutation of myosin VIIA gene segregating in a Spanish family with type-Ib Usher syndrome.

PubMed

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

1998-06-01

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

Treesearch

Brian Baltunis; Dudley Huber; Tim Wite

2006-01-01

The Forest Biology Research Cooperative recently established a series of loblolly pine clonal trials known as CCLONES (Comparing Clonal Lines on Experimental Sites). There are three primary levels of genetic structure in this study (parental, full-sib family, clone) that strengthen the power of CCLONES for examining genetic mechanisms and interactions with cultural...
Host protective ASP-based vaccine against the parasitic nematode Ostertagia ostertagi triggers NK cell activation and mixed IgG1-IgG2 response.

PubMed

González-Hernández, Ana; Van Coppernolle, Stefanie; Borloo, Jimmy; Van Meulder, Frederik; Paerewijck, Oonagh; Peelaers, Iris; Leclercq, Georges; Claerebout, Edwin; Geldhof, Peter

2016-07-11

The mucus-dwelling parasite Ostertagia ostertagi is one of the most important gastrointestinal nematodes in cattle. Our group has previously demonstrated the protective capacity of a vaccine against this parasite based on a native activation-associated secreted protein ASP1 (nASP) in combination with the saponin adjuvant QuilA. The aim of the current study was to analyse the effect of both antigen and adjuvant on the cellular and humoral vaccine-induced immune responses by comparing the native ASP to a recombinant version expressed in Pichia pastoris (pASP) and replacing QuilA by Al(OH)3. Immunization of cattle with the protective nASP+QuilA vaccine was associated with antigen-induced proliferation of natural killer (NK) cells combined with IFN-γ secretion and the induction of a mixed IgG1/IgG2 antibody response. ASP-specific activation and proliferation of NK cells was also observed in mice following the same vaccination regime. Replacing QuilA by Al(OH)3 or nASP by pASP significantly decreased the capacity of the vaccines to trigger both NK cell activation and antibody responses and failed to induce protection against a challenge infection. Reduction of the structurally anchoring disulphide bonds of the nASP completely abolished its ability to induce NK cell activation and antibody responses, highlighting the importance of protein conformation for the immunostimulatory activity.
Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period.

PubMed

Saleh, J; Summers, L K; Cianflone, K; Fielding, B A; Sniderman, A D; Frayn, K N

1998-04-01

The objective of this study was to determine whether Acylation Stimulating Protein (ASP) is generated in vivo by human adipose tissue during the postprandial period. After a fat meal, samples from 12 subjects were obtained (up to 6 h) from an arterialized hand vein and an anterior abdominal wall vein that drains adipose tissue. Veno-arterial (V-A) gradients across the subcutaneous adipose tissue bed were calculated. The data demonstrate that ASP is produced in vivo (positive V-A gradient) With maximal production at 3-5 h postprandially. The plasma triacylglycerol (TAG) clearance was evidenced by a negative V-A gradient. It increased substantially after 3 h and remained prominent until the final time point. There was, therefore, a close temporal coordination between ASP generation and TAG clearance. In contrast, plasma insulin and non-esterified fatty acid (NEFA) had an early (1-2 h) postprandial change. Fatty acid incorporation into adipose tissue (FIAT) was calculated from V-A glycerol and non-esterified fatty acid (NEFA) differences postprandially. FIAT was negative during the first hour, implying net fat mobilization. FIAT then became increasingly positive, implying net fat deposition, and overall followed the same time course as ASP and TAG clearance. There was a direct positive correlation between total ASP production and total FIAT (r = 0.566, P < 0.05). These data demonstrate that ASP is generated in vivo by human adipocytes and that this process is accentuated postprandially, supporting the concept that ASP plays an important role in clearance of TAG from plasma and fatty acid storage in adipose tissue.
[Effects of hypophyseal Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly synthetic peptides on immunity, hemostasis, morphology and functions of the thyroid gland in neonatally hypophysectomized chicken and one-year-old birds].

PubMed

Kuznik, B I; Pateiuk, A V; Rusaeva, N S; Baranchugova, L M; Obydenko, V I

2010-01-01

Neonatal hypophysectomy in chicken produces enlarged follicles of the thyroid gland, accumulation of colloids, impressed follicular epithelium, increased nucleus-cytoplasm ratio in thyrocytes, atrophied inter-follicular epithelium, depressed immunity, development of hypercoagulation and depressed fibrinolysis. When hypophysectomy is performed in one-year-old birds the impairments developing in thyroid morphology, immunity and hemostasis are less pronounced. Peptides of the anterior (Lys-Glu-Asp-Gly) and posterior (Ala-Glu-Asp-Gly) thyroid lobes injected to hypophysectomized birds prevent atrophic changes of the thyroid gland, normalize immune and hemostatic parameters.
Comparative study of (Asp)7-CHOL-modified liposome prepared using pre-insertion and post-insertion methods for bone targeting in vivo.

PubMed

Zhang, Lijing; Cao, Hua; Zhang, Jiaxin; Yang, Chengli; Hu, Tingting; Li, Huili; Yang, Wu; He, Gu; Song, Xiangrong; Tong, Aiping; Guo, Gang; Li, Rui; Jiang, Yu; Liu, Jiyan; Cai, Lulu; Zheng, Yu

2017-02-01

Specific delivery of drugs to bone tissue is very challenging due to the architecture and structure of bone tissue. A seven-repeat sequence of aspartate, a representative bone-targeting oligopeptide, is preferentially used for targeted therapy for bone diseases. In this study, Asp7-cholesterol((Asp)7-CHOL) was synthesized and (Asp)7-CHOL-modified liposome loaded with doxorubicin (DOX) was successfully prepared using both pre-insertion (pre-L) and post-insertion (post-L) methods. The formulation was optimized according to particle size, zeta potential and the drug-loading efficiency of the liposome. In addition, the bone affinity of the (Asp)7-CHOL-modified liposome was evaluated using a hydroxyapatite (HA) absorption method. The results suggested that (Asp)7-CHOL-modified liposome show excellent HA absorption; pre-L showed slightly higher HA binding than post-L. However, post-L had a higher DOX entrapment efficiency than pre-L. In vivo imaging further demonstrated that pre-L showed a higher bone-targeting efficiency than post-L, which was consistent with in vitro results. In all, (Asp)7-CHOL-modified liposome showed excellent bone-targeting activity, suggesting their potential for use as a drug delivery system for bone disease-targeted therapies.
Polymorphisms in XPD (Asp312Asn and Lys751Gln) genes, sunburn and arsenic-related skin lesions.

PubMed

McCarty, Kathleen M; Smith, Thomas J; Zhou, Wei; Gonzalez, Ernesto; Quamruzzaman, Quazzi; Rahman, Mahmuder; Mahiuddin, Golam; Ryan, Louise; Su, Li; Christiani, David C

2007-08-01

Single-nucleotide polymorphisms in genes related to DNA repair capacity and ultraviolet exposure have not been well investigated in relation to skin lesions associated with arsenic exposure. This population based case-control study, of 600 cases and 600 controls, frequency matched on age and gender in Pabna, Bangladesh, in 2001-2002, investigated the association and potential effect modification between polymorphisms in Xeroderma Pigmentosum complementation group D (XPD) (Lys751Gln and Asp312Asn) genes, tendency to sunburn and arsenic-related skin lesions. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). No significant association was observed between skin lesions and the XPD 312 Asp/Asn (adjusted OR = 0.87, 95% CI = 0.65-1.15) Asn/Asn (adjusted OR = 0.76, 95% CI = 0.50-1.15) (referent Asp/Asp); XPD 751 Lys/Gln (adjusted OR = 0.92, 95% CI = 0.69-1.23) Gln/Gln (adjusted OR = 0.98, 95% CI = 0.66-1.45) (referent Lys/Lys). While we did not observe any evidence of effect modification of these polymorphisms on the association between well arsenic concentration and skin lesions, we did observe effect modification between these polymorphisms and sunburn tendency and arsenic-related skin lesions. Individuals with the heterozygote or homozygote variant forms (Asp/Asn or Asn/Asn) had half the risk of skin lesions (OR = 0.45, 95% CI = 0.29-0.68) compared with those with the wild-type XPDAsp312Asn genotype (Asp/Asp) and individuals with heterozygote or homozygote variant forms (Lys/Gln or Gln/Gln) had half the risk of skin lesions (OR = 0.47, 95% CI = 0.31-0.72) compared with those with the wild-type XPDLys751Gln genotype (Lys/Lys), within the least sensitive strata of sunburn severity. We observed effect modification on the multiplicative scale for XPD 751 and XPD 312. XPD polymorphisms modified the relationship between tendency to sunburn and skin lesions in an arsenic exposed population. Further study is necessary

Polymorphisms in XPD (Asp312Asn and Lys751Gln) genes, sunburn and arsenic-related skin lesions

PubMed Central

McCarty, Kathleen M.; Smith, Thomas J.; Zhou, Wei; Gonzalez, Ernesto; Quamruzzaman, Quazzi; Rahman, Mahmuder; Mahiuddin, Golam; Ryan, Louise; Su, Li; Christiani, David C.

2013-01-01

Background Single-nucleotide polymorphisms in genes related to DNA repair capacity and ultraviolet exposure have not been well investigated in relation to skin lesions associated with arsenic exposure. This population based case–control study, of 600 cases and 600 controls, frequency matched on age and gender in Pabna, Bangladesh, in 2001–2002, investigated the association and potential effect modification between polymorphisms in Xeroderma Pigmentosum complementation group D (XPD) (Lys751Gln and Asp312Asn) genes, tendency to sunburn and arsenic-related skin lesions. Methods Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Result No significant association was observed between skin lesions and the XPD 312 Asp/Asn (adjusted OR = 0.87, 95% CI = 0.65–1.15) Asn/Asn (adjusted OR = 0.76, 95% CI = 0.50–1.15) (referent Asp/Asp); XPD 751 Lys/Gln (adjusted OR = 0.92, 95% CI = 0.69–1.23) Gln/Gln (adjusted OR = 0.98, 95% CI = 0.66–1.45) (referent Lys/Lys). While we did not observe any evidence of effect modification of these polymorphisms on the association between well arsenic concentration and skin lesions, we did observe effect modification between these polymorphisms and sunburn tendency and arsenic-related skin lesions. Individuals with the heterozygote or homozygote variant forms (Asp/Asn or Asn/Asn) had half the risk of skin lesions (OR = 0.45, 95% CI = 0.29–0.68) compared with those with the wild-type XPDAsp312Asn genotype (Asp/Asp) and individuals with heterozygote or homozygote variant forms (Lys/Gln or Gln/Gln) had half the risk of skin lesions (OR = 0.47, 95% CI = 0.31–0.72) compared with those with the wild-type XPDLys751Gln genotype (Lys/Lys), within the least sensitive strata of sunburn severity. We observed effect modification on the multiplicative scale for XPD 751 and XPD 312. Conclusion XPD polymorphisms modified the relationship between tendency to sunburn and skin lesions in an
Elucidating the Role of Many-Body Forces in Liquid Water. I. Simulations of Water Clusters on the VRT (ASP-W) Potential Surfaces

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

Goldman, N; Saykally, R J

We test the new VRT(ASP-W)II and VRT(ASP-W)III potentials by employing Diffusion Quantum Monte Carlo simulations to calculate the vibrational ground-state properties of water clusters. These potentials are fits of the highly detailed ASP-W ab initio potential to (D{sub 2}O){sub 2} microwave and far-IR data, and along with the SAPT5s potentials, are the most accurate water dimer potential surfaces in the literature. The results from VRT(ASP-W)II and III are compare to those from the original ASP-W potential, the SAPT5s family of potentials, and several bulk water potentials. Only VRT(ASP-W)II and the spectroscopically ''tuned'' SAPT5st (with N-body induction included) accurately reproduce themore » vibrational ground-state structures of water clusters up to the hexamer. Finally, the importance of many-body induction and three-body dispension are examined, and it is shown that the latter can have significant effects on water cluster properties despite its small magnitude.« less
Antecedents to the adoption of ASPS in healthcare.

PubMed

Randeree, Ebrahim; Judd, Susan P; Kishore, Rajiv; Rao, H Raghav

2003-01-01

The objective of this exploratory study was to identify drivers of adoption for a new form of information technology outsourcing--the ASP model--in the healthcare industry. Primary data were collected in January 2002 from a nationwide survey of senior-level healthcare information technology executives. Cost management (supplier presence, asset specificity, production costs, transaction costs, resource availability) and relative advantage (reliability, customizability, strategic alignment, and magnitude of potential loss) were found to have the largest influences on adoption behavior.
Structural and functional analysis of the ASM p.Ala359Asp mutant that causes acid sphingomyelinase deficiency.

PubMed

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

2016-10-21

Niemann-Pick disease (NPD) type A and B are recessive hereditary disorders caused by deficiency in acid sphingomyelinase (ASM). The p.Ala359Asp mutation has been described in several patients but its functional and structural effects in the protein are unknown. In order to characterize this mutation, we modeled the three-dimensional ASM structure using the recent available crystal of the mammalian ASM as a template. We found that the p.Ala359Asp mutation is localized in the hydrophobic core and far from the sphingomyelin binding site. However, energy function calculations using statistical potentials indicate that the mutation causes a decrease in ASM stability. Therefore, we investigated the functional effect of the p.Ala359Asp mutation in ASM expression, secretion, localization and activity in human fibroblasts. We found a 3.8% residual ASM activity compared to the wild-type enzyme, without changes in the other parameters evaluated. These results support the hypothesis that the p.Ala359Asp mutation causes structural alterations in the hydrophobic environment where ASM is located, decreasing its enzymatic activity. A similar effect was observed in other previously described NPDB mutations located outside the active site of the enzyme. This work shows the first full size ASM mutant model describe at date, providing a complete analysis of the structural and functional effects of the p.Ala359Asp mutation over the stability and activity of the enzyme. Copyright © 2016 Elsevier Inc. All rights reserved.
Mastocytosis in mice expressing human Kit receptor with the activating Asp816Val mutation

PubMed Central

Zappulla, Jacques P.; Dubreuil, Patrice; Desbois, Sabine; Létard, Sébastien; Hamouda, Nadine Ben; Daëron, Marc; Delsol, Georges; Arock, Michel; Liblau, Roland S.

2005-01-01

Mastocytosis is a rare neoplastic disease characterized by a pathologic accumulation of tissue mast cells (MCs). Mastocytosis is often associated with a somatic point mutation in the Kit protooncogene leading to an Asp/Val substitution at position 816 in the kinase domain of this receptor. The contribution of this mutation to mastocytosis development remains unclear. In addition, the clinical heterogeneity presented by mastocytosis patients carrying the same mutation is unexplained. We report that a disease with striking similarities to human mastocytosis develops spontaneously in transgenic mice expressing the human Asp816Val mutant Kit protooncogene specifically in MCs. This disease is characterized by clinical signs ranging from a localized and indolent MC hyperplasia to an invasive MC tumor. In addition, bone marrow–derived MCs from transgenic animals can be maintained in culture for >24 mo and acquire growth factor independency for proliferation. These results demonstrate a causal link in vivo between the Asp816Val Kit mutation and MC neoplasia and suggest a basis for the clinical heterogeneity of human mastocytosis. PMID:16352739
Comparative analysis of the immune responses induced by native versus recombinant versions of the ASP-based vaccine against the bovine intestinal parasite Cooperia oncophora.

PubMed

González-Hernández, Ana; Borloo, Jimmy; Peelaers, Iris; Casaert, Stijn; Leclercq, Georges; Claerebout, Edwin; Geldhof, Peter

2018-01-01

The protective capacities of a native double-domain activation-associated secreted protein (ndd-ASP)-based vaccine against the cattle intestinal nematode Cooperia oncophora has previously been demonstrated. However, protection analysis upon vaccination with a recombinantly produced antigen has never been performed. Therefore, the aim of the current study was to test the protective potential of a Pichia-produced double-domain ASP (pdd-ASP)-based vaccine against C. oncophora. Additionally, we aimed to compare the cellular and humoral mechanisms underlying the vaccine-induced responses by the native (ndd-ASP) and recombinant vaccines. Immunisation of cattle with the native C. oncophora vaccine conferred significant levels of protection after an experimental challenge infection, whereas the recombinant vaccine did not. Moreover, vaccination with ndd-ASP resulted in a higher proliferation of CD4-T cells both systemically and in the small intestinal mucosa when compared with animals vaccinated with the recombinant antigen. In terms of humoral response, although both native and recombinant vaccines induced similar levels of antibodies, animals vaccinated with the native vaccine were able to raise antibodies with greater specificity towards ndd-ASP in comparison with antibodies raised by vaccination with the recombinant vaccine, suggesting a differential immune recognition towards the ndd-ASP and pdd-ASP. Finally, the observation that animals displaying antibodies with higher percentages of recognition towards ndd-ASP also exhibited the lowest egg counts suggests a potential relationship between antibody specificity and protection. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Putting The "Yee-Hah!" In Astronomy Outreach: Professional Development Through The ASP "Sky Rangers" Project

NASA Astrophysics Data System (ADS)

Manning, Jim; Gurton, S.; Hurst, A.

2010-05-01

The Astronomical Society of the Pacific is conducting a NASA-funded professional development program to help increase astronomy education and outreach capacity at national parks, nature centers, and other outdoor and environmental centers--venues that still have a dark night sky as a natural resource and a yen to interpret it for their visitors. Through online workshops and on-site workshops at national parks, the ASP staff, working in conjunction with partners from the National Park Service, National Association for Interpretation, and the Association of Science and Technology Centers, provides materials and training focusing on the sky. Participants become part of ASP's "Astronomy from the Ground Up" informational education community of practice, with ongoing options to hone their new skills. The presenter will report on early progress and lessons learned, as well as future plans, as the ASP and its partners work to help wilderness and nature interpreters put a little more "yee-hah!" in their visitor presentations aimed at the sky.
Substitution of the Lys Linker with the β-Ala Linker Dramatically Decreased the Renal Uptake of 99mTc-Labeled Arg-X-Asp-Conjugated and X-Ala-Asp-Conjugated α-Melanocyte Stimulating Hormone Peptides

PubMed Central

2015-01-01

The purpose of this study was to examine whether the substitution of the Lys linker with the β-Ala could reduce the renal uptake of 99mTc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RSD-β-Ala-(Arg11)CCMSH (1) {c[Arg-Ser-Asp-dTyr-Asp]-β-Ala-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2}, RTD-β-Ala-(Arg11)CCMSH (2), RVD-β-Ala-(Arg11)CCMSH (3), RAD-β-Ala-(Arg11)CCMSH (4), NAD-β-Ala-(Arg11)CCMSH (5), and EAD-β-Ala-(Arg11)CCMSH (6) peptides were synthesized and evaluated for their melanocortin 1 (MC1) receptor binding affinities in B16/F1 melanoma cells. The biodistribution of their 99mTc-conjugates were determined in B16/F1 melanoma-bearing C57 mice. The substitution of the Lys linker with β-Ala linker dramatically reduced the renal uptake of all six 99mTc-peptides. 99mTc-4 exhibited the highest melanoma uptake (15.66 ± 6.19% ID/g) and the lowest kidney uptake (20.18 ± 3.86% ID/g) among these 99mTc-peptides at 2 h postinjection. The B16/F1 melanoma lesions could be clearly visualized by single photon emission computed tomography (SPECT)/CT using 99mTc-4 as an imaging probe. PMID:25290883
Substitution of the Lys linker with the β-Ala linker dramatically decreased the renal uptake of 99mTc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone peptides.

PubMed

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

2014-11-13

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

PubMed

Wartenberg, Dirk; Lapp, Katrin; Jacobsen, Ilse D; Dahse, Hans-Martin; Kniemeyer, Olaf; Heinekamp, Thorsten; Brakhage, Axel A

2011-11-01

Surface-associated and secreted proteins represent primarily exposed components of Aspergillus fumigatus during host infection. Several secreted proteins are known to be involved in defense mechanisms or immune evasion, thus, probably contributing to pathogenicity. Furthermore, several secreted antigens were identified as possible biomarkers for the verification of diseases caused by Aspergillus species. Nevertheless, there is only limited knowledge about the composition of the secretome and about molecular functions of particular proteins. To identify secreted proteins potentially essential for virulence, the core secretome of A. fumigatus grown in minimal medium was determined. Two-dimensional gel electrophoretic separation and subsequent MALDI-TOF-MS/MS analyses resulted in the identification of 64 different proteins. Additionally, secretome analyses of A. fumigatus utilizing elastin, collagen or keratin as main carbon and nitrogen source were performed. Thereby, the alkaline serine protease Alp1 was identified as the most abundant protein and hence presumably represents an important protease during host infection. Interestingly, the Asp-hemolysin (Asp-HS), which belongs to the protein family of aegerolysins and which was often suggested to be involved in fungal virulence, was present in the secretome under all growth conditions tested. In addition, a second, non-secreted protein with an aegerolysin domain annotated as Asp-hemolysin-like (HS-like) protein can be found to be encoded in the genome of A. fumigatus. Generation and analysis of Asp-HS and HS-like deletion strains revealed no differences in phenotype compared to the corresponding wild-type strain. Furthermore, hemolysis and cytotoxicity was not altered in both single-deletion and double-deletion mutants lacking both aegerolysin genes. All mutant strains showed no attenuation in virulence in a mouse infection model for invasive pulmonary aspergillosis. Overall, this study provides a comprehensive
ASPS performance with large payloads onboard the Shuttle Orbiter. [Annular Suspension and Pointing System

NASA Technical Reports Server (NTRS)

Keckler, C. R.

1980-01-01

A high fidelity digital computer simulation was used to establish the viability of the Annular Suspension and Pointing System (ASPS) for satisfying the pointing and stability requirements of facility class payloads, such as the Solar Optical Telescope, when subjected to the Orbiter disturbance environment. The ASPS and its payload were subjected to disturbances resulting from crew motions in the Orbiter aft flight deck and VRCS thruster firings. Worst case pointing errors of 0.005 arc seconds were experienced under the disturbance environment simulated; this is well within the 0.08 arc seconds requirement specified by the payload.
30 CFR 250.1921 - What qualifications must the ASP meet?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 2 2014-07-01 2014-07-01 false What qualifications must the ASP meet? 250.1921 Section 250.1921 Mineral Resources BUREAU OF SAFETY AND ENVIRONMENTAL ENFORCEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Safety and Environmental Management Systems (SEMS) § 250.1921...
30 CFR 250.1921 - What qualifications must the ASP meet?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 2 2013-07-01 2013-07-01 false What qualifications must the ASP meet? 250.1921 Section 250.1921 Mineral Resources BUREAU OF SAFETY AND ENVIRONMENTAL ENFORCEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Safety and Environmental Management Systems (SEMS) § 250.1921...
Evidence of major genes affecting stress response in rainbow trout using Bayesian methods of complex segregation analysis

USDA-ARS?s Scientific Manuscript database

As a first step towards the genetic mapping of quantitative trait loci (QTL) affecting stress response variation in rainbow trout, we performed complex segregation analyses (CSA) fitting mixed inheritance models of plasma cortisol using Bayesian methods in large full-sib families of rainbow trout. ...
Enabling the development of Community Extensions to GI-cat - the SIB-ESS-C case study

NASA Astrophysics Data System (ADS)

Bigagli, L.; Meier, N.; Boldrini, E.; Gerlach, R.

2009-04-01

GI-cat is a Java software package that implements discovery and access services for disparate geospatial resources. An instance of GI-cat provides a single point of service for querying and accessing remote, as well as local, heterogeneous sources of geospatial information, either through standard interfaces, or taking advantage of GI-cat advanced features, such as incremental responses, query feedback, etc. GI-cat supports a number of de-iure and de-facto standards, but can also be extended to additional community catalog/inventory services, by defining appropriate mediation components. The GI-cat and the SIB-ESS-C development teams collaborated in the development of a mediator to the Siberian Earth Science System Cluster (SIB-ESS-C), a web-based infrastructure to support the communities of environmental and Earth System research in Siberia. This activity resulted in the identification of appropriate technologies and internal mechanisms supporting the development of GI-cat extensions, that are the object of this work. GI-cat is actually built up of a modular framework of SOA components, that can be variously arranged to fit the needs of a community of users. For example, a particular GI-cat instance may be configured to provide discovery functionalities onto an OGC WMS; or to adapt a THREDDS catalog to the standard OGC CSW interface; or to merge a number of CDI repositories into a single, more efficient catalog. The flexibility of GI-cat framework is achieved thanks to its design, that follows the Tree of Responsibility (ToR) pattern and the Uniform Pipe and Filter architectural style. This approach allows the building of software blocks that can be flexibly reused and composed in multiple ways. In fact, the components that make up any GI-cat configuration all implement two common interfaces (i.e. IChainNode and ICatalogService), that support chaining one component to another . Hence, it would suffice to implement those interfaces (plus an appropriate factory
The COPD-SIB: a newly developed disease-specific item bank to measure health-related quality of life in patients with chronic obstructive pulmonary disease.

PubMed

Paap, Muirne C S; Lenferink, Lonneke I M; Herzog, Nadine; Kroeze, Karel A; van der Palen, Job

2016-06-27

Health-related quality of life (HRQoL) is widely used as an outcome measure in the evaluation of treatment interventions in patients with chronic obstructive pulmonary disease (COPD). In order to address challenges associated with existing fixed-length measures (e.g., too long to be used routinely, too short to ensure both content validity and reliability), a COPD-specific item bank (COPD-SIB) was developed. Items were selected based on literature review and interviews with Dutch COPD patients, with a strong focus on both content validity and item comprehension. The psychometric quality of the item bank was evaluated using Mokken Scale Analysis and parametric Item Response Theory, using data of 666 COPD patients. The final item bank contains 46 items that form a strong scale, tapping into eight important themes that were identified based on literature review and patient interviews: Coping with disease/symptoms, adaptability; Autonomy; Anxiety about the course/end-state of the disease, hopelessness; Positive psychological functioning; Situations triggering or enhancing breathing problems; Symptoms; Activity; Impact. The 46-item COPD-SIB has good psychometric properties and content validity. Items are available in Dutch and English. The COPD-SIB can be used as a stand-alone instrument, or to inform computerised adaptive testing.
Elucidating the role of many-body forces in liquid water. I. Simulations of water clusters on the VRT(ASP-W) potential surfaces.

PubMed

Goldman, Nir; Saykally, R J

2004-03-08

We test two new potentials for water, fit to vibration-rotation tunneling (VRT) data by employing diffusion quantum Monte Carlo simulations to calculate the vibrational ground-state properties of water clusters. These potentials, VRT(ASP-W)II and VRT(ASP-W)III, are fits of the highly detailed ASP-W (anisotropic site potential with Woermer dispersion) ab initio potential to (D(2)O)(2) microwave and far-infrared data, and along with the SAPT5s (five-site symmetry adapted perturbation theory) potentials, are the most accurate water dimer potential surfaces in the literature. The results from VRT(ASP-W)II and III are compared to those from the original ASP-W potential, the SAPT5s family of potentials, and several bulk water potentials. Only VRT(ASP-W)III and the spectroscopically "tuned" SAPT5st (with N-body induction included) accurately reproduce the vibrational ground-state structures of water clusters up to the hexamer. Finally, the importance of many-body induction and three-body dispersion are examined, and it is shown that the latter can have significant effects on water cluster properties despite its small magnitude.
Elucidating the role of many-body forces in liquid water. I. Simulations of water clusters on the VRT(ASP-W) potential surfaces

NASA Astrophysics Data System (ADS)

Goldman, Nir; Saykally, R. J.

2004-03-01

We test two new potentials for water, fit to vibration-rotation tunneling (VRT) data by employing diffusion quantum Monte Carlo simulations to calculate the vibrational ground-state properties of water clusters. These potentials, VRT(ASP-W)II and VRT(ASP-W)III, are fits of the highly detailed ASP-W (anisotropic site potential with Woermer dispersion) ab initio potential to (D2O)2 microwave and far-infrared data, and along with the SAPT5s (five-site symmetry adapted perturbation theory) potentials, are the most accurate water dimer potential surfaces in the literature. The results from VRT(ASP-W)II and III are compared to those from the original ASP-W potential, the SAPT5s family of potentials, and several bulk water potentials. Only VRT(ASP-W)III and the spectroscopically "tuned" SAPT5st (with N-body induction included) accurately reproduce the vibrational ground-state structures of water clusters up to the hexamer. Finally, the importance of many-body induction and three-body dispersion are examined, and it is shown that the latter can have significant effects on water cluster properties despite its small magnitude.
Crystallization and preliminary X-ray analysis of Na-ASP-1, a multi-domain pathogenesis-related-1 protein from the human hookworm parasite Necator americanus

PubMed Central

Asojo, Oluwatoyin A.; Loukas, Alex; Inan, Mehmet; Barent, Rick; Huang, Jicai; Plantz, Brad; Swanson, Amber; Gouthro, Mark; Meagher, Michael M.; Hotez, Peter J.

2005-01-01

Human hookworm infection is a major cause of anemia and malnutrition in the developing world. In an effort to control hookworm infection, the Human Hookworm Vaccine Initiative has identified candidate vaccine antigens from the infective larval stage (L3) of the parasite, including a family of pathogenesis-related-1 (PR-1) proteins known as the ancylostoma-secreted proteins (ASPs). The functions of the ASPs are unknown. In addition, it is unclear why some ASPs have one while others have multiple PR-1 domains. There are no known structures of a multi-domain ASP and in an effort to remedy this situation, recombinant Na-ASP-1 has been expressed, purified and crystallized. Na-ASP-1 is a 406-amino-acid multi-domain ASP from the prevalent human hookworm parasite Necator americanus. Useful X-ray data to 2.2 Å have been collected from a crystal that belongs to the monoclinic space group P21 with unit-cell parameters a = 67.7, b = 74.27, c = 84.60 Å, β = 112.12°. An initial molecular-replacement solution has been obtained with one monomer in the asymmetric unit. PMID:16511050
Heterozygous p.Asp50Asn mutation in the GJB2 gene in two Cameroonian patients with keratitis-ichthyosis-deafness (KID) syndrome

PubMed Central

2013-01-01

Background Keratitis-Ichthyosis-Deafness (KID) syndrome (OMIM 148210) is a congenital ectodermal defect that consists of an atypical ichthyosiform erythroderma associated with congenital sensorineural deafness. KID appears to be genetically heterogeneous and most cases are caused by GJB2 mutations. Mutations in African patients have been rarely described. Case presentation We report on two unrelated Cameroonian individuals affected with sporadic KID, presenting with the classic phenotypic triad. The two patients were heterozygous for the most frequent p.Asp50Asn mutation. This first report in patients from sub-Saharan African origin supports the hypothesis that the occurrence of KID due to p.Asp50Asn mutation in GJB2 seems not to be population specific. Conclusions Our finding has implication in medical genetic practice, specifically in the molecular diagnosis of KID in Africans. These cases also reveal and emphasize the urgent need to develop appropriate policies to care for patients with rare/orphan diseases in Sub-Saharan Africa, as many of these cases become more and more recognizable. PMID:23924173

[Peptide Ala-Glu-Asp-Gly and interferon gamma: their role in immune response during aging].

PubMed

Lin'kova, N S; Kuznik, B I; Khavinson, V Kh

2012-01-01

The decrease of lymphocyte interferon gamma expression during aging is one of the main mechanisms leading to the immunodeficiency state in the elderly. Cell penetrating geroprotective peptide Ala-Glu-Asp-Gly has the capability to activate the proliferation of lymphocytes in thymus during its aging. The nucleotide sequence which is complementary contacted with peptide Ala-Glu-Asp-Gly was found in promoter region of interferon gamma gene. Thus, the immune protection of this peptide can be explained by its activation of the interferon gamma production in T-cells.
Study of Water-Oil Emulsion Breaking by Stabilized Solution Consisting of Anionic Surface Acting Agent - Soda Ash - Polymer (ASP)

NASA Astrophysics Data System (ADS)

Kulichkov, S. V.; Avtomonov, E. G.; Andreeva, L. V.; Solomennik, S. F.; Nikitina, A. V.

2018-01-01

The paper provides a laboratory research of breaking natural water-oil emulsions: - by non-stabilized ASP; by stabilized ASP; by mixture of stabilized and non-stabilized ASP in different proportions and production of refinery water of the required quality with the use of IronGuard 2495 as flocculant. Oil-in-water emulsion is stable. Classic methods are not suitable for residual water treatment: sediment gravity flow; filtration; centrifuge test. Microemulsion formed after ASP application has low boundary tension and high pH. It contributes to transfer of oil phase into a water one, forming oil-in-water emulsion. Alkaline condition has adverse effect on demulsifying ability of agents, flocculation and boundary tension. For breaking of water-oil emulsion at EBU before the interchanger water or water-oil emulsion from the wells that were not APS-treated in ratio of 1:9 shall be delivered. Residual water after EBU must be prepared in water tanks by dilution in great volume.
Different HIV-1 env frames: gp120 and ASP (antisense protein) biosynthesis, and theirs co-variation tropic amino acid signatures in X4- and R5-viruses.

PubMed

Dimonte, Salvatore

2017-01-01

Antisense protein (ASP) is the new actor of viral life of Human Immunodeficiency Virus type 1 (HIV-1) although proposed above 20 years ago. The asp ORF is into complementary strand of the gp120/gp41 junction of env gene. The ASP biological role remains little known. Knowing the Env markers of viral tropism, a dataset of sequences (660 strains) was used to analyze the hypothetical ASP involvement in CCR5 (R5) and/or CXCR4 (X4) co-receptor interaction. Preliminarily, prevalence of ASP and gp120 V3 mutations was performed; following association among mutations were elaborate. The classical V3 tropic-signatures were confirmed, and 36 R5- and 22 X4-tropic ASP mutations were found. Moreover, by analyzing the ASP sequences, 36 out of 179 amino acid positions significantly associated with different co-receptor usage were found. Several statistically significant associations between gp120 V3 and ASP mutations were observed. The dendrogram showed the existence of a cluster associated with R5-usage and a large cluster associated with X4-usage. These results show that gp120 V3 and specific amino acid changes in ASP are associated together with CXCR4 and/or CCR5-usage. These findings implement previous observations on unclear ASP functions. J. Med. Virol. 89:112-122, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Readability of ASPS and ASAPS educational web sites: an analysis of consumer impact.

PubMed

Aliu, Oluseyi; Chung, Kevin C

2010-04-01

Patients use the Internet to educate themselves about health-related topics, and learning about plastic surgery is a common activity for enthusiastic consumers in the United States. How to educate consumers regarding plastic surgical procedures is a continued concern for plastic surgeons when faced with the growing portion of the American population having relatively low health care literacy. The usefulness of health-related education materials on the Internet depends largely on their comprehensibility and understandability for all who visit the Web sites. The authors studied the readability of patient education materials related to common plastic surgery procedures from the American Society of Plastic Surgeons (ASPS) and the American Society for Aesthetic Plastic Surgery (ASAPS) Web sites and compared them with materials on similar topics from 10 popular health information-providing sites. The authors found that all analyzed documents on the ASPS and ASAPS Web sites targeted to the consumers were rated to be more difficult than the recommended reading grade level for most American adults, and these documents were consistently among the most difficult to read when compared with the other health information Web sites. The Internet is an increasingly popular avenue for patients to educate themselves about plastic surgery procedures. Patient education material provided on ASPS and ASAPS Web sites should be written at recommended reading grade levels to ensure that it is readable and comprehensible to the targeted audience.
Conserved Asp-137 is important for both structure and regulatory functions of cardiac α-tropomyosin (α-TM) in a novel transgenic mouse model expressing α-TM-D137L.

PubMed

Yar, Sumeyye; Chowdhury, Shamim A K; Davis, Robert T; Kobayashi, Minae; Monasky, Michelle M; Rajan, Sudarsan; Wolska, Beata M; Gaponenko, Vadim; Kobayashi, Tomoyoshi; Wieczorek, David F; Solaro, R John

2013-06-07

α-Tropomyosin (α-TM) has a conserved, charged Asp-137 residue located in the hydrophobic core of its coiled-coil structure, which is unusual in that the residue is found at a position typically occupied by a hydrophobic residue. Asp-137 is thought to destabilize the coiled-coil and so impart structural flexibility to the molecule, which is believed to be crucial for its function in the heart. A previous in vitro study indicated that the conversion of Asp-137 to a more typical canonical Leu alters flexibility of TM and affects its in vitro regulatory functions. However, the physiological importance of the residue Asp-137 and altered TM flexibility is unknown. In this study, we further analyzed structural properties of the α-TM-D137L variant and addressed the physiological importance of TM flexibility in cardiac function in studies with a novel transgenic mouse model expressing α-TM-D137L in the heart. Our NMR spectroscopy data indicated that the presence of D137L introduced long range rearrangements in TM structure. Differential scanning calorimetry measurements demonstrated that α-TM-D137L has higher thermal stability compared with α-TM, which correlated with decreased flexibility. Hearts of transgenic mice expressing α-TM-D137L showed systolic and diastolic dysfunction with decreased myofilament Ca(2+) sensitivity and cardiomyocyte contractility without changes in intracellular Ca(2+) transients or post-translational modifications of major myofilament proteins. We conclude that conversion of the highly conserved Asp-137 to Leu results in loss of flexibility of TM that is important for its regulatory functions in mouse hearts. Thus, our results provide insight into the link between flexibility of TM and its function in ejecting hearts.
Conserved Asp-137 Is Important for both Structure and Regulatory Functions of Cardiac α-Tropomyosin (α-TM) in a Novel Transgenic Mouse Model Expressing α-TM-D137L*

PubMed Central

Yar, Sumeyye; Chowdhury, Shamim A. K.; Davis, Robert T.; Kobayashi, Minae; Monasky, Michelle M.; Rajan, Sudarsan; Wolska, Beata M.; Gaponenko, Vadim; Kobayashi, Tomoyoshi; Wieczorek, David F.; Solaro, R. John

2013-01-01

α-Tropomyosin (α-TM) has a conserved, charged Asp-137 residue located in the hydrophobic core of its coiled-coil structure, which is unusual in that the residue is found at a position typically occupied by a hydrophobic residue. Asp-137 is thought to destabilize the coiled-coil and so impart structural flexibility to the molecule, which is believed to be crucial for its function in the heart. A previous in vitro study indicated that the conversion of Asp-137 to a more typical canonical Leu alters flexibility of TM and affects its in vitro regulatory functions. However, the physiological importance of the residue Asp-137 and altered TM flexibility is unknown. In this study, we further analyzed structural properties of the α-TM-D137L variant and addressed the physiological importance of TM flexibility in cardiac function in studies with a novel transgenic mouse model expressing α-TM-D137L in the heart. Our NMR spectroscopy data indicated that the presence of D137L introduced long range rearrangements in TM structure. Differential scanning calorimetry measurements demonstrated that α-TM-D137L has higher thermal stability compared with α-TM, which correlated with decreased flexibility. Hearts of transgenic mice expressing α-TM-D137L showed systolic and diastolic dysfunction with decreased myofilament Ca2+ sensitivity and cardiomyocyte contractility without changes in intracellular Ca2+ transients or post-translational modifications of major myofilament proteins. We conclude that conversion of the highly conserved Asp-137 to Leu results in loss of flexibility of TM that is important for its regulatory functions in mouse hearts. Thus, our results provide insight into the link between flexibility of TM and its function in ejecting hearts. PMID:23609439
Clinical experiences utilizing wireless remote control and an ASP model backup archive for a disaster recovery event

NASA Astrophysics Data System (ADS)

Liu, Brent J.; Documet, Luis; Documet, Jorge; Huang, H. K.; Muldoon, Jean

2004-04-01

An Application Service Provider (ASP) archive model for disaster recovery for Saint John"s Health Center (SJHC) clinical PACS data has been implemented using a Fault-Tolerant Archive Server at the Image Processing and Informatics Laboratory, Marina del Rey, CA (IPIL) since mid-2002. The purpose of this paper is to provide clinical experiences with the implementation of an ASP model backup archive in conjunction with handheld wireless technologies for a particular disaster recovery scenario, an earthquake, in which the local PACS archive and the hospital are destroyed and the patients are moved from one hospital to another. The three sites involved are: (1) SJHC, the simulated disaster site; (2) IPIL, the ASP backup archive site; and (3) University of California, Los Angeles Medical Center (UCLA), the relocated patient site. An ASP backup archive has been established at IPIL to receive clinical PACS images daily using a T1 line from SJHC for backup and disaster recovery storage. Procedures were established to test the network connectivity and data integrity on a regular basis. In a given disaster scenario where the local PACS archive has been destroyed and the patients need to be moved to a second hospital, a wireless handheld device such as a Personal Digital Assistant (PDA) can be utilized to route images to the second hospital site with a PACS and reviewed by radiologists. To simulate this disaster scenario, a wireless network was implemented within the clinical environment in all three sites: SJHC, IPIL, and UCLA. Upon executing the disaster scenario, the SJHC PACS archive server simulates a downtime disaster event. Using the PDA, the radiologist at UCLA can query the ASP backup archive server at IPIL for PACS images and route them directly to UCLA. Implementation experiences integrating this solution within the three clinical environments as well as the wireless performance are discussed. A clinical downtime disaster scenario was implemented and successfully
Application of the ASP3D Computer Program to Unsteady Aerodynamic and Aeroelastic Analyses

NASA Technical Reports Server (NTRS)

Batina, John T.

2006-01-01

A new computer program has been developed called ASP3D (Advanced Small Perturbation - 3D), which solves the small perturbation potential flow equation in an advanced form including mass-consistent surface and trailing wake boundary conditions, and entropy, vorticity, and viscous effects. The purpose of the program is for unsteady aerodynamic and aeroelastic analyses, especially in the nonlinear transonic flight regime. The program exploits the simplicity of stationary Cartesian meshes with the movement or deformation of the configuration under consideration incorporated into the solution algorithm through a planar surface boundary condition. The paper presents unsteady aerodynamic and aeroelastic applications of ASP3D to assess the time dependent capability and demonstrate various features of the code.
Structural and Functional Importance of Transmembrane Domain 3 (TM3) in the Aspartate:Alanine Antiporter AspT: Topology and Function of the Residues of TM3 and Oligomerization of AspT▿

PubMed Central

Nanatani, Kei; Maloney, Peter C.; Abe, Keietsu

2009-01-01

AspT, the aspartate:alanine antiporter of Tetragenococcus halophilus, a membrane protein of 543 amino acids with 10 putative transmembrane (TM) helices, is the prototype of the aspartate:alanine exchanger (AAE) family of transporters. Because TM3 (isoleucine 64 to methionine 85) has many amino acid residues that are conserved among members of the AAE family and because TM3 contains two charged residues and four polar residues, it is thought to be located near (or to form part of) the substrate translocation pathway that includes the binding site for the substrates. To elucidate the role of TM3 in the transport process, we carried out cysteine-scanning mutagenesis. The substitutions of tyrosine 75 and serine 84 had the strongest inhibitory effects on transport (initial rates of l-aspartate transport were below 15% of the rate for cysteine-less AspT). Considerable but less-marked effects were observed upon the replacement of methionine 70, phenylalanine 71, glycine 74, arginine 76, serine 83, and methionine 85 (initial rates between 15% and 30% of the rate for cysteine-less AspT). Introduced cysteine residues at the cytoplasmic half of TM3 could be labeled with Oregon green maleimide (OGM), whereas cysteines close to the periplasmic half (residues 64 to 75) were not labeled. These results suggest that TM3 has a hydrophobic core on the periplasmic half and that hydrophilic residues on the cytoplasmic half of TM3 participate in the formation of an aqueous cavity in membranes. Furthermore, the presence of l-aspartate protected the cysteine introduced at glycine 62 against a reaction with OGM. In contrast, l-aspartate stimulated the reactivity of the cysteine introduced at proline 79 with OGM. These results demonstrate that TM3 undergoes l-aspartate-induced conformational alterations. In addition, nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses and a glutaraldehyde cross-linking assay suggest that functional AspT forms homo-oligomers as a
Structural and functional importance of transmembrane domain 3 (TM3) in the aspartate:alanine antiporter AspT: topology and function of the residues of TM3 and oligomerization of AspT.

PubMed

Nanatani, Kei; Maloney, Peter C; Abe, Keietsu

2009-04-01

AspT, the aspartate:alanine antiporter of Tetragenococcus halophilus, a membrane protein of 543 amino acids with 10 putative transmembrane (TM) helices, is the prototype of the aspartate:alanine exchanger (AAE) family of transporters. Because TM3 (isoleucine 64 to methionine 85) has many amino acid residues that are conserved among members of the AAE family and because TM3 contains two charged residues and four polar residues, it is thought to be located near (or to form part of) the substrate translocation pathway that includes the binding site for the substrates. To elucidate the role of TM3 in the transport process, we carried out cysteine-scanning mutagenesis. The substitutions of tyrosine 75 and serine 84 had the strongest inhibitory effects on transport (initial rates of l-aspartate transport were below 15% of the rate for cysteine-less AspT). Considerable but less-marked effects were observed upon the replacement of methionine 70, phenylalanine 71, glycine 74, arginine 76, serine 83, and methionine 85 (initial rates between 15% and 30% of the rate for cysteine-less AspT). Introduced cysteine residues at the cytoplasmic half of TM3 could be labeled with Oregon green maleimide (OGM), whereas cysteines close to the periplasmic half (residues 64 to 75) were not labeled. These results suggest that TM3 has a hydrophobic core on the periplasmic half and that hydrophilic residues on the cytoplasmic half of TM3 participate in the formation of an aqueous cavity in membranes. Furthermore, the presence of l-aspartate protected the cysteine introduced at glycine 62 against a reaction with OGM. In contrast, l-aspartate stimulated the reactivity of the cysteine introduced at proline 79 with OGM. These results demonstrate that TM3 undergoes l-aspartate-induced conformational alterations. In addition, nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses and a glutaraldehyde cross-linking assay suggest that functional AspT forms homo-oligomers as a
[Regulation of [12Asp]K-ras4B on transcriptional activity of estrogen receptor in endometrial carcinoma HEC-1A cell lines].

PubMed

Gui, Li-ming; Wei, Li-hui; Xu, Ming-xu; Wang, Jian-liu; Zhong, Ying-cheng; Li, Xiao-ping; Tu, Zheng; Sun, Peng-ming; Ma, Da-long

2004-01-01

To investigate the effect of mutant-type [(12)Asp]K-ras4B gene on the expression of estrogen receptor (ER) alpha and beta and their transcriptional activity as a transcription factor in endometrial carcinoma HEC-1A cell line. (1) Effect of [(12)Asp]K-ras4B on the expression of ER alpha and beta were determined using Western blot assay. (2) Eukaryotic expression plasmid pGL3-luciferase-ERE containing luciferase report gene and estrogen receptor element (ERE) was constructed, and co-transfected into NIH3T3 and HEC-1A cell lines with pEGFP-N1 to examine the effect of [(12)Asp]K-ras4B on ER transcription that is regulated by estradiol. In addition, they were transfected into pSV5-HER0 (containing full length wide type ERalpha cDNA) and pCMV-rafS621A (inhibiting raf kinase) plasmids to test the effect of [(12)Asp]K-ras4B/raf signal pathway on transcriptional activity of ER proteins. (1) Protein level of ERs expressed in pcDI transfected control cells was low while it was increased for 3.6-fold (97 +/- 25, 349 +/- 67, P < 0.01) and 1.9-fold (128 +/- 37, 349 +/- 30, P < 0.05) in ERalpha and ERbeta, respectively, in pcDI-[(12)Asp]K-ras4B NIH3T3 cells after transfection. (2) In pcDI-[(12)Asp]K-ras4B NIH3T3 cells, the ratios for ERalpha and and ERbeta levels before transfection of rafS621A plasmids to that after the transfection, were 2.4:1 (724 +/- 45, 310 +/- 46, P < 0.05) and 1.8:1 (493 +/- 20, 284 +/- 20, P < 0.01), respectively; In HEC-1A cells, these ratios were 2.1:1 (566 +/- 22, 279 +/- 30, P < 0.01) and 2.4:1 (405 +/- 33, 165 +/- 15, P < 0.01), respectively. (3) In low serum (2%) culture condition, estradiol (E(2)) stimulated luciferase activity with an increase of 13-fold (130 +/- 42, 1681 +/- 242, P < 0.01) in pcDI-[(12)Asp] K-ras4B NIH3T3 cells, 19-fold (141 +/- 39, 2644 +/- 331, P < 0.001) in HEC-1A cells, respectively, when compared with those in the absence of E(2). (4) In pSV5-HER0 transfected pcDI-[(12)Asp] K-ras4B NIH3T3 cells and HEC-1A cells, compared to
The peculiar architectural framework of tRNASec is fully recognized by yeast AspRS.

PubMed Central

Rudinger-Thirion, J; Giegé, R

1999-01-01

The wild-type transcript of Escherichia coli tRNASec, characterized by a peculiar core architecture and a large variable region, was shown to be aspartylatable by yeast AspRS. Similar activities were found for tRNASec mutants with methionine, leucine, and tryptophan anticodons. The charging efficiency of these molecules was found comparable to that of a minihelix derived from tRNAAsp and is accounted for by the presence of the discriminator residue G73, which is a major aspartate identity determinant. Introducing the aspartate identity elements from the anticodon loop (G34, U35, C36, C38) into tRNASec transforms this molecule into an aspartate acceptor with kinetic properties identical to tRNAAsp. Expression of the aspartate identity set in tRNASec is independent of the size of its variable region. The functional study was completed by footprinting experiments with four different nucleases as structural probes. Protection patterns by AspRS of transplanted tRNASec and tRNAAsp were found similar. They are modified, particularly in the anticodon loop, upon changing the aspartate anticodon into that of methionine. Altogether, it appears that recognition of a tRNA by AspRS is more governed by the presence of the aspartate identity set than by the structural framework that carries this set. PMID:10199566
Gearing Up for the Next 125 Years: Where Should Astronomy EPO and the ASP be Heading?

NASA Astrophysics Data System (ADS)

Manning, J.

2014-07-01

In 2014, the Astronomical Society of the Pacific will celebrate its 125th anniversary, commemorating a century and a quarter of advancing astronomy, education, and science literacy during which human perception and understanding of the Universe has undergone revolutionary change. What lies ahead for astronomy, astronomy and science education and outreach, and how can the ASP respond? Participants joined a discussion of the issues (current and future) and offered thoughts on how the ASP (and other organizations) can help to craft both the dialog and the solutions to the challenges we see ahead.
An analytical SMASH procedure (ASP) for sensitivity-encoded MRI.

PubMed

Lee, R F; Westgate, C R; Weiss, R G; Bottomley, P A

2000-05-01

The simultaneous acquisition of spatial harmonics (SMASH) method of imaging with detector arrays can reduce the number of phase-encoding steps, and MRI scan time several-fold. The original approach utilized numerical gradient-descent fitting with the coil sensitivity profiles to create a set of composite spatial harmonics to replace the phase-encoding steps. Here, an analytical approach for generating the harmonics is presented. A transform is derived to project the harmonics onto a set of sensitivity profiles. A sequence of Fourier, Hilbert, and inverse Fourier transform is then applied to analytically eliminate spatially dependent phase errors from the different coils while fully preserving the spatial-encoding. By combining the transform and phase correction, the original numerical image reconstruction method can be replaced by an analytical SMASH procedure (ASP). The approach also allows simulation of SMASH imaging, revealing a criterion for the ratio of the detector sensitivity profile width to the detector spacing that produces optimal harmonic generation. When detector geometry is suboptimal, a group of quasi-harmonics arises, which can be corrected and restored to pure harmonics. The simulation also reveals high-order harmonic modulation effects, and a demodulation procedure is presented that enables application of ASP to a large numbers of detectors. The method is demonstrated on a phantom and humans using a standard 4-channel phased-array MRI system. Copyright 2000 Wiley-Liss, Inc.
PREST-plus identifies pedigree errors and cryptic relatedness in the GAW18 sample using genome-wide SNP data.

PubMed

Sun, Lei; Dimitromanolakis, Apostolos

2014-01-01

Pedigree errors and cryptic relatedness often appear in families or population samples collected for genetic studies. If not identified, these issues can lead to either increased false negatives or false positives in both linkage and association analyses. To identify pedigree errors and cryptic relatedness among individuals from the 20 San Antonio Family Studies (SAFS) families and cryptic relatedness among the 157 putatively unrelated individuals, we apply PREST-plus to the genome-wide single-nucleotide polymorphism (SNP) data and analyze estimated identity-by-descent (IBD) distributions for all pairs of genotyped individuals. Based on the given pedigrees alone, PREST-plus identifies the following putative pairs: 1091 full-sib, 162 half-sib, 360 grandparent-grandchild, 2269 avuncular, 2717 first cousin, 402 half-avuncular, 559 half-first cousin, 2 half-sib+first cousin, 957 parent-offspring and 440,546 unrelated. Using the genotype data, PREST-plus detects 7 mis-specified relative pairs, with their IBD estimates clearly deviating from the null expectations, and it identifies 4 cryptic related pairs involving 7 individuals from 6 families.
An All-Sky Portable (ASP) Optical Catalogue

NASA Astrophysics Data System (ADS)

Flesch, Eric Wim

2017-06-01

This optical catalogue combines the all-sky USNO-B1.0/A1.0 and most-sky APM catalogues, plus overlays of SDSS optical data, into a single all-sky map presented in a sparse binary format that is easily downloaded at 9 Gb zipped. Total count is 1 163 237 190 sources and each has J2000 astrometry, red and blue magnitudes with PSFs and variability indicator, and flags for proper motion, epoch, and source survey and catalogue for each of the photometry and astrometry. The catalogue is available on http://quasars.org/asp.html, and additional data for this paper is available at http://dx.doi.org/10.4225/50/5807fbc12595f.
Genetic variation in carbon isotope discrimination and its relationship to growth under field conditions in full-sib families of Picea mariana

Treesearch

Lawrence B. Flanagan; Kurt H. Johnsen

1995-01-01

Measurements of the stable carbon isotope composition of leaf tissue were made on Picea mariana (Mill.) B.S.P. trees from four full-sib families grown on three different field sites at the Petawawa National Forestry Institute, Ontario, Canada. The four families chosen exhibited genetic variation for growth characteristics. Genetic...
Characterization and Evolutionary Implications of the Triad Asp-Xxx-Glu in Group II Phosphopantetheinyl Transferases

PubMed Central

Wang, Yue-Yue; Li, Yu-Dong; Liu, Jian-Bo; Ran, Xin-Xin; Guo, Yuan-Yang; Ren, Ni-Ni; Chen, Xin; Jiang, Hui; Li, Yong-Quan

2014-01-01

Phosphopantetheinyl transferases (PPTases), which play an essential role in both primary and secondary metabolism, are magnesium binding enzymes. In this study, we characterized the magnesium binding residues of all known group II PPTases by biochemical and evolutionary analysis. Our results suggested that group II PPTases could be classified into two subgroups, two-magnesium-binding-residue-PPTases containing the triad Asp-Xxx-Glu and three-magnesium-binding-residue-PPTases containing the triad Asp-Glu-Glu. Mutations of two three-magnesium-binding-residue-PPTases and one two-magnesium-binding-residue-PPTase indicate that the first and the third residues in the triads are essential to activities; the second residues in the triads are non-essential. Although variations of the second residues in the triad Asp-Xxx-Glu exist throughout the whole phylogenetic tree, the second residues are conserved in animals, plants, algae, and most prokaryotes, respectively. Evolutionary analysis suggests that: the animal group II PPTases may originate from one common ancestor; the plant two-magnesium-binding-residue-PPTases may originate from one common ancestor; the plant three-magnesium-binding-residue-PPTases may derive from horizontal gene transfer from prokaryotes. PMID:25036863
Characterization and evolutionary implications of the triad Asp-Xxx-Glu in group II phosphopantetheinyl transferases.

PubMed

Wang, Yue-Yue; Li, Yu-Dong; Liu, Jian-Bo; Ran, Xin-Xin; Guo, Yuan-Yang; Ren, Ni-Ni; Chen, Xin; Jiang, Hui; Li, Yong-Quan

2014-01-01

Phosphopantetheinyl transferases (PPTases), which play an essential role in both primary and secondary metabolism, are magnesium binding enzymes. In this study, we characterized the magnesium binding residues of all known group II PPTases by biochemical and evolutionary analysis. Our results suggested that group II PPTases could be classified into two subgroups, two-magnesium-binding-residue-PPTases containing the triad Asp-Xxx-Glu and three-magnesium-binding-residue-PPTases containing the triad Asp-Glu-Glu. Mutations of two three-magnesium-binding-residue-PPTases and one two-magnesium-binding-residue-PPTase indicate that the first and the third residues in the triads are essential to activities; the second residues in the triads are non-essential. Although variations of the second residues in the triad Asp-Xxx-Glu exist throughout the whole phylogenetic tree, the second residues are conserved in animals, plants, algae, and most prokaryotes, respectively. Evolutionary analysis suggests that: the animal group II PPTases may originate from one common ancestor; the plant two-magnesium-binding-residue-PPTases may originate from one common ancestor; the plant three-magnesium-binding-residue-PPTases may derive from horizontal gene transfer from prokaryotes.
eNOS gene Glu298Asp and 4b/a polymorphisms are associated with renal function parameters in Mexican patients with Fabry disease.

PubMed

Marin-Medina, A; Brambila-Tapia, A J L; Picos-Cárdenas, V J; Gallegos-Arreola, M P; Figuera, L E

2016-10-24

Fabry disease (FD) is an inherited X-linked lysosomal disease that causes renal failure in a high percentage of affected individuals. The eNOS gene encodes for endothelial nitric oxide synthase, which plays an important role in glomerular hemodynamics. This gene has two main polymorphisms (Glu298Asp and 4b/a) that have been studied in the context of many different diseases, including those involving cardiovascular and renal alterations. Considering the lack of information regarding eNOS variants and FD, we investigated whether there were associations between eNOS genetic variants and renal function parameters in Mexican patients with FD and renal impairment. In total, 15 FD patients with renal alterations were included in the present study, and associations between eNOS polymorphisms and renal function parameters (urea, creatinine, and GFR) were evaluated. The Asp298 and 4a alleles of the eNOS gene were found to be significantly associated with increased levels of urea and creatinine, and a decreased glomerular filtration rate in FD patients, and this association behaved in a co-dominant fashion. Our results coincide with previous reports showing an association between these polymorphisms and kidney disease, and along with other studies regarding their role in the nitric oxide pathway, suggest that these variants affect the severity of nephropathy in patients with FD.

The development of siblings of children with autism at 4 and 14 months: social engagement, communication, and cognition.

PubMed

Yirmiya, Nurit; Gamliel, Ifat; Pilowsky, Tammy; Feldman, Ruth; Baron-Cohen, Simon; Sigman, Marian

2006-05-01

To compare siblings of children with autism (SIBS-A) and siblings of children with typical development (SIBS-TD) at 4 and 14 months of age. At 4 months, mother-infant interactional synchrony during free play, infant gaze and affect during the still-face paradigm, and infant responsiveness to a name-calling paradigm were examined (n = 21 in each group). At 14 months, verbal and nonverbal communication skills were examined as well as cognition (30 SIBS-A and 31 SIBS-TD). Most SIBS-A were functioning as well as the SIBS-TD at 4 and 14 months of age. However, some differences in early social engagement and later communicative and cognitive skills emerged. Synchrony was weaker in the SIBS-A dyads, but only for infant-led interactions. Infant SIBS-A revealed more neutral affect during the still-face procedure and were less upset by it than was true for the SIBS-TD. A surprising result was that significantly more SIBS-A responded to their name being called by their mothers compared to SIBS-TD. At 14 months, SIBS-A made fewer nonverbal requesting gestures and achieved lower language scores on the Bayley Scale. Six SIBS-A revealed a language delay of 5 months and were responsible for some of the significant differences between SIBS-A and SIBS-TD. Furthermore, infant SIBS-A who showed more neutral affect to the still face and were less able to respond to their name being called by their mothers initiated fewer nonverbal joint attention and requesting behaviors at 14 months, respectively. Focused on the genetic liability for the broad phenotype of autism as well as the possible influence of having a sibling with autism.
Toluidine blue-O is a Nissl bright-field counterstain for lipophilic fluorescent tracers Di-ASP, DiI and DiO.

PubMed

Chelvanayagam, D K; Beazley, L D

1997-03-01

The stain toluidine blue-O (tol blue), applied to sections of neural tissue, is shown to be compatible with the vivid fluorescent lipophilic neural tracers 4-(4-dihexadecylaminostyryl)-N-methylpyridinium iodide (Di-ASP), 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO) and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI). As with other Nissl stains, toluidine blue-O fluoresces in the red end of the spectrum but such fluorescence quenches upon binding with tissue. Moreover, progressive staining occurs at concentrations low enough to minimise any background fluorescence attributable to non-specific residence of the stain. The bright yellow Di-ASP and vivid green DiO signals are spectrally removed from the red fluorescence of toluidine blue-O. With toluidine blue-O counterstaining, Di-ASP generally offers contrast superior to that with DiI, however, the latter is improved by viewing in a polarised green bright field. Visible Di-ASP emission, although broad, peaks at a more film-sensitive region of the spectrum than that for DiI, thus reducing the photographic exposure required.
The subtype-selective nicotinic acetylcholine receptor agonist SIB-1553A improves both attention and memory components of a spatial working memory task in chronic low dose 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkeys.

PubMed

Schneider, J S; Tinker, J P; Menzaghi, F; Lloyd, G K

2003-07-01

Monkeys that receive chronic low dose (CLD) 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration develop deficits in spatial delayed-response task performance. The present study examined the extent to which SIB-1553A [(+/-)-4-[[2-(1-methyl-2-pyrrolidinyl)ethyl]thio]phenol hydrochloride], a novel neuronal nicotinic acetylcholine receptor (nAChR) agonist with selectivity for beta4 subunit-containing nAChRs, could counteract this cognitive deficit produced by CLD MPTP exposure. Prior to MPTP treatment, monkeys displayed a delay-dependent decrement in performance on a variable delayed response task. CLD MPTP treatment caused a shift to a delay-independent pattern of responding on this task, such that short-delay trials were performed as poorly as long-delay trials. At lower doses (e.g., 0.025 mg/kg), SIB-1553A significantly improved performance on short-delay trials but only at 24 h after drug administration. At higher doses (e.g., 0.50 mg/kg), SIB-1553A significantly improved performance on both short- and long-delay trials at both 20 min and 24 h after drug administration. When tested 24 h after drug administration, monkeys performed long-delay trials with greater accuracy than they did under normal (pre-MPTP) conditions. These results suggest that at lower doses, SIB-1553A may be more effective in improving attentional deficits associated with CLD MPTP exposure, whereas at higher doses, SIB-1553A may effectively improve both attentional and memory performance.
Communicating with Facility Leadership; Metrics for Successful Antimicrobial Stewardship Programs (Asp) in Acute Care and Long-Term Care Facilities.

PubMed

Beganovic, Maya; LaPlante, Kerry L

2018-06-01

Up to 50% of hospital-administered and 70% of nursing home-administered antimicrobials are inappropriately prescribed. There is a great need to focus local, national and global efforts on appropriate antibiotic use. Formal programs dedicated to appropriate antibiotic use have been established in most US hospitals. These antimicrobial stewardship programs (ASP) exist to ensure that the correct drug, dose and duration of an antimicrobial is given, and only when there is a true bacterial infection (as opposed to bacterial colonization or a viral infection). These programs increase patient safety and reduce unintended consequences including Clostridium difficile infections, medication-related adverse effects, and antimicrobial resistance. Most of these programs are co-lead by an interdisciplinary team consisting of an infectious diseases (ID) pharmacist and an ID physician. However, consistent and meaningful metrics to study the impact of ASPs have not been elucidated. With the Joint Commission Standards for Acute Care facilities, and Centers for Medicare and Medicare (CMS) for long-term care facilities making antimicrobial stewardship (AMS) a condition of participation, both facilities will be scrambling to create appropriate quality care indicators to measure program success. One major theme across all healthcare settings is that ASPs must collaborate with facility leadership and key stakeholders at each institution in order to have an impactful benefit on patient quality of care, and safety. It is the purpose of this review to offer several economic, process, and patient-outcome measurements for ASP to optimally communicate with facility leadership. [Full article available at http://rimed.org/rimedicaljournal-2018-06.asp].
Stringency of the 2-His–1-Asp Active-Site Motif in Prolyl 4-Hydroxylase

PubMed Central

Gorres, Kelly L.; Pua, Khian Hong; Raines, Ronald T.

2009-01-01

The non-heme iron(II) dioxygenase family of enzymes contain a common 2-His–1-carboxylate iron-binding motif. These enzymes catalyze a wide variety of oxidative reactions, such as the hydroxylation of aliphatic C–H bonds. Prolyl 4-hydroxylase (P4H) is an α-ketoglutarate-dependent iron(II) dioxygenase that catalyzes the post-translational hydroxylation of proline residues in protocollagen strands, stabilizing the ensuing triple helix. Human P4H residues His412, Asp414, and His483 have been identified as an iron-coordinating 2-His–1-carboxylate motif. Enzymes that catalyze oxidative halogenation do so by a mechanism similar to that of P4H. These halogenases retain the active-site histidine residues, but the carboxylate ligand is replaced with a halide ion. We replaced Asp414 of P4H with alanine (to mimic the active site of a halogenase) and with glycine. These substitutions do not, however, convert P4H into a halogenase. Moreover, the hydroxylase activity of D414A P4H cannot be rescued with small molecules. In addition, rearranging the two His and one Asp residues in the active site eliminates hydroxylase activity. Our results demonstrate a high stringency for the iron-binding residues in the P4H active site. We conclude that P4H, which catalyzes an especially demanding chemical transformation, is recalcitrant to change. PMID:19890397
Functional and genetic characterization of gas exchange and intrinsic water use efficiency in a full-sib family of Pinus pinaster Ait. in response to drought.

PubMed

de Miguel, Marina; Sánchez-Gómez, David; Cervera, María Teresa; Aranda, Ismael

2012-01-01

Drought is an important environmental factor in Mediterranean ecosystems affecting seedling recruitment, productivity or susceptibility to fires and pathogens. Studying water use efficiency in these environments is crucial due to its adaptive value allowing trees to cope with low water availability. We studied the phenotypic variability and genetic control of intrinsic water use efficiency (WUE(i)) and related traits in a full-sib family of Pinus pinaster under drought imposition. We detected significant differences in WUE(i) between clones of the same family and moderate heritability estimates that indicate some degree of genetic control over this trait. Stomatal conductance to water vapor was the trait most affected by drought imposition and it showed the strongest influence in WUE(i). Stomatal conductance to water vapor and specific leaf area (SLA) were the traits with highest heritabilities and they showed a significant genetic correlation with WUE(i), suggesting that selection of needles with low SLA values will improve WUE(i) in this species by reducing water losses through stomatal control.
Association of single Nucleotide Missence Polymorphism Val109Asp of Omentin-1 gene and coronary artery disease in Pakistani population: Multicenter study

PubMed Central

Nazar, Shazia; Zehra, Sitwat; Azhar, Abid

2017-01-01

Background & Objective: Coronary artery disease (CAD) is a most important cause of morbidity and mortality worldwide as well as in Pakistan. Recent studies have shown that the combination of obesity, insulin resistance and fluctuation in circulating adipocytokines levels is associated with the pathogenesis of coronary artery disease. Omentin-1 is recently found adipocytokine that is highly expressed in visceral adipose tissue. It has anti- inflammatory properties and is negatively correlated with ischemic heart disease. Therefore, this study was designed to investigate the relationship between omentin-1 Val109Asp polymorphism and CAD in Pakistani population. Methods: A total of 350 subjects were included in the study. Two hundred fifty were diagnosed with coronary artery disease while 100 served as healthy controls. PCR-RFLP was performed at Dr. A Q. Khan Institute of Biotechnology (KIBGE) to analyze Val109Asp polymorphism. In this, case control study SPSS software version 16 (Chicago, IL, USA) was used for data analysis. Continuous variables and categorical variables were presented as mean±SD or in percentage. Independent sample test and chi-square test was performed to compare the differences in means between cases and controls. Genotype distribution was analyzed by chi-square test and results were presented as percentage and frequency. Multivarible regression analysis indicated that Val109Asp SNP might be an independent risk factor for CAD susceptibility after adjustment for some well- known CAD risk factors including age, gender, body mass index, smoking, hypertension, diabetes mellitus and lipid abnormalities. There was estimation of odd ratios (OR) and 95% confidence intervals (CIs) to determine the correlation between genotypes and the risk of CAD. (p> 0.05). Genotype frequencies were compared by Chi-square test. Results: There was prevalence of Omentin-1 Val109Asp polymorphism in both case and control groups. However, Val/Asp (heterozygous mutant) genotype
Modeling Impact of Urbanization in US Cities Using Simple Biosphere Model SiB2

NASA Technical Reports Server (NTRS)

Zhang, Ping; Bounoua, Lahouari; Thome, Kurtis; Wolfe, Robert

2016-01-01

We combine Landsat- and the Moderate Resolution Imaging Spectroradiometer (MODIS)-based products, as well as climate drivers from Phase 2 of the North American Land Data Assimilation System (NLDAS-2) in a Simple Biosphere land surface model (SiB2) to assess the impact of urbanization in continental USA (excluding Alaska and Hawaii). More than 300 cities and their surrounding suburban and rural areas are defined in this study to characterize the impact of urbanization on surface climate including surface energy, carbon budget, and water balance. These analyses reveal an uneven impact of urbanization across the continent that should inform upon policy options for improving urban growth including heat mitigation and energy use, carbon sequestration and flood prevention.
Maximizing the significance in Higgs boson pair analyses [Mad-Maximized Higgs Pair Analyses

DOE PAGES

Kling, Felix; Plehn, Tilman; Schichtel, Peter

2017-02-22

Here, we study Higgs pair production with a subsequent decay to a pair of photons and a pair of bottoms at the LHC. We use the log-likelihood ratio to identify the kinematic regions which either allow us to separate the di-Higgs signal from backgrounds or to determine the Higgs self-coupling. We find that both regions are separate enough to ensure that details of the background modeling will not affect the determination of the self-coupling. Assuming dominant statistical uncertainties we determine the best precision with which the Higgs self-coupling can be probed in this channel. We finally comment on the samemore » questions at a future 100 TeV collider.« less
Maximizing the significance in Higgs boson pair analyses [Mad-Maximized Higgs Pair Analyses

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

Kling, Felix; Plehn, Tilman; Schichtel, Peter

Here, we study Higgs pair production with a subsequent decay to a pair of photons and a pair of bottoms at the LHC. We use the log-likelihood ratio to identify the kinematic regions which either allow us to separate the di-Higgs signal from backgrounds or to determine the Higgs self-coupling. We find that both regions are separate enough to ensure that details of the background modeling will not affect the determination of the self-coupling. Assuming dominant statistical uncertainties we determine the best precision with which the Higgs self-coupling can be probed in this channel. We finally comment on the samemore » questions at a future 100 TeV collider.« less
An Arabidopsis ATP-dependent, DEAD-box RNA helicase loses activity upon iosAsp formation but is restored by Protein Isoaspartyl Methltransferase

USDA-ARS?s Scientific Manuscript database

Arabidopsis thaliana PLANT RNA HELICASE75 (AtPRH75) demonstrated an ATP-dependent, RNA duplex unwinding capacity and an ATP-independent, RNA duplex reforming ability. It is known to accumulate isoAsp, but the consequences of isoAsp formation in AtPRH75 are unknown. Duplex unwinding was abolished by ...
The functional consequences of mis-sense mutations affecting an intra-molecular salt bridge in arylsulphatase A.

PubMed Central

Schestag, Frank; Yaghootfam, Afshin; Habetha, Matthias; Poeppel, Peter; Dietz, Frank; Klein, Roger A; Zlotogora, Joel; Gieselmann, Volkmar

2002-01-01

Metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of arylsulphatase A. We describe the functional consequences of three mis-sense mutations in the arylsulphatase A gene (Asp-335-Val, Arg-370-Trp and Arg-370-Gln), affecting an apparent intramolecular Asp-335 to Arg-370 salt bridge, and interpret the effects and clinical consequences on the basis of the three-dimensional structure of arylsulphatase A. Asp-335-Val and Arg-370-Trp substitutions each cause a complete loss of enzyme activity and are associated with the most severe form of the human disease, whereas the Arg-370-Gln-substituted enzyme retains some residual activity, being found in a patient suffering from the milder juvenile form of the disease. Detailed analysis reveals that formation of the apparent salt bridge depends critically on the presence of aspartic acid and arginine residues at positions 335 and 370, respectively. Substitution by various other amino acids, including glutamic acid and lysine, affects enzyme function severely. Biosynthesis and immunoprecipitation studies indicate that the Asp-335-Val substitution affects folding of arylsulphatase A more severely than either the Arg-370-Trp or Arg-370-Gln substitutions. In vitro mutagenesis data show that clinical severity correlates with the space occupied by residue 370. The combination with structural data suggests that the bulky tryptophan residue broadens the cleft held together by the apparent salt bridge, whereas the smaller glutamine residue still allows the cleft to close, yielding a less severely affected enzyme. The position of residue 370 in the three-dimensional structure of the enzyme provides a plausible explanation for the differing severities in loss of enzyme function caused by the mutations and thus the clinical phenotype. PMID:12086582
Sequential activities of Dynein, Mud and Asp in centrosome-spindle coupling maintain centrosome number upon mitosis.

PubMed

Bosveld, Floris; Ainslie, Anna; Bellaïche, Yohanns

2017-10-15

Centrosomes nucleate microtubules and are tightly coupled to the bipolar spindle to ensure genome integrity, cell division orientation and centrosome segregation. While the mechanisms of centrosome-dependent microtubule nucleation and bipolar spindle assembly have been the focus of numerous works, less is known about the mechanisms ensuring the centrosome-spindle coupling. The conserved NuMA protein (Mud in Drosophila ) is best known for its role in spindle orientation. Here, we analyzed the role of Mud and two of its interactors, Asp and Dynein, in the regulation of centrosome numbers in Drosophila epithelial cells. We found that Dynein and Mud mainly initiate centrosome-spindle coupling prior to nuclear envelope breakdown (NEB) by promoting correct centrosome positioning or separation, while Asp acts largely independently of Dynein and Mud to maintain centrosome-spindle coupling. Failure in the centrosome-spindle coupling leads to mis-segregation of the two centrosomes into one daughter cell, resulting in cells with supernumerary centrosomes during subsequent divisions. Altogether, we propose that Dynein, Mud and Asp operate sequentially during the cell cycle to ensure efficient centrosome-spindle coupling in mitosis, thereby preventing centrosome mis-segregation to maintain centrosome number. © 2017. Published by The Company of Biologists Ltd.
The Human Immunodeficiency Virus 1 ASP RNA promotes viral latency by recruiting the Polycomb Repressor Complex 2 and promoting nucleosome assembly

PubMed Central

Zapata, Juan C.; Campilongo, Federica; Barclay, Robert A.; DeMarino, Catherine; Iglesias-Ussel, Maria D.; Kashanchi, Fatah; Romerio, Fabio

2017-01-01

Various epigenetic marks at the HIV-1 5′LTR suppress proviral expression and promote latency. Cellular antisense transcripts known as long noncoding RNAs (lncRNAs) recruit the polycomb repressor complex 2 (PRC2) to gene promoters, which catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3), thus promoting nucleosome assembly and suppressing gene expression. We found that an HIV-1 antisense transcript expressed from the 3′LTR and encoding the antisense protein ASP promotes proviral latency. Expression of ASP RNA reduced HIV-1 replication in Jurkat cells. Moreover, ASP RNA expression promoted the establishment and maintenance of HIV-1 latency in Jurkat E4 cells. We show that this transcript interacts with and recruits PRC2 to the HIV-1 5′LTR, increasing accumulation of the suppressive epigenetic mark H3K27me3, while reducing RNA Polymerase II and thus proviral transcription. Altogether, our results suggest that the HIV-1 ASP transcript promotes epigenetic silencing of the HIV-1 5′LTR and proviral latency through the PRC2 pathway. PMID:28340355
Investigations of Baikal Lake water absorption with ASP-15 device: measurement method and experimental data

NASA Astrophysics Data System (ADS)

Kokhanenko, Grigorii P.; Tarashchansky, Boris A.; Budnev, Nikolai M.; Mirgazov, Rashid R.

2006-02-01

Operation of the device ASP-15 is analyzed in the paper. The device is arranged in the south part of Lake Baikal, and it is capable of all-the-year-round measurements of hydro-optical characteristics at the depths down to 1300 m. The method for determining the absorption coefficient is based on measurement of the rate of decrease of the irradiance from an isotropic source with the distance between the source and the receiver. Possible reasons of appearance of anomalous dependences of the irradiance with the distance are revealed on the basis of numerical simulation, and the errors of the applied method are estimated. The experimental data obtained by means of the device ASP-15 last years are presented.
Effect of plastic deformation on the magnetic properties and dislocation luminescence of isotopically enriched silicon {sup 29}Si:B

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

Koplak, O. V.; Shteynman, E. A.; Tereschenko, A. N.

2015-09-15

A correlation between the temperature dependences of the D1-line intensity of dislocation luminescence and the magnetic moment of plastically deformed isotopically enriched crystals {sup 29}Si:B is found. It is established that the magnetic susceptibility of the deformed crystals obtained by integration of the spectra of electron spin resonance and the D1-line intensity undergo similar nonmonotonic variations with temperature varying in the range of 20–32 K.
Water Dimers in the Atmosphere II: Results from the VRT(ASP-W)III Potential Surface

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

Goldman, N; Saykally, R J; Leforestier, C

We report refined results for the equilibrium constant for water dimerization (K{sub P}), computed as a function of temperature via fully-coupled 6-D calculation of the canonical (H{sub 2}O){sub 2} partition function on VRT(ASP-W)III, the most accurate water dimer potential energy surface currently available. Partial pressure isotherms calculated for a range of temperatures and relative humidities indicate that water dimers can exist in sufficient concentrations (e.g., 10{sup 18}m{sup -3} at 30 C and 100% relative humidity) to affect physical and chemical processes in the atmosphere. The determinations of additional thermodynamic properties ({Delta}G, {Delta}H, {Delta}S, C{sub P}, C{sub V}) for (H{sub 2}O){submore » 2} are presented, and the role of quasi-bound states in the calculation of K{sub P} is discussed at length.« less
Glu298Asp polymorphism influences the beneficial effects of fish oil fatty acids on postprandial vascular function[S

PubMed Central

Thompson, Abby K.; Newens, Katie J.; Jackson, Kim G.; Wright, John; Williams, Christine M.

2012-01-01

Our objective was to determine whether the endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism influences vascular response to raised NEFA enriched with saturated fatty acids (SFA) or long-chain (LC) n-3 polyunsaturated fatty acids (PUFA). Subjects were prospectively recruited for genotype (Glu298, n = 30 and Asp298, n = 29; balanced for age and gender) consumed SFA on two occasions, with and without the substitution of 0.07 g fat/kg body weight with LC n-3 PUFA, and with heparin infusion to elevate NEFA. Endothelial function was measured before and after NEFA elevation (240 min), with blood samples taken every 30 min. Flow-mediated dilation (FMD) decreased following SFA alone and increased following SFA+LC n-3 PUFA. There were 2-fold differences in the change in FMD response to the different fat loads between the Asp298 and Glu298 genotypes (P = 0.002) and between genders (P < 0.02). Sodium nitroprusside-induced reactivity, measured by laser Doppler imaging with iontophoresis, was significantly greater with SFA+LC n-3 PUFA in all female subjects (P < 0.001) but not in males. Elevated NEFA influences both endothelial-dependent and endothelial-independent vasodilation during the postprandial phase. Effects of fat composition appear to be genotype and gender dependent, with the greatest difference in vasodilatory response to the two fat loads seen in the Asp298 females. PMID:22847178
Lack of association between the Glu298Asp polymorphism of endothelial nitric oxide synthase and slow coronary flow in the Turkish population

PubMed Central

Caglayan, Ahmet Okay; Kalay, Nihat; Saatci, Cetin; Yalcın, Arif; Akalın, Hilal; Dundar, Munis

2009-01-01

BACKGROUND: Coronary endothelial dysfunction plays an important pathogenetic role in patients with slow coronary flow (SCF). No data exist regarding the possible contribution of the Glu298Asp polymorphism genotype of the endothelial nitric oxide synthase (eNOS) gene to human SCF in the literature. OBJECTIVE: To investigate the association between SCF and the Glu298Asp polymorphism of the eNOS gene. METHODS: The study population consisted of 85 consecutive patients. The patient group included 66 patients with angiographically proven normal coronary arteries with SCF, and 19 subjects with normal coronary arteries with no SCF. The thrombolysis in myocardial infarction frame count was used for the diagnosis of SCF. The Glu298Asp polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: The baseline characteristics were similar between the two groups, except for high-density lipoprotein cholesterol, which was higher in the SCF group than in the controls. The genotype distribution of Glu298Asp was as follows: GG 26%, GT 56% and TT 12%, where G is guanine and T is thymine. There was no difference in the frequency of the various genotypes or the alleles in patients with SCF versus normal controls. CONCLUSIONS: The Glu298Asp polymorphism genotype of the eNOS gene is not a risk factor for SCF in the present study population. PMID:19279989
Asp f6, an Aspergillus allergen specifically recognized by IgE from patients with allergic bronchopulmonary aspergillosis, is differentially expressed during germination.

PubMed

Schwienbacher, M; Israel, L; Heesemann, J; Ebel, F

2005-11-01

Aspergillus fumigatus is a pathogenic mould causing allergic and invasive respiratory diseases. Allergic bronchopulmonary Aspergillosis (ABPA) is a severe pulmonary complication resulting from hypersensitivity to A. fumigatus proteins. Aspergillus allergen Asp f6 is recognized by IgE from ABPA patients, but not from sensitized individuals, a fact that can be used to differentiate between these two groups of allergic patients. Proteins from hyphae, resting and germinating conidia of A. fumigatus were compared by SDS-PAGE. Protein identification was performed using MALDI-TOF mass spectrometry. Recombinant A. fumigatus allergens were used to isolate specific monoclonal antibodies (mab) from a hybridoma bank generated against Aspergillus proteins. A hyphae-specific 23 kDa A. fumigatus protein was identified as the allergen Asp f6/manganese-dependent superoxide dismutase (MnSOD). Differential expression of MnSOD was confirmed by immunoblot using a specific mab. In contrast, Asp f8 another intracellular, but not ABPA-specific allergen, was detected in hyphae and conidia. Aspergillus fumigatus is able to colonize its environment by the formation of hyphae. Hyphae are found in the lung of ABPA patients, but not in patients suffering from atopic asthma. Our finding that Asp f6 is specifically expressed in hyphae might explain why an IgE response to Asp f6 is specific for ABPA patients.

Identification and expression of an allergen Asp f 13 from Aspergillus fumigatus and epitope mapping using human IgE antibodies and rabbit polyclonal antibodies.

PubMed Central

Chow, L P; Liu, S L; Yu, C J; Liao, H K; Tsai, J J; Tang, T K

2000-01-01

The Aspergillus genus of fungi is known to be one of the most prevalent aeroallergens. On two-dimensional immunoblotting using patients' sera containing IgE specific for Asp f 13, an allergen with a molecular mass of 33 kDa and a pI of 6.2 was identified. This allergen was also present in A. fumigatus culture filtrates. Furthermore, the sequence of the Asp f 13 cDNA was identical to that for alkaline protease isolated from A. fumigatus and showed 42-49% identity of amino acids with two proteases from P. cyclopium and T. album and with the Pen c 1 allergen from P. citrinum. Asp f 13 coding sequences were expressed in Escherichia coli as a [His](6)-tagged fusion protein which was purified by Ni(2+)-chelate affinity chromatography. Recombinant Asp f 13 was recognized by rabbit polyclonal antibodies against Asp f 13 and by IgE antibodies from subject allergic to A. fumigatus. To identify and characterize the linear epitopes of this allergen, a combination of chemical and enzymatic cleavage and immunoblotting techniques, with subsequent N-terminal sequencing and mass spectrometry, were performed. At least 13 different linear epitopes reacting with the rabbit anti-Asp f 13 antiserum were identified, located throughout the entire molecule. In contrast, IgE from A. fumigatus-sensitive patients bound to three immunodominant epitopes at the C-terminal of the protein. PMID:10677362
Stability assessment of a new antithrombotic small peptide, Arg-Gly-Asp-Trp-Arg (RGDWR), and its derivative.

PubMed

Yang, Lijun; Zhang, Litao; Yan, Lihong; Zheng, Haifeng; Lu, Peifen; Chen, Junjun; Dai, Jie; Sun, Haibiao; Xu, Yong; Yang, Tao

2017-08-01

To assess the stabilities of Arg-Gly-Asp-Trp-Arg (RGDWR, designated as RWR), a new patented antithrombotic small peptide, and its derivative with ω-aminocaprylic acid on its N-terminus (ωRWR). RWR in rat plasma was decreased by between 32 and 48% after 4 h incubation on ice, indicating its instability in plasma. In contrast, ωRWR in plasma remained at 96-107%. Concentration changes were within 6.2% for ωRWR after storage in various conditions. ωRWR is therefore stable in rat plasma, as well as under different storage methods. Furthermore, ω-aminocaprylic acid added onto the RWR peptide did not affect its antiplatelet aggregation activity. A novel small peptide, ωRWR, has been developed with a good stability for possible antithrombotic use.
Female phenotype and multiple abnormalities in sibs with a Y chromosome and partial X chromosome duplication: H--Y antigen and Xg blood group findings.

PubMed Central

Bernstein, R; Jenkins, T; Dawson, B; Wagner, J; Dewald, G; Koo, G C; Wachtel, S S

1980-01-01

A mentally retarded female child with multiple congenital abnormalities had an abnormal X chromosome and a Y chromosome; the karyotype was interpreted as 46,dup(X)(p21 leads to pter)Y. Prenatal chromosome studies in a later pregnancy indicated the same chromosomal abnormality in the fetus. The fetus and proband had normal female genitalia and ovarian tissue. H--Y antigen was virtually absent in both sibs, a finding consistent with the view that testis-determining genes of the Y chromosome may be suppressed by regulatory elements of the X. The abnormal X chromosome was present in the mother, the maternal grandmother, and a female sib: all were phenotypically normal and showed the karyotype 46,Xdup(X)(p21 leads to pter) with non-random inactivation of the abnormal X. Anomalous segregation of the Xga allele suggests that the Xg locus was involved in the inactivation process or that crossing-over at meiosis occurred. Images PMID:7193738
Importance of the residue Asp 290 on chain length selectivity and catalytic efficiency of recombinant Staphylococcus simulans lipase expressed in E. coli.

PubMed

Sayari, Adel; Mosbah, Habib; Gargouri, Youssef

2007-05-01

In addition to their physiological importance, microbial lipases, like staphylococcal ones, are of considerable commercial interest for biotechnological applications such as detergents, food production, and pharmaceuticals and industrial synthesis of fine chemicals. The gene encoding the extracellular lipase of Staphylococcus simulans (SSL) was subcloned in the pET-14b expression vector and expressed in Esherichia coli BL21 (DE3). The wild-type SSL was expressed as amino terminal His6-tagged recombinant protein. One-step purification of the recombinant lipase was achieved with nickel metal affinity column. The purified His-tagged SSL (His6-SSL) is able to hydrolyse triacylglycerols without chain length selectivity. The major differences among lipases are reflected in their chemical specificity in the hydrolysis of peculiar ester bonds, and their respective capacity to hydrolyse substrates having different physico-chemical properties. It has been proposed, using homology alignment, that the region around the residue 290 of Staphylococcus hyicus lipase could be involved in the selection of the substrate. To evaluate the importance of this environment, the residue Asp290 of Staphylococcus simulans lipase was mutated to Ala using site-directed mutagenesis. The mutant expression plasmid was also overexpressed in Esherichia coli and purified with a nickel metal affinity column. The substitution of Asp290 by Ala was accompanied by a significant shift of the acyl-chain length specificity of the mutant towards short chain fatty acid esters. Kinetic studies of wild-type SSL and its mutant D290A were carried out, and show essentially that the catalytic efficiency (k cat /K M ) of the mutant was affected. Our results confirmed that Asp290 is important for the chain length selectivity and catalytic efficiency of Staphylococcus simulans lipase.
ASPsiRNA: A Resource of ASP-siRNAs Having Therapeutic Potential for Human Genetic Disorders and Algorithm for Prediction of Their Inhibitory Efficacy

PubMed Central

Monga, Isha; Qureshi, Abid; Thakur, Nishant; Gupta, Amit Kumar; Kumar, Manoj

2017-01-01

Allele-specific siRNAs (ASP-siRNAs) have emerged as promising therapeutic molecules owing to their selectivity to inhibit the mutant allele or associated single-nucleotide polymorphisms (SNPs) sparing the expression of the wild-type counterpart. Thus, a dedicated bioinformatics platform encompassing updated ASP-siRNAs and an algorithm for the prediction of their inhibitory efficacy will be helpful in tackling currently intractable genetic disorders. In the present study, we have developed the ASPsiRNA resource (http://crdd.osdd.net/servers/aspsirna/) covering three components viz (i) ASPsiDb, (ii) ASPsiPred, and (iii) analysis tools like ASP-siOffTar. ASPsiDb is a manually curated database harboring 4543 (including 422 chemically modified) ASP-siRNAs targeting 78 unique genes involved in 51 different diseases. It furnishes comprehensive information from experimental studies on ASP-siRNAs along with multidimensional genetic and clinical information for numerous mutations. ASPsiPred is a two-layered algorithm to predict efficacy of ASP-siRNAs for fully complementary mutant (Effmut) and wild-type allele (Effwild) with one mismatch by ASPsiPredSVM and ASPsiPredmatrix, respectively. In ASPsiPredSVM, 922 unique ASP-siRNAs with experimentally validated quantitative Effmut were used. During 10-fold cross-validation (10nCV) employing various sequence features on the training/testing dataset (T737), the best predictive model achieved a maximum Pearson’s correlation coefficient (PCC) of 0.71. Further, the accuracy of the classifier to predict Effmut against novel genes was assessed by leave one target out cross-validation approach (LOTOCV). ASPsiPredmatrix was constructed from rule-based studies describing the effect of single siRNA:mRNA mismatches on the efficacy at 19 different locations of siRNA. Thus, ASPsiRNA encompasses the first database, prediction algorithm, and off-target analysis tool that is expected to accelerate research in the field of RNAi-based therapeutics
ASPsiRNA: A Resource of ASP-siRNAs Having Therapeutic Potential for Human Genetic Disorders and Algorithm for Prediction of Their Inhibitory Efficacy.

PubMed

Monga, Isha; Qureshi, Abid; Thakur, Nishant; Gupta, Amit Kumar; Kumar, Manoj

2017-09-07

Allele-specific siRNAs (ASP-siRNAs) have emerged as promising therapeutic molecules owing to their selectivity to inhibit the mutant allele or associated single-nucleotide polymorphisms (SNPs) sparing the expression of the wild-type counterpart. Thus, a dedicated bioinformatics platform encompassing updated ASP-siRNAs and an algorithm for the prediction of their inhibitory efficacy will be helpful in tackling currently intractable genetic disorders. In the present study, we have developed the ASPsiRNA resource (http://crdd.osdd.net/servers/aspsirna/) covering three components viz (i) ASPsiDb , (ii) ASPsiPred , and (iii) analysis tools like ASP-siOffTar ASPsiDb is a manually curated database harboring 4543 (including 422 chemically modified) ASP-siRNAs targeting 78 unique genes involved in 51 different diseases. It furnishes comprehensive information from experimental studies on ASP-siRNAs along with multidimensional genetic and clinical information for numerous mutations. ASPsiPred is a two-layered algorithm to predict efficacy of ASP-siRNAs for fully complementary mutant (Eff mut ) and wild-type allele (Eff wild ) with one mismatch by ASPsiPred SVM and ASPsiPred matrix , respectively. In ASPsiPred SVM , 922 unique ASP-siRNAs with experimentally validated quantitative Eff mut were used. During 10-fold cross-validation (10nCV) employing various sequence features on the training/testing dataset (T737), the best predictive model achieved a maximum Pearson's correlation coefficient (PCC) of 0.71. Further, the accuracy of the classifier to predict Eff mut against novel genes was assessed by leave one target out cross-validation approach (LOTOCV). ASPsiPred matrix was constructed from rule-based studies describing the effect of single siRNA:mRNA mismatches on the efficacy at 19 different locations of siRNA. Thus, ASPsiRNA encompasses the first database, prediction algorithm, and off-target analysis tool that is expected to accelerate research in the field of RNAi
The Human Immunodeficiency Virus 1 ASP RNA promotes viral latency by recruiting the Polycomb Repressor Complex 2 and promoting nucleosome assembly.

PubMed

Zapata, Juan C; Campilongo, Federica; Barclay, Robert A; DeMarino, Catherine; Iglesias-Ussel, Maria D; Kashanchi, Fatah; Romerio, Fabio

2017-06-01

Various epigenetic marks at the HIV-1 5'LTR suppress proviral expression and promote latency. Cellular antisense transcripts known as long noncoding RNAs (lncRNAs) recruit the polycomb repressor complex 2 (PRC2) to gene promoters, which catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3), thus promoting nucleosome assembly and suppressing gene expression. We found that an HIV-1 antisense transcript expressed from the 3'LTR and encoding the antisense protein ASP promotes proviral latency. Expression of ASP RNA reduced HIV-1 replication in Jurkat cells. Moreover, ASP RNA expression promoted the establishment and maintenance of HIV-1 latency in Jurkat E4 cells. We show that this transcript interacts with and recruits PRC2 to the HIV-1 5'LTR, increasing accumulation of the suppressive epigenetic mark H3K27me3, while reducing RNA Polymerase II and thus proviral transcription. Altogether, our results suggest that the HIV-1 ASP transcript promotes epigenetic silencing of the HIV-1 5'LTR and proviral latency through the PRC2 pathway. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Asp133 Residue in NhaA Na+/H+ Antiporter Is Required for Stability Cation Binding and Transport.

PubMed

Rimon, Abraham; Dwivedi, Manish; Friedler, Assaf; Padan, Etana

2018-03-16

Na + /H + antiporters have a crucial role in pH and Na + homeostasis in cells. The crystal structure of NhaA, the main antiporter of Escherichia coli, has provided general insights into antiporter mechanisms and revealed a previously unknown structural fold, which has since been identified in several secondary active transporters. This unique structural fold is very delicately electrostatically balanced. Asp133 and Lys 300 have been ascribed essential roles in this balance and, more generally, in the structure and function of the antiporter. In this work, we show the multiple roles of Asp133 in NhaA: (i) The residue's negative charge is critical for the stability of the NhaA structure. (ii) Its main chain is part of the active site. (iii) Its side chain functions as an alkaline-pH-dependent gate, changing the protein's conformation from an inward-facing conformation at acidic pH to an outward-open conformation at alkaline pH, opening the periplasm funnel. On the basis of the experimental data, we propose a tentative mechanism integrating the structural and functional roles of Asp133. Copyright © 2018 Elsevier Ltd. All rights reserved.
Comparison of GCM subgrid fluxes calculated using BATS and SiB schemes with a coupled land-atmosphere high-resolution model

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

Shen, Jinmei; Arritt, R.W.

The importance of land-atmosphere interactions and biosphere in climate change studies has long been recognized, and several land-atmosphere interaction schemes have been developed. Among these, the Simple Biosphere scheme (SiB) of Sellers et al. and the Biosphere Atmosphere Transfer Scheme (BATS) of Dickinson et al. are two of the most widely known. The effects of GCM subgrid-scale inhomogeneities of surface properties in general circulation models also has received increasing attention in recent years. However, due to the complexity of land surface processes and the difficulty to prescribe the large number of parameters that determine atmospheric and soil interactions with vegetation,more » many previous studies and results seem to be contradictory. A GCM grid element typically represents an area of 10{sup 4}-10{sup 6} km{sup 2}. Within such an area, there exist variations of soil type, soil wetness, vegetation type, vegetation density and topography, as well as urban areas and water bodies. In this paper, we incorporate both BATS and SiB2 land surface process schemes into a nonhydrostatic, compressible version of AMBLE model (Atmospheric Model -- Boundary-Layer Emphasis), and compare the surface heat fluxes and mesoscale circulations calculated using the two schemes. 8 refs., 5 figs.« less
Scaling from instantaneous remote-sensing-based latent heat flux to daytime integrated value with the help of SiB2

NASA Astrophysics Data System (ADS)

Song, Yi; Ma, Mingguo; Li, Xin; Wang, Xufeng

2011-11-01

This research dealt with a daytime integration method with the help of Simple Biosphere Model, Version 2 (SiB2). The field observations employed in this study were obtained at the Yingke (YK) oasis super-station, which includes an Automatic Meteorological Station (AMS), an eddy covariance (EC) system and a Soil Moisture and Temperature Measuring System (SMTMS). This station is located in the Heihe River Basin, the second largest inland river basin in China. The remotely sensed data and field observations employed in this study were derived from Watershed Allied Telemetry Experimental Research (WATER). Daily variations of EF in temporal and spatial scale would be detected by using SiB2. An instantaneous midday EF was calculated based on a remote-sensing-based estimation of surface energy budget. The invariance of daytime EF was examined using the instantaneous midday EF calculated from a remote-sensing-based estimation. The integration was carried out using the constant EF method in the intervals with a steady EF. Intervals with an inconsistent EF were picked up and ET in these intervals was integrated separately. The truth validation of land Surface ET at satellite pixel scale was carried out using the measurement of eddy covariance (EC) system.
The potential role of toll-like receptor 4 Asp299Gly polymorphism and its association with recurrent cystic echinococcosis in postoperative patients.

PubMed

Noori, Jafar; Spotin, Adel; Ahmadpour, Ehsan; Mahami-Oskouei, Mahmoud; Sadeghi-Bazargani, Homayoun; Kazemi, Tohid; Sakhinia, Ebrahim; Aghebati-Maleki, Leili; Shahrivar, Firooz

2018-06-01

The study of pathogenesis mechanisms of larval stages in the Taeniidae has recently focused on host genetic factors, particularly toll-like receptor (TLR) variations. However, the potential role of TLR4 polymorphism in hydatidosis has not yet been sufficiently elucidated in postoperative patients. In this case-control investigation, 80 patients from Iran, including 40 with acute hydatidosis (AH) and 40 with recurrent hydatidosis (RH), and 80 ethnically matched controls were evaluated from February 2015 to February 2017. Hydatidosis patients were confirmed using radiological, immunological, and histopathological examinations. Genotyping of Asp299Gly and Thr399Ile of TLR4 single-nucleotide polymorphisms was determined by restriction fragment length polymorphism, sequencing, and phylogenetic strategies. The heterozygous mutant-type TLR4 Asp299Gly genotype indicated a tendency to be associated with the occurrence of RH (P = 0.060) and conferred a 3-fold risk for susceptibility. There was no difference in genotype frequency of Asp299Gly between patients with AH and healthy controls (P = 0.42; OR, 1.82; 95% CI, 0.11-30.1%). Interestingly, a frequency of the G allele (12%: Gly) was observed to be a risk factor for susceptibility to RH patients (P = 0.050; OR, 7.08; 95% CI, 0.97-51.5%). A relative genetic variability of TLR4 Asp299Gly was found in RH patients (haplotype diversity: 0.700) compared to AH patients and healthy controls (Hd: 0.000). The Asp299Gly genotype was dominantly identified in patients with hepatic hydatid cysts. The TLR4 Thr399Ile codon was not detected except in a patient with a pulmonary hydatid cyst. The current findings enhance our knowledge regarding the TLR4 Asp299Gly polymorphism potentially leading to the development of RH, by skewing the immune system towards a Th2 response. Identification of the Asp299Gly codon may be a diagnostic hallmark in RH patients who have undergone unsuccessful postoperative intervention. However, further
The Fourth Joint Meeting of the AAS and ASP, Victoria, June 1952

NASA Astrophysics Data System (ADS)

Garstang, R. H.

1999-05-01

This meeting was my most memorable because (1) it was the first AAS meeting to be held in Western Canada, (2) it was my first visit to Canada, (3) it was the occasion of the dedication of the Dominion Astrophysical Observatory 72-inch telescope to the memory of J. S. Plaskett, in the presence of Mrs. Plaskett, (4) there was a special symposium on emission line stars, which included a lecture by Paul Merrill to celebrate his retirement, and C. S. Beals and J. A. Rottenberg as the other main speakers, (5) Robert McMath gave the first Aitken lecture in memory of the famous double star astronomer, (6) I was elected a member of the AAS by the Council at this meeting, (7) I was already a member of the ASP, and this was my first opportunity to present a paper at an ASP meeting, and I could choose to put my abstract in the P.A.S.P., (8) I met many astronomers there who have been friends ever since, (9) along with many attendees I visited Butchart's Gardens, and (10) there was an excellent banquet at the Empress Hotel.
Linkage of the VNTR/insulin-gene and type I diabetes mellitus: Increased gene sharing in affected sibling pairs

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

Owerbach, D.; Gabbay, K.H.

1994-05-01

Ninety-six multiplex type I diabetic families were typed at the 5' flanking region of the insulin gene by using a PCR assay that better resolves the VNTR into multiple alleles. Affected sibling pairs shared 2, 1, and 0 VNTR alleles - identical by descent - at a frequency of .47, .45, and .08, respectively, a ratio that deviated from the expected 1:2:1 ratio (P<.001). These results confirm linkage of the chromosome 11p15.5 region with type I diabetes mellitus susceptibility. 20 refs., 2 tabs.
Analysis of Arg-Gly-Asp mimetics and soluble receptor of tumour necrosis factor as therapeutic modalities for concanavalin A induced hepatitis in mice.

PubMed Central

Bruck, R; Shirin, H; Hershkoviz, R; Lider, O; Kenet, G; Aeed, H; Matas, Z; Zaidel, L; Halpern, Z

1997-01-01

BACKGROUND/AIMS: It has been shown that synthetic non-peptidic analogues of Arg-Gly-Asp, a major cell adhesive ligand of extracellular matrix, prevented an increase in serum aminotransferase activity, as a manifestation of concanavalin A induced liver damage in mice. This study examined the effects of an Arg-Gly-Asp mimetic on liver histology and cytokine release in response to concanavalin A administration, and the efficacy of soluble receptor of tumour necrosis factor (TNF) alpha in preventing hepatitis in this model of liver injury. METHODS: Mice were pretreated with either the Arg-Gly-Asp mimetic SF-6,5 or recombinant soluble receptor of TNF alpha before their inoculation with 10 mg/kg concanavalin A. Liver enzymes, histology, and the serum values of TNF alpha and interleukin (IL)6 were examined. RESULTS: The histopathological damage in the liver, and the concanavalin A induced release of TNF alpha and IL6 were significantly inhibited by the synthetic Arg-Gly-Asp mimetic (p < 0.001). Liver injury, manifested by the increase in serum aminotransferase and cytokines, as well as by histological manifestations of hepatic damage, was effectively prevented by pretreatment of the mice with the soluble TNF receptor (p < 0.001). CONCLUSIONS: This study confirms the efficacy of a synthetic Arg-Gly-Asp mimetic and soluble TNF receptor in the prevention of immune mediated liver damage in mice. Images PMID:9155591
Identification and characterization of metabolites of ASP015K, a novel oral Janus kinase inhibitor, in rats, chimeric mice with humanized liver, and humans.

PubMed

Nakada, Naoyuki; Oda, Kazuo

2015-01-01

1. Here, we elucidated the structure of metabolites of novel oral Janus kinase inhibitor ASP015K in rats and humans and evaluated the predictability of human metabolites using chimeric mice with humanized liver (PXB mice). 2. Rat biological samples collected after oral dosing of (14)C-labelled ASP015K were examined using a liquid chromatography-radiometric detector and mass spectrometer (LC-RAD/MS). The molecular weight of metabolites in human and the liver chimeric mouse biological samples collected after oral dosing of non-labelled ASP015K was also investigated via LC-MS. Metabolites were also isolated from rat bile samples and analyzed using nuclear magnetic resonance. 3. Metabolic pathways of ASP015K in rats and humans were found to be glucuronide conjugation, methyl conjugation, sulfate conjugation, glutathione conjugation, hydroxylation of the adamantane ring and N-oxidation of the 1H-pyrrolo[2,3-b]pyridine ring. The main metabolite of ASP015K in rats was the glucuronide conjugate, while the main metabolite in humans was the sulfate conjugate. Given that human metabolites were produced by human hepatocytes in chimeric mice with humanized liver, this human model mouse was believed to be useful in predicting the human metabolic profile of various drug candidates.
Catalysis in human hypoxanthine-guanine phosphoribosyltransferase: Asp 137 acts as a general acid/base.

PubMed

Xu, Y; Grubmeyer, C

1998-03-24

Hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) catalyzes the reversible formation of IMP and GMP from their respective bases hypoxanthine (Hx) and guanine (Gua) and the phosphoribosyl donor 5-phosphoribosyl-1-pyrophosphate (PRPP). The net formation and cleavage of the nucleosidic bond requires removal/addition of a proton at the purine moiety, allowing enzymic catalysis to reduce the energy barrier associated with the reaction. The pH profile of kcat for IMP pyrophosphorolysis revealed an essential acidic group with pKa of 7.9 whereas those for IMP or GMP formation indicated involvement of essential basic groups. Based on the crystal structure of human HGPRTase, protonation/deprotonation is likely to occur at N7 of the purine ring, and Lys 165 or Asp 137 are each candidates for the general base/acid. We have constructed, purified, and kinetically characterized two mutant HGPRTases to test this hypothesis. D137N displayed an 18-fold decrease in kcat for nucleotide formation with Hx as substrate, a 275-fold decrease in kcat with Gua, and a 500-fold decrease in kcat for IMP pyrophosphorolysis. D137N also showed lower KD values for nucleotides and PRPP. The pH profiles of kcat for D137N were severely altered. In contrast to D137N, the kcat for K165Q was decreased only 2-fold in the forward reaction and was slightly increased in the reverse reaction. The Km and KD values showed that K165Q interacts with substrates more weakly than does the wild-type enzyme. Pre-steady-state experiments with K165Q indicated that the phosphoribosyl transfer step was fast in the forward reaction, as observed with the wild type. In contrast, D137N showed slower phosphoribosyl transfer chemistry, although guanine (3000-fold reduction) was affected much more than hypoxanthine (32-fold reduction). In conclusion, Asp137 acts as a general catalytic acid/base for HGPRTase and Lys165 makes ground-state interactions with substrates.
Characterization of a Novel BCHE “Silent” Allele: Point Mutation (p.Val204Asp) Causes Loss of Activity and Prolonged Apnea with Suxamethonium

PubMed Central

Delacour, Herve; Lushchekina, Sofya; Mabboux, Isabelle; Bousquet, Aurore; Ceppa, Franck; Schopfer, Lawrence M.; Lockridge, Oksana; Masson, Patrick

2014-01-01

Butyrylcholinesterase deficiency is characterized by prolonged apnea after the use of muscle relaxants (suxamethonium or mivacurium) in patients who have mutations in the BCHE gene. Here, we report a case of prolonged neuromuscular block after administration of suxamethonium leading to the discovery of a novel BCHE variant (c.695T>A, p.Val204Asp). Inhibition studies, kinetic analysis and molecular dynamics were undertaken to understand how this mutation disrupts the catalytic triad and determines a “silent” phenotype. Low activity of patient plasma butyrylcholinesterase with butyrylthiocholine (BTC) and benzoylcholine, and values of dibucaine and fluoride numbers fit with heterozygous atypical silent genotype. Electrophoretic analysis of plasma BChE of the proband and his mother showed that patient has a reduced amount of tetrameric enzyme in plasma and that minor fast-moving BChE components: monomer, dimer, and monomer-albumin conjugate are missing. Kinetic analysis showed that the p.Val204Asp/p.Asp70Gly-p.Ala539Thr BChE displays a pure Michaelian behavior with BTC as the substrate. Both catalytic parameters Km = 265 µM for BTC, two times higher than that of the atypical enzyme, and a low Vmax are consistent with the absence of activity against suxamethonium. Molecular dynamic (MD) simulations showed that the overall effect of the mutation p.Val204Asp is disruption of hydrogen bonding between Gln223 and Glu441, leading Ser198 and His438 to move away from each other with subsequent disruption of the catalytic triad functionality regardless of the type of substrate. MD also showed that the enzyme volume is increased, suggesting a pre-denaturation state. This fits with the reduced concentration of p.Ala204Asp/p.Asp70Gly-p.Ala539Thr tetrameric enzyme in the plasma and non-detectable fast moving-bands on electrophoresis gels. PMID:25054547
Increased anxiety and other similarities in temperament of alcoholics with and without antisocial personality disorder across three diverse populations

PubMed Central

Ducci, Francesca; Enoch, Mary-Anne; Funt, Samuel; Virkkunen, Matti; Albaugh, Bernard; Goldman, David

2007-01-01

According to Cloninger’s model, Type I alcoholics are thought to be innately vulnerable to anxiety and depression. In contrast, Type-II alcoholics are thought to have increased likelihood of antisocial personality disorder (ASPD) and reduced anxiety. However, allostatic activations of stress, anxiety and dysphoria may be a common thread in alcohol use disorders (AUD). Our aim was to find commonalities and differences in temperament of alcoholics with and without ASPD in three diverse populations. By sib-sib comparisons, we also evaluated the extent to which the temperament traits were moderated by familial factors including inheritance. We compared harm avoidance (HA), novelty seeking (NS), and reward dependence (RD) in alcoholics with ASPD, alcoholics without ASPD and controls. Correlations for each temperament dimension were evaluated in pairs of siblings concordant and discordant for AUD. Participants were derived from three independent populations: Finnish Caucasians (N=453, men = 100%, including a sample of alcoholic criminals), a Plains American Indian community sample (N=378; men = 42%) and a subset of the familial and predominantly Caucasian COGA sample (N=967, men = 47%). In all three populations both alcoholics with and without ASPD were higher in HA than controls. The increase of HA among alcoholics as compared to controls ranged from 54% to 12%. In two populations (COGA and Finns), NS was highest in alcoholics with ASPD, intermediate in alcoholics without ASPD, and lowest in controls. HA levels were correlated in sib-pairs concordant (either affected or unaffected) for AUD but not in discordant pairs. In conclusions, despite cultural diversity and different modes of ascertainment we found a consistent pattern of elevated HA in all groups of alcoholics, including alcoholics with ASPD. Even in alcoholics with long-term exposure to the anxiogenic effects of repeated cycles of alcohol withdrawal, genetic and other familial influences seem to play a role
Highly sensitive and adaptable fluorescence-quenched pair discloses the substrate specificity profiles in diverse protease families

PubMed Central

Poreba, Marcin; Szalek, Aleksandra; Rut, Wioletta; Kasperkiewicz, Paulina; Rutkowska-Wlodarczyk, Izabela; Snipas, Scott J.; Itoh, Yoshifumi; Turk, Dusan; Turk, Boris; Overall, Christopher M.; Kaczmarek, Leszek; Salvesen, Guy S.; Drag, Marcin

2017-01-01

Internally quenched fluorescent (IQF) peptide substrates originating from FRET (Förster Resonance Energy Transfer) are powerful tool for examining the activity and specificity of proteases, and a variety of donor/acceptor pairs are extensively used to design individual substrates and combinatorial libraries. We developed a highly sensitive and adaptable donor/acceptor pair that can be used to investigate the substrate specificity of cysteine proteases, serine proteases and metalloproteinases. This novel pair comprises 7-amino-4-carbamoylmethylcoumarin (ACC) as the fluorophore and 2,4-dinitrophenyl-lysine (Lys(DNP)) as the quencher. Using caspase-3, caspase-7, caspase-8, neutrophil elastase, legumain, and two matrix metalloproteinases (MMP2 and MMP9), we demonstrated that substrates containing ACC/Lys(DNP) exhibit 7 to 10 times higher sensitivity than conventional 7-methoxy-coumarin-4-yl acetic acid (MCA)/Lys(DNP) substrates; thus, substantially lower amounts of substrate and enzyme can be used for each assay. We therefore propose that the ACC/Lys(DNP) pair can be considered a novel and sensitive scaffold for designing substrates for any group of endopeptidases. We further demonstrate that IQF substrates containing unnatural amino acids can be used to investigate protease activities/specificities for peptides containing post-translationally modified amino acids. Finally, we used IQF substrates to re-investigate the P1-Asp characteristic of caspases, thus demonstrating that some human caspases can also hydrolyze substrates after glutamic acid. PMID:28230157
XPD Asp312Asn and Lys751Gln polymorphisms and breast cancer susceptibility: a meta-analysis.

PubMed

Yan, Yulan; Liang, Hongjie; Light, Morning; Li, Taijie; Deng, Yan; Li, Meng; Li, Shan; Qin, Xue

2014-03-01

The association between xeroderma pigmentosum complementation group D (XPD) Asp312Asn and Lys751Gln gene polymorphisms and breast cancer risk has been widely reported, but the results were inconsistent. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. A comprehensive search strategy was conducted towards the electronic databases including Medline, PubMed, Web of Science, Embase, and Chinese Biomedical Literature Database (Chinese). The association between the XPD polymorphism and breast cancer risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). A total of 22 studies with 18,136 cases and 18,351 controls were included in our meta-analysis. Among these, 12 studies with 7,667 cases and 7,480 controls for Asp312Asn polymorphism and 20 studies with 10,469 cases and 10,871 controls for Lys751Gln polymorphism. With regard to Asp312Asn polymorphism, no significantly associated was found with breast cancer risk. However, significant association was found between Lys751Gln polymorphism and breast cancer risk under all genetic models in overall populations (C vs. A-OR = 1.10, 95% CI = 1.04-1.17, P = 0.002; CC vs. AA-OR = 1.17, 95% CI = 1.06-1.30, P = 0.003; AC vs. AA-OR = 1.06, 95% CI = 1.01-1.12, P = 0.032; CC vs. AC/AA-OR = 1.17, 95% CI = 1.04-1.32, P = 0.009; CC/AC vs. AA-OR = 1.07, 95% CI = 1.02-1.12, P = 0.005). In subgroup analysis base on ethnicity, significance was found in Caucasians and mix. The results suggest that XPD Asp312Asn polymorphism was not associated with breast cancer. The XPD Lys751Gln polymorphism significantly increased breast cancer risk, especially for Caucasian and mix.

Juvenile social experience affects pairing success at adulthood: congruence with the loser effect?

PubMed Central

Mariette, Mylene M.; Cathaud, Charlène; Chambon, Rémi; Vignal, Clémentine

2013-01-01

Social interactions with adults are often critical for the development of mating behaviours. However, the potential role of other primary social partners such as juvenile counterparts is rarely considered. Most interestingly, it is not known whether interactions with juvenile females improve males’ courtship and whether, similar to the winner and loser effects in a fighting context—outcome of these interactions shapes males’ behaviour in future encounters. We investigated the combined effects of male quality and juvenile social experience on pairing success at adulthood in zebra finches (Taeniopygia guttata). We manipulated brood size to alter male quality and then placed males in either same- or mixed-sex juvenile dyads until adulthood. We found that males from reduced broods obtained more copulations and males from mixed-sex dyads had more complete courtships. Furthermore, independent of their quality, males that failed to pair with juvenile females, but not juvenile males, had a lower pairing success at adulthood. Our study shows that negative social experience with peers during adolescence may be a potent determinant of pairing success that can override the effects of early environmental conditions on male attractiveness and thereby supports the occurrence of an analogous process to the loser effect in a mating context. PMID:23902911
Juvenile social experience affects pairing success at adulthood: congruence with the loser effect?

PubMed

Mariette, Mylene M; Cathaud, Charlène; Chambon, Rémi; Vignal, Clémentine

2013-09-22

Social interactions with adults are often critical for the development of mating behaviours. However, the potential role of other primary social partners such as juvenile counterparts is rarely considered. Most interestingly, it is not known whether interactions with juvenile females improve males' courtship and whether, similar to the winner and loser effects in a fighting context--outcome of these interactions shapes males' behaviour in future encounters. We investigated the combined effects of male quality and juvenile social experience on pairing success at adulthood in zebra finches (Taeniopygia guttata). We manipulated brood size to alter male quality and then placed males in either same- or mixed-sex juvenile dyads until adulthood. We found that males from reduced broods obtained more copulations and males from mixed-sex dyads had more complete courtships. Furthermore, independent of their quality, males that failed to pair with juvenile females, but not juvenile males, had a lower pairing success at adulthood. Our study shows that negative social experience with peers during adolescence may be a potent determinant of pairing success that can override the effects of early environmental conditions on male attractiveness and thereby supports the occurrence of an analogous process to the loser effect in a mating context.
Formation of crystalline nanoparticles by iron binding to pentapeptide (Asp-His-Thr-Lys-Glu) from egg white hydrolysates.

PubMed

Sun, Na; Cui, Pengbo; Li, Dongmei; Jin, Ziqi; Zhang, Shuyu; Lin, Songyi

2017-09-20

A novel peptide from egg white, Asp-His-Thr-Lys-Glu (DHTKE), contains specific amino acids associated with iron binding. The present study aims to better understand the molecular basis of interactions between the DHTKE peptide and iron ions. The ultraviolet-visible and fluorescence spectra indicate an interaction between the DHTKE peptide and iron ions, which leads to the formation of a DHTKE-iron complex. Notably, Asp, Glu, His, and Lys in the DHTKE peptide play crucial roles in the formation of the DHTKE-iron complex, and the iron-binding site of the DHTKE peptide corresponds primarily to the amide and carboxyl groups. The DHTKE peptide can bind iron ions in a 1 : 2 ratio with a binding constant of 1.312 × 10 5 M -1 . Moreover, the DHTKE-iron complex belongs to thermodynamically stable nanoparticles that are present in the crystalline structure, which might be attributed to peptide folding induced by iron binding. Meanwhile, the DHTKE-iron complex exhibits a relatively high iron-releasing percentage and exerts excellent solubility in the human gastrointestinal tract in vitro. This suggests a potential application of peptides containing Asp, Glu, His, or Lys residues as potential iron supplements.
An ecological vegetation-activated sludge process (V-ASP) for decentralized wastewater treatment: system development, treatment performance, and mathematical modeling.

PubMed

Yuan, Jiajia; Dong, Wenyi; Sun, Feiyun; Li, Pu; Zhao, Ke

2016-05-01

An environment-friendly decentralized wastewater treatment process that is comprised of activated sludge process (ASP) and wetland vegetation, named as vegetation-activated sludge process (V-ASP), was developed for decentralized wastewater treatment. The long-term experimental results evidenced that the vegetation sequencing batch reactor (V-SBR) process had consistently stable higher removal efficiencies of organic substances and nutrients from domestic wastewater compared with traditional sequencing batch reactor (SBR). The vegetation allocated into V-SBR system could not only remove nutrients through its vegetation transpiration ratio but also provide great surface area for microorganism activity enhancement. This high vegetation transpiration ratio enhanced nutrients removal effectiveness from wastewater mainly by flux enhancement, oxygen and substrate transportation acceleration, and vegetation respiration stimulation. A mathematical model based on ASM2d was successfully established by involving the specific function of vegetation to simulate system performance. The simulation results on the influence of operational parameters on V-ASP treatment effectiveness demonstrated that V-SBR had a high resistance to seasonal temperature fluctuations and influent loading shocking.
Genetic polymorphisms of xeroderma pigmentosum group D gene Asp312Asn and Lys751Gln and susceptibility to prostate cancer: a systematic review and meta-analysis.

PubMed

Ma, Qingtong; Qi, Can; Tie, Chong; Guo, Zhanjun

2013-11-10

Many studies have reported the role of xeroderma pigmentosum group D (XPD) with prostate cancer risk, but the results remained controversial. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between XPD Asp312Asn and Lys751Gln polymorphisms and prostate cancer risk. A total of 8 studies including 2620 cases and 3225 controls described Asp312Asn genotypes, among which 10 articles involving 3230 cases and 3582 controls described Lys751Gln genotypes and were also involved in this meta-analysis. When all the eligible studies were pooled into this meta-analysis, a significant association between prostate cancer risk and XPD Asp312Asn polymorphism was found. For Asp312Asn polymorphism, in the stratified analysis by ethnicity and source of controls, prostate cancer risk was observed in co-dominant, dominant and recessive models, while no evidence of any associations of XPD Lys751Gln polymorphism with prostate cancer was found in the overall or subgroup analyses. Our meta-analysis supports that the XPD Asp312Asn polymorphism contributed to the risk of prostate cancer from currently available evidence. However, a study with a larger sample size is needed to further evaluate gene-environment interaction on XPD Asp312Asn and Lys751Gln polymorphisms and prostate cancer risk. © 2013.
Preliminary X-ray crystallographic studies of BthTX-II, a myotoxic Asp49-phospholipase A{sub 2} with low catalytic activity from Bothrops jararacussu venom

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

Corrêa, L. C.; Marchi-Salvador, D. P.; Cintra, A. C. O.

2006-08-01

A myotoxic Asp49-PLA{sub 2} with low catalytic activity from B. jararacussu (BthTX-II) was crystallized in the monoclinic crystal system; a complete X-ray diffraction data set was collected and a molecular-replacement solution was obtained. The oligomeric structure of BthTX-II resembles those of the Asp49-PLA{sub 2} PrTX-III and all bothropic Lys49-PLA{sub 2}s. For the first time, a complete X-ray diffraction data set has been collected from a myotoxic Asp49-phospholipase A{sub 2} (Asp49-PLA{sub 2}) with low catalytic activity (BthTX-II from Bothrops jararacussu venom) and a molecular-replacement solution has been obtained with a dimer in the asymmetric unit. The quaternary structure of BthTX-II resemblesmore » the myotoxin Asp49-PLA{sub 2} PrTX-III (piratoxin III from B. pirajai venom) and all non-catalytic and myotoxic dimeric Lys49-PLA{sub 2}s. In contrast, the oligomeric structure of BthTX-II is different from the highly catalytic and non-myotoxic BthA-I (acidic PLA{sub 2} from B. jararacussu). Thus, comparison between these structures should add insight into the catalytic and myotoxic activities of bothropic PLA{sub 2}s.« less
Inhibition of angiogenesis in vitro by Arg-Gly-Asp-containing synthetic peptide.

PubMed Central

Nicosia, R. F.; Bonanno, E.

1991-01-01

This study was designed to evaluate the effect of the synthetic peptide Gly-Arg-Gly-Asp-Ser (GRGDS) on angiogenesis in serum-free collagen gel culture of rat aorta. The GRGDS peptide contains the amino acid sequence Arg-Gly-Asp (RGD), which has been implicated as a recognition site in interactions between extracellular matrix (ECM) molecules and cell membrane receptors. RGD-containing synthetic peptides are known to inhibit attachment of endothelial cells to substrates, but their effect on angiogenesis has not been fully characterized. Aortic explants embedded in collagen gel in the absence of GRGDS generated branching microvessels through a process of endothelial migration and proliferation. Addition of GRGDS to the culture medium caused a marked inhibition of angiogenesis. In contrast, GRGES, a control peptide lacking the RGD sequence, failed to inhibit angiogenesis. The inhibitory effect of GRGDS was nontoxic and reversible. The angiogenic activity of aortic explants previously inhibited with GRGDS could be restored by incubating the cultures in GRGDS-free medium. These findings suggest that angiogenesis is an anchorage-dependent process that can be inhibited by interfering with the attachment of endothelial cells to the ECM. It also indicates that synthetic peptides can be used as probes to study the mechanisms by which the ECM regulates angiogenesis. Images Figure 1 PMID:1707235
[Paired kidneys in transplant].

PubMed

Regueiro López, Juan C; Leva Vallejo, Manuel; Prieto Castro, Rafael; Anglada Curado, Francisco; Vela Jiménez, Francisco; Ruiz García, Jesús

2009-02-01

Many factors affect the graft and patient survival on the renal transplant outcome. These factors depend so much of the recipient and donor. We accomplished a study trying to circumvent factors that depend on the donor. We checked the paired kidneys originating of a same donor cadaver. We examined the risk factors in the evolution and follow-up in 278 couples of kidney transplant. We describe their differences, significance, the graft and patient survival, their functionality in 3 and 5 years and the risk factors implicated in their function. We study immunogenic and no immunogenic variables, trying to explain the inferior results in the grafts that are established secondly. We regroup the paired kidneys in those that they did not show paired initial function within the same couple. The results yield a discreet deterioration in the graft and patient survival for second group establish, superior creatinina concentration, without obtaining statistical significance. The Cox regression study establishes the early rejection (inferior to three months) and DR incompatibility values like risk factors. This model of paired kidneys would be able to get close to best-suited form for risk factors analysis in kidney transplant from cadaver donors, if more patients examine themselves in the same way. The paired kidneys originating from the same donor do not show the same function in spite of sharing the same conditions of the donor and perioperative management.
Assessing Workshop Models for Informal Educators: ASP's "Astronomy from the Ground Up” Experiment.

NASA Astrophysics Data System (ADS)

Manning, Jim; Gurton, S.; Hurst Schmitt, A.; Pompea, S.; Glass, M.; Haley, K.

2011-01-01

The classic workshop model for science educators in the past has been largely in situ: you show up somewhere, meet your fellow workshoppers, get personal treatment from instructors over several intensive days of content delivery, illustrative activities, and practice in technique, and try to incorporate what you've learned once you get back. But in an age when everybody's digitally connected, and many can't afford to travel, can an "online” workshop be as effective? This was a key question in the Astronomical Society of the Pacific (ASP) NSF-funded project "Astronomy from the Ground Up,” designed to increase astronomy education capacity at small and medium-sized science and nature centers and museums around the U.S. Together with its institutional partners, the Association of Science and Technology Centers (ASTC) and the Institute for Learning Innovation (ILI), and a cadre of individual partners, the ASP conducted both on-site and online workshops and created an online community of practice to increase informal educator capacity to present astronomy to their audiences, and to evaluate the relative effectiveness of the on-site and online delivery schemes. The presenter(s) will share some initial results and findings of the project.
Social Smiling and its Components in High-Risk Infant Siblings Without Later ASD Symptomatology

PubMed Central

Nichols, Caitlin McMahon; Ibañez, Lisa V.; Foss-Feig, Jennifer H.; Stone, Wendy L.

2013-01-01

Impaired affective expression, including social smiling, is common in children with autism spectrum disorder (ASD), and may represent an early marker for ASD in their infant siblings (Sibs-ASD). Social smiling and its component behaviors (eye contact and non-social smiling) were examined at 15 months in Sibs-ASD who demonstrated later ASD symptomatology (Sibs-ASD/AS), those who did not (Sibs-ASD/NS), and low-risk controls (Sibs-TD). Both Sibs-ASD subgroups demonstrated lower levels of social smiling than Sibs-TD, suggesting that early social smiling may reflect elevated genetic vulnerability rather than a specific marker for ASD. Only the Sibs-ASD/AS demonstrated less eye contact and non-social smiling than Sibs-TD, suggesting that different processes, threshold effects, or protective factors may underlie social smiling development in the two Sibs-ASD subgroups. PMID:24057094
TLR4 Asp299Gly polymorphism may be protective against chronic periodontitis.

PubMed

Sellers, R M; Payne, J B; Yu, F; LeVan, T D; Walker, C; Mikuls, T R

2016-04-01

Periodontitis results from interplay between genetic and environmental factors. Single nucleotide polymorphisms (SNPs) in the coding region of the toll-like receptor 4 gene (TLR4) may be associated with periodontitis, although previous studies have been inconclusive. Moreover, the interaction between environmental factors, such as cigarette smoking (a major risk factor for periodontitis), and Porphyromonas gingivalis (a major periodontal pathogen) with the TLR4 coding region Asp299Gly SNP (rs4986790; a SNP associated with lipopolysaccharide-mediated inflammatory responses in periodontitis), have been largely ignored in previous reports. Therefore, the objective of this study was to examine the association between TLR4 Asp299Gly (rs4986790) with alveolar bone height loss (ABHL) and periodontitis, accounting for interactions between this SNP with smoking and P. gingivalis prevalence. The CD14/-260 SNP (rs2569190) served as a control, as a recent meta-analysis suggested no relationship between this SNP and periodontitis. This multicenter study included 617 participants who had rheumatoid arthritis or osteoarthritis. This report presents a secondary outcome from the primary case-control study examining the relationship of periodontitis with established rheumatoid arthritis. The Centers for Disease Control/American Academy of Periodontology case definitions of periodontitis were used for this analysis. Participants received a full-mouth clinical periodontal examination and panoramic radiograph. Percentage ABHL was measured on posterior teeth. The TLR4 Asp299Gly and CD14/-260 SNPs were selected a priori and genotypes were determined using the ImmunoChip array (Illumina(®) ). Minor allele frequencies and associations with periodontitis and ABHL did not differ according to rheumatoid arthritis vs. osteoarthritis status; therefore, data from these two groups were pooled. The presence of P. gingivalis was detected in subgingival plaque by PCR. Multivariate ordinal
Interactions and Interventions: Current Research on Improving Informal Astronomy Education via the Astronomical Society of the Pacific (ASP)

NASA Astrophysics Data System (ADS)

Manning, James G.; Gurton, S.; Hurst, A.; Berendsen, M.; Storksdieck, M.; Haley-Goldman, K.; Stein, J.; Pompea, S.; Garmany, C.; Sparks, R.; Pollock, W.

2007-12-01

In building national capacity for better informal astronomy education and public outreach (EPO), what sorts of professional development interactions are most effective in what situations--and what interventions for improvement can be effectively applied? Building on previous experience, the ASP, in conjunction with its partners, is conducting two National Science Foundation (NSF) funded projects investigating astronomy teaching and learning in informal contexts to explore these questions in both museum-based and amateur astronomy club settings. "Astronomy from the Ground Up" (AfGU) develops capacity for hands-on astronomy education in small and medium-sized science centers and nature centers through on-site and online professional development workshops and the establishment of a "community of practice" network. The ASP, in collaboration with the National Optical Astronomy Observatory (NOAO) and the Association of Science and Technology Centers (ASTC), is investigating which model--face-to-face or online professional development--works best and will be sustainable for that target group. "Sharing the Universe" (STU) builds on the Night Sky Network in which amateur astronomy clubs, through the ASP with financial and logistical support from NASA and its missions, are provided tools and training to conduct EPO activities with their public audiences. The ASP, in collaboration with the Institute for Learning Innovation (ILI), launched a national survey in late 2007 to investigate the factors that either support or discourage sustained amateur astronomer EPO efforts, followed by an in-depth study of a subset of both successful and struggling clubs, and leading to the development of interventions that support amateur astronomy outreach within the context of a nurturing club environment. The presentation will offer some early and initial results of the AfGU project--which reveal some interesting and unforeseen advantages of the online model over the on-site model--and some
The WRKY57 Transcription Factor Affects the Expression of Jasmonate ZIM-Domain Genes Transcriptionally to Compromise Botrytis cinerea Resistance.

PubMed

Jiang, Yanjuan; Yu, Diqiu

2016-08-01

Although necrotrophic pathogens cause many devastating plant diseases, our understanding of the plant defense response to them is limited. Here, we found that loss of function of WRKY57 enhanced the resistance of Arabidopsis (Arabidopsis thaliana) against Botrytis cinerea infection. Further investigation suggested that the negative regulation of WRKY57 against B cinerea depends on the jasmonic acid (JA) signaling pathway. Chromatin immunoprecipitation experiments revealed that WRKY57 directly binds to the promoters of JASMONATE ZIM-DOMAIN1 (JAZ1) and JAZ5, encoding two important repressors of the JA signaling pathway, and activates their transcription. In vivo and in vitro experiments demonstrated that WRKY57 interacts with nuclear-encoded SIGMA FACTOR BINDING PROTEIN1 (SIB1) and SIB2. Further experiments display that the same domain, the VQ motif, of SIB1 and SIB2 interact with WRKY33 and WRKY57. Moreover, transient transcriptional activity assays confirmed that WRKY57 and WRKY33 competitively regulate JAZ1 and JAZ5, SIB1 and SIB2 further enhance these competitions of WRKY57 to WRKY33. Therefore, coordinated regulation of Arabidopsis against B cinerea by transcription activators and repressors would benefit plants by allowing fine regulation of defense. © 2016 American Society of Plant Biologists. All Rights Reserved.
Characterization of diabetic nephropathy in CaM kinase IIalpha (Thr286Asp) transgenic mice.

PubMed

Suzuki, Hikari; Kato, Ichiro; Usui, Isao; Takasaki, Ichiro; Tabuchi, Yoshiaki; Oya, Takeshi; Tsuneyama, Koichi; Kawaguchi, Hiroshi; Hiraga, Koichi; Takasawa, Shin; Okamoto, Hiroshi; Tobe, Kazuyuki; Sasahara, Masakiyo

2009-01-30

Detailed studies were performed on diabetic kidneys derived from transgenic mice overexpressing the mutant form (Thr286Asp) of Ca(2+)/calmodulin-dependent protein kinase IIalpha (CaM kinase IIalpha) in pancreatic beta-cells. Kidney weight/body weight ratio, urinary albumin/creatinine ratio, serum BUN level, and mesangial/glomerular area ratio were all significantly higher in transgenic mice than in wild-type mice. cDNA microarray analysis revealed 17 up-regulated genes and 12 down-regulated genes in transgenic kidney. Among up-regulated genes, cyclin D2 (6.70-fold) and osteopontin (2.35-fold) were thought to play important roles in the progression of diabetic nephropathy. Transgenic glomeruli and tubular epithelial cells were strongly stained for osteopontin, a molecule which induces immune response. In quantitative real-time RT-PCR analyses, expressions of not only M1 macrophage marker genes but also M2 macrophage marker genes were elevated in renal cortex of transgenic mice. Overall results indicate that CaM kinase IIalpha (Thr286Asp) transgenic mice serve as an excellent model for diabetic nephropathy.
Evaluation of architectures for an ASP MPEG-4 decoder using a system-level design methodology

NASA Astrophysics Data System (ADS)

Garcia, Luz; Reyes, Victor; Barreto, Dacil; Marrero, Gustavo; Bautista, Tomas; Nunez, Antonio

2005-06-01

Trends in multimedia consumer electronics, digital video and audio, aim to reach users through low-cost mobile devices connected to data broadcasting networks with limited bandwidth. An emergent broadcasting network is the digital audio broadcasting network (DAB) which provides CD quality audio transmission together with robustness and efficiency techniques to allow good quality reception in motion conditions. This paper focuses on the system-level evaluation of different architectural options to allow low bandwidth digital video reception over DAB, based on video compression techniques. Profiling and design space exploration techniques are applied over the ASP MPEG-4 decoder in order to find out the best HW/SW partition given the application and platform constraints. An innovative SystemC-based system-level design tool, called CASSE, is being used for modelling, exploration and evaluation of different ASP MPEG-4 decoder HW/SW partitions. System-level trade offs and quantitative data derived from this analysis are also presented in this work.
Characterization of various types of mast cells derived from model mice of familial gastrointestinal stromal tumors with KIT-Asp818Tyr mutation

PubMed Central

Kajimoto, Noriko; Nakai, Norihiro; Ohkouchi, Mizuka; Hashikura, Yuka; Liu-Kimura, Ning-Ning; Isozaki, Koji; Hirota, Seiichi

2015-01-01

Sporadic mast cell neoplasms and gastrointestinal stromal tumors (GISTs) often have various types of somatic gain-of-function mutations of the c-kit gene which encodes a receptor tyrosine kinase, KIT. Several types of germline gain-of-function mutations of the c-kit gene have been detected in families with multiple GISTs. All three types of model mice for the familial GISTs with germline c-kit gene mutations at exon 11, 13 or 17 show development of GIST, while they are different from each other in skin mast cell number. Skin mast cell number in the model mice with exon 17 mutation was unchanged compared to the corresponding wild-type mice. In the present study, we characterized various types of mast cells derived from the model mice with exon 17 mutation (KIT-Asp818Tyr) corresponding to human familial GIST case with human KIT-Asp820Tyr to clarify the role of the c-kit gene mutation in mast cells. Bone marrow-derived cultured mast cells (BMMCs) derived from wild-type mice, heterozygotes and homozygotes were used for the experiments. Immortalized BMMCs, designated as IMC-G4 cells, derived from BMMCs of a homozygote during long-term culture were also used. Ultrastructure, histamine contents, proliferation profiles and phosphorylation of various signaling molecules in those cells were examined. In IMC-G4 cells, presence of additional mutation(s) of the c-kit gene and effect of KIT inhibitors on both KIT autophosphorylation and cell proliferation were also analyzed. We demonstrated that KIT-Asp818Tyr did not affect ultrastructure and proliferation profiles but did histamine contents in BMMCs. IMC-G4 cells had an additional novel c-kit gene mutation of KIT-Tyr421Cys which is considered to induce neoplastic transformation of mouse mast cells and the mutation appeared to be resistant to a KIT inhibitor of imatinib but sensitive to another KIT inhibitor of nilotinib. IMC-G4 cells might be a useful mast cell line to investigate mast cell biology. PMID:26722383
Screening of Pro-Asp Sequences Exposed on Bacteriophage M13 as an Ideal Anchor for Gold Nanocubes.

PubMed

Lee, Hwa Kyoung; Lee, Yujean; Kim, Hyori; Lee, Hye-Eun; Chang, Hyejin; Nam, Ki Tae; Jeong, Dae Hong; Chung, Junho

2017-09-15

Bacteriophages are thought to be ideal vehicles for linking antibodies to nanoparticles. Here, we define the sequence of peptides exposed as a fusion protein on M13 bacteriophages to yield optimal binding of gold nanocubes and efficient bacteriophage amplification. We generated five helper bacteriophage libraries using AE(X) 2 DP, AE(X) 3 DP, AE(X) 4 DP, AE(X) 5 DP, and AE(X) 6 DP as the exposed portion of pVIII, in which X was a randomized amino acid residue encoded by the nucleotide sequence NNK. Efficient phage amplification was achievable only in the AE(X) 2 DP, AE(X) 3 DP, and AE(X) 4 DP libraries. Through biopanning with gold nanocubes, we enriched the phage clones and selected the clone with the highest fold change after enrichment. This clone displayed Pro-Asp on the surface of the bacteriophage and had amplification yields similar to those of the wild-type helper bacteriophage (VCSM13). The clone displayed even binding of gold nanocubes along its length and minimal aggregation after binding. We conclude that, for efficient amplification, the exposed pVIII amino acid length should be limited to six residues and Ala-Glu-Pro-Asp-Asp-Pro (AEPDDP) is the ideal fusion protein sequence for guaranteeing the optimal formation of a complex with gold nanocubes.
[Therapeutic Efficacy of VICP+L-ASP/TKI on Adult Patients with B-ALL].

PubMed

Shen, Ming-Fang; Wei, Ju-Ying; Yu, Wen-Juan; Wang, Jing-Han; Tong, Hong-Yan; Meng, Hai-Tao; Mai, Wen-Yuan; Qian, Wen-Bin; Jin, Jie

2016-12-01

To evaluate the therapeutic efficacy of VICP+L-ASP/TKI on adult patients with B-ALL and to explore the influence factors. Forty-one adult B-ALL patients treated with VICP+L-ASP/TKI from August 2008 to June 2014 were following-up. The complete remission(CR) rate, toxicity, overall survival(OS) and event free survival(EFS) after induction treatment were analyzed, the therapeutic outcome of patients between different risk stratification subgroups was compared, the influence of standardized consolidatory and maintaining treatment as well as allogeneic hematopoietic stem cell transplantation(allo-HSCT) on survival time was analyzed. The early death not occurred in 41 patients with B-ALL including 37 cases with CR; the CR rate of 1 course treatment was 90.2%. The follow-up time lasted to March 17, 2015, the median follow-up time was 25(9-79) months; the 1 year OS rate was 75.3%, the EFS rate was 58.3%. Analysis of risk factors showed that the initial WBC count over 30×10 9 /L, LDH over 250 U/L and minimal residual disease(MRD) over 10 -4 after treatment were poor prognostic factors. After remission, the standardized consolidatory treatment or allo-HSCT according to the "2012 China adult ALL diagnosis and treatment expert consensus" could improve long-term survival, 3 years OS rate was 73.8% and 61.5% respectively, 3 years EFS were 63.5% and 65.7% respectively. The main toxic and side effects were hematologic reactions, the hematologic adverse reaction of IV grade was observed in 97.6%(40/41) during induction treatment. Induction chemotherapy based on VICP+L-ASP/TKI and standardized consolidatory after remission according to the "2012 China adult acute lymphoblastic leukemia diagnosis and treatment expert consensus" can improve the therapeutic efficacy. The allo-HSCT should be actively performed for B-ALL paients with high risk(elevated initial WBC count and LDH level); at some time, the regularly monitoring MRD and adjusting therapeutic protocol according to monitoring
[Characterization of microbial community in produced water from a petroleum reservoir subjected to alkali-surfactant-polymer ASP flooding].

PubMed

Hao, Qin Qin; Shi, Rong Jiu; Hao, Jin Sheng; Zhao, Jin Yi; Li, Guo Qiao; Zhao, Feng; Han, Si Qin; Zhang, Ying

2017-10-01

Injection of alkali, surfactant and polymer (ASP) into oil reservoir can substantially increase oil recovery compared with water-flooding strategy. However, the effects of these agents on the microbial diversity and community structure, which is important for water management and corrosion control in oil industry, are hitherto poorly understood. Here, we disclosed the microbial diversity and community structure in the produced water collected from four producing wells of an ASP-flooded oilfield at Daqing, China, using high-throughput sequencing technique. Results showed that the average pH in produced water was as high as 9.65. The microbial diversity varied from well to well, and the Shannon diversity index was between 2.00 to 3.56. The Proteobacteria (85.5%-98.3%), γ-proteobacteria (83.7%-97.8%), and alkaliphilic Nitrincola (51.8%-82.5%) were the most dominant phylogenetic taxa at the phylum, class, and genus levels, respectively. A total of 12 potentially sulfide-producing genera were detected, and the most abundant taxon was Sulfurospirillum (0.4%-7.4%). The microbial community of ASP-flooded petroleum reservoir was distinct, showing an alkaliphilic or alkalitolerant potential; a reduced diversity and more simple structure were observed compared with those of the water-flooded petroleum reservoirs that were previously reported.
Role of toll-like receptor 4 Asp299Gly polymorphism in the development of cardiovascular diseases in HIV-infected patients.

PubMed

Tarancon-Diez, Laura; De Pablo-Bernal, Rebeca S; Jiménez, José L; Álvarez-Ríos, Ana I; Genebat, Miguel; Rosado-Sánchez, Isaac; Muñoz-Fernández, María-Ángeles; Ruiz-Mateos, Ezequiel; Leal, Manuel

2018-05-15

Cardiovascular diseases (CVDs) are one of the main causes of morbimortality in HIV-infected patients on suppressive antiretroviral therapy. The objective of this work was to evaluate the role of single nucleotide polymorphisms (SNPs) in lipopolysaccharide (LPS) Toll-like receptor 4 (TLR4) and CVDs occurrence in HIV-infected patients. Additionally, the functional consequences of carrying these SNPs were analyzed. The association of TLR4 SNPs, Asp299Gly/Thr399Ile with CVDs occurrence was analyzed using multivariate logistic regression models. Clinical, immunological, and traditional cardiovascular risk factors were used as covariates. The monocyte phenotype and response were assessed by multiparametric flow cytometry comparing carriers with noncarriers of this SNP. Asp299Gly SNP, assayed in 253 HIV-infected patients, was independently associated with the occurrence of CVDs after adjusting for CD4 T-cell nadir, HCV-coinfection, bacterial pneumonia, diabetes mellitus, and traditional cardiovascular risk factors [odds ratio (confidence interval 95%) = 3.672 (1.061-12.712), P = 0.04). Carriers of Asp299Gly SNP showed higher percentage of patrolling and intermediate monocytes producing a proinflammatory combination of cytokines compared with noncarriers (P = 0.037 and P = 0.046, respectively). Intermediate monocyte subset levels correlated with soluble interleukin-6 levels only in carriers (r = 0.89; P = 0.01). TLR4 Asp299Gly polymorphism is independently associated with the occurrence of CVDs in HIV-infected patients. The proinflammatory profile associated to this variant could be involved in the development of atherosclerotic pathologies.

Multilevel modelling of somatotype components: the Portuguese sibling study on growth, fitness, lifestyle and health.

PubMed

Pereira, Sara; Katzmarzyk, Peter T; Gomes, Thayse Natacha; Souza, Michele; Chaves, Raquel N; Santos, Fernanda K Dos; Santos, Daniel; Hedeker, Donald; Maia, José A R

2017-06-01

Somatotype is a complex trait influenced by different genetic and environmental factors as well as by other covariates whose effects are still unclear. To (1) estimate siblings' resemblance in their general somatotype; (2) identify sib-pair (brother-brother (BB), sister-sister (SS), brother-sister (BS)) similarities in individual somatotype components; (3) examine the degree to which between and within variances differ among sib-ships; and (4) investigate the effects of physical activity (PA) and family socioeconomic status (SES) on these relationships. The sample comprises 1058 Portuguese siblings (538 females) aged 9-20 years. Somatotype was calculated using the Health-Carter method, while PA and SES information was obtained by questionnaire. Multi-level modelling was done in SuperMix software. Older subjects showed the lowest values for endomorphy and mesomorphy, but the highest values for ectomorphy; and more physically active subjects showed the highest values for mesomorphy. In general, the familiality of somatotype was moderate (ρ = 0.35). Same-sex siblings had the strongest resemblance (endomorphy: ρ SS > ρ BB > ρ BS ; mesomorphy: ρ BB = ρ SS > ρ BS ; ectomorphy: ρ BB > ρ SS > ρ BS ). For the ectomorphy and mesomorphy components, BS pairs showed the highest between sib-ship variance, but the lowest within sib-ship variance; while for endomorphy BS showed the lowest between and within sib-ship variances. These results highlight the significant familial effects on somatotype and the complexity of the role of familial resemblance in explaining variance in somatotypes.
The aspartyl protease TgASP5 mediates the export of the Toxoplasma GRA16 and GRA24 effectors into host cells.

PubMed

Curt-Varesano, Aurélie; Braun, Laurence; Ranquet, Caroline; Hakimi, Mohamed-Ali; Bougdour, Alexandre

2016-02-01

Toxoplasma gondii and Plasmodium species are obligatory intracellular parasites that export proteins into the infected cells in order to interfere with host-signalling pathways, acquire nutrients or evade host defense mechanisms. With regard to export mechanism, a wealth of information in Plasmodium spp. is available, while the mechanisms operating in T. gondii remain uncertain. The recent discovery of exported proteins in T. gondii, mainly represented by dense granule resident proteins, might explain this discrepancy and offers a unique opportunity to study the export mechanism in T. gondii. Here, we report that GRA16 export is mediated by two protein elements present in its N-terminal region. Because the first element contains a putative Plasmodium export element linear motif (RRLAE), we hypothesized that GRA16 export depended on a maturation process involving protein cleavage. Using both N- and C-terminal epitope tags, we provide evidence for protein proteolysis occurring in the N-terminus of GRA16. We show that TgASP5, the T. gondii homolog of Plasmodium plasmepsin V, is essential for GRA16 export and is directly responsible for its maturation in a Plasmodium export element-dependent manner. Interestingly, TgASP5 is also involved in GRA24 export, although the GRA24 maturation mechanism is TgASP5-independent. Our data reveal different modus operandi for protein export, in which TgASP5 should play multiple functions. © 2015 John Wiley & Sons Ltd.
To pair or not to pair: chromosome pairing and evolution.

PubMed

Moore, G

1998-04-01

Chromosome pairing in wild-type wheat closely resembles the process in both yeast and Drosophila. The recent characterisation of a mutant Ph1 wheat and the observation that chromosome pairing in the absence of Ph1 more closely resembles that of mammals and maize has shed light on the evolution of chromosome pairing in the cereals.
Psychometric Properties of the ASPeCT-DD: Measuring Positive Traits in Persons with Developmental Disabilities

ERIC Educational Resources Information Center

Woodard, Cooper

2009-01-01

Background: The Assessment Scale for Positive Character Traits-Developmental Disabilities (ASPeCT-DD) was designed to measure the presence and strength of selected positive or strength-based traits in persons with developmental disabilities. These traits may help to determine level of happiness or value associated with the more commonly measured…
NLGN3/NLGN4 gene mutations are not responsible for autism in the Quebec population.

PubMed

Gauthier, Julie; Bonnel, Anna; St-Onge, Judith; Karemera, Liliane; Laurent, Sandra; Mottron, Laurent; Fombonne, Eric; Joober, Ridha; Rouleau, Guy A

2005-01-05

Jamain [2003: Nat Genet 34:27-29] recently reported mutations in two neuroligin genes in sib-pairs affected with autism. In order to confirm these causative mutations in our autistic population and to determine their frequency we screened 96 individuals affected with autism. We found no mutations in these X-linked genes. These results indicate that mutations in NLGN3 and NLGN4 genes are responsible for at most a small fraction of autism cases and additional screenings in other autistic populations are needed to better determine the frequency with which mutations in NLGN3 and NLGN4 occur in autism. Copyright 2004 Wiley-Liss, Inc.
Statistical analysis of Amenamevir (ASP2151) between pharmacokinetics and clinical efficacies with non-linear effect model for the treatment of genital herpes.

PubMed

Takada, Akitsugu; Katashima, Masataka; Kaibara, Atsunori; Sawamoto, Taiji; Zhang, Wenhui; Keirns, James

2014-09-01

Amenamevir is the international non-proprietary name for ASP2151 synthesized by Astellas Pharma, Inc. It is a structurally novel class of helicase-primase inhibitor and demonstrated more potency in vitro anti-viral activity with low cytotoxicity against varicella-zoster virus (VZV), herpes simplex virus type 1 (HSV-1), and herpes simplex virus type 2 (HSV-2) than acyclovir (ACV). Phase II randomized trial assessed the safety and efficacy of ASP2151 for episodic therapy of recurrent genital herpes was conducted. Participants self-initiated with ASP2151 (100, 200, or 400 mg daily for 3 days), ASP2151 (1,200 mg as a single dose), placebo for 3 days, or Valacyclovir (500 mg twice daily for 3 days). We present a first population pharmacokinetic (PPK) modeling analysis of Amenamevir for genital herpes patients. The final model retained the effect of Weight and Albumin on CL. Statistical analysis between pharmacokinetics and clinical efficacies was done by using the time above 200 ng/mL (T200 ). T200 derived from the final PPK model to consider the correlation with Time to lesion healing and viral shedding. This finding suggested that it could be necessary to maintain the Amenamevir concentration above the threshold level to prevent the virus replication. © 2014, The American College of Clinical Pharmacology.
Schizophrenia: A genome search targets chromosomes 3 and 8 for exploration

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

Lasseter, V.K.; Pulver, A.E.; Wolyniec, P.

1994-09-01

Using a systematically ascertained sample of 57 families, each having 2 or more members with a consensus diagnosis of schizophrenia (DSM-III-R criteria), we have searched approximately 75% of the genome for susceptibility loci for schizophrenia. Genetic linkage studies of 520 loci have been performed using a complex autosomal dominant model incorporating age-at-onset and certainty of the diagnosis. Results were analyzed under the hypothesis of heterogeneity using the A-test and the Liang test. A two-stage strategy based on lod score thresholds from simulation studies of our sample identified regions for further exploration (hot spots). In each region, a dense map ofmore » highly informative dinucleotide repeat polymorphisms (heterozygosity greater than .70) is analyzed using linkage studies with dominant, recessive, and affected only models and non-parametric sib pair identity-by-descent methods (SIBPAL, S.A.G.E. 2.1). In no region has a lod score > 3 been observed; however, affected sib pair analyses gave a p-value of .0001 corresponding to a lod score > 3. Current {open_quote}hot spots{close_quote} on chromosomes 3p26-p24 and 8p22-p21 will be presented. For 3p26-p24, the maximum two-point lod score is 1.97 (dominant model) and the SIBPAL p-value is .02. For 8p22-p21, the maximum two-point lod score is 2.02 (recessive model) and the SIBPAL p-value is .0001.« less
Long QT syndrome type 5-Lite: Defining the clinical phenotype associated with the potentially proarrhythmic p.Asp85Asn-KCNE1 common genetic variant.

PubMed

Lane, Conor; Giudicessi, John R; Ye, Dan; Tester, David J; Rohatgi, Ram K; Bos, J Martijn; Ackerman, Michael J

2018-04-03

Long QT syndrome (LQTS) genetic test reports commonly exclude potentially proarrhythmic common variants such as p.Asp85Asn-KCNE1. The purpose of this study was to determine whether a discernible phenotype is associated with p.Asp85Asn-KCNE1 and whether relatively common KCNE1 variants underlie transient QT prolongation pedigrees with negative commercial LQTS genetic tests. Retrospective review was used to compare demographics, symptomatology, and QT parameters of individuals with p.Asp85Asn-KCNE1 in the absence of other rare/ultra-rare variants in LQTS-susceptibility genes and those who underwent comprehensive LQTS genetic testing. Compared to the Genome Aggregation Database, p.Asp85Asn-KCNE1 was more prevalent in individuals undergoing LQTS genetic testing (33/1248 [2.6%] vs 1552/126,652 [1.2%]; P = .0001). In 19 of 33 patients (58%), only p.Asp85Asn-KCNE1 was observed. These patients were predominantly female (90% vs 62%; P = .02) and were less likely to experience syncope (0% vs 34%; P = .0007), receive β-blockers (53% vs 85%; P = .001), or require an implantable cardioverter-defibrillator (5.3% vs 33%; P = .01). However, they exhibited a similar degree of QT prolongation (QTc 460 ms vs 467 ms; P = NS). Whole exome sequencing of 2 commercially genotype-negative pedigrees revealed that p.Asp85Asn-KCNE1 and p.Arg36His-KCNE1 traced with a transient QT prolongation phenotype. Functional characterization of p.Arg36His-KCNE1 demonstrated loss of function, with a 47% reduction in peak I Ks current density in the heterozygous state. We provide further evidence that relatively common variants in KCNE1 may result in a mild QT phenotype designated as "LQT5-Lite" to distinguish such potentially proarrhythmic common variants (ie, functional risk alleles) from rare pathogenic variants that truly confer monogenic disease susceptibility, albeit with incomplete penetrance. Copyright © 2018. Published by Elsevier Inc.
[Telecardiology: clinical, technical and social aspects. The project of the ASP of Cosenza, Italy].

PubMed

Bisignani, Giovanni; De Bonis, Silvana; Bisignani, Antonio; Verta, Antonella

2016-12-01

The aim of this paper is to present the project of telecardiology within the ASP of Cosenza, one of the largest provinces of Italy characterized by a particular orography, with difficult and inaccessible roads. The goal of this project is to manage the emergency more efficiently by reducing the time of intervention by bringing the patient not to the nearest hospital, but more importantly to the hospital more appropriately suited to better manage the cardiological emergency. This system also uses the most modern web-based interface technology protected by login and password. The project also provides the integration, supply and installation of advanced and modern central by ensuring efficient screening is carried out using monitors in all the coronary care units of the ASP of Cosenza, networking with electrocardiography of all the point of first medical contact and all the 118 emergency rescue service. By integrating all these procedures and information and making them available to any point in the hospital and territorial network, this project becomes not only a more efficient system for managing cardiac emergency but also a pathway that will guarantee increased care of patients from the onset of symptoms to discharge.
The frequent mutation Gly/Asp in CDR1H may determine a cross-reactive idiotope in anti-I cold agglutinins

PubMed Central

ABATANGELO, C; PLOTKIN, L; MATHOV, I; SQUIQUERA, L; LEONI, J

1996-01-01

Variable domains (VH) of all known anti i/I cold agglutinin (CA) heavy chains are codified by the VH4–21 gene. While anti-i CAs are the expression of gene rearrangement without mutations represented by amino acid changes, anti-I CAs present, among others, a frequent somatic mutation of Gly by Asp at position 31. The hydropathy profile calculated for the CDR1H (position 30 to position 35), as well as some adjacent positions of the heavy chain belonging to anti-i and anti-I antibodies, showed the conformational changes accompanying the replacement of Gly by Asp. A MoAb (LP91), which had been obtained in BALB/c mice immunized with a Fabμ fragment from a monoclonal IgMκIIIb anti-I CA (protein KAU), proved capable of inhibiting human adult erythrocyte cryoagglutination by anti-I CAs but not that of fetal erythrocytes by anti-i CAs. Western blot analysis disclosed that such MoAbs recognized a sequential epitope located in the Fd fragment of all anti-I CAs employed in this study. With the purpose of checking whether Asp31 was involved in the epitope recognized by the MoAb, two peptides, D and G, were synthesized which mimicked the CDR1H structure of anti-I and anti-i, respectively; the MoAb only reacted with peptide D by ELISA. Subsequent experimental results indicate that the Gly/Asp mutation could be associated with the diverse specificity presented by these autoantibodies, a change determining a characteristic epitope/idiotope, recognized by LP91 in the CDR1H. PMID:8603526
Effects of experimental light at night on extra-pair paternity in a songbird.

PubMed

de Jong, Maaike; Lamers, Koosje P; Eugster, Mark; Ouyang, Jenny Q; Da Silva, Arnaud; Mateman, A Christa; van Grunsven, Roy H A; Visser, Marcel E; Spoelstra, Kamiel

2018-06-27

Light pollution is increasing worldwide and significantly affects animal behavior. In birds, these effects include advancement of morning activity and onset of dawn song, which may affect extra-pair paternity. Advanced dawn song of males may stimulate females to engage in extra-pair copulations, and the earlier activity onset may affect the males' mate guarding behavior. Earlier work showed an effect of light at night on extra-pair behavior, but this was in an area with other anthropogenic disturbances. Here, we present a two-year experimental study on effects of light at night on extra-pair paternity of great tits (Parus major). Previously dark natural areas were illuminated with white, red, and green LED lamps and compared to a dark control. In 2014, the proportion of extra-pair young in broods increased with distance to the red and white lamps (i.e., at lower light intensities), but decreased with distance to the poles in the dark control. In 2013, we found no effects on the proportion of extra-pair young. The total number of offspring sired by a male was unaffected by artificial light at night in both years, suggesting that potential changes in female fidelity in pairs breeding close to white and red light did not translate into fitness benefits for the males of these pairs. Artificial light at night might disrupt the natural patterns of extra-pair paternity, possibly negates potential benefits of extra-pair copulations and thus could alter sexual selection processes in wild birds. © 2018 Wiley Periodicals, Inc.
The relationship of Asperger's syndrome to autism: a preliminary EEG coherence study.

PubMed

Duffy, Frank H; Shankardass, Aditi; McAnulty, Gloria B; Als, Heidelise

2013-07-31

It has long been debated whether Asperger's Syndrome (ASP) should be considered part of the Autism Spectrum Disorders (ASD) or whether it constitutes a unique entity. The Diagnostic and Statistical Manual, fourth edition (DSM-IV) differentiated ASP from high functioning autism. However, the new DSM-5 umbrellas ASP within ASD, thus eliminating the ASP diagnosis. To date, no clear biomarkers have reliably distinguished ASP and ASD populations. This study uses EEG coherence, a measure of brain connectivity, to explore possible neurophysiological differences between ASP and ASD. Voluminous coherence data derived from all possible electrode pairs and frequencies were previously reduced by principal components analysis (PCA) to produce a smaller number of unbiased, data-driven coherence factors. In a previous study, these factors significantly and reliably differentiated neurotypical controls from ASD subjects by discriminant function analysis (DFA). These previous DFA rules are now applied to an ASP population to determine if ASP subjects classify as control or ASD subjects. Additionally, a new set of coherence based DFA rules are used to determine whether ASP and ASD subjects can be differentiated from each other. Using prior EEG coherence based DFA rules that successfully classified subjects as either controls or ASD, 96.2% of ASP subjects are classified as ASD. However, when ASP subjects are directly compared to ASD subjects using new DFA rules, 92.3% ASP subjects are identified as separate from the ASD population. By contrast, five randomly selected subsamples of ASD subjects fail to reach significance when compared to the remaining ASD populations. When represented by the discriminant variable, both the ASD and ASD populations are normally distributed. Within a control-ASD dichotomy, an ASP population falls closer to ASD than controls. However, when compared directly with ASD, an ASP population is distinctly separate. The ASP population appears to constitute a
Synthesis of aspartyl-tRNA(Asp) in Escherichia coli--a snapshot of the second step.

PubMed Central

Eiler, S; Dock-Bregeon, A; Moulinier, L; Thierry, J C; Moras, D

1999-01-01

The 2.4 A crystal structure of the Escherichia coli aspartyl-tRNA synthetase (AspRS)-tRNA(Asp)-aspartyl-adenylate complex shows the two substrates poised for the transfer of the aspartic acid moiety from the adenylate to the 3'-hydroxyl of the terminal adenosine of the tRNA. A general molecular mechanism is proposed for the second step of the aspartylation reaction that accounts for the observed conformational changes, notably in the active site pocket. The stabilization of the transition state is mediated essentially by two amino acids: the class II invariant arginine of motif 2 and the eubacterial-specific Gln231, which in eukaryotes and archaea is replaced by a structurally non-homologous serine. Two archetypal RNA-protein modes of interactions are observed: the anticodon stem-loop, including the wobble base Q, binds to the N-terminal beta-barrel domain through direct protein-RNA interactions, while the binding of the acceptor stem involves both direct and water-mediated hydrogen bonds in an original recognition scheme. PMID:10562565
Simulating Aerosol Optical Properties With the Aerosol Simulation Program (ASP): Closure Studies Using ARCTAS Data

NASA Astrophysics Data System (ADS)

Alvarado, M. J.; Macintyre, H. L.; Bian, H.; Chin, M.; Wang, C.

2012-12-01

The scattering and absorption of ultraviolet and visible radiation by aerosols can significantly alter actinic fluxes and photolysis rates. Accurate modeling of aerosol optical properties is thus essential to simulating atmospheric chemistry, air quality, and climate. Here we evaluate the aerosol optical property predictions of the Aerosol Simulation Program (ASP) with in situ data on aerosol scattering and absorption gathered during the Arctic Research of the Composition of the Troposphere from Aircraft and Satellites (ARCTAS) campaign. The model simulations are initialized with in situ data on the aerosol size distribution and composition. We perform a set of sensitivity studies (e.g., internal vs. external mixture, core-in-shell versus Maxwell-Garnett, fraction of the organic carbon mass that is light-absorbing "brown carbon," etc.) to determine the model framework and parameters most consistent with the observations. We compare the ASP results to the aerosol optical property lookup tables in FAST-JX and suggest improvements that will better enable FAST-JX to simulate the impact of aerosols on photolysis rates and atmospheric chemistry.
Clinical correlates of the presence of the Asp816Val c-kit mutation in the peripheral blood mononuclear cells of patients with mastocytosis.

PubMed

Worobec, A S; Semere, T; Nagata, H; Metcalfe, D D

1998-11-15

The Asp816Val mutation in the catalytic domain of the c-kit receptor has been identified in patients with systemic mastocytosis. To determine whether this mutation is associated with identifiable clinical patterns of disease and prognosis, a total of 65 patients with mastocytosis were screened for the presence of the Asp816Val mutation in peripheral blood mononuclear cells (PBMCs). By analysis of HinfI digestion products, the authors found that the overall prevalence of this mutation in the current patient series was 25%. The presence of the Asp816Val mutation in PBMCs was observed in 15 adults (of 16 Asp816Val mutation positive patients) and 1 infant, but not in any children with mastocytosis. Patients whose PBMCs were positive for this mutation (category II and a subset of category Ib mastocytosis patients) manifested a more severe disease pattern, with clinical features ranging in severity from early to advanced myelodysplastic or myeloproliferative syndromes. These patients more commonly had osteosclerotic bone involvement (a clinical feature primarily observed in mastocytosis patients with an associated hematologic disorder) as well as immunoglobulin dysregulation and peripheral blood abnormalities. Furthermore, pedigree analysis of three families provided evidence that the mutation was somatic. Twenty-five percent of all patients with mastocytosis had the Asp816Val mutation in PBMCs; 56% of these patients had evidence of a myelodysplastic or myeloproliferative syndrome, and 44% had been clinically placed in the indolent mastocytosis category, suggesting that the current classification scheme used to assign prognosis may be inadequate. Therefore, determination of the presence or absence of this mutation in PBMCs of mastocytosis patients offers a useful adjunct in determining the extent of workup and assigning prognosis in this complex and heterogeneous disease.
Case-Deletion Diagnostics for Maximum Likelihood Multipoint Quantitative Trait Locus Linkage Analysis

PubMed Central

Mendoza, Maria C.B.; Burns, Trudy L.; Jones, Michael P.

2009-01-01

Objectives Case-deletion diagnostic methods are tools that allow identification of influential observations that may affect parameter estimates and model fitting conclusions. The goal of this paper was to develop two case-deletion diagnostics, the exact case deletion (ECD) and the empirical influence function (EIF), for detecting outliers that can affect results of sib-pair maximum likelihood quantitative trait locus (QTL) linkage analysis. Methods Subroutines to compute the ECD and EIF were incorporated into the maximum likelihood QTL variance estimation components of the linkage analysis program MAPMAKER/SIBS. Performance of the diagnostics was compared in simulation studies that evaluated the proportion of outliers correctly identified (sensitivity), and the proportion of non-outliers correctly identified (specificity). Results Simulations involving nuclear family data sets with one outlier showed EIF sensitivities approximated ECD sensitivities well for outlier-affected parameters. Sensitivities were high, indicating the outlier was identified a high proportion of the time. Simulations also showed the enormous computational time advantage of the EIF. Diagnostics applied to body mass index in nuclear families detected observations influential on the lod score and model parameter estimates. Conclusions The EIF is a practical diagnostic tool that has the advantages of high sensitivity and quick computation. PMID:19172086
Characterization of sulfonylurea-resistant Schoenoplectus juncoides having a target-site Asp(376)Glu mutation in the acetolactate synthase.

PubMed

Sada, Yoshinao; Ikeda, Hajime; Yamato, Seiji; Kizawa, Satoru

2013-09-01

Schoenoplectus juncoides, a noxious weed for paddy rice, is known to become resistant to sulfonylurea (SU) herbicides by a target-site mutation in either of the two acetolactate synthase (ALS) genes (ALS1 and ALS2). SU-resistant S. juncoides plants having an Asp376Glu mutation in ALS2 were found from a paddy rice field in Japan, but their resistance profile has not been quantitatively investigated. In this study, dose-response of the SU-resistant accession was compared with that of a SU-susceptible accession at in vivo whole-plant level as well as at in vitro enzymatic level. In whole-plant tests, resistance factors (RFs) based on 50% growth reduction (GR50) for imazosulfuron (ISF), bensulfuron-methyl (BSM), metsulfuron-methyl (MSM), bispyribac-sodium (BPS), and imazaquin (IMQ) were 176, 40, 14, 5.2 and 1.5, respectively. Thus, the accession having an Asp376Glu mutation in ALS2 was highly resistant to the three SU herbicides and moderately resistant to BPS, but was not substantially resistant to IMQ. This is slightly different from the earlier results reported from other weeds with an Asp376Glu mutation, in which the mutation confers resistance to broadly all the chemical classes of ALS-inhibiting herbicides. In enzymatic tests, ALS2 of S. juncoides was expressed in E. coli; the resultant ALS2 was subjected to an in vitro assay. RFs of the mutated ALS2 based on 50% enzymatic inhibition (I50) for ISF, BSM, MSM, BPS, and IMQ were 3699, 2438, 322, 80, and 4.8, respectively. The RFs of ALS2 were highly correlated with those of the whole-plant; this suggests that the Asp376Glu mutation in ALS2 is a molecular basis for the whole-plant resistance. The presence of two ALS genes in S. juncoides can at least partially explain why the whole-plant RFs were less than those of the expressed ALS2 enzymes. Copyright © 2013 Elsevier Inc. All rights reserved.
Crystal structures of sampatrilat and sampatrilat-Asp in complex with human ACE - a molecular basis for domain selectivity.

PubMed

Cozier, Gyles E; Schwager, Sylva L; Sharma, Rajni K; Chibale, Kelly; Sturrock, Edward D; Acharya, K Ravi

2018-04-01

Angiotensin-1-converting enzyme (ACE) is a zinc metallopeptidase that consists of two homologous catalytic domains (known as nACE and cACE) with different substrate specificities. Based on kinetic studies it was previously reported that sampatrilat, a tight-binding inhibitor of ACE, K i = 13.8 nm and 171.9 nm for cACE and nACE respectively [Sharma et al., Journal of Chemical Information and Modeling (2016), 56, 2486-2494], was 12.4-fold more selective for cACE. In addition, samAsp, in which an aspartate group replaces the sampatrilat lysine, was found to be a nonspecific and lower micromolar affinity inhibitor. Here, we report a detailed three-dimensional structural analysis of sampatrilat and samAsp binding to ACE using high-resolution crystal structures elucidated by X-ray crystallography, which provides a molecular basis for differences in inhibitor affinity and selectivity for nACE and cACE. The structures show that the specificity of sampatrilat can be explained by increased hydrophobic interactions and a H-bond from Glu403 of cACE with the lysine side chain of sampatrilat that are not observed in nACE. In addition, the structures clearly show a significantly greater number of hydrophilic and hydrophobic interactions with sampatrilat compared to samAsp in both cACE and nACE consistent with the difference in affinities. Our findings provide new experimental insights into ligand binding at the active site pockets that are important for the design of highly specific domain selective inhibitors of ACE. The atomic coordinates and structure factors for N- and C-domains of ACE bound to sampatrilat and sampatrilat-Asp complexes (6F9V, 6F9R, 6F9T and 6F9U respectively) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/). © 2018 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
Kinetic studies of the yeast His-Asp phosphorelay signaling pathway

PubMed Central

Kaserer, Alla O.; Andi, Babak; Cook, Paul F.; West, Ann H.

2010-01-01

For both prokaryotic and eukaryotic His-Asp phosphorelay signaling pathways, the rates of protein phosphorylation and dephosphorylation determine the stimulus-to-response time frame. Thus, kinetic studies of phosphoryl group transfer between signaling partners are important for gaining a full understanding of how the system is regulated. In many cases, the phosphotransfer reactions are too fast for rates to be determined by manual experimentation. Rapid quench flow techniques thus provide a powerful method for studying rapid reactions that occur in the millisecond time frame. In this chapter, we describe experimental design and procedures for kinetic characterization of the yeast SLN1-YPD1-SSK1 osmoregulatory phosphorelay system using a rapid quench flow kinetic instrument. PMID:20946842
Changes of CFTR functional measurements and clinical improvements in cystic fibrosis patients with non p.Gly551Asp gating mutations treated with ivacaftor.

PubMed

Mesbahi, Myriam; Shteinberg, Michal; Wilschanski, Michael; Hatton, Aurelie; Nguyen-Khoa, Thao; Friedman, Hannah; Cohen, Michael; Escabasse, Virginie; Le Bourgeois, Muriel; Lucidi, Vicenzina; Sermet-Gaudelus, Isabelle; Bassinet, Laurence; Livnat, Galit

2017-01-01

Ivacaftor, a CFTR potentiator, has been found to improve CFTR function and clinical outcomes in patients with cystic fibrosis (CF) gating mutations. We investigated the effects of ivacaftor on CFTR functional measurement in CF patients carrying gating mutations other than p.Gly551Asp. Two siblings aged 13 and 12 carrying the p.Ser549Asn mutation, two sisters (45 and 43years old) compound heterozygotes for p.Asp1152His and p.Gly1244Glu, a 37year old man homozygous for the p.Gly1244Glu mutation, and a 7year old girl with p.Arg352Gln and p.Gly1244Glu mutations commenced treatment with ivacaftor. NPD was performed in all the patients and approached normal for four patients who had also clinical improvement (p.Ser549Asn compound heterozygotes, and p.Asp1152His/p.Gly1244Glu siblings). Beta-adrenergic sweat chloride secretion performed in thep.Asp1152His/p.Gly1244Glu patients improved significantly. The p.Gly1244Glu mutation homozygous patient, who had undergone an ileal resection with ileostomy and enterocutaneous fistula, did not respond clinically to ivacaftor and did not modify his sweat test. These results highlight the importance of different CFTR activity measurements to explore CFTR modulator efficacy. Copyright © 2016. Published by Elsevier B.V.

(±)-Japonones A and B, two pairs of new enantiomers with anti-KSHV activities from Hypericum japonicum

NASA Astrophysics Data System (ADS)

Hu, Linzhen; Zhu, Hucheng; Li, Lei; Huang, Jinfeng; Sun, Weiguang; Liu, Junjun; Li, Hua; Luo, Zengwei; Wang, Jianping; Xue, Yongbo; Zhang, Yu; Zhang, Yonghui

2016-06-01

Two pairs of new enantiomers with unusual 5,5-spiroketal cores, termed (±)-japonones A and B [(±)-1 and (±)-2], were obtained from Hypericum japonicum Thunb. The absolute configurations of (±)-1 and (±)-2 were characterized by extensive analyses of spectroscopic data and calculated electronic circular dichroism (ECD) spectra, the application of modified Mosher’s methods, and the assistance of quantum chemical predictions (QCP) of 13C NMR chemical shifts. Among these metabolites, (+)-1 exhibited some inhibitory activity on Kaposi’s sarcoma associated herpesvirus (KSHV). Virtual screening of (±)-1 and (±)-2 were conducted using the Surflex-Dock module in the Sybyl software, and (+)-1 exhibited ability to bind with ERK to form key interactions with residues Lys52, Pro56, Ile101, Asp165, Gly167 and Val99.
Study on the technology of dual-tube layered injection in ASP flooding

NASA Astrophysics Data System (ADS)

Yang, Ye; Zhang, Yongping; Xu, Dekui; Cai, Meng; Yang, Zhigang; Wang, Hailong; Song, Xingliang

2017-10-01

For the single-tube layered injection technology cannot solve the problem of interlayer pressure difference is greater than 2MPa injection wells, through the development of dual-tube packer, dual-tube injection allocator, downhole plug, the ground pressure regulator and molecular weight regulator. Dual-tube layered injection technology is formed. According to the data of ASP flooding injection wells in the field, the whole well is divided into high permeability and low permeability oil reservoir. Two separate injection channels can be formed by using dual-tube packer and dual-tube injection allocator. Through the use of the ground pressure regulator, the problem of the high permeability layer and low permeability layer of the injection pressure difference is solved. Through the use of the ground molecular weight regulator, the problem that the same molecular weight ASP solution is not suitable for high and low permeability is solved. By replacing the downhole plug, the grouping transformation of some oil layer can be achieved. The experiment and field application of 3 wells results show that: the flow control range is 20m3/d-70m3/d; the max. Throttling differential pressure is 3.5MPa; the viscosity loss rate of solution is less than 5%; and the molecular weight adjusting range is 20%-50%. The utilization degree of oil layer is obviously increased through the use of the dual-tube layered injection technology.
Identification of homozygous WFS1 mutations (p.Asp211Asn, p.Gln486*) causing severe Wolfram syndrome and first report of male fertility

PubMed Central

Haghighi, Amirreza; Haghighi, Alireza; Setoodeh, Aria; Saleh-Gohari, Nasrollah; Astuti, Dewi; Barrett, Timothy G

2013-01-01

Wolfram syndrome (WFS) is a neurodegenerative genetic condition characterized by juvenile-onset of diabetes mellitus and optic atrophy. We studied clinical features and the molecular basis of severe WFS (neurodegenerative complications) in two consanguineous families from Iran. A clinical and molecular genetic investigation was performed in the affected and healthy members of two families. The clinical diagnosis of WFS was confirmed by the existence of diabetes mellitus and optic atrophy in the affected patients, who in addition had severe neurodegenerative complications. Sequencing of WFS1 was undertaken in one affected member from each family. Targeted mutations were tested in all members of relevant families. Patients had most of the reported features of WFS. Two affected males in the first family had fathered unaffected children. We identified two homozygous mutations previously reported with apparently milder phenotypes: family 1: c.631G>A (p.Asp211Asn) in exon 5, and family 2: c.1456C>T (p.Gln486*) in exon 8. Heterozygous carriers were unaffected. This is the first report of male Wolfram patients who have successfully fathered children. Surprisingly, they also had almost all the complications associated with WFS. Our report has implications for genetic counseling and family planning advice for other affected families. PMID:22781099
ASP8273 tolerability and antitumor activity in TKI-naive Japanese patients with EGFR mutation-positive non-small cell lung cancer.

PubMed

Azuma, Koichi; Nishio, Makoto; Hayashi, Hidetoshi; Kiura, Katsuyuki; Satouchi, Miyako; Sugawara, Shunichi; Hida, Toyoaki; Iwamoto, Yasuo; Inoue, Akira; Takeda, Koji; Ikeda, Satoshi; Nakagawa, Tomoki; Takeda, Kentaro; Asahina, Seitaro; Komatsu, Kanji; Morita, Satoshi; Fukuoka, Masahiro; Nakagawa, Kazuhiko

2018-05-28

Epidermal growth factor receptor (EGFR) activating mutations occur in approximately 50% of East Asian patients with non-small cell lung cancer (NSCLC) and confer sensitivity to tyrosine kinase inhibitors (TKI). ASP8273 is an orally administered, irreversible EGFR-TKI that inhibits EGFR activating mutations and has demonstrated clinical activity in patients with EGFR mutation-positive NSCLC. EGFR-TKI-naïve Japanese adult patients (≥20 years) with NSCLC harboring EGFR mutations were enrolled in this open-label, single-arm, Phase 2 study (NCT02500927). Patients received ASP8273 300mg once daily until discontinuation criteria were met. The primary endpoint was to determine the safety of ASP8273 300mg; secondary endpoint was antitumor activity defined by RECIST v1.1. Thirty-one patients (12M/19F; median age 64 years [range: 31-82]) with EGFR mutation-positive NSCLC were enrolled; as of 23 February 2016, 25 patients (81%) were still on study. Of the 31 patients, 27 (87%) had an ex19del (n=13, 42%) or a L858R (n=14, 45%) EGFR activating mutation; 2 (7%) had L861Q mutation and 5 (16%) had other EGFR activating mutations, two had an activating mutation and the T790M resistance mutation. The most commonly reported treatment-emergent adverse event was diarrhea [n=24, 77%]. All patients had at least 1 post-baseline scan; 1 patient (3%) achieved a confirmed complete response, 13 (42%) had a confirmed partial response, and 15 (48%) had confirmed stable disease (disease control rate: 94% [n=29/31]) per investigator assessment. Once-daily ASP8273 300 mg was generally well tolerated and demonstrated antitumor activity in TKI-naïve Japanese patients with EGFR mutation-positive NSCLC. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Genetic Mapping of Quantitative Trait Loci Controlling Growth and Wood Quality Traits in Eucalyptus Grandis Using a Maternal Half-Sib Family and Rapd Markers

PubMed Central

Grattapaglia, D.; Bertolucci, FLG.; Penchel, R.; Sederoff, R. R.

1996-01-01

Quantitative trait loci (QTL) mapping of forest productivity traits was performed using an open pollinated half-sib family of Eucalyptus grandis. For volume growth, a sequential QTL mapping approach was applied using bulk segregant analysis (BSA), selective genotyping (SG) and cosegregation analysis (CSA). Despite the low heritability of this trait and the heterogeneous genetic background employed for mapping. BSA detected one putative QTL and SG two out of the three later found by CSA. The three putative QTL for volume growth were found to control 13.7% of the phenotypic variation, corresponding to an estimated 43.7% of the genetic variation. For wood specific gravity five QTL were identified controlling 24.7% of the phenotypic variation corresponding to 49% of the genetic variation. Overlapping QTL for CBH, WSG and percentage dry weight of bark were observed. A significant case of digenic epistasis was found, involving unlinked QTL for volume. Our results demonstrate the applicability of the within half-sib design for QTL mapping in forest trees and indicate the existence of major genes involved in the expression of economically important traits related to forest productivity in Eucalyptus grandis. These findings have important implications for marker-assisted tree breeding. PMID:8913761
QTL variations for growth-related traits in eight distinct families of common carp (Cyprinus carpio).

PubMed

Lv, Weihua; Zheng, Xianhu; Kuang, Youyi; Cao, Dingchen; Yan, Yunqin; Sun, Xiaowen

2016-05-05

Comparing QTL analyses of multiple pair-mating families can provide a better understanding of important allelic variations and distributions. However, most QTL mapping studies in common carp have been based on analyses of individual families. In order to improve our understanding of heredity and variation of QTLs in different families and identify important QTLs, we performed QTL analysis of growth-related traits in multiple segregating families. We completed a genome scan for QTLs that affect body weight (BW), total length (TL), and body thickness (BT) of 522 individuals from eight full-sib families using 250 microsatellites evenly distributed across 50 chromosomes. Sib-pair and half-sib model mapping identified 165 QTLs on 30 linkage groups. Among them, 10 (genome-wide P <0.01 or P < 0.05) and 28 (chromosome-wide P < 0.01) QTLs exhibited significant evidence of linkage, while the remaining 127 exhibited a suggestive effect on the above three traits at a chromosome-wide (P < 0.05) level. Multiple QTLs obtained from different families affect BW, TL, and BT and locate at close or identical positions. It suggests that same genetic factors may control variability in these traits. Furthermore, the results of the comparative QTL analysis of multiple families showed that one QTL was common in four of the eight families, nine QTLs were detected in three of the eight families, and 26 QTLs were found common to two of the eight families. These common QTLs are valuable candidates in marker-assisted selection. A large number of QTLs were detected in the common carp genome and associated with growth-related traits. Some of the QTLs of different growth-related traits were identified at similar chromosomal regions, suggesting a role for pleiotropy and/or tight linkage and demonstrating a common genetic basis of growth trait variations. The results have set up an example for comparing QTLs in common carp and provided insights into variations in the identified QTLs
Evolution subverting essentiality: Dispensability of the cell attachment Arg-Gly-Asp motif in multiply passaged foot-and-mouth disease virus

PubMed Central

Martínez, Miguel A.; Verdaguer, Nuria; Mateu, Mauricio G.; Domingo, Esteban

1997-01-01

Aphthoviruses use a conserved Arg-Gly-Asp triplet for attachment to host cells and this motif is believed to be essential for virus viability. Here we report that this triplet—which is also a widespread motif involved in cell-to-cell adhesion—can become dispensable upon short-term evolution of the virus harboring it. Foot-and-mouth disease virus (FMDV), which was multiply passaged in cell culture, showed an altered repertoire of antigenic variants resistant to a neutralizing monoclonal antibody. The altered repertoire includes variants with substitutions at the Arg-Gly-Asp motif. Mutants lacking this sequence replicated normally in cell culture and were indistinguishable from the parental virus. Studies with individual FMDV clones indicate that amino acid replacements on the capsid surface located around the loop harboring the Arg-Gly-Asp triplet may mediate in the dispensability of this motif. The results show that FMDV quasispecies evolving in a constant biological environment have the capability of rendering totally dispensable a receptor recognition motif previously invariant, and to ensure an alternative pathway for normal viral replication. Thus, variability of highly conserved motifs, even those that viruses have adapted from functional cellular motifs, can contribute to phenotypic flexibility of RNA viruses in nature. PMID:9192645
Model-free nuclear magnetic resonance study of intermolecular free energy landscapes in liquids with paramagnetic Ln3+ spotlights: theory and application to Arg-Gly-Asp.

PubMed

Fries, Pascal H

2012-01-28

We propose an easily applicable method for investigating the pair distribution function of a lanthanide Ln(3+) complex LnL (L = ligand) with respect to any solvent or solute molecule A carrying observable nuclear spins. Let r be the distance of Ln(3+) to the observed nuclear spin I. We derive a simple expression of the experimental value of the configurational average of 1/r(6) in terms of longitudinal paramagnetic relaxation (rate) enhancements (PREs) of the spin I measured on a standard high-resolution NMR spectrometer and due to well-chosen concentrations of LnL complexes in which Ln(3+) is a fast-relaxing paramagnetic lanthanide or the slowly-relaxing gadolinium Gd(3+). The derivation is justified in the general case of a molecule A which is by turns in a bound state where it follows the complex and a free state where it moves independently. It rests on the expression of the underlying PRE theory in terms of the angle-dependent pair distribution function of LnL and A. The simplifications of this theory in the high-field regime and under the condition of fast exchange between bound and free states are carefully discussed. We also show that original information on the angle dependence of the molecular pair distribution function can be gained from the measured paramagnetic dipolar shifts induced by complexed fast-relaxing Ln(3+) ions. The method is illustrated by the case study of the anionic Lnttha(3-) = [Ln(3+)(ttha)](3-) (ttha(6-) = triethylene tetraamine hexacetate) complex interacting with the biologically important tripeptide Arg-Gly-Asp (RGD) which carries peripheral ionic groups. The usefulness of an auxiliary reference outer sphere probe solute is emphasized. © 2012 American Institute of Physics
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
42 CFR 414.806 - Penalties associated with the failure to submit timely and accurate ASP data.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 3 2013-10-01 2013-10-01 false Penalties associated with the failure to submit timely and accurate ASP data. 414.806 Section 414.806 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) PAYMENT FOR PART B MEDICAL AND OTHER HEALTH SERVICES...
42 CFR 414.806 - Penalties associated with the failure to submit timely and accurate ASP data.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 3 2012-10-01 2012-10-01 false Penalties associated with the failure to submit timely and accurate ASP data. 414.806 Section 414.806 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) PAYMENT FOR PART B MEDICAL AND OTHER HEALTH SERVICES...
42 CFR 414.806 - Penalties associated with the failure to submit timely and accurate ASP data.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Penalties associated with the failure to submit timely and accurate ASP data. 414.806 Section 414.806 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM PAYMENT FOR PART B MEDICAL AND OTHER HEALTH SERVICES Submission of...
42 CFR 414.806 - Penalties associated with the failure to submit timely and accurate ASP data.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 3 2011-10-01 2011-10-01 false Penalties associated with the failure to submit timely and accurate ASP data. 414.806 Section 414.806 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM PAYMENT FOR PART B MEDICAL AND OTHER HEALTH SERVICES Submission of...
42 CFR 414.806 - Penalties associated with the failure to submit timely and accurate ASP data.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 3 2014-10-01 2014-10-01 false Penalties associated with the failure to submit timely and accurate ASP data. 414.806 Section 414.806 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) PAYMENT FOR PART B MEDICAL AND OTHER HEALTH SERVICES...
The Power to Detect Linkage Disequilibrium with Quantitative Traits in Selected Samples

PubMed Central

Abecasis, Gonçalo R.; Cookson, William O. C.; Cardon, Lon R.

2001-01-01

Results from power studies for linkage detection have led to many ongoing and planned collections of phenotypically extreme nuclear families. Given the great expense of collecting these families and the imminent availability of a dense diallelic marker map, the families are likely to be used in allelic-association as well as linkage studies. However, optimal selection strategies for linkage may not be equally powerful for association. We examine the power to detect linkage disequilibrium for quantitative traits after phenotypic selection. The results encompass six selection strategies that are in widespread use, including single selection (two designs), affected sib pairs, concordant and discordant pairs, and the extreme-concordant and -discordant design. Selection of sibships on the basis of one extreme proband with high or low trait scores provides as much power as discordant sib pairs but requires the screening and phenotyping of substantially fewer initial families from which to select. Analysis of the role of allele frequencies within each selection design indicates that common trait alleles generally offer the most power, but similarities between the marker- and trait-allele frequencies are much more important than the trait-locus frequency alone. Some of the most widespread selection designs, such as single selection, yield power gains only when both the marker and quantitative trait loci (QTL) are relatively rare in the population. In contrast, discordant pairs and the extreme-proband design provide power for the broadest range of QTL–marker-allele frequency differences. Overall, proband selection from either tail provides the best balance of power, robustness, and simplicity of ascertainment for family-based association analysis. PMID:11349228
Training Older Siblings to be Better Supervisors: An RCT Evaluating the "Safe Sibs" Program.

PubMed

Schell, Stacey L; Morrongiello, Barbara A; Pogrebtsova, Ekaterina

2015-09-01

This study evaluated a new online training program, Safe Sibs, aimed at improving supervision knowledge and behaviors of sibling supervisors. Participants included older children (7-11 years) and their younger siblings (2-5 years). A randomized controlled trial design was used, with older siblings randomly assigned to either an intervention or wait-list control group. Before and after either the intervention or wait-list period, older siblings completed measures of supervision knowledge and their supervision behaviors were unobtrusively observed when with their younger sibling. Compared with the control group, the intervention group showed significant improvements in supervision knowledge (child development, knowledge of effective supervision practices, injury beliefs, intervention-specific knowledge) and in some aspects of supervision behavior (frequency of proactive safety behaviors to prevent supervisee access to injury hazards). Although adult supervision is ideal, this new program can support older children to become more knowledgeable and improved supervisors of younger ones. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Asp- and Glu-specific Novel Dipeptidyl Peptidase 11 of Porphyromonas gingivalis Ensures Utilization of Proteinaceous Energy Sources*

PubMed Central

Ohara-Nemoto, Yuko; Shimoyama, Yu; Kimura, Shigenobu; Kon, Asako; Haraga, Hiroshi; Ono, Toshio; Nemoto, Takayuki K.

2011-01-01

Porphyromonas gingivalis and Porphyromonas endodontalis, asaccharolytic black-pigmented anaerobes, are predominant pathogens of human chronic and periapical periodontitis, respectively. They incorporate di- and tripeptides from the environment as carbon and energy sources. In the present study we cloned a novel dipeptidyl peptidase (DPP) gene of P. endodontalis ATCC 35406, designated as DPP11. The DPP11 gene encoded 717 amino acids with a molecular mass of 81,090 Da and was present as a 75-kDa form with an N terminus of Asp22. A homology search revealed the presence of a P. gingivalis orthologue, PGN0607, that has been categorized as an isoform of authentic DPP7. P. gingivalis DPP11 was exclusively cell-associated as a truncated 60-kDa form, and the gene ablation retarded cell growth. DPP11 specifically removed dipeptides from oligopeptides with the penultimate N-terminal Asp and Glu and has a P2-position preference to hydrophobic residues. Optimum pH was 7.0, and the kcat/Km value was higher for Asp than Glu. Those activities were lost by substitution of Ser652 in P. endodontalis and Ser655 in P. gingivalis DPP11 to Ala, and they were consistently decreased with increasing NaCl concentration. Arg670 is a unique amino acid completely conserved in all DPP11 members distributed in the genera Porphyromonas, Bacteroides, and Parabacteroides, whereas this residue is converted to Gly in all authentic DPP7 members. Substitution analysis suggested that Arg670 interacts with an acidic residue of the substrate. Considered to preferentially utilize acidic amino acids, DPP11 ensures efficient degradation of oligopeptide substrates in these Gram-negative anaerobic rods. PMID:21896480
Asp- and Glu-specific novel dipeptidyl peptidase 11 of Porphyromonas gingivalis ensures utilization of proteinaceous energy sources.

PubMed

Ohara-Nemoto, Yuko; Shimoyama, Yu; Kimura, Shigenobu; Kon, Asako; Haraga, Hiroshi; Ono, Toshio; Nemoto, Takayuki K

2011-11-04

Porphyromonas gingivalis and Porphyromonas endodontalis, asaccharolytic black-pigmented anaerobes, are predominant pathogens of human chronic and periapical periodontitis, respectively. They incorporate di- and tripeptides from the environment as carbon and energy sources. In the present study we cloned a novel dipeptidyl peptidase (DPP) gene of P. endodontalis ATCC 35406, designated as DPP11. The DPP11 gene encoded 717 amino acids with a molecular mass of 81,090 Da and was present as a 75-kDa form with an N terminus of Asp(22). A homology search revealed the presence of a P. gingivalis orthologue, PGN0607, that has been categorized as an isoform of authentic DPP7. P. gingivalis DPP11 was exclusively cell-associated as a truncated 60-kDa form, and the gene ablation retarded cell growth. DPP11 specifically removed dipeptides from oligopeptides with the penultimate N-terminal Asp and Glu and has a P2-position preference to hydrophobic residues. Optimum pH was 7.0, and the k(cat)/K(m) value was higher for Asp than Glu. Those activities were lost by substitution of Ser(652) in P. endodontalis and Ser(655) in P. gingivalis DPP11 to Ala, and they were consistently decreased with increasing NaCl concentration. Arg(670) is a unique amino acid completely conserved in all DPP11 members distributed in the genera Porphyromonas, Bacteroides, and Parabacteroides, whereas this residue is converted to Gly in all authentic DPP7 members. Substitution analysis suggested that Arg(670) interacts with an acidic residue of the substrate. Considered to preferentially utilize acidic amino acids, DPP11 ensures efficient degradation of oligopeptide substrates in these Gram-negative anaerobic rods.
[Mutation analysis for a pedigree affected with keratitis-ichthyosis-deafness syndrome].

PubMed

Li, Lulu; Li, Yuan; Lin, Wei; Zhao, Xiuli

2017-10-10

To identify mutation of GJB2 gene and provide genetic counseling for a family affected with keratitis-ichthyosis-deafness (KID) syndrome. Genomic DNA was extracted from peripheral blood samples with a standard phenol-chloroform method. PCR and Sanger sequencing were used to analyze potential mutation in the proband. Suspected mutation was verified with a PCR-high-resolution melting (PCR-HRM) method. T-clone sequencing was applied to determine the parental origin of the mutation. A heterozygous mutation, c.148G>A (p.Asp50Asn), which is located in the exon 1 of the GJB2 gene, was found in the proband. The results was confirmed by HRM analysis. Cloning sequencing suggested that the mutation was derived from the father's germline. The hot-spot mutation c.148G>A (p.Asp50Asn) in the GJB2 gene probably underlies the KID syndrome in this Chinese family. A PCR-HRM method has been established to rapidly detect common mutations associated with this disease.
Trp-Asp (WD) Repeat Domain 1 Is Essential for Mouse Peri-implantation Development and Regulates Cofilin Phosphorylation.

PubMed

Xiao, Yi; Ma, Haixia; Wan, Ping; Qin, Dandan; Wang, Xiaoxiao; Zhang, Xiaoxin; Xiang, Yunlong; Liu, Wenbo; Chen, Jiong; Yi, Zhaohong; Li, Lei

2017-01-27

Trp-Asp (WD) repeat domain 1 (WDR1) is a highly conserved actin-binding protein across all eukaryotes and is involved in numerous actin-based processes by accelerating Cofilin severing actin filament. However, the function and the mechanism of WDR1 in mammalian early development are still largely unclear. We now report that WDR1 is essential for mouse peri-implantation development and regulates Cofilin phosphorylation in mouse cells. The disruption of maternal WDR1 does not obviously affect ovulation and female fertility. However, depletion of zygotic WDR1 results in embryonic lethality at the peri-implantation stage. In WDR1 knock-out cells, we found that WDR1 regulates Cofilin phosphorylation. Interestingly, WDR1 is overdosed to regulate Cofilin phosphorylation in mouse cells. Furthermore, we showed that WDR1 interacts with Lim domain kinase 1 (LIMK1), a well known phosphorylation kinase of Cofilin. Altogether, our results provide new insights into the role and mechanism of WDR1 in physiological conditions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Pinpoint chemical modification of Asp160 in the 49 kDa subunit of bovine mitochondrial complex I via a combination of ligand-directed tosyl chemistry and click chemistry.

PubMed

Masuya, Takahiro; Murai, Masatoshi; Morisaka, Hironobu; Miyoshi, Hideto

2014-12-16

Through a ligand-directed tosyl (LDT) chemistry strategy using the synthetic acetogenin ligand AL1, we succeeded in the pinpoint alkynylation (-C≡CH) of Asp160 in the 49 kDa subunit of bovine complex I, which may be located in the inner part of the putative quinone binding cavity of the enzyme [Masuya, T., et al. (2014) Biochemistry, 53, 2307-2317]. This study provided a promising technique for diverse chemical modifications of complex I. To further improve this technique for its adaptation to intact complex I, we here synthesized the new acetogenin ligand AL2, possessing an azido (-N₃) group in place of the terminal alkyne in AL1, and attempted the pinpoint azidation of complex I in bovine heart submitochondrial particles. Careful proteomic analyses revealed that, just as in the case of AL1, azidation occurred at 49 kDa Asp160 with a reaction yield of ∼50%, verifying the high site specificity of our LDT chemistry using acetogenin ligands. This finding prompted us to speculate that a reactivity of the azido group incorporated into Asp160 (Asp160-N₃) against externally added chemicals can be employed to characterize the structural features of the quinone/inhibitor binding cavity. Consequently, we used a ring-strained cycloalkyne possessing a rhodamine fluorophore (TAMRA-DIBO), which can covalently attach to an azido group via so-called click chemistry without Cu¹⁺ catalysis, as the reaction partner of Asp160-N₃. We found that bulky TAMRA-DIBO is capable of reacting directly with Asp160-N₃ in intact complex I. Unexpectedly, the presence of an excess amount of short-chain ubiquinones as well as some strong inhibitors (e.g., quinazoline and fenpyroximate) did not interfere with the reaction between TAMRA-DIBO and Asp160-N₃; nevertheless, bullatacin, a member of the natural acetogenins, markedly interfered with this reaction. Taking the marked bulkiness of TAMRA-DIBO into consideration, it appears to be difficult to reconcile these results with the
Role of the conserved amino acids of the 'SDN' loop (Ser130, Asp131 and Asn132) in a class A beta-lactamase studied by site-directed mutagenesis.

PubMed

Jacob, F; Joris, B; Lepage, S; Dusart, J; Frère, J M

1990-10-15

Ser130, Asp131 and Asn132 ('SDN') are highly conserved residues in class A beta-lactamases forming one wall of the active-site cavity. All three residues of the SDN loop in Streptomyces albus G beta-lactamase were modified by site-directed mutagenesis. The mutant proteins were expressed in Streptomyces lividans, purified from culture supernatants and their kinetic parameters were determined for several substrates. Ser130 was substituted by Asn, Ala and Gly. The first modification yielded an almost totally inactive protein, whereas the smaller-side-chain mutants (A and G) retained some activity, but were less stable than the wild-type enzyme. Ser130 might thus be involved in maintaining the structure of the active-site cavity. Mutations of Asp131 into Glu and Gly proved to be highly detrimental to enzyme stability, reflecting significant structural perturbations. Mutation of Asn132 into Ala resulted in a dramatically decreased enzymic activity (more than 100-fold) especially toward cephalosporin substrates, kcat. being the most affected parameter, which would indicate a role of Asn132 in transition-state stabilization rather than in ground-state binding. Comparison of the N132A and the previously described N132S mutant enzymes underline the importance of an H-bond-forming residue at position 132 for the catalytic process.
The Asp(327)Asn polymorphism in the sex hormone-binding globulin gene modifies the association of soy food and tea intake with endometrial cancer risk.

PubMed

Xu, Wang Hong; Zheng, Wei; Cai, Qiuyin; Cheng, Jia-Rong; Cai, Hui; Xiang, Yong-Bing; Shu, Xiao Ou

2008-01-01

We evaluated the interactive effect of polymorphisms in the sex hormone-binding globulin (SHBG) gene with soy isoflavones, tea consumption, and dietary fiber on endometrial cancer risk in a population-based, case-control study of 1,199 endometrial cancer patients and 1,212 controls. Genotyping of polymorphisms was performed by using TaqMan (Applied Biosystems, Foster City, CA) assays (rs6259) or the Affymetrix MegAllele Targeted Genotyping System (Affymetrix, Inc., US) (rs13894, rs858521, and rs2955617). Dietary information was obtained using a validated food frequency questionnaire. A logistic regression model was employed to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs). We found that the Asp(327)Asn (rs6259) polymorphism was associated with decreased risk of endometrial cancer, particularly among postmenopausal women (OR = 0.79, 95% CI = 0.62-1.00). This single nucleotide polymorphism (SNP) modified associations of soy isoflavones and tea consumption but not fiber intake with endometrial cancer, with the inverse association of soy intake and tea consumption being more evident for those with the Asp/Asp genotype of the SHBG gene at Asp(327)Asn (rs6259), particularly premenopausal women (P(interaction) = 0.06 and 0.02, respectively, for soy isoflavones and tea intake). This study suggests that gene-diet interaction may play an important role in the etiology of endometrial cancer risk.
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.
Structural Investigation of a Phosphorylation-Catalyzed, Isoaspartate-Free, Protein Succinimide: Crystallographic Structure of Post-Succinimide His15Asp Histidine-Containing Protein

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

Napper, Scott; Prasad, Lata; Delbaere, Louis T.J.

2008-09-08

Aspartates and asparagines can spontaneously cyclize with neighboring main-chain amides to form succinimides. These succinimides hydrolyze to a mixture of isoaspartate and aspartate products. Phosphorylation of aspartates is a common mechanism of protein regulation and increases the propensity for succinimide formation. Although typically regarded as a form of protein damage, we hypothesize succinimides could represent an effective mechanism of phosphoaspartate autophosphatase activity, provided hydrolysis is limited to aspartate products. We previously reported the serendipitous creation of a protein, His15Asp histidine-containing protein (HPr), which undergoes phosphorylation-catalyzed formation of a succinimide whose hydrolysis is seemingly exclusive for aspartate formation. Here, through themore » high-resolution structure of postsuccinimide His15Asp HPr, we confirm the absence of isoaspartate residues and propose mechanisms for phosphorylation-catalyzed succinimide formation and its directed hydrolysis to aspartate. His15Asp HPr represents the first characterized protein example of an isoaspartate-free succinimide and lends credence to the hypothesis that intramolecular cyclization could represent a physiological mechanism of autophosphatase activity. Furthermore, this indicates that current strategies for succinimide evaluation, based on isoaspartate detection, underestimate the frequencies of these reactions. This is considerably significant for evaluation of protein stability and integrity.« less
Inhomogeneous ensembles of radical pairs in chemical compasses

PubMed Central

Procopio, Maria; Ritz, Thorsten

2016-01-01

The biophysical basis for the ability of animals to detect the geomagnetic field and to use it for finding directions remains a mystery of sensory biology. One much debated hypothesis suggests that an ensemble of specialized light-induced radical pair reactions can provide the primary signal for a magnetic compass sensor. The question arises what features of such a radical pair ensemble could be optimized by evolution so as to improve the detection of the direction of weak magnetic fields. Here, we focus on the overlooked aspect of the noise arising from inhomogeneity of copies of biomolecules in a realistic biological environment. Such inhomogeneity leads to variations of the radical pair parameters, thereby deteriorating the signal arising from an ensemble and providing a source of noise. We investigate the effect of variations in hyperfine interactions between different copies of simple radical pairs on the directional response of a compass system. We find that the choice of radical pair parameters greatly influences how strongly the directional response of an ensemble is affected by inhomogeneity. PMID:27804956
Inhomogeneous ensembles of radical pairs in chemical compasses

NASA Astrophysics Data System (ADS)

Procopio, Maria; Ritz, Thorsten

2016-11-01

The biophysical basis for the ability of animals to detect the geomagnetic field and to use it for finding directions remains a mystery of sensory biology. One much debated hypothesis suggests that an ensemble of specialized light-induced radical pair reactions can provide the primary signal for a magnetic compass sensor. The question arises what features of such a radical pair ensemble could be optimized by evolution so as to improve the detection of the direction of weak magnetic fields. Here, we focus on the overlooked aspect of the noise arising from inhomogeneity of copies of biomolecules in a realistic biological environment. Such inhomogeneity leads to variations of the radical pair parameters, thereby deteriorating the signal arising from an ensemble and providing a source of noise. We investigate the effect of variations in hyperfine interactions between different copies of simple radical pairs on the directional response of a compass system. We find that the choice of radical pair parameters greatly influences how strongly the directional response of an ensemble is affected by inhomogeneity.
A randomized, phase 2 study of ASP0113, a DNA-based vaccine, for the prevention of CMV in CMV-seronegative kidney transplant recipients receiving a kidney from a CMV-seropositive donor.

PubMed

Vincenti, Flavio; Budde, Klemens; Merville, Pierre; Shihab, Fuad; Peddi, V Ram; Shah, Malay; Wyburn, Kate; Cassuto-Viguier, Elisabeth; Weidemann, Alexander; Lee, Misun; Flegel, Teresa; Erdman, Jay; Wang, Xuegong; Lademacher, Christopher

2018-05-09

Cytomegalovirus (CMV) is a latent infection in most infected individuals, but can be pathogenic in immunocompromised kidney transplant recipients. ASP0113 is a DNA-based vaccine for the prevention of CMV-related mortality and end-organ disease in transplant recipients. The efficacy, safety, and immunogenicity of ASP0113 was assessed in a phase 2, double-blind, placebo-controlled study in CMV-seronegative kidney transplant recipients receiving a kidney from a CMV-seropositive donor. Transplant recipients were randomized (1:1) to receive five doses of ASP0113 (5 mg; n=75) or placebo (n=74) on Days 30/60/90/120/180 post transplant, and received prophylactic valganciclovir/ganciclovir 10-100 days post transplant. The primary endpoint was the proportion of transplant recipients with CMV viremia ≥1000 IU/mL from Day 100 through to 1 year after first study vaccine injection. There was no statistically significant difference in the primary endpoint between the ASP0113 and placebo groups (odds ratio 0.79, 95% confidence interval 0.43-1.47; p=0.307). There were similar numbers of transplant recipients with treatment-emergent adverse events between groups; however, more transplant recipients reported injection site pain in the ASP0113 group compared with placebo. ASP0113 did not demonstrate efficacy in the prevention of CMV viremia in this CMV-seronegative kidney transplant population, but demonstrated a safety profile similar to placebo. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
The relationship of Asperger’s syndrome to autism: a preliminary EEG coherence study

PubMed Central

2013-01-01

Background It has long been debated whether Asperger’s Syndrome (ASP) should be considered part of the Autism Spectrum Disorders (ASD) or whether it constitutes a unique entity. The Diagnostic and Statistical Manual, fourth edition (DSM-IV) differentiated ASP from high functioning autism. However, the new DSM-5 umbrellas ASP within ASD, thus eliminating the ASP diagnosis. To date, no clear biomarkers have reliably distinguished ASP and ASD populations. This study uses EEG coherence, a measure of brain connectivity, to explore possible neurophysiological differences between ASP and ASD. Methods Voluminous coherence data derived from all possible electrode pairs and frequencies were previously reduced by principal components analysis (PCA) to produce a smaller number of unbiased, data-driven coherence factors. In a previous study, these factors significantly and reliably differentiated neurotypical controls from ASD subjects by discriminant function analysis (DFA). These previous DFA rules are now applied to an ASP population to determine if ASP subjects classify as control or ASD subjects. Additionally, a new set of coherence based DFA rules are used to determine whether ASP and ASD subjects can be differentiated from each other. Results Using prior EEG coherence based DFA rules that successfully classified subjects as either controls or ASD, 96.2% of ASP subjects are classified as ASD. However, when ASP subjects are directly compared to ASD subjects using new DFA rules, 92.3% ASP subjects are identified as separate from the ASD population. By contrast, five randomly selected subsamples of ASD subjects fail to reach significance when compared to the remaining ASD populations. When represented by the discriminant variable, both the ASD and ASD populations are normally distributed. Conclusions Within a control-ASD dichotomy, an ASP population falls closer to ASD than controls. However, when compared directly with ASD, an ASP population is distinctly separate. The
Pair Housing of Dairy Calves and Age at Pairing: Effects on Weaning Stress, Health, Production and Social Networks

PubMed Central

Mlynski, David T.; James, Richard; Croft, Darren P.

2017-01-01

The early social environment can influence the health and behaviour of animals, with effects lasting into adulthood. In Europe, around 60% of dairy calves are reared individually during their first eight weeks of life, while others may be housed in pairs or small groups. This study assessed the effects of varying degrees of social contact on weaning stress, health and production during pen rearing, and on the social networks that calves later formed when grouped. Forty female Holstein-Friesian calves were allocated to one of three treatments: individually housed (I, n = 8), pair-housed from day five (P5, n = 8 pairs), and pair-housed from day 28 (P28, n = 8 pairs). From day 48, calves were weaned by gradual reduction of milk over three days, and vocalisations were recorded as a measure of stress for three days before, during and after weaning. Health and production (growth rate and concentrate intakes) were not affected by treatment during the weaning period or over the whole study. Vocalisations were highest post-weaning, and were significantly higher in I calves than pair-reared calves. Furthermore, P28 calves vocalised significantly more than P5 calves. The social network of calves was measured for one month after all calves were grouped in a barn, using association data from spatial proximity loggers. We tested for week-week stability, social differentiation and assortment in the calf network. Additionally, we tested for treatment differences in: coefficient of variation (CV) in association strength, percentage of time spent with ex-penmate (P5 and P28 calves only) and weighted degree centrality (the sum of the strength of an individual’s associations). The network was relatively stable from weeks one to four and was significantly differentiated, with individuals assorting based on prior familiarity. P5 calves had significantly higher CV in association strength than I calves in week one (indicating more heterogeneous social associations) but there were no
Pair Housing of Dairy Calves and Age at Pairing: Effects on Weaning Stress, Health, Production and Social Networks.

PubMed

Bolt, Sarah L; Boyland, Natasha K; Mlynski, David T; James, Richard; Croft, Darren P

2017-01-01

The early social environment can influence the health and behaviour of animals, with effects lasting into adulthood. In Europe, around 60% of dairy calves are reared individually during their first eight weeks of life, while others may be housed in pairs or small groups. This study assessed the effects of varying degrees of social contact on weaning stress, health and production during pen rearing, and on the social networks that calves later formed when grouped. Forty female Holstein-Friesian calves were allocated to one of three treatments: individually housed (I, n = 8), pair-housed from day five (P5, n = 8 pairs), and pair-housed from day 28 (P28, n = 8 pairs). From day 48, calves were weaned by gradual reduction of milk over three days, and vocalisations were recorded as a measure of stress for three days before, during and after weaning. Health and production (growth rate and concentrate intakes) were not affected by treatment during the weaning period or over the whole study. Vocalisations were highest post-weaning, and were significantly higher in I calves than pair-reared calves. Furthermore, P28 calves vocalised significantly more than P5 calves. The social network of calves was measured for one month after all calves were grouped in a barn, using association data from spatial proximity loggers. We tested for week-week stability, social differentiation and assortment in the calf network. Additionally, we tested for treatment differences in: coefficient of variation (CV) in association strength, percentage of time spent with ex-penmate (P5 and P28 calves only) and weighted degree centrality (the sum of the strength of an individual's associations). The network was relatively stable from weeks one to four and was significantly differentiated, with individuals assorting based on prior familiarity. P5 calves had significantly higher CV in association strength than I calves in week one (indicating more heterogeneous social associations) but there were no
Pick a Pair. Pancake Pairs

ERIC Educational Resources Information Center

Miller, Pat

2005-01-01

Cold February weather and pancakes are a traditional pairing. Pancake Day began as a way to eat up the foods that were abstained from in Lent--traditionally meat, fat, eggs and dairy products. The best-known pancake event is The Pancake Day Race in Buckinghamshire, England, which has been run since 1445. This column describes pairs of books that…
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
Affected twins in the familial intracranial aneurysm study.

PubMed

Mackey, Jason; Brown, Robert D; Sauerbeck, Laura; Hornung, Richard; Moomaw, Charles J; Koller, Daniel L; Foroud, Tatiana; Deka, Ranjan; Woo, Daniel; Kleindorfer, Dawn; Flaherty, Matthew L; Meissner, Irene; Anderson, Craig; Rouleau, Guy; Connolly, E Sander; Huston, John; Broderick, Joseph P

2015-01-01

Very few cases of intracranial aneurysms (IAs) in twins have been reported. Previous work has suggested that vulnerability to IA formation is heritable. Twin studies provide an opportunity to evaluate the impact of genetics on IA characteristics, including IA location. We therefore sought to examine IA location concordance, multiplicity, and rupture status within affected twin-pairs. The Familial Intracranial Aneurysm study was a multicenter study whose goal was to identify genetic and other risk factors for formation and rupture of IAs. The study required at least three affected family members or an affected sibling pair for inclusion. Subjects with fusiform aneurysms, an IA associated with an AVM, or a family history of conditions known to predispose to IA formation, such as polycystic kidney disease, Ehlers-Danlos syndrome, Marfan syndrome, fibromuscular dysplasia, or moyamoya syndrome were excluded. Twin-pairs were identified by birth date and were classified as monozygotic (MZ) or dizygotic (DZ) through DNA marker genotypes. In addition to zygosity, we evaluated twin-pairs by smoking status, major arterial territory of IAs, and rupture status. Location concordance was defined as the presence of an IA in the same arterial distribution (ICA, MCA, ACA, and vertebrobasilar), irrespective of laterality, in both members of a twin-pair. The Fisher exact test was used for comparisons between MZ and DZ twin-pairs. A total of 16 affected twin-pairs were identified. Location concordance was observed in 8 of 11 MZ twin-pairs but in only 1 of 5 DZ twin-pairs (p = 0.08). Three MZ subjects had unknown IA locations and comprised the three instances of MZ discordance. Six of the 11 MZ twin-pairs and none of the 5 DZ twin-pairs had IAs in the ICA distribution (p = 0.03). Multiple IAs were observed in 11 of 22 MZ and 5 of 10 DZ twin-pairs. Thirteen (13) of the 32 subjects had an IA rupture, including 10 of 22 MZ twins. We found that arterial location concordance was greater in
Night Sky Network: A partnership with NASA, the ASP and Astronomical League

NASA Astrophysics Data System (ADS)

Chippindale, S.; Berendsen, M.

2003-12-01

In 2002, the Astronomical Society of the Pacific (ASP) surveyed amateur astronomers to determine their views and experiences with public outreach. The ultimate goal was to discover methods to support amateur astronomers in their outreach efforts. The survey discovered that they are looking for ready-made, themed materials, training in astronomy content and presentation skills, mentoring, and networking to enhance their astronomy events and support their ability to do educational outreach. Acting on these results and with funding from NASA, the ASP is forming a nationwide coalition of amateur astronomy clubs whose members bring the science, technology and inspiration of NASA's missions to the general public. The program consists of three primary components: outreach materials, training, and community building. Member-based astronomy clubs will receive kits of materials on various astronomy topics to supplement and enhance their events as well as a "professional development" component that includes training on how to use the materials and tips to strengthen their individual presentation skills. The Night Sky Network web site includes public pages and a user area where success stories and challenges can be exchanged, new information downloaded, and a support area for amateur astronomers doing outreach. We are currently testing our first kit, "PlanetQuest: The Search for Another Earth", in over two dozen clubs across the country. The second kit, "Big Bang to Black Holes" is under development for NASA's Structure and Evolution of the Universe Forum through the SAO and will be beta tested over the spring and summer of 2004. Sponsored and supported by NASA-Navigator Program, NASA-SAO Education Forum, the Astronomical Society of the Pacific, and the Astronomical League.
Antinociceptive potency of a fluorinated cyclopeptide Dmt-c[D-Lys-Phe-p-CF3-Phe-Asp]NH2.

PubMed

Piekielna-Ciesielska, Justyna; Mollica, Adriano; Pieretti, Stefano; Fichna, Jakub; Szymaszkiewicz, Agata; Zielińska, Marta; Kordek, Radzisław; Janecka, Anna

2018-12-01

Opioid peptides and opiate drugs such as morphine, mediate their analgesic effects, but also undesired side effects, mostly through activation of the mu opioid receptor. However, delta- and kappa-opioid receptors can also contribute to the analgesic effects of opioids. Recent findings showed that simultaneous activation of multiple opioid receptors may result in additional analgesia with fewer side effects. Here, we evaluated the pharmacological profile of our formerly developed mixed mu/kappa-opioid receptor ligands, Dmt-c[D-Lys-Phe-Phe-Asp]NH 2 (C-36) and Dmt-c[D-Lys-Phe-p-CF 3 -Phe-Asp]NH 2 (F-81). The ability of these peptides to cross the blood-brain barrier was tested in the parallel artificial membrane permeability (PAMPA) assay. On the basis of the hot-plate test in mice after central and peripheral administration, analog F-81 was selected for the anti-nociceptive and anti-inflammatory activity assessment after peripheral administration.
Quantitative trait locus for reading disability on chromosome 6

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

Cardon, L.R.; Smith, S.D.; Kimberling, W.J.

1994-10-14

Interval mapping of data from two independent samples of sib pairs, at least one member of whom was reading disabled, revealed evidence for a quantitative trait locus (QTL) on chromosome 6. Results obtained from analyses of reading performance from 114 sib pairs genotyped for DNA markers localized the QTL to 6p21.3. Analyses of corresponding data from an independent sample of 50 dizygotic twin pairs provided evidence for linkage to the same region. In combination, the replicate samples yielded a x{sup 2} value of 16.73 (P = 0.0002). Examination of twin and kindred siblings with more extreme deficits in reading performancemore » yielded even stronger evidence for a QTL (x{sup 2} = 27.35, P < 0.00001). The position of the QTL was narrowly defined with a 100:1 confidence interval to a 2-centimorgan region within the human leukocyte antigen complex. 23 refs., 4 figs.« less
Roles of Asp179 and Glu270 in ADP-Ribosylation of Actin by Clostridium perfringens Iota Toxin

PubMed Central

Belyy, Alexander; Tabakova, Irina; Lang, Alexander E.; Jank, Thomas; Belyi, Yury; Aktories, Klaus

2015-01-01

Clostridium perfringens iota toxin is a binary toxin composed of the enzymatically active component Ia and receptor binding component Ib. Ia is an ADP-ribosyltransferase, which modifies Arg177 of actin. The previously determined crystal structure of the actin-Ia complex suggested involvement of Asp179 of actin in the ADP-ribosylation reaction. To gain more insights into the structural requirements of actin to serve as a substrate for toxin-catalyzed ADP-ribosylation, we engineered Saccharomyces cerevisiae strains, in which wild type actin was replaced by actin variants with substitutions in residues located on the Ia-actin interface. Expression of the actin mutant Arg177Lys resulted in complete resistance towards Ia. Actin mutation of Asp179 did not change Ia-induced ADP-ribosylation and growth inhibition of S. cerevisiae. By contrast, substitution of Glu270 of actin inhibited the toxic action of Ia and the ADP-ribosylation of actin. In vitro transcribed/translated human β-actin confirmed the crucial role of Glu270 in ADP-ribosylation of actin by Ia. PMID:26713879
Centromere pairing precedes meiotic chromosome pairing in plants.

PubMed

Zhang, Jing; Han, Fangpu

2017-11-01

Meiosis is a specialized eukaryotic cell division, in which diploid cells undergo a single round of DNA replication and two rounds of nuclear division to produce haploid gametes. In most eukaryotes, the core events of meiotic prophase I are chromosomal pairing, synapsis and recombination. To ensure accurate chromosomal segregation, homologs have to identify and align along each other at the onset of meiosis. Although much progress has been made in elucidating meiotic processes, information on the mechanisms underlying chromosome pairing is limited in contrast to the meiotic recombination and synapsis events. Recent research in many organisms indicated that centromere interactions during early meiotic prophase facilitate homologous chromosome pairing, and functional centromere is a prerequisite for centromere pairing such as in maize. Here, we summarize the recent achievements of chromosome pairing research on plants and other organisms, and outline centromere interactions, nuclear chromosome orientation, and meiotic cohesin, as main determinants of chromosome pairing in early meiotic prophase.

Comparison of taurine, GABA, Glu, and Asp as scavengers of malondialdehyde in vitro and in vivo

NASA Astrophysics Data System (ADS)

Deng, Yan; Wang, Wei; Yu, Pingfeng; Xi, Zhijiang; Xu, Lijian; Li, Xiaolong; He, Nongyue

2013-04-01

The purpose of this study is to determine if amino acid neurotransmitters such as gamma-aminobutyric acid (GABA), taurine, glutamate (Glu), and aspartate (Asp) can scavenge activated carbonyl toxicants. In vitro, direct reaction between malondialdehyde (MDA) and amino acids was researched using different analytical methods. The results indicated that scavenging activated carbonyl function of taurine and GABA is very strong and that of Glu and Asp is very weak in pathophysiological situations. The results provided perspective into the reaction mechanism of taurine and GABA as targets of activated carbonyl such as MDA in protecting nerve terminals. In vivo, we studied the effect of taurine and GABA as antioxidants by detecting MDA concentration and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. It was shown that MDA concentration was decreased significantly, and the activities of SOD and GSH-Px were increased significantly in the cerebral cortex and hippocampus of acute epileptic state rats, after the administration of taurine and GABA. The results indicated that the peripherally administered taurine and GABA can scavenge free radicals and protect the tissue against activated carbonyl in vivo and in vitro.
The Amazon rainforest, climate change, and drought: How will what is below the surface affect the climate of tropical South America?

NASA Astrophysics Data System (ADS)

Harper, A.; Denning, A. S.; Baker, I.; Randall, D.; Dazlich, D.

2008-12-01

Several climate models have predicted an increase in long-term droughts in tropical South America due to increased greenhouse gases in the atmosphere. Although the Amazon rainforest is resilient to seasonal drought, multi-year droughts pose a definite problem for the ecosystem's health. Furthermore, drought- stressed vegetation participates in feedbacks with the atmosphere that can exacerbate drought. Namely, reduced evapotranspiration further dries out the atmosphere and affects the regional climate. Trees in the rainforest survive seasonal drought by using deep roots to access adequate stores of soil moisture. We investigate the climatic impacts of deep roots and soil moisture by coupling the Simple Biosphere (SiB3) model to Colorado State University's general circulation model (BUGS5). We compare two versions of SiB3 in the GCM during years with anomalously low rainfall. The first has strong vegetative stress due to soil moisture limitations. The second experiences less stress and has more realistic representations of surface biophysics. In the model, basin-wide reductions in soil moisture stress result in increased evapotranspiration, precipitation, and moisture recycling in the Amazon basin. In the savannah region of southeastern Brazil, the unstressed version of SiB3 produces decreased precipitation and weaker moisture flux, which is more in-line with observations. The improved simulation of precipitation and evaporation also produces a more realistic Bolivian high and Nordeste low. These changes highlight the importance of subsurface biophysics for the Amazonian climate. The presence of deep roots and soil moisture will become even more important if climate change brings more frequent droughts to this region in the future.
OBSESSIVE-COMPULSIVE PERSONALITY DISORDER: EVIDENCE FOR TWO DIMENSIONS.

PubMed

Riddle, Mark A; Maher, Brion S; Wang, Ying; Grados, Marco; Bienvenu, O Joseph; Goes, Fernando S; Cullen, Bernadette; Murphy, Dennis L; Rauch, Scott L; Greenberg, Benjamin D; Knowles, James A; McCracken, James T; Pinto, Anthony; Piacentini, John; Pauls, David L; Rasmussen, Steven A; Shugart, Yin Yao; Nestadt, Gerald; Samuels, Jack

2016-02-01

To determine possible dimensions that underlie obsessive-compulsive personality disorder (OCPD) and to investigate their clinical correlates, familiality, and genetic linkage. Participants were selected from 844 adults assessed with the Structured Instrument for the Diagnosis of DSM-IV Personality Disorders (SIDP) in the OCD Collaborative Genetics Study (OCGS) that targeted families with obsessive-compulsive disorder (OCD) affected sibling pairs. We conducted an exploratory factor analysis, which included the eight SIDP-derived DSM-IV OCPD traits and the indecision trait from the DSM-III, assessed clinical correlates, and estimated sib-sib correlations to evaluate familiality of the factors. Using MERLIN and MINX, we performed genome-wide quantitative trait locus (QTL) linkage analysis to test for allele sharing among individuals. Two factors were identified: Factor 1: order/control (perfectionism, excessive devotion to work, overconscientiousness, reluctance to delegate, and rigidity); and Factor 2: hoarding/indecision (inability to discard and indecisiveness). Factor 1 score was associated with poor insight, whereas Factor 2 score was associated with task incompletion. A significant sib-sib correlation was found for Factor 2 (rICC = .354, P < .0001) but not Factor 1 (rICC = .129, P = .084). The linkage findings were different for the two factors. When Factor 2 was analyzed as a quantitative trait, a strong signal was detected on chromosome 10 at marker d10s1221: KAC LOD = 2.83, P = .0002; and marker d10s1225: KAC LOD = 1.35, P = .006. The results indicate two factors of OCPD, order/control and hoarding/indecision. The hoarding/indecision factor is familial and shows modest linkage to a region on chromosome 10. © 2015 Wiley Periodicals, Inc.
Bloom syndrome in sibs: first reports of hepatocellular carcinoma and Wilms tumor with documented anaplasia and nephrogenic rests.

PubMed

Jain, D; Hui, P; McNamara, J; Schwartz, D; German, J; Reyes-Múgica, M

2001-01-01

The triad of small body size, immunodeficiency, and sun-sensitive facial erythema characterizes the phenotype Bloom syndrome (BS), a rare autosomal recessive disorder with a striking predisposition to multiple types of cancers that arise earlier than expected in the general population. Here we report two sibs with BS. The older, a 15-year-old-girl, developed a hepatocellular carcinoma, a neoplasm not yet reported in association with BS. Her younger brother developed an anaplastic Wilms tumor (WT) associated with nephrogenic rests at the age of 31/2 years, and this was followed by a myelodysplastic syndrome. Complex cytogenetic abnormalities were identified in all three neoplasms. These examples expand the spectrum of malignancies occurring in BS to include liver cell neoplasms, and confirm the association of nephrogenic rests with WT, even in the setting of BS.
Moisture-Absorption and Water Dynamics in the Powder of Egg Albumen Peptide, Met-Pro-Asp-Ala-His-Leu.

PubMed

Yang, Shuailing; Liu, Xuye; Zhang, Mingdi; Lin, Songyi; Chen, Feng

2017-01-01

Moisture absorbed into the powder of Met-Pro-Asp-Ala-His-Leu (MPDAHL)-a novel egg albumen antioxidant peptide-profoundly affects its properties. In this study, we elucidated water dynamics in MPDAHL using DVS, DSC, and low-field 1 H NMR. Based on the DVS data, we found that MPDAHL sorption kinetics obey a parallel exponential model. DSC results indicated that both water and heating could change the microstructure of MPDAHL. The T 2 parameters of NMR reflected the different phases of moisture absorption revealed that there were 4 categories of water with different states or mobility in the MPDAHL during the moisture absorption process. The fastest fraction T 2b mainly dominated the hygroscopicity of MPDAHL and the absorbed water significantly changed the proton distribution and structure of MPDAHL. Thus, this study shows that DVS, DSC, and low-field 1 H NMR are effective methods for monitoring water mobility and distribution in synthetic peptides. It can be used to improve the quality assurance of functional peptides. © 2016 Institute of Food Technologists®.
Simultaneous master-slave Omega pairs. [navigation system featuring low cost receiver

NASA Technical Reports Server (NTRS)

Burhans, R. W.

1974-01-01

Master-slave sequence ordering of the Omega system is suggested as a method of improving the pair geometry for low-cost receiver user benefit. The sequence change will not affect present sophisticated processor users other than require new labels for some pair combinations, but may require worldwide transmitter operators to slightly alter their long-range synchronizing techniques.
Affective priming using a color-naming task: a test of an affective-motivational account of affective priming effects.

PubMed

Hermans, D; Van den Broeck, A; Eelen, P

1998-01-01

The affective priming effect, i.e. shorter response latencies for affectively congruent as compared to affectively incongruent prime-target pairs, is now a well-documented phenomenon. Nevertheless, little is known about the specific processes that underlie the affective priming effect. Several mechanisms have been put forward by different authors, but these theoretical accounts only apply to specific types of tasks (e.g. evaluation lexical decisions) or are rather unparsimonious. Hermans, De Houwer, and Eelen (1996) recently proposed a model of the affective priming effect that is based on the idea of the activation of corresponding or conflicting affective-motivational action tendencies. According to this model, affectively incongruent prime-target pairs should not only lead to relatively longer response latencies on tasks that concern the target word itself (target-specific tasks, e.g. evaluation pronunciation), but also on tasks that are unrelated to the actual identity of the specific target word. This hypothesis was tested in a series of four experiments in which participants had to name the color in which the target word was printed. In spite of procedural variations, results showed that the congruence between the valence of prime and target did not influence the color-naming times. The present results therefore provide no direct support for the affective-motivational account of the affective priming effect. Suggestions for future research are provided.
Interlayer neurones in the rat superior colliculus: a tracer study using Dil/Di-ASP.

PubMed

Hilbig, H; Schierwagen, A

1994-01-12

Five different populations of interlayer neurones (ILNs) can be described after DiI/Di-ASP tracing in rat superior colliculus (SC). All of these labelled neurones preferentially lay in the rostro-medial part of the SC. Most of them are located in the stratum opticum and in the stratum griseum superficiale. Our results indicate that ILNs represent a minority of neurones in the superficial layers but may constitute a substantial population of neurones in the stratum opticum connecting the visual and the multimodal collicular layers.
Search for a schizophrenia susceptibility locus of human chromosome 22

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

Coon, H.; Hoff, M.; Holik, J.

1994-06-15

We used 10 highly informative DNA polymorphic markers and genetic linkage analysis to examine whether a gene locus predisposing to schizophrenia is located on chromosome 22, in 105 families with schizophrenia and schizoaffective disorder. The LOD score method, including analysis for heterogeneity, provided no conclusive evidence of linkage under a dominant, recessive, or penetrance free model of inheritance. Affected sib-pair analysis was inconclusive. Affected Pedigree Member (APM) analysis gave only suggestive evidence for linkage. Multipoint APM analysis, using 4 adjacent loci including D22S281 and IL2RB, a region of interest from the APM analysis, gave non-significant results for the three differentmore » weighting functions. 18 refs., 1 fig., 7 tabs.« less
Concreteness and relational effects on recall of adjective-noun pairs.

PubMed

Paivio, A; Khan, M; Begg, I

2000-09-01

Extending previous research on the problem, we studied the effects of concreteness and relatedness of adjective-noun pairs on free recall, cued recall, and memory integration. Two experiments varied the attributes in paired associates lists or sentences. Consistent with predictions from dual coding theory and prior results with noun-noun pairs, both experiments showed that the effects of concreteness were strong and independent of relatedness in free recall and cued recall. The generally positive effects of relatedness were absent in the case of free recall of sentences. The two attributes also had independent (additive) effects on integrative memory as measured by conditionalized free recall of pairs. Integration as measured by the increment from free to cued recall occurred consistently only when pairs were high in both concreteness and relatedness. Explanations focused on dual coding and relational-distinctiveness processing theories as well as task variables that affect integration measures.
Physiological implications of pair-bond status in greylag geese.

PubMed

Wascher, Claudia A F; Weiß, Brigitte M; Arnold, Walter; Kotrschal, Kurt

2012-06-23

In group-living vertebrates, reliable social allies play a decisive role in dealing with stressors. For example, support by social allies is known to dampen glucocorticoid responses. It remains unknown, however, how social embedding affects the sympatho-adrenergic axis as indicated by heart rate (HR) in non-human animals. We studied the relationships between HR, pair-bond status and distance from the pair-partner in twenty-five free-ranging greylag geese (Anser anser) in a natural social environment. In three individuals, we investigated HR responses following partner loss. Overall, we found a context- and sex-dependent difference in HR between paired and unpaired individuals, paired males having a lower HR during agonistic encounters, and unpaired females having a lower HR during resting. Also, in paired females HR increased with increasing distance from the partner. Our data suggest that HR is modulated by pair-bond status in greylag geese in a context- and sex-dependent manner, which may be representative for social vertebrates in general. Despite the low sample size, the present study indicates that proper social embedding may optimize an individual's physiological investment in the social domain. This reduces individual energy expenditure and may benefit health and reproductive success.
Structure-activity relationship of cyclic peptide penta-c[Asp-His(6)-DPhe(7)-Arg(8)-Trp(9)-Lys]-NH(2) at the human melanocortin-1 and -4 receptors: His(6) substitution.

PubMed

Cheung, Adrian Wai-Hing; Danho, Waleed; Swistok, Joseph; Qi, Lida; Kurylko, Grazyna; Rowan, Karen; Yeon, Mitch; Franco, Lucia; Chu, Xin-Jie; Chen, Li; Yagaloff, Keith

2003-04-07

A series of MT-II related cyclic peptides, based on potent but non-selective hMC4R agonist (Penta-c[Asp-His(6)-DPhe(7)-Arg(8)-Trp(9)-Lys]-NH(2)) was prepared in which His(6) residue was systematically substituted. Two of the most interesting peptides identified in this study are Penta-c[Asp-5-ClAtc-DPhe-Arg-Trp-Lys]-NH(2) and Penta-c[Asp-5-ClAtc-DPhe-Cit-Trp-Lys]-NH(2) which are potent hMC4R agonists and are either inactive or weak partial agonists (not tested for their antagonist activities) in hMC1R, hMC3R and hMC5R agonist assays.
Extra-Pair Mating and Evolution of Cooperative Neighbourhoods

PubMed Central

Eliassen, Sigrunn; Jørgensen, Christian

2014-01-01

A striking but unexplained pattern in biology is the promiscuous mating behaviour in socially monogamous species. Although females commonly solicit extra-pair copulations, the adaptive reason has remained elusive. We use evolutionary modelling of breeding ecology to show that females benefit because extra-pair paternity incentivizes males to shift focus from a single brood towards the entire neighbourhood, as they are likely to have offspring there. Male-male cooperation towards public goods and dear enemy effects of reduced territorial aggression evolve from selfish interests, and lead to safer and more productive neighbourhoods. The mechanism provides adaptive explanations for the common empirical observations that females engage in extra-pair copulations, that neighbours dominate as extra-pair sires, and that extra-pair mating correlates with predation mortality and breeding density. The models predict cooperative behaviours at breeding sites where males cooperate more towards public goods than females. Where maternity certainty makes females care for offspring at home, paternity uncertainty and a potential for offspring in several broods make males invest in communal benefits and public goods. The models further predict that benefits of extra-pair mating affect whole nests or neighbourhoods, and that cuckolding males are often cuckolded themselves. Derived from ecological mechanisms, these new perspectives point towards the evolution of sociality in birds, with relevance also for mammals and primates including humans. PMID:24987839
A comparative intracellular proteomic profiling of Pseudomonas aeruginosa strain ASP-53 grown on pyrene or glucose as sole source of carbon and identification of some key enzymes of pyrene biodegradation pathway.

PubMed

Mukherjee, Ashis K; Bhagowati, Pabitra; Biswa, Bhim Bahadur; Chanda, Abhishek; Kalita, Bhargab

2017-09-07

Pseudomonas aeruginosa strain ASP-53, isolated from a petroleum oil-contaminated soil sample, was found to be an efficient degrader of pyrene. PCR amplification of selected hydrocarbon catabolic genes (alkB gene, which encodes for monooxygenase, and the C12O, C23O, and PAH-RHDα genes encoding for the dioxygenase enzyme) from the genomic DNA of P. aeruginosa strain ASP-53 suggested its hydrocarbon degradation potential. The GC-MS analysis demonstrated 30.1% pyrene degradation by P. aeruginosa strain ASP-53 after 144h of incubation at pH6.5, 37°C. Expressions of 115 and 196 intracellular proteins were unambiguously identified and quantitated by shotgun proteomics analysis when the isolate was grown in medium containing pyrene and glucose, respectively. The pyrene-induced uniquely expressed and up-regulated proteins in P. aeruginosa strain ASP-53 in addition to substrate (pyrene) metabolism are also likely to be associated with different cellular functions for example-related to protein folding (molecular chaperone), stress response, metabolism of carbohydrate, proteins and amino acids, and fatty acids; transport of metabolites, energy generation such as ATP synthesis, electron transport and nitrate assimilation, and other oxidation-reduction reactions. Proteomic analyses identified some important enzymes involved in pyrene degradation by P. aeruginosa ASP-53 which shows that this bacterium follows the salicylate pathway of pyrene degradation. This study is the first report on proteomic analysis of pyrene biodegradation pathway by Pseudomonas aeruginosa, isolated from a petroleum-oil contaminated soil sample. The pathway displays partial similarity with deduced pyrene degradation mechanisms of Mycobacterium vanbaalenii PYR-1. The GC-MS analysis as well as PCR amplification of hydrocarbon catabolic genes substantiated the potency of the bacterium under study to effectively degrade high molecular weight, toxic PAH such as pyrene for its filed scale bioremediation
Characteristics of mutants designed to incorporate a new ion pair into the structure of a cold adapted subtilisin-like serine proteinase.

PubMed

Sigurdardóttir, Anna Gudný; Arnórsdóttir, Jóhanna; Thorbjarnardóttir, Sigrídur H; Eggertsson, Gudmundur; Suhre, Karsten; Kristjánsson, Magnús M

2009-03-01

Structural comparisons of VPR, a subtilisin-like serine proteinase from a psychrotrophic Vibrio species and a thermophilic homologue, aqualysin I, have led us to hypothesize about the roles of different residues in the temperature adaptation of the enzymes. Some of these hypotheses are now being examined by analysis of mutants of the enzymes. The selected substitutions are believed to increase the stability of the cold adapted enzyme based on structural analysis of the thermostable structure. We report here on mutants, which were designed to incorporate an ion pair into the structure of VPR. The residues Asp17 and Arg259 are assumed to form an ion pair in aqualysin I. The cold adapted VPR contains Asn (Asn15) and Lys (Lys257) at corresponding sites in its structure. In VPR, Asn 15 is located on a surface loop with its side group pointing towards the side chain of Lys257. By substituting Asn15 by Asp (N15D) it was considered feasible that a salt bridge would form between the oppositely charged groups. To mimic further the putative salt bridge from the thermophile enzyme the corresponding double mutant (N15D/K257R) was also produced. The N15D mutation increased the thermal stability of VPR by approximately 3 degrees C, both in T(50%) and T(m). Addition of the K257R mutation did not however, increase the stability of the double mutant any further. Despite this stabilization of the VPR mutants the catalytic activity (k(cat)) against the substrate Suc-AAPF-NH-Np was increased in the mutants. Molecular dynamics simulations on wild type and the two mutant proteins suggested that indeed a salt bridge was formed in both cases. Furthermore, a truncated form of the N15D mutant (N15DDeltaC) was produced, lacking a 15 residue long C-terminal extended sequence not present in the thermophilic enzyme. In wild type VPR this supposedly moveable, negatively charged arm on the protein molecule might interfere with the new salt bridge introduced as a result of the N15D mutation
Structure of N-terminal sequence Asp-Ala-Glu-Phe-Arg-His-Asp-Ser of Aβ-peptide with phospholipase A2 from venom of Andaman Cobra sub-species Naja naja sagittifera at 2.0 Å resolution.

PubMed

Mirza, Zeenat; Pillai, Vikram Gopalakrishna; Zhong, Wei-Zhu

2014-03-10

Alzheimer's disease (AD) is one of the most significant social and health burdens of the present century. Plaques formed by extracellular deposits of amyloid β (Aβ) are the prime player of AD's neuropathology. Studies have implicated the varied role of phospholipase A2 (PLA2) in brain where it contributes to neuronal growth and inflammatory response. Overall contour and chemical nature of the substrate-binding channel in the low molecular weight PLA2s are similar. This study involves the reductionist fragment-based approach to understand the structure adopted by N-terminal fragment of Alzheimer's Aβ peptide in its complex with PLA2. In the current communication, we report the structure determined by X-ray crystallography of N-terminal sequence Asp-Ala-Glu-Phe-Arg-His-Asp-Ser (DAEFRHDS) of Aβ-peptide with a Group I PLA2 purified from venom of Andaman Cobra sub-species Naja naja sagittifera at 2.0 Å resolution (Protein Data Bank (PDB) Code: 3JQ5). This is probably the first attempt to structurally establish interaction between amyloid-β peptide fragment and hydrophobic substrate binding site of PLA2 involving H bond and van der Waals interactions. We speculate that higher affinity between Aβ and PLA2 has the therapeutic potential of decreasing the Aβ-Aβ interaction, thereby reducing the amyloid aggregation and plaque formation in AD.
Enhancing the Activity of Peptide-Based Artificial Hydrolase with Catalytic Ser/His/Asp Triad and Molecular Imprinting.

PubMed

Wang, Mengfan; Lv, Yuqi; Liu, Xiaojing; Qi, Wei; Su, Rongxin; He, Zhimin

2016-06-08

In this study, an artificial hydrolase was developed by combining the catalytic Ser/His/Asp triad with N-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF), followed by coassembly of the peptides into nanofibers (CoA-HSD). The peptide-based nanofibers provide an ideal supramolecular framework to support the functional groups. Compared with the self-assembled catalytic nanofibers (SA-H), which contain only the catalytic histidine residue, the highest activity of CoA-HSD occurs when histidine, serine, and aspartate residues are at a ratio of 40:1:1. This indicates that the well-ordered nanofiber structure and the synergistic effects of serine and aspartate residues contribute to the enhancement in activity. Additionally, for the first time, molecular imprinting was applied to further enhance the activity of the peptide-based artificial enzyme (CoA-HSD). p-NPA was used as the molecular template to arrange the catalytic Ser/His/Asp triad residues in the proper orientation. As a result, the activity of imprinted coassembled CoA-HSD nanofibers is 7.86 times greater than that of nonimprinted CoA-HSD and 13.48 times that of SA-H.
The road not taken: life experiences in monozygotic twin pairs discordant for major depression

PubMed Central

Kendler, KS; Halberstadt, LJ

2012-01-01

In an effort to understand how environmental experiences contribute to risk for major depression (MD), we conducted joint autobiographical interviews with 14 pairs of monozygotic twins (mean age 51.2) rigorously discordant for a lifetime history of MD. Twelve of the pairs could be sorted into four broad categories. In two pairs, discordance was associated with a single traumatic event occurring to the affected twin. In seven pairs, the well twin had one stable, long-term, successful romantic relationship, whereas the affected co-twin had romantic reversals one or more of which precipitated depressive episodes. These pairs varied in the degree to which the romantic problems seemed to arise from bad luck or poor choices. In one pair, occupational difficulties were strongly related to discordance in experiences with MD. In two pairs, several mechanisms seemed to be at work. Discordance in the quality of intimate love relationships was the most common etiological factor revealed by interview in these discordant pairs, with single dramatic events and occupational problems being considerably rarer. Even in this best of natural experiments, the causal interrelationship between personality, environment and depressive episodes was not always clear. Many pairs illustrated the protective effects of planfulness and the malignant effect of cumulative continuity where early difficulties in relationships shaped the subsequent life course. These results speak both to the importance of environmental influences on human well-being and psychopathology, and the complexity of the causal paths underlying their effects. PMID:22641178
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
Base pairing and base mis-pairing in nucleic acids

NASA Technical Reports Server (NTRS)

Wang, A. H. J.; Rich, A.

1986-01-01

In recent years we have learned that DNA is conformationally active. It can exist in a number of different stable conformations including both right-handed and left-handed forms. Using single crystal X-ray diffraction analysis we are able to discover not only additional conformations of the nucleic acids but also different types of hydrogen bonded base-base interactions. Although Watson-Crick base pairings are the predominant type of interaction in double helical DNA, they are not the only types. Recently, we have been able to examine mismatching of guanine-thymine base pairs in left-handed Z-DNA at atomic resolution (1A). A minimum amount of distortion of the sugar phosphate backbone is found in the G x T pairing in which the bases are held together by two hydrogen bonds in the wobble pairing interaction. Because of the high resolution of the analysis we can visualize water molecules which fill in to accommodate the other hydrogen bonding positions in the bases which are not used in the base-base interactions. Studies on other DNA oligomers have revealed that other types of non-Watson-Crick hydrogen bonding interactions can occur. In the structure of a DNA octamer with the sequence d(GCGTACGC) complexed to an antibiotic triostin A, it was found that the two central AT base pairs are held together by Hoogsteen rather than Watson-Crick base pairs. Similarly, the G x C base pairs at the ends are also Hoogsteen rather than Watson-Crick pairing. Hoogsteen base pairs make a modified helix which is distinct from the Watson-Crick double helix.

Toll receptor 4 Asp299Gly polymorphism and its association with preterm birth and premature rupture of membranes in a South American population

PubMed Central

Rey, G.; Skowronek, F.; Alciaturi, J.; Alonso, J.; Bertoni, B.; Sapiro, R.

2008-01-01

Preterm birth (PTB) is a worldwide health problem and remains the leading cause of perinatal morbidity and mortality. Systemic and local intrauterine infections have been implicated in the pathogenesis of preterm labor and delivery. Common pathways between PTB, premature rupture of ovular membranes (PROM) and altered molecular routes of inflammation have been proposed. There is evidence to support a genetic component in these conditions. Lipopolysaccharide (LPS), a component of the cell wall of Gram-negative bacteria, is thought to play a key role in eliciting an inflammatory response. LPS is recognized by proteins of the innate immune system, including Toll-like receptor 4 (TLR4). Individuals from some European countries carrying the variant alleles resulting in an amino acid substitution (Asp299Gly) are at increased risk of Gram-negative infections and premature birth. The objective of this study was to determine if preterm newborns have different allele frequency of the Asp299Gly TLR4 variant from healthy term neonates in Uruguay. The impact of PROM was also examined. There was an increase in the risk for fetuses carrying the Asp299Gly substitution in TLR4 of being severely premature (<33 weeks) and to present PROM at the same time. PMID:18723631
Flexible Xxx–Asp/Asn and Gly–Xxx Residues of Equine Cytochrome c in Matrix-Assisted Laser Desorption/Ionization In-Source Decay Mass Spectrometry

PubMed Central

Takayama, Mitsuo

2012-01-01

The backbone flexibility of a protein has been studied from the standpoint of the susceptibility of amino acid residues to in-source decay (ISD) in matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). Residues more susceptible to MALDI-ISD, namely Xxx–Asp/Asn and Gly–Xxx, were identified from the discontinuous intense peak of c′-ions originating from specific cleavage at N–Cα bonds of the backbone of equine cytochrome c. The identity of the residues susceptible to ISD was consistent with the known flexible backbone amides as estimated by hydrogen/deuterium exchange (HDX) experiments. The identity of these flexible amino acid residues (Asp, Asn, and Gly) is consistent with the fact that these residues are preferred in flexible secondary structure free from intramolecular hydrogen-bonded structures such as α-helix and β-sheet. The MALDI-ISD spectrum of equine cytochrome c gave not only intense N-terminal side c′-ions originating from N–Cα bond cleavage at Xxx–Asp/Asn and Gly–Xxx residues, but also C-terminal side complement z′-ions originating from the same cleavage sites. The present study implies that MALDI-ISD can give information about backbone flexibility of proteins, comparable with the protection factors estimated by HDX. PMID:24349908
Flexible xxx-asp/asn and gly-xxx residues of equine cytochrome C in matrix-assisted laser desorption/ionization in-source decay mass spectrometry.

PubMed

Takayama, Mitsuo

2012-01-01

The backbone flexibility of a protein has been studied from the standpoint of the susceptibility of amino acid residues to in-source decay (ISD) in matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). Residues more susceptible to MALDI-ISD, namely Xxx-Asp/Asn and Gly-Xxx, were identified from the discontinuous intense peak of c'-ions originating from specific cleavage at N-Cα bonds of the backbone of equine cytochrome c. The identity of the residues susceptible to ISD was consistent with the known flexible backbone amides as estimated by hydrogen/deuterium exchange (HDX) experiments. The identity of these flexible amino acid residues (Asp, Asn, and Gly) is consistent with the fact that these residues are preferred in flexible secondary structure free from intramolecular hydrogen-bonded structures such as α-helix and β-sheet. The MALDI-ISD spectrum of equine cytochrome c gave not only intense N-terminal side c'-ions originating from N-Cα bond cleavage at Xxx-Asp/Asn and Gly-Xxx residues, but also C-terminal side complement z'-ions originating from the same cleavage sites. The present study implies that MALDI-ISD can give information about backbone flexibility of proteins, comparable with the protection factors estimated by HDX.
The coevolution of long-term pair bonds and cooperation.

PubMed

Song, Z; Feldman, M W

2013-05-01

The evolution of social traits may not only depend on but also change the social structure of the population. In particular, the evolution of pairwise cooperation, such as biparental care, depends on the pair-matching distribution of the population, and the latter often emerges as a collective outcome of individual pair-bonding traits, which are also under selection. Here, we develop an analytical model and individual-based simulations to study the coevolution of long-term pair bonds and cooperation in parental care, where partners play a Snowdrift game in each breeding season. We illustrate that long-term pair bonds may coevolve with cooperation when bonding cost is below a threshold. As long-term pair bonds lead to assortative interactions through pair-matching dynamics, they may promote the prevalence of cooperation. In addition to the pay-off matrix of a single game, the evolutionarily stable equilibrium also depends on bonding cost and accidental divorce rate, and it is determined by a form of balancing selection because the benefit from pair-bond maintenance diminishes as the frequency of cooperators increases. Our findings highlight the importance of ecological factors affecting social bonding cost and stability in understanding the coevolution of social behaviour and social structures, which may lead to the diversity of biological social systems. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.
Genetic variation for resistance to ergot (Claviceps purpurea [Fr.] Tul.) among full-sib families of five populations of winter rye (Secale cereale L.).

PubMed

Mirdita, V; Dhillon, B S; Geiger, H H; Miedaner, T

2008-12-01

Ergot (Claviceps purpurea [Fr.] Tul.) is a serious disease of rye (Secale cereale L.) and it adversely affects the quality of grain. The present investigation was undertaken to study genotypic variability among full-sib families (FSF) of five open-pollinated (OP) winter rye populations of highly diverse origin, namely Dankovskie Selekcyine (Poland), Charkovskaja (Ukraine), NEM4 (Russia), Halo and Carokurz, both from Germany. About 50 FSF were developed at random in each population, and the FSF of each population were evaluated in separate but adjacent experiments conducted in four environments under artificial inoculation. A mixture of conidia of C. purpurea isolates was sprayed thrice during the flowering period. The materials were manually harvested at yellow-ripe stage. Resistance trait recorded was disease severity, i.e. percent ergot sclerotia in grain by weight. Mean ergot severity ranged from 2.29 to 4.08% for the five populations across environments. Significant genotypic variation (P < 0.01) due to FSF and FSF x environment interaction was observed within each population. Genotypic variation within all populations was higher than that among five populations. All populations showed high estimates of heritability (0.72-0.89). The study indicated that the evaluated OP populations are rich reservoirs of genetic variation that should also be used in hybrid breeding. Recurrent selection to further improve ergot resistance should be successful.
Active Space Dependence in Multiconfiguration Pair-Density Functional Theory.

PubMed

Sharma, Prachi; Truhlar, Donald G; Gagliardi, Laura

2018-02-13

In multiconfiguration pair-density functional theory (MC-PDFT), multiconfiguration self-consistent-field calculations and on-top density functionals are combined to describe both static and dynamic correlation. Here, we investigate how the MC-PDFT total energy and its components depend on the active space choice in the case of the H 2 and N 2 molecules. The active space dependence of the on-top pair density, the total density, the ratio of on-top pair density to half the square of the electron density, and the satisfaction of the virial theorem are also explored. We find that the density and on-top pair density do not change significantly with changes in the active space. However, the on-top ratio does change significantly with respect to active space change, and this affects the on-top energy. This study provides a foundation for designing on-top density functionals and automatizing the active space choice in MC-PDFT.
Further development of YBOCS dimensions in the OCD Collaborative Genetics Study: Symptoms vs Categories

PubMed Central

Pinto, Anthony; Greenberg, Benjamin D.; Grados, Marco A.; Bienvenu, O. Joseph; Samuels, Jack F.; Murphy, Dennis L.; Hasler, Gregor; Stout, Robert L.; Rauch, Scott L.; Shugart, Yin Y.; Pauls, David L.; Knowles, James A.; Fyer, Abby J.; McCracken, James T.; Piacentini, John; Wang, Ying; Willour, Virginia L.; Cullen, Bernadette; Liang, Kung-Yee; Hoehn-Saric, Rudolf; Riddle, Mark A.; Rasmussen, Steven A.; Nestadt, Gerald

2008-01-01

Despite progress in identifying homogeneous subphenotypes of obsessive compulsive disorder (OCD) through factor analysis of the Yale-Brown Obsessive Compulsive Scale Symptom Checklist (YBOCS-SC), prior solutions have been limited by a reliance on presupposed symptom categories rather than discrete symptoms. Furthermore, there have been only limited attempts to evaluate the familiality of OCD symptom dimensions. The purpose of this study was to extend prior work by this collaborative group in category-based dimensions by conducting the first-ever exploratory dichotomous factor analysis using individual OCD symptoms, comparing these results to a refined category-level solution, and testing the familiality of derived factors. Participants were 485 adults in the six-site OCD Collaborative Genetics Study, diagnosed with lifetime OCD using semi-structured interviews. YBOCS-SC data were factor analyzed at both the individual item and symptom category levels. Factor score intraclass correlations were calculated using a subsample of 145 independent affected sib pairs. The item- and category-level factor analyses yielded nearly identical 5-factor solutions. While significant sib-sib associations were found for 4 of the 5 factors, Hoarding and Taboo Thoughts were the most robustly familial (rICC ≥ 0.2). This report presents considerable converging evidence for a 5-factor structural model of OCD symptoms, including separate factor analyses employing individual symptoms and symptom categories, as well as sibling concordance. The results support investigation of this multidimensional model in OCD genetic linkage studies. PMID:18514325
Robinow syndrome: phenotypic variability in a family with a novel intragenic ROR2 mutation.

PubMed

Brunetti-Pierri, Nicola; Del Gaudio, Daniela; Peters, Hartmut; Justino, Henri; Ott, Claus-Eric; Mundlos, Stefan; Bacino, Carlos A

2008-11-01

Robinow syndrome comprises dysmorphic facial features, short stature, brachymesomelia, segmental spine defects, and genital hypoplasia. The range of severity in this disorder is broad. We report on the clinical and molecular findings of two sib pairs from the same extended family with Robinow syndrome due to a novel intragenic ROR2 deletion involving exons 6 and 7 that could not be detected by sequencing. The affected individuals exhibited variability with respect to the cleft lip, cleft palate, and cardiac findings and for the presence in one of the patients of syringomyelia, which has not been previously reported in Robinow syndrome. Copyright 2008 Wiley-Liss, Inc.
Processing negative valence of word pairs that include a positive word.

PubMed

Itkes, Oksana; Mashal, Nira

2016-09-01

Previous research has suggested that cognitive performance is interrupted by negative relative to neutral or positive stimuli. We examined whether negative valence affects performance at the word or phrase level. Participants performed a semantic decision task on word pairs that included either a negative or a positive target word. In Experiment 1, the valence of the target word was congruent with the overall valence conveyed by the word pair (e.g., fat kid). As expected, response times were slower in the negative condition relative to the positive condition. Experiment 2 included target words that were incongruent with the overall valence of the word pair (e.g., fat salary). Response times were longer for word pairs whose overall valence was negative relative to positive, even though these word pairs included a positive word. Our findings support the Cognitive Primacy Hypothesis, according to which emotional valence is extracted after conceptual processing is complete.
Fibrinogen Bastia (gamma 318 Asp-->Tyr) a novel abnormal fibrinogen characterized by defective fibrin polymerization.

PubMed

Lounes, K C; Soria, C; Valognes, A; Turchini, M F; Soria, J; Koopman, J

1999-12-01

A new congenital dysfibrinogen, Fibrinogen Bastia, was discovered in a 20-year-old woman with no clinical symptoms. The plasma thrombin-clotting time was severely prolonged. The functional plasma fibrinogen concentration was low (0.2 mg/ml), whereas the immunological concentration was normal (2.9 mg/ml). Purified fibrinogen Bastia displayed a markedly prolonged thrombin-clotting time related to a delayed thrombin-induced fibrin polymerization. Both the thrombin-clotting time and the fibrin polymerization were partially corrected by the addition of calcium ions. The anomaly of fibrinogen Bastia was found to be located in the gamma-chain since by SDS-PAGE performed according to the method of Laemmli two gamma-chains were detected, one normal and one with an apparently lower molecular weight. Furthermore, analysis of plasmin degradation products demonstrated that calcium ions only partially protect fibrinogen Bastia gamma-chain against plasmin digestion, suggesting that the anomaly is located in the C-terminal part of the gamma-chain. Sequence analysis of PCR-amplified genomic DNA fragments of the propositus demonstrated a single base substitution (G-->T) in the exon VIII of the gamma chain gene, resulting in the amino acid substitution 318 Asp (GAC)-->Tyr (TAC). The PCR clones were recloned and 50% of them contained the mutation, indicating that the patient was heterozygous. These data indicate that residue Asp 318 is important for normal fibrin polymerization and the protective effect of calcium ions against plasmin degradation of the C-terminal part of the gamma-chain.
Theoretical determination of one-electron redox potentials for DNA bases, base pairs, and stacks.

PubMed

Paukku, Y; Hill, G

2011-05-12

Electron affinities, ionization potentials, and redox potentials for DNA bases, base pairs, and N-methylated derivatives are computed at the DFT/M06-2X/6-31++G(d,p) level of theory. Redox properties of a guanine-guanine stack model are explored as well. Reduction and oxidation potentials are in good agreement with the experimental ones. Electron affinities of base pairs were found to be negative. Methylation of canonical bases affects the ionization potentials the most. Base pair formation and base stacking lower ionization potentials by 0.3 eV. Pairing of guanine with the 5-methylcytosine does not seem to influence the redox properties of this base pair much.
Using remote-sensing and the Simple Biosphere model (SiB4) to analyze the seasonality and productivity of the terrestrial biosphere.

NASA Astrophysics Data System (ADS)

Cheeseman, M.; Denning, S.; Baker, I. T.

2017-12-01

Understanding the variability and seasonality of carbon fluxes from the terrestrial biosphere is integral to understanding the mechanisms and drivers of the global carbon cycle. However, there are many regions across the globe where in situ observations are sparse, such as the Amazon rainforest and the African Sahel. The latest version of the Simple-Biosphere model (SiB4) predicts a suite of biophysical variables such as terrestrial carbon flux (GPP), solar induced fluorescence (SIF), fraction of photosynthetically active radiation (FPAR), and leaf area index (LAI). By comparing modeled values to a suite of satellite and in situ observations we produce a robust analysis of the seasonality and productivity of the terrestrial biosphere in a variety of biome types across the globe.
Evolution of separate screening soliton pairs in a biased series photorefractive crystal circuit.

PubMed

Liu, Jinsong; Hao, Zhonghua

2002-06-01

This paper presents calculations for an idea in photorefractive spatial soliton, namely, screening solitons form in a biased series photorefractive crystal circuit consisting of two photorefractive crystals connected electronically by electrode leads in a chain with a voltage source. A system of two coupled equations is derived under appropriate conditions for two-beam propagation in the crystal circuit. The possibility of obtaining steady-state bright and dark screening soliton solutions is investigated in one dimension and, the existence of dark-dark, bright-dark, and bright-bright separate screening soliton pairs in such a circuit is proved. The numerical results show that the two solitons in a soliton pair can affect each other by the light-induced current and their coupling can affect their spatial profiles, dynamical evolutions, stabilities, and self-deflection. Under the limit in which the optical wave has a spatial extent much less than the width of the crystal, only the dark soliton can affect the other soliton by the light-induced current, but the bright soliton cannot. For a bright-dark or dark-dark soliton pair, the dark soliton in a weak input intensity can be obtained for a larger nonlinearity than for a stronger input intensity. For a bright-dark soliton pair, increasing the input intensity of the dark soliton can increase the bending angle of the bright soliton. Some potential applications are discussed.
Parents' first concerns about toddlers with autism spectrum disorder: effect of sibling status.

PubMed

Herlihy, Lauren; Knoch, Kelley; Vibert, Bethany; Fein, Deborah

2015-01-01

Symptoms of autism spectrum disorders may appear as early as 6 months, but parent concern, which can precipitate evaluation, often lags significantly. The presence of typical or atypical older siblings can change parents' sensitivity to departures from typical development. This study investigated type and age of parent's first concerns in toddlers with autism spectrum disorder, prior to diagnosis. Participants had (1) at least one older sibling with autism spectrum disorder (Sibs-ASD); (2) only typically developing older siblings (Sibs-TD), or (3) were only/oldest (No-Sibs). Specific autism spectrum disorder diagnoses and symptom severity were similar among groups. Developmentally, No-Sibs showed the largest delays, followed by Sibs-TD, followed by Sibs-ASD. Mean age of first concern was 16 months for No-Sibs, 14 months for Sibs-TD, and 10 months for Sibs-ASD. Age of first concern differed significantly by group, even after controlling for mother's age and education. Concern about language was prevalent in all groups. Thus, the presence of an older child with typical or, especially, atypical development was associated with earlier concerns for the affected child, despite milder developmental delays. These findings underscore the importance of encouraging parents to report concerns to pediatricians, routine standardized screening for autism spectrum disorder, and the need for pediatrician vigilance, especially for only or oldest children. © The Author(s) 2013.
Cardiac Myosin Binding Protein C Phosphorylation Affects Cross-Bridge Cycle's Elementary Steps in a Site-Specific Manner

PubMed Central

Wang, Li; Sadayappan, Sakthivel; Kawai, Masakata

2014-01-01

Based on our recent finding that cardiac myosin binding protein C (cMyBP-C) phosphorylation affects muscle contractility in a site-specific manner, we further studied the force per cross-bridge and the kinetic constants of the elementary steps in the six-state cross-bridge model in cMyBP-C mutated transgenic mice for better understanding of the influence of cMyBP-C phosphorylation on contractile functions. Papillary muscle fibres were dissected from cMyBP-C mutated mice of ADA (Ala273-Asp282-Ala302), DAD (Asp273-Ala282-Asp302), SAS (Ser273-Ala282-Ser302), and t/t (cMyBP-C null) genotypes, and the results were compared to transgenic mice expressing wide-type (WT) cMyBP-C. Sinusoidal analyses were performed with serial concentrations of ATP, phosphate (Pi), and ADP. Both t/t and DAD mutants significantly reduced active tension, force per cross-bridge, apparent rate constant (2πc), and the rate constant of cross-bridge detachment. In contrast to the weakened ATP binding and enhanced Pi and ADP release steps in t/t mice, DAD mice showed a decreased ADP release without affecting the ATP binding and the Pi release. ADA showed decreased ADP release, and slightly increased ATP binding and cross-bridge detachment steps, whereas SAS diminished the ATP binding step and accelerated the ADP release step. t/t has the broadest effects with changes in most elementary steps of the cross-bridge cycle, DAD mimics t/t to a large extent, and ADA and SAS predominantly affect the nucleotide binding steps. We conclude that the reduced tension production in DAD and t/t is the result of reduced force per cross-bridge, instead of the less number of strongly attached cross-bridges. We further conclude that cMyBP-C is an allosteric activator of myosin to increase cross-bridge force, and its phosphorylation status modulates the force, which is regulated by variety of protein kinases. PMID:25420047
Cardiac myosin binding protein C phosphorylation affects cross-bridge cycle's elementary steps in a site-specific manner.

PubMed

Wang, Li; Sadayappan, Sakthivel; Kawai, Masakata

2014-01-01

Based on our recent finding that cardiac myosin binding protein C (cMyBP-C) phosphorylation affects muscle contractility in a site-specific manner, we further studied the force per cross-bridge and the kinetic constants of the elementary steps in the six-state cross-bridge model in cMyBP-C mutated transgenic mice for better understanding of the influence of cMyBP-C phosphorylation on contractile functions. Papillary muscle fibres were dissected from cMyBP-C mutated mice of ADA (Ala273-Asp282-Ala302), DAD (Asp273-Ala282-Asp302), SAS (Ser273-Ala282-Ser302), and t/t (cMyBP-C null) genotypes, and the results were compared to transgenic mice expressing wide-type (WT) cMyBP-C. Sinusoidal analyses were performed with serial concentrations of ATP, phosphate (Pi), and ADP. Both t/t and DAD mutants significantly reduced active tension, force per cross-bridge, apparent rate constant (2πc), and the rate constant of cross-bridge detachment. In contrast to the weakened ATP binding and enhanced Pi and ADP release steps in t/t mice, DAD mice showed a decreased ADP release without affecting the ATP binding and the Pi release. ADA showed decreased ADP release, and slightly increased ATP binding and cross-bridge detachment steps, whereas SAS diminished the ATP binding step and accelerated the ADP release step. t/t has the broadest effects with changes in most elementary steps of the cross-bridge cycle, DAD mimics t/t to a large extent, and ADA and SAS predominantly affect the nucleotide binding steps. We conclude that the reduced tension production in DAD and t/t is the result of reduced force per cross-bridge, instead of the less number of strongly attached cross-bridges. We further conclude that cMyBP-C is an allosteric activator of myosin to increase cross-bridge force, and its phosphorylation status modulates the force, which is regulated by variety of protein kinases.
May TLR4 Asp299Gly and IL17 His161Arg polymorphism be associated with progression of primary measles infection to subacute sclerosing panencephalitis?

PubMed

Karakas-Celik, Sevim; Piskin, Ibrahim Etem; Keni, Mehmet Fatih; Calık, Mustafa; Iscan, Akın; Dursun, Ahmet

2014-09-01

SSPE is a progressive neurological disorder of children. Only some of the children who are infected with measles virus develop SSPE, which supports individual variation. TLR-2 and TLR-4 play an important role in innate immunity by recognizing envelope proteins of MV. Another important cytokine that plays an important role in orchestrating innate immune function is IL-17. The purpose of our study is to elucidate whether the TLR2, TLR4, IL17F and IL17A gene polymorphisms are susceptibility genes for the development of SSPE. Using the PCR-RFLP methods, the single nucleotide polymorphisms of TLR2 (Arg753Gln, Arg677Trp, -194 to -174 del), TLR4 (Asp299Gly and Thr399Ile) IL17F (His161Arg, Glu126Gly) and IL17A were studied in 54 patients with SSPE and 81 healthy controls. For Asp299Gly polymorphism of the TLR4 gene we found that there were no control individuals who were homozygous carriers of the Gly/Gly genotype, and the risk for SSPE increased at approximately 4.7 fold for the heterozygous carriers of the Asp/Gly genotype (OR 4.727, 95%-CI 1.192-18.742; P=0.01), when compared to healthy controls. Also our findings demonstrate that homozygosity for the Arg161 variant of the IL17F His161Arg polymorphism is inversely associated with development of SSPE (OR 0.114 95%-CI 0.026-0.494; P<0.001). In conclusion, it is suggested that variation in susceptibility to SSPE disease may be in part due to variations in TLR4 and IL17 function resulting from polymorphisms of TLR4 Asp299Gly and IL17F His161Arg. Copyright © 2014 Elsevier B.V. All rights reserved.
The Role of the Asn40Asp Polymorphism of the Mu Opioid Receptor Gene (OPRM1) on Alcoholism Etiology and Treatment: A Critical Review

PubMed Central

Ray, Lara A.; Barr, Christina S.; Blendy, Julie A.; Oslin, David; Goldman, David; Anton, Raymond F.

2011-01-01

The endogenous opioid system has been implicated in the pathophysiology of alcoholism as it modulates the neurobehavioral effects of alcohol. A variant in the mu opioid receptor gene (OPRM1), the Asn40Asp polymorphism, has received attention as a functional variant that may influence a host of behavioral phenotypes for alcoholism as well as clinical response to opioid antagonists. This paper will review converging lines of evidence on the effect of the Asn40Asp SNP on alcoholism phenotypes, including: (i) genetic association studies; (ii) behavioral studies of alcoholism; (iii) neuroimaging studies; (iv) pharmacogenetic studies and clinical trials; and (v) preclinical animal studies. Together, these lines of research seek to elucidate the effects of this functional polymorphism on alcoholism etiology and treatment response. PMID:21895723
Probing the Catalytic Mechanism of Vibrio harveyi GH20 β-N-Acetylglucosaminidase by Chemical Rescue

PubMed Central

Meekrathok, Piyanat; Suginta, Wipa

2016-01-01

Background Vibrio harveyi GH20 β-N-acetylglucosaminidase (VhGlcNAcase) is a chitinolytic enzyme responsible for the successive degradation of chitin fragments to GlcNAc monomers, activating the onset of the chitin catabolic cascade in marine Vibrios. Methods Two invariant acidic pairs (Asp303-Asp304 and Asp437-Glu438) of VhGlcNAcase were mutated using a site-directed mutagenesis strategy. The effects of these mutations were examined and the catalytic roles of these active-site residues were elucidated using a chemical rescue approach. Enhancement of the enzymic activity of the VhGlcNAcase mutants was evaluated by a colorimetric assay using pNP-GlcNAc as substrate. Results Substitution of Asp303, Asp304, Asp437 or Glu438 with Ala/Asn/Gln produced a dramatic loss of the GlcNAcase activity. However, the activity of the inactive D437A mutant was recovered in the presence of sodium formate. Our kinetic data suggest that formate ion plays a nucleophilic role by mimicking the β-COO-side chain of Asp437, thereby stabilizing the reaction intermediate during both the glycosylation and the deglycosylation steps. Conclusions Chemical rescue of the inactive D437A mutant of VhGlcNAcase by an added nucleophile helped to identify Asp437 as the catalytic nucleophile/base, and hence its acidic partner Glu438 as the catalytic proton donor/acceptor. General Significance Identification of the catalytic nucleophile of VhGlcNAcases supports the proposal of a substrate-assisted mechanism of GH20 GlcNAcases, requiring the catalytic pair Asp437-Glu438 for catalysis. The results suggest the mechanistic basis of the participation of β-N-acetylglucosaminidase in the chitin catabolic pathway of marine Vibrios. PMID:26870945
The parasite-derived rOv-ASP-1 is an effective antigen-sparing CD4+ T cell-dependent adjuvant for the trivalent inactivated influenza vaccine, and functions in the absence of MyD88 pathway.

PubMed

Jain, Sonia; George, Parakkal Jovvian; Deng, Wanyan; Koussa, Joseph; Parkhouse, Kaela; Hensley, Scott E; Jiang, Jiu; Lu, Jie; Liu, Zhuyun; Wei, Junfei; Zhan, Bin; Bottazzi, Maria Elena; Shen, Hao; Lustigman, Sara

2018-06-14

Vaccination remains the most cost-effective biomedical approach for controlling influenza disease. In times of pandemics, however, these vaccines cannot be produced in sufficient quantities for worldwide use by the current manufacturing capacities and practices. What is needed is the development of adjuvanted vaccines capable of inducing an adequate or better immune response at a decreased antigen dose. Previously we showed that the protein adjuvant rOv-ASP-1 augments influenza-specific antibody titers and survival after virus challenge in both young adult and old-age mice when administered with the trivalent inactivated influenza vaccine (IIV3). In this study we show that a reduced amount of rOv-ASP-1, with 40-times less IIV3 can also induce protection. Apparently the potency of the rOv-ASP-1 adjuvanted IIV3 vaccine is independent of the IIV3-specific Th1/Th2 associated antibody responses, and independent of the presence of HAI antibodies. However, CD4 + T helper cells were indispensable for the protection. Further, rOv-ASP-1 with or without IIV3 elicited the increased level of various chemokines, which are known chemoattractant for immune cells, into the muscle 4 h after immunization, and significantly induced the recruitment of monocytes, macrophages and neutrophils into the muscles. The recruited monocytes had higher expression of the activation marker MHCII on their surface as well as CXCR3 and CCR2; receptors for IP-10 and MCP-1, respectively. These results show that the rOv-ASP-1 adjuvant allows substantial antigen sparing of IIV3 by stimulating at the site of injection the accumulation of chemokines and the recruitment of immune cells that can augment the activation of CD4 + T cell immune responses, essential for the production of antibody responses. Protection elicited by the rOv-ASP-1 adjuvanted IIV3 vaccine also appears to function in the absence of MyD88-signaling. Future studies will attempt to delineate the precise mechanisms by which the rOv-ASP-1

Experimental extraction of an entangled photon pair from two identically decohered pairs.

PubMed

Yamamoto, Takashi; Koashi, Masato; Ozdemir, Sahin Kaya; Imoto, Nobuyuki

2003-01-23

Entanglement is considered to be one of the most important resources in quantum information processing schemes, including teleportation, dense coding and entanglement-based quantum key distribution. Because entanglement cannot be generated by classical communication between distant parties, distribution of entangled particles between them is necessary. During the distribution process, entanglement between the particles is degraded by the decoherence and dissipation processes that result from unavoidable coupling with the environment. Entanglement distillation and concentration schemes are therefore needed to extract pairs with a higher degree of entanglement from these less-entangled pairs; this is accomplished using local operations and classical communication. Here we report an experimental demonstration of extraction of a polarization-entangled photon pair from two decohered photon pairs. Two polarization-entangled photon pairs are generated by spontaneous parametric down-conversion and then distributed through a channel that induces identical phase fluctuations to both pairs; this ensures that no entanglement is available as long as each pair is manipulated individually. Then, through collective local operations and classical communication we extract from the two decohered pairs a photon pair that is observed to be polarization-entangled.
Regulated bioanalysis of conformers - A case study with ASP2151 in dog plasma and urine.

PubMed

Ohtsu, Yoshiaki; Otsuka, Shohei; Nakamura, Takeshi; Noguchi, Kiyoshi

2015-08-01

We developed and validated bioanalytical methods for a potent helicase-primase inhibitor ASP2151 that has two conformers. These conformers elute as unseparated broad peaks under ordinary high-performance liquid chromatographic conditions, indicating discernable differences in hydrophobicity. We observed that column temperature and mobile phase pH have no effect on these peaks and that conformers form a single symmetrical peak when tetrahydrofuran is added to the mobile phase. In addition, we needed to develop semi-automated methods where inter-conversion of the conformers is unlikely to cause sample-to-sample extraction variability. Briefly, following the addition of deuterium-labeled ASP2151 as an internal standard (IS), dog plasma samples or acetonitrile-added urine samples were filtrated. The filtrates were then injected into a column-switching liquid chromatography-tandem mass spectrometry (LC-MS/MS) system and trapped onto an extraction column. Extracts were back-flushed onto an analytical C18 column (4.6×50mm, 3μm) with a mobile phase consisting of methanol, tetrahydrofuran, and 20mmol/L ammonium acetate (45:5:50, v/v/v). The eluent was monitored in the negative atmospheric pressure chemical ionization mode. The calibration curve was linear over a range of 5-1000ng/mL for plasma and 0.5-100μg/mL for urine. Validation data met the acceptance criteria in accordance with regulatory guidance and demonstrated that these methods were selective, accurate, and reproducible. In addition, the present methods were successfully applied to a pharmacokinetic study in dogs. Copyright © 2015 Elsevier B.V. All rights reserved.
Effect of Box-Cox transformation on power of Haseman-Elston and maximum-likelihood variance components tests to detect quantitative trait Loci.

PubMed

Etzel, C J; Shete, S; Beasley, T M; Fernandez, J R; Allison, D B; Amos, C I

2003-01-01

Non-normality of the phenotypic distribution can affect power to detect quantitative trait loci in sib pair studies. Previously, we observed that Winsorizing the sib pair phenotypes increased the power of quantitative trait locus (QTL) detection for both Haseman-Elston (HE) least-squares tests [Hum Hered 2002;53:59-67] and maximum likelihood-based variance components (MLVC) analysis [Behav Genet (in press)]. Winsorizing the phenotypes led to a slight increase in type 1 error in H-E tests and a slight decrease in type I error for MLVC analysis. Herein, we considered transforming the sib pair phenotypes using the Box-Cox family of transformations. Data were simulated for normal and non-normal (skewed and kurtic) distributions. Phenotypic values were replaced by Box-Cox transformed values. Twenty thousand replications were performed for three H-E tests of linkage and the likelihood ratio test (LRT), the Wald test and other robust versions based on the MLVC method. We calculated the relative nominal inflation rate as the ratio of observed empirical type 1 error divided by the set alpha level (5, 1 and 0.1% alpha levels). MLVC tests applied to non-normal data had inflated type I errors (rate ratio greater than 1.0), which were controlled best by Box-Cox transformation and to a lesser degree by Winsorizing. For example, for non-transformed, skewed phenotypes (derived from a chi2 distribution with 2 degrees of freedom), the rates of empirical type 1 error with respect to set alpha level=0.01 were 0.80, 4.35 and 7.33 for the original H-E test, LRT and Wald test, respectively. For the same alpha level=0.01, these rates were 1.12, 3.095 and 4.088 after Winsorizing and 0.723, 1.195 and 1.905 after Box-Cox transformation. Winsorizing reduced inflated error rates for the leptokurtic distribution (derived from a Laplace distribution with mean 0 and variance 8). Further, power (adjusted for empirical type 1 error) at the 0.01 alpha level ranged from 4.7 to 17.3% across all tests
Characterization of mechanisms underlying degradation of sclerotia of Sclerotinia sclerotiorum by Aspergillus aculeatus Asp-4 using a combined qRT-PCR and proteomic approach.

PubMed

Hu, Xiaojia; Qin, Lu; Roberts, Daniel P; Lakshman, Dilip K; Gong, Yangmin; Maul, Jude E; Xie, Lihua; Yu, Changbing; Li, Yinshui; Hu, Lei; Liao, Xiangsheng; Liao, Xing

2017-08-31

The biological control agent Aspergillus aculeatus Asp-4 colonizes and degrades sclerotia of Sclerotinia sclerotiorum resulting in reduced germination and disease caused by this important plant pathogen. Molecular mechanisms of mycoparasites underlying colonization, degradation, and reduction of germination of sclerotia of this and other important plant pathogens remain poorly understood. An RNA-Seq screen of Asp-4 growing on autoclaved, ground sclerotia of S. sclerotiorum for 48 h identified 997 up-regulated and 777 down-regulated genes relative to this mycoparasite growing on potato dextrose agar (PDA) for 48 h. qRT-PCR time course experiments characterized expression dynamics of select genes encoding enzymes functioning in degradation of sclerotial components and management of environmental conditions, including environmental stress. This analysis suggested co-temporal up-regulation of genes functioning in these two processes. Proteomic analysis of Asp-4 growing on this sclerotial material for 48 h identified 26 up-regulated and 6 down-regulated proteins relative to the PDA control. Certain proteins with increased abundance had putative functions in degradation of polymeric components of sclerotia and the mitigation of environmental stress. Our results suggest co-temporal up-regulation of genes involved in degradation of sclerotial compounds and mitigation of environmental stress. This study furthers the analysis of mycoparasitism of sclerotial pathogens by providing the basis for molecular characterization of a previously uncharacterized mycoparasite-sclerotial interaction.
Linking infant-directed speech and face preferences to language outcomes in infants at risk for autism spectrum disorder.

PubMed

Droucker, Danielle; Curtin, Suzanne; Vouloumanos, Athena

2013-04-01

In this study, the authors aimed to examine whether biases for infant-directed (ID) speech and faces differ between infant siblings of children with autism spectrum disorder (ASD) (SIBS-A) and infant siblings of typically developing children (SIBS-TD), and whether speech and face biases predict language outcomes and risk group membership. Thirty-six infants were tested at ages 6, 8, 12, and 18 months. Infants heard 2 ID and 2 adult-directed (AD) speech passages paired with either a checkerboard or a face. The authors assessed expressive language at 12 and 18 months and general functioning at 12 months using the Mullen Scales of Early Learning (Mullen, 1995). Both infant groups preferred ID to AD speech and preferred faces to checkerboards. SIBS-TD demonstrated higher expressive language at 18 months than did SIBS-A, a finding that correlated with preferences for ID speech at 12 months. Although both groups looked longer to face stimuli than to the checkerboard, the magnitude of the preference was smaller in SIBS-A and predicted expressive vocabulary at 18 months in this group. Infants' preference for faces contributed to risk-group membership in a logistic regression analysis. Infants at heightened risk of ASD differ from typically developing infants in their preferences for ID speech and faces, which may underlie deficits in later language development and social communication.
Structural and Phylogenetic Analysis of a Conserved Actinobacteria-Specific Protein (ASP1; SCO1997) from Streptomyces Coelicolor

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

Gao, B.; Sugiman-Marangos, S; Junop, M

2009-01-01

The Actinobacteria phylum represents one of the largest and most diverse groups of bacteria, encompassing many important and well-characterized organisms including Streptomyces, Bifidobacterium, Corynebacterium and Mycobacterium. Members of this phylum are remarkably diverse in terms of life cycle, morphology, physiology and ecology. Recent comparative genomic analysis of 19 actinobacterial species determined that only 5 genes of unknown function uniquely define this large phylum [1]. The cellular functions of these actinobacteria-specific proteins (ASP) are not known.
Dopamine receptor blockade attenuates the general incentive motivational effects of noncontingently delivered rewards and reward-paired cues without affecting their ability to bias action selection.

PubMed

Ostlund, Sean B; Maidment, Nigel T

2012-01-01

Environmental cues affect our behavior in a variety of ways. Despite playing an invaluable role in guiding our daily activities, such cues also appear to trigger the harmful, compulsive behaviors that characterize addiction and other disorders of behavioral control. In instrumental conditioning, rewards and reward-paired cues bias action selection and invigorate reward-seeking behaviors, and appear to do so through distinct neurobehavioral processes. Although reward-paired cues are known to invigorate performance through a dopamine-dependent incentive motivational process, it is not known if dopamine also mediates the influence of rewards and reward-paired cues over action selection. The current study contrasted the effects of systemic administration of the nonspecific dopamine receptor antagonist flupentixol on response invigoration and action bias in Pavlovian-instrumental transfer, a test of cue-elicited responding, and in instrumental reinstatement, a test of noncontingent reward-elicited responding. Hungry rats were trained on two different stimulus-outcome relationships (eg, tone-grain pellets and noise-sucrose solution) and two different action-outcome relationships (eg, left press-grain and right press-sucrose). At test, we found that flupentixol pretreatment blocked the response invigoration generated by the cues but spared their ability to bias action selection to favor the action whose outcome was signaled by the cue being presented. The response-biasing influence of noncontingent reward deliveries was also unaffected by flupentixol. Interestingly, although flupentixol had a modest effect on the immediate response invigoration produced by those rewards, it was particularly potent in countering the lingering enhancement of responding produced by multiple reward deliveries. These findings indicate that dopamine mediates the general incentive motivational effects of noncontingent rewards and reward-paired cues but does not support their ability to bias
Using an innovative multiple regression procedure in a cancer population (Part II): fever, depressive affect, and mobility problems clarify an influential symptom pair (pain-fatigue/weakness) and cluster (pain-fatigue/weakness-sleep problems).

PubMed

Francoeur, Richard B

2015-01-01

Most patients with advanced cancer experience symptom pairs or clusters among pain, fatigue, and insomnia. However, only combinations where symptoms are mutually influential hold potential for identifying patient subgroups at greater risk, and in some contexts, interventions with "cross-over" (multisymptom) effects. Improved methods to detect and interpret interactions among symptoms, signs, or biomarkers are needed to reveal these influential pairs and clusters. I recently created sequential residual centering (SRC) to reduce multicollinearity in moderated regression, which enhances sensitivity to detect these interactions. I applied SRC to moderated regressions of single-item symptoms that interact to predict outcomes from 268 palliative radiation outpatients. I investigated: 1) the hypothesis that the interaction, pain × fatigue/weakness × sleep problems, predicts depressive affect only when fever presents, and 2) an exploratory analysis, when fever is absent, that the interaction, pain × fatigue/weakness × sleep problems × depressive affect, predicts mobility problems. In the fever context, three-way interactions (and derivative terms) of the four symptoms (pain, fatigue/weakness, fever, sleep problems) are tested individually and simultaneously; in the non-fever context, a single four-way interaction (and derivative terms) is tested. Fever interacts separately with fatigue/weakness and sleep problems; these comoderators each magnify the pain-depressive affect relationship along the upper or full range of pain values. In non-fever contexts, fatigue/weakness, sleep problems, and depressive affect comagnify the relationship between pain and mobility problems. Different mechanisms contribute to the pain × fatigue/weakness × sleep problems interaction, but all depend on the presence of fever, a sign/biomarker/symptom of proinflammatory sickness behavior. In non-fever contexts, depressive affect is no longer an outcome representing malaise from the physical
Association study between monoamine oxidase A (MAOA) gene polymorphisms and schizophrenia: lack of association with schizophrenia and possible association with affective disturbances of schizophrenia.

PubMed

Kim, Su Kang; Park, Hae Jeong; Seok, Hosik; Jeon, Hye Sook; Chung, Joo-Ho; Kang, Won Sub; Kim, Jong Woo; Yu, Gyeong Im; Shin, Dong Hoon

2014-05-01

Monoamine oxidase A (MAOA) catalyzes monoamine neurotransmitters including dopamine, 5-hydroxytryptamine (5-HT, serotonin), and norepinephrine. MAOA also plays a key role in emotional regulation. The aim of this study was to investigate the associations between the exonic single nucleotide polymorphisms (SNPs) of the MAOA gene located on the X chromosome and schizophrenia. We also analyzed the relationships between these SNPs and the common clinical symptoms of schizophrenia such as persecutory delusion, auditory hallucinations, affective disturbances, and poor concentration. Two hundred seventy five Korean schizophrenia patients and 289 control subjects were recruited. Three SNPs [rs6323 (Arg294Arg), rs1137070 (Asp470Asp), and rs3027407 (3'-untranslated region)] of the MAOA gene were selected and genotyped by direct sequencing. The common clinical symptoms of schizophrenia according to the Operation Criteria Checklist were analyzed. Three examined SNPs showed no associations with male and female schizophrenia, respectively (p>0.05). In the analysis of the common clinical symptoms of schizophrenia patients, three examined SNPs were associated with affective disturbances, especially restricted affect and blunted affect in male schizophrenia, respectively (restricted affect, p=0.002, OR=2.71, 95% CI 1.45-5.00; blunted affect, p=0.009, OR 2.25, 95% CI 1.22-4.12). The SNPs were not associated with other clinical symptoms of schizophrenia (persecutory delusion, auditory hallucinations, and poor concentration). These results suggest that exonic SNPs (rs6323, rs1137070, and rs3027407) of the MAOA gene may be contributed to affective disturbances of Korean males schizophrenia, especially restricted affect and blunted affect.
Genetic analysis of motor milestones attainment in early childhood.

PubMed

Peter, I; Vainder, M; Livshits, G

1999-03-01

The age of attainment for four motor developmental traits, such as turning over, sitting up without support, pulling up to a standing position and walking without support, was examined in 822 children, including 626 siblings from families with 2 to 6 children, 68 pairs of dizygotic twins and 30 pairs of monozygotic twins. Correlation analysis, carried out separately for each type of sibship, showed the highest pairwise correlations in monozygotic twins and the lowest correlation in non-twin siblings for all motor milestones. Variance component analysis was used to decompose the different independent components forming the variation of the studied trait, such as genetic effect, common twin environment, common sib environment and residual factors. The results revealed that the major proportion of the total variance after adjustment for gestation age for the attainment of each motor skill, except pulling up to standing position, is explained by the common twin environment (50.5 to 66.6%), whilst a moderate proportion is explained by additive genetic factors (22.2 to 33.5%). Gestational age was found to be an important predictor of appearance of all motor milestones, affecting delay of 4.5 to 8.6 days for the attainment of the motor abilities for each week of earlier gestation. The age of attainment of the standing position was affected only by shared sibs environment (33.3% of the total variance) and showed no influence of either genetic or common twin environment. Phenotypic between trait correlations were high and significant for all studied traits (range between 0.40 and 0.67, P < 0.01 in all instances). Genetic cross correlations, however, were not easily interpreted and did not show clear variance trends among the different groups of children.
Soil Surface Runoff Scheme for Improving Land-Hydrology and Surface Fluxes in Simple SiB (SSiB)

NASA Technical Reports Server (NTRS)

Sud, Y. C.; Mocko, David M.

1999-01-01

Evapotranspiration on land is hard to measure and difficult to simulate. On the scale of a GCM grid, there is large subgrid-scale variability of orography, soil moisture, and vegetation. Our hope is to be able to tune the biophysical constants of vegetation and soil parameters to get the most realistic space-averaged diurnal cycle of evaporation and its climatology. Field experiments such as First ISLSCP Field Experiment (FIFE), Boreal Ecosystem-Atmosphere Study (BOREAS), and LBA help a great deal in improving our evapotranspiration schemes. However, these improvements have to be matched with, and coupled to, consistent improvement in land-hydrology; otherwise, the runoff problems will intrinsically reflect on the soil moisture and evapotranspiration errors. Indeed, a realistic runoff simulation also ensures a reasonable evapotranspiration simulation provided the precipitation forcing is reliable. We have been working on all of the above problems to improve the simulated hydrologic cycle. Through our participation in the evaluation and intercomparison of land-models under the behest of Global Soil Wetness Project (GSWP), we identified a few problems with Simple SiB (SSIB; Xue et al., 1991) hydrology in regions of significant snowmelt. Sud and Mocko (1999) show that inclusion of a separate snowpack model, with its own energy budget and fluxes with the atmosphere aloft and soil beneath, helps to ameliorate some of the deficiencies of delayed snowmelt and excessive spring season runoff. Thus, much more realistic timing of melt water generation was simulated with the new snowpack model in the subsequent GSWP re-evaluations using 2 years of ISLSCP Initiative I forcing data for 1987 and 1988. However, we noted an overcorrection of the low meltwater infiltration of SSiB. While the improvement in snowmelt timing was found everywhere, the snowmelt infiltration has became excessive in some regions, e.g., Lena river basin. This leads to much reduced runoff in many basins as
Self-injurious behavior in adolescent girls. Association with psychopathology and neuropsychological functions.

PubMed

Ohmann, S; Schuch, B; Konig, M; Blaas, S; Fliri, C; Popow, C

2008-01-01

Self-injurious behavior (SIB) is increasingly popular in psychically ill adolescents, especially in girls with posttraumatic stress (PTSD) and personality disorders. Adolescents with SIB frequently exhibit neurofunctional and psychopathological deficits. We speculated that specific neuropsychological deficits and temperamental factors could predispose patients to SIB and prospectively explored adolescent psychiatric patients with and without SIB in order to find out differences in psychopathology, and neuropsychological or temperamental factors. Ninety-nine psychically ill adolescent girls with SIB, aged 12-19 years and treated at our clinic, were prospectively recruited during a period of 5.5 years (1999-2005). The clinical (ICD-10) diagnoses were mainly substance abuse, eating disorders, depression, PTSD and personality disorders. The control group was also prospectively recruited during the same period and consisted of 77 girls with similar diagnoses and ages but no SIB. All patients were subjected to the same selection of clinical and neuropsychological tests, mainly self-rating questionnaires and tests evaluating executive functions. Adolescent girls with psychiatric disease and SIB were more severely traumatized and depressed. They reported severe emotional and behavioral problems and deficits of self-regulation. In addition, their parents more frequently had psychiatric problems. Temperament, intelligence, investigated executive functions and presence of dissociative symptoms were not different in patients with and without SIB. We could not verify our primary hypothesis that SIB is related to specific neuropsychological deficits or temperamental factors. SIB was associated with traumatic experience, depression, problems of self-regulation and parental psychiatric disease. The prevention of SIB should therefore focus on improving affect regulation, the management of emotional distress and problem-solving strategies. (c) 2008 S. Karger AG, Basel
Analysis of the surface expression of c-kit and occurrence of the c-kit Asp816Val activating mutation in T cells, B cells, and myelomonocytic cells in patients with mastocytosis.

PubMed

Akin, C; Kirshenbaum, A S; Semere, T; Worobec, A S; Scott, L M; Metcalfe, D D

2000-02-01

The Asp816Val c-kit activating mutation is detectable in the peripheral blood cells of some patients with mastocytosis and in lesional skin biopsies obtained from adult patients with urticaria pigmentosa. These observations led to the conclusion that this mutation is present in mast cells and mast cell precursors that express c-kit. However, the distribution of the Asp816Val mutation among hematopoietic lineages is unknown. To determine the distribution of the Asp816Val mutation among hematopoietic lineages and to explore its relationship to clinical disease, we examined cells bearing differentiation markers for myelomonocytic cells as well as T and B lymphocytes, in both peripheral blood and bone marrow obtained from patients with mastocytosis. The presence of Asp816Val c-kit mutation in cells magnetically sorted from peripheral blood or bone marrow according to surface differentiation markers was studied by reverse transcriptase polymerase chain reaction (RT-PCR) restriction fragment length polymorphism (RFLP) analysis. The surface expression of c-kit was determined by flow cytometry. The mutation was detectable by RT-PCR in at least one cell lineage in the bone marrow in 7 of 7 patients examined and in the peripheral blood of 11 of 11 adult patients with urticaria pigmentosa and indolent disease. The mutation was identified most frequently in B cells and myeloid cells. Flow cytometric analysis demonstrated that the differentiated cells expressing mutated c-kit were negative for surface KIT. These results are consistent with the conclusion that the c-kit Asp816Val mutation occurs in an early progenitor cell and is carried by myelomonocytic cells, T cells, and B cells in addition to mast cells. However, unlike mast cells, these myelomonocytic cells, T cells, and B cells do not concomitantly express surface c-kit and thus may be less susceptible to the effects of this mutation.
Polyaspartic Acid Concentration Controls the Rate of Calcium Phosphate Nanorod Formation in High Concentration Systems

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

Krogstad, Daniel V.; Wang, Dongbo; Lin-Gibson, Sheng

Polyelectrolytes are known to greatly affect calcium phosphate (CaP) mineralization. The reaction kinetics as well as the CaP phase, morphology and aggregation state depend on the relative concentrations of the polyelectrolyte and the inorganic ions in a complex, nonlinear manner. This study examines the structural evolution and kinetics of polyaspartic acid (pAsp) directed CaP mineralization at high concentrations of polyelectrolytes, calcium, and total phosphate (19–30 mg/mL pAsp, 50–100 mM Ca2+, Ca/P = 2). Using a novel combination of characterization techniques including cryogenic transmission electron microscopy (cryo-TEM), spectrophotometry, X-ray total scattering pair distribution function analysis, and attenuated total reflectance Fourier transformmore » infrared spectroscopy (ATR-FTIR), it was determined that the CaP mineralization occurred over four transition steps. The steps include the formation of aggregates of pAsp stabilized CaP spherical nanoparticles (sNP), crystallization of sNP, oriented attachment of the sNP into nanorods, and further crystallization of the nanorods. The intermediate aggregate sizes and the reaction kinetics were found to be highly polymer concentration dependent while the sizes of the particles were not concentration dependent. This study demonstrates the complex role of pAsp in controlling the mechanism as well as the kinetics of CaP mineralization.« less
Limited Associations of Dopamine System Genes With Alcohol Dependence and Related Traits in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD)

PubMed Central

Hack, Laura M.; Kalsi, Gursharan; Aliev, Fazil; Kuo, Po-Hsiu; Prescott, Carol A.; Patterson, Diana G.; Walsh, Dermot; Dick, Danielle M.; Riley, Brien P.; Kendler, Kenneth S.

2012-01-01

Background Over 50 years of evidence from research has established that the central dopaminergic reward pathway is likely involved in alcohol dependence (AD). Additional evidence supports a role for dopamine (DA) in other disinhibitory psychopathology, which is often comorbid with AD. Family and twin studies demonstrate that a common genetic component accounts for most of the genetic variance in these traits. Thus, DA-related genes represent putative candidates for the genetic risk that underlies not only AD but also behavioral disinhibition. Many linkage and association studies have examined these relationships with inconsistent results, possibly because of low power, poor marker coverage, and/or an inappropriate correction for multiple testing. Methods We conducted an association study on the products encoded by 10 DA-related genes (DRD1-D5, SLC18A2, SLC6A3, DDC, TH, COMT) using a large, ethnically homogeneous sample with severe AD (n = 545) and screened controls (n = 509). We collected genotypes from linkage disequilibrium (LD)-tagging single nucleotide polymorphisms (SNPs) and employed a gene-based method of correction. We tested for association with AD diagnosis in cases and controls and with a variety of alcohol-related traits (including age-at-onset, initial sensitivity, tolerance, maximum daily drinks, and a withdrawal factor score), disinhibitory symptoms, and a disinhibitory factor score in cases only. A total of 135 SNPs were genotyped using the Illumina GoldenGate and Taqman Assays-on-Demand protocols. Results Of the 101 SNPs entered into standard analysis, 6 independent SNPs from 5 DA genes were associated with AD or a quantitative alcohol-related trait. Two SNPs across 2 genes were associated with a disinhibitory symptom count, while 1 SNP in DRD5 was positive for association with the general disinhibitory factor score. Conclusions Our study provides evidence of modest associations between a small number of DA-related genes and AD as well as a range of alcohol-related traits and measures of behavioral disinhibition. While we did conduct gene-based correction for multiple testing, we did not correct for multiple traits because the traits are correlated. However, false-positive findings remain possible, so our results must be interpreted with caution. PMID:21083670
Bacillus thuringiensis Crystal Protein Cry6Aa Triggers Caenorhabditis elegans Necrosis Pathway Mediated by Aspartic Protease (ASP-1)

PubMed Central

Zhang, Fengjuan; Peng, Donghai; Cheng, Chunsheng; Zhou, Wei; Ju, Shouyong; Wan, Danfeng; Yu, Ziquan; Shi, Jianwei; Deng, Yaoyao; Wang, Fenshan; Ye, Xiaobo; Hu, Zhenfei; Lin, Jian; Ruan, Lifang; Sun, Ming

2016-01-01

Cell death plays an important role in host-pathogen interactions. Crystal proteins (toxins) are essential components of Bacillus thuringiensis (Bt) biological pesticides because of their specific toxicity against insects and nematodes. However, the mode of action by which crystal toxins to induce cell death is not completely understood. Here we show that crystal toxin triggers cell death by necrosis signaling pathway using crystal toxin Cry6Aa-Caenorhabditis elegans toxin-host interaction system, which involves an increase in concentrations of cytoplasmic calcium, lysosomal lyses, uptake of propidium iodide, and burst of death fluorescence. We find that a deficiency in the necrosis pathway confers tolerance to Cry6Aa toxin. Intriguingly, the necrosis pathway is specifically triggered by Cry6Aa, not by Cry5Ba, whose amino acid sequence is different from that of Cry6Aa. Furthermore, Cry6Aa-induced necrosis pathway requires aspartic protease (ASP-1). In addition, ASP-1 protects Cry6Aa from over-degradation in C. elegans. This is the first demonstration that deficiency in necrosis pathway confers tolerance to Bt crystal protein, and that Cry6A triggers necrosis represents a newly added necrosis paradigm in the C. elegans. Understanding this model could lead to new strategies for nematode control. PMID:26795495
Growth inhibitory and proapoptotic effects of l-asparaginase from Fusarium culmorum ASP-87 on human leukemia cells (Jurkat).

PubMed

Meghavarnam, Anil K; Salah, Maryam; Sreepriya, Meenakshisundaram; Janakiraman, Savitha

2017-06-01

The objective of this study was to evaluate the anticancer properties of l-asparaginase purified from fungal isolate Fusarium culmorum ASP-87 against human T-cell leukemia cell line (Jurkat). The growth inhibitory and proapoptotic effects of purified l-asparaginase on Jurkat cell lines were investigated by determining its influence on cell viability, colony formation, DNA fragmentation, and cell cycle progression. The results revealed that purified l-asparaginase showed significant decrease in cell survival with IC 50 value of 90 μg/mL (9 IU/mL). The enzyme inhibited colony formation and showed characteristic laddering pattern on agarose gel thereby confirming the induction of apoptosis. Further, cell cycle analysis revealed that the enzyme induced apoptotic cell death by arresting the growth of cells at G 2 -M phase. However, the enzyme did not elicit any toxic effects on human erythrocytes. l-asparaginase purified from F. culmorum ASP-87 showed significant and selective cytotoxic and apoptotic effects on human T-cell leukemic cells in dose-dependent manner. Results of the study give leads for the anticancer effects of fungal l-asparaginase and its potential usefulness in the chemotherapy of leukemia. © 2016 Société Française de Pharmacologie et de Thérapeutique.
GC Glu416Asp and Thr420Lys polymorphisms contribute to gastrointestinal cancer susceptibility in a Chinese population

PubMed Central

Zhou, Liqing; Zhang, Xiaojiao; Chen, Xuechao; Liu, Li; Lu, Chao; Tang, Xiaohu; Shi, Juan; Li, Meng; Zhou, Mo; Zhang, Zhouwei; Xiao, Lingchen; Yang, Ming

2012-01-01

Vitamin D has potent anticancer properties, especially against gastrointestinal cancers. Group-specific component (GC), a key member of vitamin D pathway proteins, could bind to and transport vitamin D to target organs. As a polymorphic protein, two common coding single nucleotide polymorphisms (SNP) [Glu416Asp (rs7041) and Thr420Lys (rs4588)] were identified in its gene. These SNPs have been associated to circulating vitamin D levels and several cancer risks in different populations. However, there is no report on their role in gastrointestinal cancer development among Chinese to date. Therefore, we examined the association between these variants and risk of gastrointestinal cancers in a case-control cohort including 964 patients with four gastrointestinal cancers (hepatocellular carcinoma, esophageal cancer, gastric cancer and colorectal cancer) and 1187 controls. Odds ratios and 95% confidence intervals were estimated by logistic regression. We found that GC Thr420Lys polymorphism has significant impact on the risk of developing gastrointestinal cancers, especially colorectal cancer. Additionally, subjects who carrying GC Asp416-Lys420 haplotype, which contains the at-risk 420Lys allele, also showed significantly increased risk to develop gastrointestinal cancers. In conclusion, our study demonstrated that common genetic variants and haplo-types in GC may influence individual susceptibility to gastrointestinal cancers in Chinese population. PMID:22328951
A Comparison of Repetitive Behaviors in Aspergers Disorder and High Functioning Autism

ERIC Educational Resources Information Center

Cuccaro, Michael L.; Nations, Laura; Brinkley, Jason; Abramson, Ruth K.; Wright, Harry H.; Hall, Alicia; Gilbert, John; Pericak-Vance, Margaret A.

2007-01-01

In this study we compared 33 IQ and age matched pairs of individuals with Aspergers Disorder (ASP) and high functioning autism (HFA) on measures of repetitive behavior. On the Repetitive Behavior Scale-Revised (RBS-R), the ASP and HFA groups showed no differences in RBS-R Intensity score (severity) score or Frequency score (number of problems…
Language performance in siblings of nonverbal children with autism.

PubMed

Levy, Yonata; Bar-Yuda, Chanit

2011-05-01

The study focuses on language and cognitive abilities of siblings of the linguistically most affected children with autism (i.e. siblings of nonverbal children - SIBS-ANV). Twenty-eight SIBS-ANV (17 boys), ages 4-9 years, took part in the study. All children attended regular schools, and none had received a diagnosis of autism. Controls were 27 typically developing children (SIBS-TD; 16 boys) matched to the SIBS-ANV on age, family background, socioeconomic status and type of school they attended. Significant IQ differences, as well as language differences as measured on the Clinical Evaluation of Language Fundamentals (CELF), emerged between SIBS-ANV and SIBS-TD. However, differences in the language scores mostly disappeared when PIQ and FSIQ were controlled for. Furthermore, grammatical analysis of spontaneous speech samples produced in the course of testing did not reveal any significant differences between the groups. These results add to recent work suggesting that language deficits may not be part of the Broad Autism Phenotype (BAP). It further suggests that the cognitive deficit characteristic of nonverbal people with autism may be familial.

Experimental many-pairs nonlocality

NASA Astrophysics Data System (ADS)

Poh, Hou Shun; Cerè, Alessandro; Bancal, Jean-Daniel; Cai, Yu; Sangouard, Nicolas; Scarani, Valerio; Kurtsiefer, Christian

2017-08-01

Collective measurements on large quantum systems together with a majority voting strategy can lead to a violation of the Clauser-Horne-Shimony-Holt Bell inequality. In the presence of many entangled pairs, this violation decreases quickly with the number of pairs and vanishes for some critical pair number that is a function of the noise present in the system. Here we show that a different binning strategy can lead to a more substantial Bell violation when the noise is sufficiently small. Given the relation between the critical pair number and the source noise, we then present an experiment where the critical pair number is used to quantify the quality of a high visibility photon pair source. Our results demonstrate nonlocal correlations using collective measurements operating on clusters of more than 40 photon pairs.
Particle dynamics and pair production in tightly focused standing wave

NASA Astrophysics Data System (ADS)

Jirka, M.; Klimo, O.; Vranić, M.; Weber, S.; Korn, G.

2017-05-01

With the advent of 10 PW laser facilities, new regimes of laser-matter interaction are opening since effects of quantum electrodynamics, such as electron-positron pair production and cascade development, start to be important. The dynamics of light charged particles, such as electrons and positrons, is affected by the radiation reaction force. This effect can strongly influence the interaction of intense laser pulses with matter since it lowers the energy of emitting particles and transforms their energy to the gamma radiation. Consequently, electron-positron pairs can be generated via Breit-Wheeler process. To study this new regime of interaction, numerical simulations are required. With their help it is possible to predict and study quantum effects which may occur in future experiments at modern laser facilities. In this work we present results of electron interaction with an intense standing wave formed by two colliding laser pulses. Due to the necessity to achieve ultra intense laser field, the laser beam has to be focused to a μm-diameter spot. Since the paraxial approximation is not valid for tight focusing, the appropriate model describing the tightly focused laser beam has to be employed. In tightly focused laser beam the longitudinal component of the electromagnetic field becomes significant and together with the ponderomotive force they affect the dynamics of interacting electrons and also newly generated Breit-Wheeler electron-positron pairs. Using the Particle-In-Cell code we study electron dynamics, gamma radiation and pair production in such a configuration for linear polarization and different types of targets.
The Highly Conserved Asp23 Family Protein YqhY Plays a Role in Lipid Biosynthesis in Bacillus subtilis

PubMed Central

Tödter, Dominik; Gunka, Katrin; Stülke, Jörg

2017-01-01

In most bacteria, fatty acid biosynthesis is an essential process that must be controlled by the availability of precursors and by the needs of cell division. So far, no mechanisms controlling synthesis of malonyl-coenzyme A (CoA), the committed step in fatty acid synthesis, have been identified in the Gram-positive model bacterium Bacillus subtilis. We have studied the localization and function of two highly expressed proteins of unknown function, YqhY and YloU. Both proteins are members of the conserved and widespread Asp23 family. While the deletion of yloU had no effect, loss of the yqhY gene induced the rapid acquisition of suppressor mutations. The vast majority of these mutations affect subunits of the acetyl-CoA carboxylase (ACCase) complex, the enzyme that catalyzes the formation of malonyl-CoA. Moreover, lack of yqhY is accompanied by the formation of lipophilic clusters in the polar regions of the cells indicating an increased activity of ACCase. Our results suggest that YqhY controls the activity of ACCase and that this control results in inhibition of ACCase activity. Hyperactivity of the enzyme complex in the absence of YqhY does then provoke mutations that cause reduced ACCase activity. PMID:28579978
Pharmacological treatments in asthma-affected horses: A pair-wise and network meta-analysis.

PubMed

Calzetta, L; Roncada, P; di Cave, D; Bonizzi, L; Urbani, A; Pistocchini, E; Rogliani, P; Matera, M G

2017-11-01

Equine asthma is a disease characterised by reversible airflow obstruction, bronchial hyper-responsiveness and airway inflammation following exposure of susceptible horses to specific airborne agents. Although clinical remission can be achieved in a low-airborne dust environment, repeated exacerbations may lead to irreversible airway remodelling. The available data on the pharmacotherapy of equine asthma result from several small studies, and no head-to-head clinical trials have been conducted among the available medications. To assess the impact of the pharmacological interventions in equine asthma and compare the effect of different classes of drugs on lung function. Pair-wise and network meta-analysis. Literature searches for clinical trials on the pharmacotherapy of equine asthma were performed. The risk of publication bias was assessed by funnel plots and Egger's test. Changes in maximum transpulmonary or pleural pressure, pulmonary resistance and dynamic lung compliance vs. control were analysed via random-effects models and Bayesian networks. The results obtained from 319 equine asthma-affected horses were extracted from 32 studies. Bronchodilators, corticosteroids and chromones improved maximum transpulmonary or pleural pressure (range: -8.0 to -21.4 cmH 2 O; P<0.001). Bronchodilators, corticosteroids and furosemide reduced pulmonary resistance (range: -1.2 to -1.9 cmH 2 O/L/s; P<0.001), and weakly increased dynamic lung compliance. Inhaled β 2 -adrenoreceptor (β 2 -AR) agonists and inhaled corticosteroids had the highest probability of being the best therapies. Long-term treatments were more effective than short-term treatments. Weak publication bias was detected. This study demonstrates that long-term treatments with inhaled corticosteroids and long-acting β 2 -AR agonists may represent the first choice for treating equine asthma. Further high quality clinical trials are needed to clarify whether inhaled bronchodilators should be preferred to inhaled
Characterization of mechamisms underlying degradation of sclerotia of Sclerotinia sclerotiorum by Aspergillus aculeatus Asp-4 using a combined qRT-PCR and proteomic approach

USDA-ARS?s Scientific Manuscript database

Background: The biological control agent Aspergillus Asp-4 colonizes and degrades sclerotia of Sclerotinia sclerotiorum resulting in reduced germination and disease caused by this important plant pathogen. Molecular mechanisms of mycoparasites underlying colonization, degradation, and reduction of...
EXPERIMENTAL STUDIES OF THE EVOLUTIONARY SIGNIFICANCE OF SEXUAL REPRODUCTION. V. A FIELD TEST OF THE SIB-COMPETITION LOTTERY HYPOTHESIS.

PubMed

Kelley, Steven E

1989-08-01

Sexually and asexually derived tillers of Anthoxanthum odoratum were planted directly in the field to test the hypothesis that competition among groups of sexual and asexual siblings favors the maintenance of sexual reproduction in populations. The results showed a substantial fitness advantage for sexual tillers. However, in contrast with the models, the advantage of sex did not increase with increasing numbers of colonists in the patch, there were multiple survivors among colonists, and an advantage was observed even for singly planted tillers. When a truncation-selection scheme was imposed ex post facto on the data, the relative performance of sexual tillers was similar to that predicted by the Bulmer (1980) model, suggesting that sib-competition models fail due to the violation of the assumption of truncation selection. The advantage of sex was not correlated with the presence of other species, total percentage cover, or species diversity, although sites where sex was favored were physically clustered. © 1989 The Society for the Study of Evolution.
Social Smiling and Its Components in High-Risk Infant Siblings without Later ASD Symptomatology

ERIC Educational Resources Information Center

Nichols, Caitlin McMahon; Ibañez, Lisa V.; Foss-Feig, Jennifer H.; Stone, Wendy L.

2014-01-01

Impaired affective expression, including social smiling, is common in children with autism spectrum disorder (ASD), and may represent an early marker for ASD in their infant siblings (Sibs-ASD). Social smiling and its component behaviors (eye contact and non-social smiling) were examined at 15 months in Sibs-ASD who demonstrated later ASD…
Bilateral Parietal Cortex Damage Does Not Impair Associative Memory for Paired Stimuli

PubMed Central

Berryhill, Marian E.; Drowos, David B.; Olson, Ingrid R.

2010-01-01

Recent neuroimaging and neuropsychological findings indicate that the posterior parietal cortex (PPC) plays an important, albeit undefined, role in episodic memory. Here we ask whether this region is specifically involved in associative aspects of episodic memory. Experiment 1 tested whether PPC damage affects the ability to learn and retrieve novel word-pair associations. Experiment 2 tested whether PPC damage affects the retrieval of object-location associations, in a spatial fan task. In both experiments, patients showed normal levels of associative memory. These findings demonstrated that PPC damage did not prevent association memory for verbal items. Finally Experiment 3 tested whether PPC damage affects memory for non-verbal audio-visual pairs. The patients performed with normal accuracy, but with significantly reduced confidence. These findings indicate that the PPC does not have a central role in association formation per se and instead, indicate that the PPC is involved in other aspects of episodic memory. PMID:20104378
Simultaneous integrated boost (SIB) radiation therapy of right sided breast cancer with and without flattening filter - A treatment planning study.

PubMed

Maier, Johannes; Knott, Bernadette; Maerz, Manuel; Loeschel, Rainer; Koelbl, Oliver; Dobler, Barbara

2016-08-31

The aim of the study was to compare the two irradiation modes with (FF) and without flattening filter (FFF) for three different treatment techniques for simultaneous integrated boost radiation therapy of patients with right sided breast cancer. An Elekta Synergy linac with Agility collimating device is used to simulate the treatment of 10 patients. Six plans were generated in Monaco 5.0 for each patient treating the whole breast and a simultaneous integrated boost (SIB) volume: intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT) and a tangential arc VMAT (tVMAT), each with and without flattening filter. Plan quality was assessed considering target coverage, sparing of the contralateral breast, the lungs, the heart and the normal tissue. All plans were verified by a 2D-ionisation-chamber-array and delivery times were measured and compared. The Wilcoxon test was used for statistical analysis with a significance level of 0.05. Significantly best target coverage and homogeneity was achieved using VMAT FFF with V95% = (98.7 ± 0.8) % and HI = (8.2 ± 0.9) % for the SIB and V95% = (98.3 ± 0.7) % for the PTV, whereas tVMAT showed significantly lowest doses to the contralateral organs at risk with a Dmean of (0.7 ± 0.1) Gy for the contralateral lung, (1.0 ± 0.2) Gy for the contralateral breast and (1.4 ± 0.2) Gy for the heart. All plans passed the gamma evaluation with a mean passing rate of (99.2 ± 0.8) %. Delivery times were significantly reduced for VMAT and tVMAT but increased for IMRT, when FFF was used. Lowest delivery times were observed for tVMAT FFF with (1:20 ± 0:07) min. Balancing target coverage, OAR sparing and delivery time, VMAT FFF and tVMAT FFF are considered the preferable of the investigated treatment options in simultaneous integrated boost irradiation of right sided breast cancer for the combination of an Elekta Synergy linac with Agility and the treatment planning
WE-AB-204-03: A Novel 3D Printed Phantom for 4D PET/CT Imaging and SIB Radiotherapy Verification

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

Soultan, D; Murphy, J; Moiseenko, V

Purpose: To construct and test a 3D printed phantom designed to mimic variable PET tracer uptake seen in lung tumor volumes. To assess segmentation accuracy of sub-volumes of the phantom following 4D PET/CT scanning with ideal and patient-specific respiratory motion. To plan, deliver and verify delivery of PET-driven, gated, simultaneous integrated boost (SIB) radiotherapy plans. Methods: A set of phantoms and inserts were designed and manufactured for a realistic representation of lung cancer gated radiotherapy steps from 4D PET/CT scanning to dose delivery. A cylindrical phantom (40x 120 mm) holds inserts for PET/CT scanning. The novel 3D printed insert dedicatedmore » to 4D PET/CT mimics high PET tracer uptake in the core and lower uptake in the periphery. This insert is a variable density porous cylinder (22.12×70 mm), ABS-P430 thermoplastic, 3D printed by uPrint SE Plus with inner void volume (5.5×42 mm). The square pores (1.8×1.8 mm2 each) fill 50% of outer volume, resulting in a 2:1 SUV ratio of PET-tracer in the void volume with respect to porous volume. A matching in size cylindrical phantom is dedicated to validate gated radiotherapy. It contains eight peripheral holes matching the location of the porous part of the 3D printed insert, and one central hole. These holes accommodate adaptors for Farmer-type ion chamber and cells vials. Results: End-to-end test were performed from 4D PET/CT scanning to transferring data to the planning system and target volume delineation. 4D PET/CT scans were acquired of the phantom with different respiratory motion patterns and gating windows. A measured 2:1 18F-FDG SUV ratio between inner void and outer volume matched the 3D printed design. Conclusion: The novel 3D printed phantom mimics variable PET tracer uptake typical of tumors. Obtained 4D PET/CT scans are suitable for segmentation, treatment planning and delivery in SIB gated treatments of NSCLC.« less
Socio-affective touch expression database

PubMed Central

Op de Beeck, Hans

2018-01-01

Socio-affective touch communication conveys a vast amount of information about emotions and intentions in social contexts. In spite of the complexity of the socio-affective touch expressions we use daily, previous studies addressed only a few aspects of social touch mainly focusing on hedonics, such as stroking, leaving a wide range of social touch behaviour unexplored. To overcome this limit, we present the Socio-Affective Touch Expression Database (SATED), which includes a large range of dynamic interpersonal socio-affective touch events varying in valence and arousal. The original database contained 26 different social touch expressions each performed by three actor pairs. To validate each touch expression, we conducted two behavioural experiments investigating perceived naturalness and affective values. Based on the rated naturalness and valence, 13 socio-affective touch expressions along with 12 corresponding non-social touch events were selected as a complete set, achieving 75 video clips in total. Moreover, we quantified motion energy for each touch expression to investigate its intrinsic correlations with perceived affective values and its similarity among actor- and action-pairs. As a result, the touch expression database is not only systematically defined and well-controlled, but also spontaneous and natural, while eliciting clear affective responses. This database will allow a fine-grained investigation of complex interpersonal socio-affective touch in the realm of social psychology and neuroscience along with potential application areas in affective computing and neighbouring fields. PMID:29364988
The study on the relationship between IRS-1 Gly972Arg and IRS-2 Gly1057Asp polymorphisms and type 2 diabetes in the Kurdish ethnic group in West Iran.

PubMed

Haghani, Karimeh; Bakhtiyari, Salar

2012-11-01

An association between the IRS-1 Gly972Arg and IRS-2 Gly1057Asp polymorphisms and type 2 diabetes mellitus (T2DM) in different ethnic groups is controversial. We aimed to identify the association of these polymorphisms with T2DM in the Kurdish ethnic group of Iran. Study groups included 336 T2DM and 341 normoglycemic subjects. Genotyping was determined by polymerase chain reaction-restriction fragment length polymorphism. Genotypic and allelic frequencies were then evaluated. GR and RR genotypes of IRS-1 Gly972Arg variant gave a higher risk for T2DM (odds ratios [OR]=1.76 and OR=3.86, respectively). IRS-1 Gly972Arg polymorphism was found to be significantly associated with T2DM (OR=1.63) for the dominant model (GG vs. GR+RR). GD genotypes of the IRS-2 Gly1057Asp variant gave a higher risk for T2DM (OR=1.63). The dominant model analysis of the IRS-2 Gly1057Asp genotypes (GG vs. GD+DD) also showed an enhanced association with T2DM (OR=1.69). Among several combinations, GR/GD gave the highest risk for T2DM (OR=3.1). Other combinations were also significantly associated with T2DM, including, GR/GG (OR=1.86), RR/GG (OR=1.76), GG/GD (OR=1.83), and GG/DD (OR=2.35). HbA1c, serum triglyceride, and systolic blood pressure were higher in the control subjects with GR+RR genotypes compared with the GG genotype. Among the T2DM subjects, fasting plasma glucose was significantly lower in subjects with the GG genotype in relation to those with the GR+RR genotypes. Normoglycemic subjects carrying GD+DD genotypes of IRS-2 Gly1057Asp variation had a significantly higher fasting plasma glucose and total cholesterol, as compared with those with the GG genotype. Our findings revealed that IRS-1 Gly972Arg and IRS-2 Gly1057Asp polymorphisms are associated with T2DM in the Kurdish ethnic group.
Analysis of HIV-1 intersubtype recombination breakpoints suggests region with high pairing probability may be a more fundamental factor than sequence similarity affecting HIV-1 recombination.

PubMed

Jia, Lei; Li, Lin; Gui, Tao; Liu, Siyang; Li, Hanping; Han, Jingwan; Guo, Wei; Liu, Yongjian; Li, Jingyun

2016-09-21

With increasing data on HIV-1, a more relevant molecular model describing mechanism details of HIV-1 genetic recombination usually requires upgrades. Currently an incomplete structural understanding of the copy choice mechanism along with several other issues in the field that lack elucidation led us to perform an analysis of the correlation between breakpoint distributions and (1) the probability of base pairing, and (2) intersubtype genetic similarity to further explore structural mechanisms. Near full length sequences of URFs from Asia, Europe, and Africa (one sequence/patient), and representative sequences of worldwide CRFs were retrieved from the Los Alamos HIV database. Their recombination patterns were analyzed by jpHMM in detail. Then the relationships between breakpoint distributions and (1) the probability of base pairing, and (2) intersubtype genetic similarities were investigated. Pearson correlation test showed that all URF groups and the CRF group exhibit the same breakpoint distribution pattern. Additionally, the Wilcoxon two-sample test indicated a significant and inexplicable limitation of recombination in regions with high pairing probability. These regions have been found to be strongly conserved across distinct biological states (i.e., strong intersubtype similarity), and genetic similarity has been determined to be a very important factor promoting recombination. Thus, the results revealed an unexpected disagreement between intersubtype similarity and breakpoint distribution, which were further confirmed by genetic similarity analysis. Our analysis reveals a critical conflict between results from natural HIV-1 isolates and those from HIV-1-based assay vectors in which genetic similarity has been shown to be a very critical factor promoting recombination. These results indicate the region with high-pairing probabilities may be a more fundamental factor affecting HIV-1 recombination than sequence similarity in natural HIV-1 infections. Our
Dye adsorbates BrPDI, BrGly, and BrAsp on anatase TiO2(001) for dye-sensitized solar cell applications

NASA Astrophysics Data System (ADS)

Çakır, D.; Gülseren, O.; Mete, E.; Ellialtıoǧlu, Ş.

2009-07-01

Using the first-principles plane-wave pseudopotential method within density functional theory, we systematically investigated the interaction of perylenediimide (PDI)-based dye compounds (BrPDI, BrGly, and BrAsp) with both unreconstructed (UR) and reconstructed (RC) anatase TiO2(001) surfaces. All dye molecules form strong chemical bonds with surface in the most favorable adsorption structures. In UR-BrGly, RC-BrGly, and RC-BrAsp cases, we have observed that highest occupied molecular orbital and lowest unoccupied molecular orbital levels of molecules appear within band gap and conduction-band region, respectively. Moreover, we have obtained a gap narrowing upon adsorption of BrPDI on the RC surface. Because of the reduction in effective band gap of surface-dye system and possibly achieving the visible-light activity, these results are valuable for photovoltaic and photocatalytic applications. We have also considered the effects of hydration of surface to the binding of BrPDI. It has been found that the binding energy drops significantly for the completely hydrated surfaces.
Benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD.FMK) inhibits apoptosis by blocking the processing of CPP32.

PubMed Central

Slee, E A; Zhu, H; Chow, S C; MacFarlane, M; Nicholson, D W; Cohen, G M

1996-01-01

Interleukin-1 beta converting enzyme (ICE)-like proteases, which are synthesized as inactive precursors, play a key role in the induction of apoptosis. We now demonstrate that benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD.FMK), an ICE-like protease inhibitor, inhibits apoptosis by preventing the processing of CPP32 to its active form. These results suggest that novel inhibitors of apoptosis can be developed which prevent processing of proforms of ICE-like proteases. PMID:8670109
Complete characterization of the water dimer vibrational ground state and testing the VRT(ASP-W)III, SAPT-5st, and VRT(MCY-5f) surfaces

NASA Astrophysics Data System (ADS)

Keutsch, Frank N.; Goldman, Nir; Harker, Heather A.; Leforestier, Claude; Saykally, Richard J.

We report the observation of extensive a- and c-type rotation-tunnelling (RT) spectra of (H2O)2 for Ka =0-3, and (D2O)2 for Ka =0-4. These data allow a detailed characterization of the vibrational ground state to energies comparable to those of the low-lying (70-80 cm-1) intermolecular vibrations. We present a comparison of the experimentally determined molecular constants and tunnelling splittings with those calculated on the VRT(ASP-W)III, SAPT-5st, and VRT(MCY-5f) intermolecular potential energy surfaces. The SAPT-5st potential reproduces the vibrational ground state properties of the water dimer very well. The VRT(MCY-5f) and especially the VRT(ASP-W)III potentials show larger disagreements, in particular for the bifurcation tunnelling splitting.
The Development of Siblings of Children with Autism at 4 and 14 Months: Social Engagement, Communication, and Cognition

ERIC Educational Resources Information Center

Yirmiya, Nurit; Gamliel, Ifat; Pilowsky, Tammy; Feldman, Ruth; Baron-Cohen, Simon; Sigman, Marian

2006-01-01

Aims: To compare siblings of children with autism (SIBS-A) and siblings of children with typical development (SIBS-TD) at 4 and 14 months of age. Methods: At 4 months, mother-infant interactional synchrony during free play, infant gaze and affect during the still-face paradigm, and infant responsiveness to a name-calling paradigm were examined (n…
Neural correlates of cross-domain affective priming.

PubMed

Zhang, Qin; Li, Xiaohua; Gold, Brian T; Jiang, Yang

2010-05-06

The affective priming effect has mostly been studied using reaction time (RT) measures; however, the neural bases of affective priming are not well established. To understand the neural correlates of cross-domain emotional stimuli presented rapidly, we obtained event-related potential (ERP) measures during an affective priming task using short SOA (stimulus onset asynchrony) conditions. Two sets of 480 picture-word pairs were presented at SOAs of either 150ms or 250ms between prime and target stimuli. Participants decided whether the valence of each target word was pleasant or unpleasant. Behavioral results from both SOA conditions were consistent with previous reports of affective priming, with longer RTs for incongruent than congruent pairs at SOAs of 150ms (771 vs. 738ms) and 250ms (765 vs. 720ms). ERP results revealed that the N400 effect (associated with incongruent pairs in affective processing) occurred at anterior scalp regions at an SOA of 150ms, and this effect was only observed for negative target words across the scalp at an SOA of 250ms. In contrast, late positive potentials (LPPs) (associated with attentional resource allocation) occurred across the scalp at an SOA of 250ms. LPPs were only observed for positive target words at posterior parts of the brain at an SOA of 150ms. Our finding of ERP signatures at very short SOAs provides the first neural evidence that affective pictures can exert an automatic influence on the evaluation of affective target words. Copyright 2010 Elsevier B.V. All rights reserved.
Base pair probability estimates improve the prediction accuracy of RNA non-canonical base pairs

PubMed Central

2017-01-01

Prediction of RNA tertiary structure from sequence is an important problem, but generating accurate structure models for even short sequences remains difficult. Predictions of RNA tertiary structure tend to be least accurate in loop regions, where non-canonical pairs are important for determining the details of structure. Non-canonical pairs can be predicted using a knowledge-based model of structure that scores nucleotide cyclic motifs, or NCMs. In this work, a partition function algorithm is introduced that allows the estimation of base pairing probabilities for both canonical and non-canonical interactions. Pairs that are predicted to be probable are more likely to be found in the true structure than pairs of lower probability. Pair probability estimates can be further improved by predicting the structure conserved across multiple homologous sequences using the TurboFold algorithm. These pairing probabilities, used in concert with prior knowledge of the canonical secondary structure, allow accurate inference of non-canonical pairs, an important step towards accurate prediction of the full tertiary structure. Software to predict non-canonical base pairs and pairing probabilities is now provided as part of the RNAstructure software package. PMID:29107980
Clericuzio-type poikiloderma with neutropenia syndrome in three sibs with mutations in the C16orf57 gene: delineation of the phenotype.

PubMed

Concolino, D; Roversi, G; Muzzi, G L; Sestito, S; Colombo, E A; Volpi, L; Larizza, L; Strisciuglio, P

2010-10-01

We report on three sibs who have autosomal recessive Clericuzio-type poikiloderma neutropenia (PN) syndrome. Recently, this consanguineous family was reported and shown to be informative in identifying the C16orf57 gene as the causative gene for this syndrome. Here we present the clinical data in detail. PN is a distinct and recognizable entity belonging to the group of poikiloderma syndromes among which Rothmund-Thomson is perhaps the best described and understood. PN is characterized by cutaneous poikiloderma, hyperkeratotic nails, generalized hyperkeratosis on palms and soles, neutropenia, short stature, and recurrent pulmonary infections. In order to delineate the phenotype of this rare genodermatosis, the clinical presentation together with the molecular investigations in our patients are reported and compared to those from the literature. Copyright © 2010 Wiley-Liss, Inc.

Hippocampus is required for paired associate memory with neither delay nor trial uniqueness

PubMed Central

Yoon, Jinah; Seo, Yeran; Kim, Jangjin; Lee, Inah

2012-01-01

Cued retrieval of memory is typically examined with delay when testing hippocampal functions, as in delayed matching-to-sample tasks. Equally emphasized in the literature, on the other hand, is the hippocampal involvement in making arbitrary associations. Paired associate memory tasks are widely used for examining this function. However, the two variables (i.e., delay and paired association) were often mixed in paired associate tasks, and this makes it difficult to localize the cognitive source of deficits with hippocampal perturbation. Specifically, a few studies have recently shown that rats can learn arbitrary paired associations between certain locations and nonspatial items (e.g., object or flavor) and later can retrieve the paired location when cued by the item remotely. Such tasks involve both (1) delay between sampling the cue and retrieving the target location and (2) arbitrary association between the cueing object and its paired location. Here, we tested whether delay was necessary in a cued paired associate task by using a task in which no delay existed between object cueing and the choice of its paired associate. Moreover, fixed associative relationships between the cueing objects and their paired locations were repeatedly used, thus involving no trial-unique association. Nevertheless, inactivations of the dorsal hippocampus with muscimol severely disrupted retrieval of paired associates, whereas the same manipulations did not affect discriminating individual objects or locations. The results powerfully demonstrate that the hippocampus is inherently required for retrieving paired associations between objects and places, and that delay and trial uniqueness of the paired associates are not necessarily required. PMID:22174309
Prospective very young asteroid pairs

NASA Astrophysics Data System (ADS)

Galád, A.; Vokrouhlický, D.; Zizka, J.

2014-07-01

Several tens of asteroid pairs can be discerned from the background main-belt asteroids. The majority of them are thought to have formed within only the last few 10^6 yr. The youngest recognized pairs have formed more than ≈ 10 kyr ago. As some details of pair formation are still not understood well, the study of young pairs is of great importance. It is mainly because the conditions at the time of the pair formation could be deduced much more reliably for young pairs. For example, space weathering on the surfaces of the components, or changes in their rotational properties (in spin rates, tumbling, coordinates of rotational pole) could be negligible since the formation of young pairs. Also, possible strong perturbations by main-belt bodies on pair formation can be reliably studied only for extremely young pairs. Some pairs can quickly blend in with the background asteroids, so even the frequency of asteroid pair formation could be determined more reliably based on young pairs (though only after a statistically significant sample is at disposal). In our regular search for young pairs in the growing asteroid database, only multiopposition asteroids with very similar orbital and proper elements are investigated. Every pair component is represented by a number of clones within orbital uncertainties and drifting in semimajor axis due to the Yarkovsky effect. We found that, if the previously unrecognized pairs (87887) 2000 SS_{286} - 2002 AT_{49} and (355258) 2007 LY_{4} - 2013AF_{40} formed at the recent very close approach of their components, they could become the youngest known pairs. In both cases, the relative encounter velocities of the components were only ˜ 0.1 m s^{-1}. However, the minimum distances between some clones are too large and a few clones of the latter pair did not encounter recently (within ≈ 10 kyr). The age of some prospective young pairs cannot be determined reliably without improved orbital properties (e.g., the second component of a pair
Characteristics of the postcounseling reproductive decision-making process: an explorative study.

PubMed

Frets, P G; Verhage, F; Niermeijer, M F

1991-09-01

An in-depth, recorded interview of 30 couples 2-3 years after genetic counseling explored the characteristics of the postcounseling decision-making process, including the role of guilt feelings towards the proband. The study concerned couples with an affected child, sib, or spouse. Results were evaluated by 2 to 4 judges. In contrast to other studies, a generally unstructured decision-making process was found whereby guilt feelings played a significant role in more than half the couples. Guilt feelings were more predominant in couples with an affected sib than in those with an affected spouse. Lack of structure did not seem to complicate the decision-making process. Therefore, authors do not advocate promotion of structuring the decision-making process. Genetic counselors might focus on understanding counselees' feelings concerning the reproductive decision. Acceptance of apparently irrational considerations is particularly important, because these feelings indicate the influence of unconscious motives. Another important aspect of supporting counselees is to understand the role played by guilt feelings toward parents or an affected sib.
Paired Comparisons.

DTIC Science & Technology

1982-05-01

including multidimensional scaling. Applications have arisen in many areas, but most notably in food technolog, marketing research, and sports ... competition .- An extensive bibliography on paired comparisons by Davidson and Farquhar (1976) contains some 400 references. - Paired comparisons have been...consideration of chess competition . Ford (1957) pro- posed the model independently. Both Zermelo and Ford concentrated on solution of normal equations for
Report on Pairing-based Cryptography.

PubMed

Moody, Dustin; Peralta, Rene; Perlner, Ray; Regenscheid, Andrew; Roginsky, Allen; Chen, Lily

2015-01-01

This report summarizes study results on pairing-based cryptography. The main purpose of the study is to form NIST's position on standardizing and recommending pairing-based cryptography schemes currently published in research literature and standardized in other standard bodies. The report reviews the mathematical background of pairings. This includes topics such as pairing-friendly elliptic curves and how to compute various pairings. It includes a brief introduction to existing identity-based encryption (IBE) schemes and other cryptographic schemes using pairing technology. The report provides a complete study of the current status of standard activities on pairing-based cryptographic schemes. It explores different application scenarios for pairing-based cryptography schemes. As an important aspect of adopting pairing-based schemes, the report also considers the challenges inherent in validation testing of cryptographic algorithms and modules. Based on the study, the report suggests an approach for including pairing-based cryptography schemes in the NIST cryptographic toolkit. The report also outlines several questions that will require further study if this approach is followed.
Report on Pairing-based Cryptography

PubMed Central

Moody, Dustin; Peralta, Rene; Perlner, Ray; Regenscheid, Andrew; Roginsky, Allen; Chen, Lily

2015-01-01

This report summarizes study results on pairing-based cryptography. The main purpose of the study is to form NIST’s position on standardizing and recommending pairing-based cryptography schemes currently published in research literature and standardized in other standard bodies. The report reviews the mathematical background of pairings. This includes topics such as pairing-friendly elliptic curves and how to compute various pairings. It includes a brief introduction to existing identity-based encryption (IBE) schemes and other cryptographic schemes using pairing technology. The report provides a complete study of the current status of standard activities on pairing-based cryptographic schemes. It explores different application scenarios for pairing-based cryptography schemes. As an important aspect of adopting pairing-based schemes, the report also considers the challenges inherent in validation testing of cryptographic algorithms and modules. Based on the study, the report suggests an approach for including pairing-based cryptography schemes in the NIST cryptographic toolkit. The report also outlines several questions that will require further study if this approach is followed. PMID:26958435
Protein changes associated with reprotonation of the Schiff base in the photocycle of Asp96-->Asn bacteriorhodopsin. The MN intermediate with unprotonated Schiff base but N-like protein structure

NASA Technical Reports Server (NTRS)

Sasaki, J.; Shichida, Y.; Lanyi, J. K.; Maeda, A.

1992-01-01

The difference Fourier transform infrared spectrum for the N intermediate in the photoreaction of the light-adapted form of bacteriorhodopsin can be recorded at pH 10 at 274 K (Pfefferle, J.-M., Maeda, A., Sasaki, J., and Yoshizawa, T. (1991) Biochemistry 30, 6548-6556). Under these conditions, Asp96-->Asn bacteriorhodopsin gives a photoproduct which shows changes in protein structure similar to those observed in N of wild-type bacteriorhodopsin. However, decreased intensity of the chromophore bands and the single absorbance maximum at about 400 nm indicate that the Schiff base is unprotonated, as in the M intermediate. This photoproduct was named MN. At pH 7, where the supply of proton is not as restricted as at pH 10, Asp96-->Asn bacteriorhodopsin yields N with a protonated Schiff base. The Asn96 residue, which cannot deprotonate as Asp96 in wild-type bacteriorhodopsin, is perturbed upon formation of both MN at pH 10 and N at pH 7. We suggest that the reprotonation of the Schiff base is preceded by a large change in the protein structure including perturbation of the residue at position 96.
Reactance in affective-evaluative learning: Outside of conscious control?

PubMed

Fulcher, Eamon P; Hammerl, Marianne

2005-02-01

Recent studies have shown that the basic evaluative conditioning (EC) effect (originally neutral stimuli acquiring an affective value congruent with the valence of the affective stimulus they were paired with) seems to be limited to participants who are unaware of the stimulus pairings. If participants are aware of the pairings, reactance effects occur (i.e., changes in the opposite direction of the valence of the affective stimulus). To examine whether these reactance effects are due to processes of conscious countercontrol or whether the ratings reflect intrinsic feelings towards the stimuli, a new procedure was developed that included a bogus-pipeline condition. In this procedure, which was adapted from attitude research, participants were connected to bogus lie detector equipment leading them to believe that their "true" affective-evaluative responses were being observed. In Experiment 1, reactance effects occurred also in this procedure, suggesting that the effect is spontaneous and not due to processes of conscious countercontrol. In Experiment 2, these effects were replicated using a between-subjects design in addition to the standard within-subjects control condition.
Conceptual design of a noncontacting power transfer device for the ASPS Vernier system

NASA Technical Reports Server (NTRS)

Kroeger, J.; Drilling, J.; Gunderman, T.

1984-01-01

The conceptual of electrical power transfer across a magnetically controlled gap as discussed for several years. The design represents the culmination of the first serious attempt to design a very low force, noncontracting power transfer mechanism. The electromagnetic device advanced herein is an ironless, translatable secondary transformer in which one of the two coils is fixed to the entire magnetic core. The second coil is free to move within the core over the full range of motions required. The specific application considered for this design was the Vernier subsystem of the Annular Suspension and Pointing System (ASPS). The development of and rationale for the electromagnetics design is presented. Similar documentation is provided for the Electronics Design. The Appendices detail the results of small scale model tests, disturbance force calculations, the baseline transformer fabrication drawings, the AVS Converter Parts List, and model schematic diagrams.
Solid-phase synthesis of the nucleopeptide fragment H-Asp-Ser[pAAAGTAAGCC]-Glu-OH from the nucleoprotein of Bacillus subtilis phage phi 29.

PubMed Central

Dreef-Tromp, C M; van der Maarel, J C; van den Elst, H; van der Marel, G A; van Boom, J H

1992-01-01

The naturally occurring DNA-nucleopeptide H-Asp-Ser[5'-pAAAGTAAGCC-3']-Glu-OH was prepared via a solid-phase phosphite triester approach using N-2-(tert-butyldiphenylsilyloxymethyl)benzoyl protected nucleosides. The oligonucleotide was linked via the extremely base-labile oxalyl ester anchor to the solid support. PMID:1508685
The Development of After-School Program Educators through University-Community Partnerships

ERIC Educational Resources Information Center

Mahoney, Joseph L.; Levine, Mark D.; Hinga, Briana

2010-01-01

Participation in after-school programs (ASPs) "can" positively affect the development of young people. However, "whether" ASPs are beneficial depends on program quality. Although many factors influence the quality of a program, the competencies of adult staff who lead ASPs are a critical determinant. Unfortunately, ASP staff…
Effect of number of rooms and sibs on nutritional status among rural Bengalee preschool children from eastern India.

PubMed

Biswas, Sadaruddin; Bose, Kaushik

2011-12-01

In developing countries including rural India, undernutrition among preschool children is one of the main barriers of the national development. However, there exists scanty information on the prevalence of underweight and stunting and their socio-demographic predictors among preschool children in India and West Bengal. The aim of the present study was to investigate the prevalence of underweight and stunting and the impact of two socio-demographic indicators, namely number of living rooms (NLR) and number of sibs (NS), on them among 1-5 year old Bengalee rural preschool children of Integrated Child Development Services (ICDS) Centres. This cross sectional study was undertaken at 30 randomly selected ICDS centre of Chapra Block, Nadia District, West Bengal, India. A total of 673 children, aged 1-5 years were studied. The overall (age and sex combined) rates of underweight and stunting were 54.40% and 39.20%, respectively. NLR was significantly associated with the prevalence of underweight (chi2 = 4.34, df = 1, p < 0.05) and stunting (chi2 = 8.98, df = 1, p < 0.01) among girls. Similarly, NS had a significant association with prevalence of underweight (chi2 = 10.29, df = 1, p < 0.001) and stunting (chi2 = 5.42, df = 1, p < 0.05) among girls. Girls with < 2 NLR had significant higher risk of being underweight (OR = 1.64, C.I = 1.30-2.62) or stunted (OR=2.23, C.I = 1.31-3.80) than those with > or = 2 NLR. Moreover, girls with > or = 3 NS had significant higher rate of underweight (OR = 2.03, CI = 1.32-3.146) or stunting (OR = 1.69, C.I = 1.09-2.63) than those with < 3 sibs. Logistic regression analyses also revealed that both NLR as well as NS were strong predictors of underweight (NLR: Wald = 4.30, p < 0.05; NS: Wald = 8.74, p < 0.001) and stunting (NLR: Wald = 10.17, p < 0.001; NS: Wald = 5.38, p < 0.05) among girls. Gender discrimination could be a likely cause for this sex difference in the impact of NRL and NS. Moreover, logistic regression were also undertaken
Metal-mediated DNA base pairing: alternatives to hydrogen-bonded Watson-Crick base pairs.

PubMed

Takezawa, Yusuke; Shionoya, Mitsuhiko

2012-12-18

With its capacity to store and transfer the genetic information within a sequence of monomers, DNA forms its central role in chemical evolution through replication and amplification. This elegant behavior is largely based on highly specific molecular recognition between nucleobases through the specific hydrogen bonds in the Watson-Crick base pairing system. While the native base pairs have been amazingly sophisticated through the long history of evolution, synthetic chemists have devoted considerable efforts to create alternative base pairing systems in recent decades. Most of these new systems were designed based on the shape complementarity of the pairs or the rearrangement of hydrogen-bonding patterns. We wondered whether metal coordination could serve as an alternative driving force for DNA base pairing and why hydrogen bonding was selected on Earth in the course of molecular evolution. Therefore, we envisioned an alternative design strategy: we replaced hydrogen bonding with another important scheme in biological systems, metal-coordination bonding. In this Account, we provide an overview of the chemistry of metal-mediated base pairing including basic concepts, molecular design, characteristic structures and properties, and possible applications of DNA-based molecular systems. We describe several examples of artificial metal-mediated base pairs, such as Cu(2+)-mediated hydroxypyridone base pair, H-Cu(2+)-H (where H denotes a hydroxypyridone-bearing nucleoside), developed by us and other researchers. To design the metallo-base pairs we carefully chose appropriate combinations of ligand-bearing nucleosides and metal ions. As expected from their stronger bonding through metal coordination, DNA duplexes possessing metallo-base pairs exhibited higher thermal stability than natural hydrogen-bonded DNAs. Furthermore, we could also use metal-mediated base pairs to construct or induce other high-order structures. These features could lead to metal-responsive functional
Cooper Pairs in Insulators?!

ScienceCinema

James Valles

2017-12-09

Nearly 50 years elapsed between the discovery of superconductivity and the emergence of the microscopic theory describing this zero resistance state. The explanation required a novel phase of matter in which conduction electrons joined in weakly bound pairs and condensed with other pairs into a single quantum state. Surprisingly, this Cooper pair formation has also been invoked to account for recently uncovered high-resistance or insulating phases of matter. To address this possibility, we have used nanotechnology to create an insulating system that we can probe directly for Cooper pairs. I will present the evidence that Cooper pairs exist and dominate the electrical transport in these insulators and I will discuss how these findings provide new insight into superconductor to insulator quantum phase transitions.Â
Extracellular pH Regulates Zinc Signaling via an Asp Residue of the Zinc-sensing Receptor (ZnR/GPR39)*

PubMed Central

Cohen, Limor; Asraf, Hila; Sekler, Israel; Hershfinkel, Michal

2012-01-01

Zinc activates a specific Zn2+-sensing receptor, ZnR/GPR39, and thereby triggers cellular signaling leading to epithelial cell proliferation and survival. Epithelial cells that express ZnR, particularly colonocytes, face frequent changes in extracellular pH that are of physiological and pathological implication. Here we show that the ZnR/GPR39-dependent Ca2+ responses in HT29 colonocytes were maximal at pH 7.4 but were reduced by about 50% at pH 7.7 and by about 62% at pH 7.1 and were completely abolished at pH 6.5. Intracellular acidification did not attenuate ZnR/GPR39 activity, indicating that the pH sensor of this protein is located on an extracellular domain. ZnR/GPR39-dependent activation of extracellular-regulated kinase (ERK)1/2 or AKT pathways was abolished at acidic extracellular pH of 6.5. A similar inhibitory effect was monitored for the ZnR/GPR39-dependent up-regulation of Na+/H+ exchange activity at pH 6.5. Focusing on residues putatively facing the extracellular domain, we sought to identify the pH sensor of ZnR/GPR39. Replacing the histidine residues forming the Zn2+ binding site, His17 or His19, or other extracellular-facing histidines to alanine residues did not abolish the pH dependence of ZnR/GPR39. In contrast, replacing Asp313 with alanine resulted in similar Ca2+ responses triggered by ZnR/GPR39 at pH 7.4 or 6.5. This mutant also showed similar activation of ERK1/2 and AKT pathways, and ZnR-dependent up-regulation of Na+/H+ exchange at pH 7.4 and pH 6.5. Substitution of Asp313 to His or Glu residues restored pH sensitivity of the receptor. This indicates that Asp313, which was shown to modulate Zn2+ binding, is an essential residue of the pH sensor of GPR39. In conclusion, ZnR/GPR39 is tuned to sense physiologically relevant changes in extracellular pH that thus regulate ZnR-dependent signaling and ion transport activity. PMID:22879599
Extracellular pH regulates zinc signaling via an Asp residue of the zinc-sensing receptor (ZnR/GPR39).

PubMed

Cohen, Limor; Asraf, Hila; Sekler, Israel; Hershfinkel, Michal

2012-09-28

Zinc activates a specific Zn(2+)-sensing receptor, ZnR/GPR39, and thereby triggers cellular signaling leading to epithelial cell proliferation and survival. Epithelial cells that express ZnR, particularly colonocytes, face frequent changes in extracellular pH that are of physiological and pathological implication. Here we show that the ZnR/GPR39-dependent Ca(2+) responses in HT29 colonocytes were maximal at pH 7.4 but were reduced by about 50% at pH 7.7 and by about 62% at pH 7.1 and were completely abolished at pH 6.5. Intracellular acidification did not attenuate ZnR/GPR39 activity, indicating that the pH sensor of this protein is located on an extracellular domain. ZnR/GPR39-dependent activation of extracellular-regulated kinase (ERK)1/2 or AKT pathways was abolished at acidic extracellular pH of 6.5. A similar inhibitory effect was monitored for the ZnR/GPR39-dependent up-regulation of Na(+)/H(+) exchange activity at pH 6.5. Focusing on residues putatively facing the extracellular domain, we sought to identify the pH sensor of ZnR/GPR39. Replacing the histidine residues forming the Zn(2+) binding site, His(17) or His(19), or other extracellular-facing histidines to alanine residues did not abolish the pH dependence of ZnR/GPR39. In contrast, replacing Asp(313) with alanine resulted in similar Ca(2+) responses triggered by ZnR/GPR39 at pH 7.4 or 6.5. This mutant also showed similar activation of ERK1/2 and AKT pathways, and ZnR-dependent up-regulation of Na(+)/H(+) exchange at pH 7.4 and pH 6.5. Substitution of Asp(313) to His or Glu residues restored pH sensitivity of the receptor. This indicates that Asp(313), which was shown to modulate Zn(2+) binding, is an essential residue of the pH sensor of GPR39. In conclusion, ZnR/GPR39 is tuned to sense physiologically relevant changes in extracellular pH that thus regulate ZnR-dependent signaling and ion transport activity.
Introducing a model of pairing based on base pair specific interactions between identical DNA sequences

NASA Astrophysics Data System (ADS)

(O' Lee, Dominic J.

2018-02-01

At present, there have been suggested two types of physical mechanism that may facilitate preferential pairing between DNA molecules, with identical or similar base pair texts, without separation of base pairs. One mechanism solely relies on base pair specific patterns of helix distortion being the same on the two molecules, discussed extensively in the past. The other mechanism proposes that there are preferential interactions between base pairs of the same composition. We introduce a model, built on this second mechanism, where both thermal stretching and twisting fluctuations are included, as well as the base pair specific helix distortions. Firstly, we consider an approximation for weak pairing interactions, or short molecules. This yields a dependence of the energy on the square root of the molecular length, which could explain recent experimental data. However, analysis suggests that this approximation is no longer valid at large DNA lengths. In a second approximation, for long molecules, we define two adaptation lengths for twisting and stretching, over which the pairing interaction can limit the accumulation of helix disorder. When the pairing interaction is sufficiently strong, both adaptation lengths are finite; however, as we reduce pairing strength, the stretching adaptation length remains finite but the torsional one becomes infinite. This second state persists to arbitrarily weak values of the pairing strength; suggesting that, if the molecules are long enough, the pairing energy scales as length. To probe differences between the two pairing mechanisms, we also construct a model of similar form. However, now, pairing between identical sequences solely relies on the intrinsic helix distortion patterns. Between the two models, we see interesting qualitative differences. We discuss our findings, and suggest new work to distinguish between the two mechanisms.
Vortex pairs on surfaces

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

Koiller, Jair; Boatto, Stefanella

2009-05-06

A pair of infinitesimally close opposite vortices moving on a curved surface moves along a geodesic, according to a conjecture by Kimura. We outline a proof. Numerical simulations are presented for a pair of opposite vortices at a close but nonzero distance on a surface of revolution, the catenoid. We conjecture that the vortex pair system on a triaxial ellipsoid is a KAM perturbation of Jacobi's geodesic problem. We outline some preliminary calculations required for this study. Finding the surfaces for which the vortex pair system is integrable is in order.
Application of ASP Technology to Realize the Online Administrative License of the earthquake in Hunan Province

NASA Astrophysics Data System (ADS)

Tang, Hongliang; Kang, Chengxu; Tian, Youping

2018-01-01

Realizing the online handling of administrative approval of earthquakes is an important measure to improve work efficiency and facilitate people’s convenience. Based on the analysis of the characteristics and processes of the administrative licensing in the earthquake industry, this paper proposes an online processing model based on ASP technology and an online processing system based on B/S architecture. This paper presents the design and implementation methods. The application of the system shows that the system is simple in design and full in function, and can be used on mobile platforms such as computers and mobile phones, and has good practicability and forward-lookingness.
Profound microcephaly, primordial dwarfism with developmental brain malformations: a new syndrome.

PubMed

Abdel-Salam, Ghada M H; Abdel-Hamid, Mohamed S; Saleem, Sahar N; Ahmed, Mahmoud K H; Issa, Mahmoud; Effat, Laila K; Kayed, Hisham F; Zaki, Maha S; Gaber, Khaled R

2012-08-01

We describe two sibs with a lethal form of profound congenital microcephaly, intrauterine and postnatal growth retardation, subtle skeletal changes, and poorly developed brain. The sibs had striking absent cranial vault with sloping of the forehead, large beaked nose, relatively large ears, and mandibular micro-retrognathia. Brain magnetic resonance imaging (MRI) revealed extremely simplified gyral pattern, large interhemispheric cyst and agenesis of corpus callosum, abnormally shaped hippocampus, and proportionately affected cerebellum and brainstem. In addition, fundus examination showed foveal hypoplasia with optic nerve atrophy. No abnormalities of the internal organs were found. This profound form of microcephaly was identified at 17 weeks gestation by ultrasound and fetal brain MRI helped in characterizing the developmental brain malformations in the second sib. Molecular analysis excluded mutations in potentially related genes such as RNU4ATAC, SLC25A19, and ASPM. These clinical and imaging findings are unlike that of any recognized severe forms of microcephaly which is believed to be a new microcephalic primordial dwarfism (MPD) with developmental brain malformations with most probably autosomal recessive inheritance based on consanguinity and similarly affected male and female sibs. Copyright © 2012 Wiley Periodicals, Inc.

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