Phenotypic Index Research Articles

Phenotypic diversity and relationships among a worldwide durum wheat (Triticum turgidum L. var. durum) germplasm collection under rainfed conditions of Iran

Information on the variation available for different plant attributes has enabled germplasm collections to be effectively utilised in crop improvement. This study evaluated 380 durum wheat landraces, representing a worldwide durum wheat collection from 16 geographical origins, for several phenological and agronomic traits under rainfed conditions of Iran during three consecutive cropping seasons (2008–11). The experimental design was an unreplicated trial for all landraces, augmented by four repeated check cultivars. Best linear unbiased predictions (BLUPs) representing adjusted genotypic means were generated for individual trials using a mixed model. Multivariate analyses were used to measure the phenotypic diversity within the germplasm collection and relationships among landraces from different geographical regions. Combined analysis of variance indicated significant differences between years, landraces, and their interaction effects, indicating high variability among the germplasm across the years for each studied trait. Low heritability coupled with low genetic advance as a percentage of the mean was observed for days to heading (DTH) and days to maturity (DTM), whereas moderate heritability with moderate genetic advance as a percentage of the mean was exhibited for grain yield (YLD) followed by 1000-kernel weight (TKW) and plant height (PHT). According to Shannon’s phenotypic diversity index, collections from Iran (which represented a high percentage of germplasm tested) exhibited lower diversity in quantitative traits, especially for phenological traits, i.e. DTH and DTM, relative to landraces from other origins. Biplot analyses indicated several significant patterns among landraces from different geographical regions. The landraces with American and Australian origins were closely associated with each other and can be characterised by low yield productivity, high PHT, and high infestation by wheat stem sawfly (WSS). In contrast, the germplasm from Asian origins showed high yield potential and high TKW with good tolerance to WSS. The results indicated that the Iranian landraces with the lowest yield tend to be late in flowering and maturity. In conclusion, landraces with a wide genetic diversity were identified and can be used to achieve breakthrough in the durum wheat genetic improvement.

Hematoxylin staining of seedling roots is a potential phenotypic index for screening of aluminium tolerance in rice (Oryza sativaL.)

Hematoxylin staining is an early indicator of Aluminium (Al) toxicity effects on the apices of young, developing roots and has also been used as a precocious, nondestructive way of studying Al-sensitivity in plant species. Al(H2O)63+ which is known as Al3+ is dominant in acid soil below pH 5.0 and is the most toxic form. Presence of Al in the rhizosphere of rice in acid soil restricts root growth and significantly reduces the crop productivity. In this present study, 40 rice genotypes were screened for Al-toxicity tolerance based on the hematoxylin staining of root apex of rice seedlings. The genotypes were classified into tolerant, moderately tolerant and susceptible. Based on staining intensity the genotypes IET 22838, Gobindabhog, Kalabhog, Khasha, Badshahbhog, Radhunipagal, Mohanbhog, Pusa Basmati-1, UBKVR-18, UBKVR-16, UBKVR-6 were found tolerant against Al-toxicity in the nutrient solution at 30 ppm.

Effects of clopidogrel and itraconazole on the disposition of efavirenz and its hydroxyl metabolites: exploration of a novel CYP2B6 phenotyping index

To evaluate the effects of clopidogrel and itraconazole on the disposition of efavirenz and its hydroxyl metabolites in relation to the CYP2B6*6 genotype and explore potential phenotyping indices for CYP2B6 activity in vivo using a low dose of oral efavirenz. We conducted a randomized three phase crossover study in 17 healthy Korean subjects pre-genotyped for the CYP2B6*6 allele (CYP2B6*1/*1, n = 6; *1/*6, n = 6; *6/*6, n = 5). Subjects were pretreated with clopidogrel (75 mg day(-1) for 4 days), itraconazole (200 mg day(-1) for 6 days), or placebo and then given a single dose of efavirenz (200 mg). The plasma (0-120 h) and urine (0-24 h) concentrations of efavirenz and its metabolites (7- and 8-hydroxyefavirenz and 8,14-dihydroxyefavirenz) were determined by LC/MS/MS. This study is the first to delineate quantitatively the full (phase I and II) metabolic profile of efavirenz and its three hydroxyl metabolites in humans. Clopidogrel pretreatment markedly decreased AUC(0,48 h), C(max) and Ae(0,24 h) for 8,14-dihydroxyefavirenz, compared with placebo; 95% CI of the ratios were 0.55, 0.73, 0.30, 0.45 and 0.25, 0.47, respectively. The 8,14-dihydroxyefavirenz : efavirenz AUC(0,120 h) ratio was significantly correlated with the weight-adjusted CL/F of efavirenz (r(2) ≈ 0.4, P < 0.05), differed with CYP2B6*6 genotype and was affected by clopidogrel pretreatment (P < 0.05) but not by itraconazole pretreatment. The disposition of 8,14-dihydroxy-EFV appears to be sensitive to CYP2B6 activity alterations in human subjects. The 8,14-dihydroxyefaviremz : efavirenz AUC(0,120 h) ratio is attractive as a candidate phenotyping index for CYP2B6 activity in vivo.

The association of frailty with serum 25-hydroxyvitamin D and parathyroid hormone levels in older European men.

the link between the vitamin D endocrine axis and frailty remains undefined, with few studies examining the joint effect of vitamin D and parathyroid hormone (PTH) levels. Our objective was to determine the association of frailty with serum 25-hydroxyvitamin D (25(OH)D) and PTH. cross-sectional analysis within the European Male Ageing Study (EMAS). a total of 1,504 community-dwelling men aged 60-79 years. frailty was classified using a frailty phenotype (FP) and frailty index (FI). The association of frailty with 25(OH)D and PTH was examined using multinomial logistic regression; individual FP criteria with 25(OH)D and PTH using binary logistic regression. Results were expressed as relative odds ratios (ROR) and 95% confidence intervals (CIs) for multinomial; odds ratios (OR) and 95% CIs for binary models. using the FP, 5.0% of subjects were classified as frail and 36.6% as prefrail. Lower levels of 25(OH)D were associated with being prefrail (per 1 SD decrease: ROR = 1.45; 95% CI: 1.26-1.67) and frail (ROR = 1.89; 95% CI: 1.30-2.76), after adjusting for age, centre and health and lifestyle confounders (robust group = base category). Higher levels of PTH were associated with being frail after adjustment for confounders (per 1 SD increase: ROR = 1.24; 95% CI: 1.01-1.52). Comparable results were found using the FI. Among the five FP criteria only sarcopenia was not associated with 25(OH)D levels, while only weakness was associated with PTH. lower 25(OH)D and higher PTH levels were positively associated with frailty in older men. Prospective data would enable the temporal nature of this relationship to be explored further.

Frailty and Sexual Health in Older European Men

There has been little research on how late-life frailty interrelates with sexual health. Our objective was to examine the association of frailty with sexual functioning and satisfaction among older men. The study population consisted of 1,504 men aged 60 to 79 years, participating in the European Male Aging Study. Self-report questionnaires measured overall sexual functioning, sexual function-related distress, and erectile dysfunction. Frailty status was defined using a phenotype (FP) or index (FI). Associations between frailty and sexual function were explored using regression models. Based on the frailty phenotype, 5% of men were classified as frail, and the mean frailty index was 0.18 (SD = 0.12). Frailty was associated with decreasing overall sexual functioning and increasing sexual function-related distress in multiple linear regressions adjusted for age, smoking, alcohol consumption, living arrangements, comorbidities, and depression. Frailty was also associated with an increased odds of erectile dysfunction after adjustment for the same confounders: odds ratio = 1.99 (95% confidence interval = 1.14, 3.48) and 4.08 (95% confidence interval = 2.63, 6.36) for frailty phenotype and frailty index, respectively. Frailty was associated with impaired overall sexual functioning, sexual function-related distress, and erectile dysfunction. Individuals assessed for frailty-related deficits may also benefit from an appraisal of sexual health as an important aspect of well-being and quality of life.

Alternative oxidase 1 (Aox1) gene expression in roots of Medicago truncatula is a genotype-specific component of salt stress tolerance

Alternative oxidase (AOX) is the central component of the non-phosphorylating alternative respiratory pathway in plants and may be important for mitochondrial function during environmental stresses. Recently it has been proposed that Aox can be used as a functional marker for breeding stress tolerant plant varieties. This requires characterization of Aox alleles in plants with different degree of tolerance in a certain stress, affecting plant phenotype in a recognizable way. In this study we examined Aox1 gene expression levels in Medicago truncatula genotypes differing in salt stress tolerance, in order to uncover any correlation between Aox expression and tolerance to salt stress. Results demonstrated a specific induction of Aox1 gene expression in roots of the tolerant genotype that presented the lowest modulation in phenotypic and biochemical stress indices such as morphologic changes, protein level, lipid peroxidation and ROS generation. Similarly, in a previous study we reported that induction of antioxidant gene expression in the tolerant genotype contributed to the support of the antioxidant cellular machinery and stress tolerance. Correlation between expression patterns of the two groups of genes was revealed mainly in 48h treated roots. Taken together, results from both experiments suggest that M. truncatula tolerance to salt stress may in part due to an efficient control of oxidative balance thanks to (i) induction of antioxidant systems and (ii) involvement of the AOX pathway. This reinforces the conclusion that differences in antioxidant mechanisms can be essential for salt stress tolerance in M. truncatula and possibly the corresponding genes, especially Aox, could be utilized as functional marker.

Exploring the association between the 2-repeat allele of the MAOA gene promoter polymorphism and psychopathic personality traits, arrests, incarceration, and lifetime antisocial behavior

A line of research has revealed that a polymorphism in the promoter region of the MAOA gene is related to antisocial phenotypes. Most of these studies examine the effects of low MAOA activity alleles (2-repeat and 3-repeat alleles) against the effects of high MAOA activity alleles (3.5-repeat, 4-repeat, and sometimes 5-repeat alleles), with research indicating that the low MAOA activity alleles confer an increased risk to antisocial phenotypes. The current study examined whether the 2-repeat allele, which has been shown to be functionally different from the 3-repeat allele, was associated with a range of antisocial phenotypes in a sample of males drawn from the National Longitudinal Study of Adolescent Health. Analyses revealed that African-American males who carried the 2-repeat allele were, in comparison with other African-American male genotypes, significantly more likely to be arrested and incarcerated. Additional analyses revealed that African-American male carriers of the 2-repeat allele scored significantly higher on an antisocial phenotype index and on measures assessing involvement in violent behaviors over the life course. There was not any association between the 2-repeat allele and a continuously measured psychopathic personality traits scale. The effects of the 2-repeat allele could not be examined in Caucasian males because only 0.1% carried it.

An SNP downstream of the OsBEIIb gene is significantly associated with amylose content and viscosity properties in rice (Oryza sativa L.)

Allele mining in starch synthesis-related genes (SSRGs) has facilitated the discovery of desired natural sequence variations for eating quality in rice. This study investigated the sequence variations from 10 SSRGs, and further evaluated their relationship with the amylose content (AC) and rapid viscosity analysis profiles in a global collection of rice accessions by association mapping (AM). In total, 83 sequence variations were found in 10 sequenced amplicons, including 73 single nucleotide polymorphisms (SNPs), eight insertion-deletions (InDels) and two polymorphic simple sequence repeats (SSRs). Four subpopulations were identified by population structure analysis based on 170 genome-wide SSR genotypes. AM revealed 11 significant associations between three phenotypic indices and three sequence variations. One SNP with a g/c transversion at the 63rd nucleotide downstream of the OsBEIIb gene termination codon on rice chromosome 2 was significantly associated with multiple trait indices in both the general linear and mixed linear models (GLM and MLM), including the final viscosity (p < 0.001, R2 = 23.87%) in both 2009 and 2010, and AC (p < 0.01, R2 = 11.25%) and trough viscosity (p < 0.01, R2 = 20.43) in 2010. This study provides a new perspective of allele mining for breeding strategies based on marker-assisted selection.

Landscape management and domestication of Stenocereus pruinosus (Cactaceae) in the Tehuacán Valley: human guided selection and gene flow.

BackgroundUse of plant resources and ecosystems practiced by indigenous peoples of Mesoamerica commonly involves domestication of plant populations and landscapes. Our study analyzed interactions of coexisting wild and managed populations of the pitaya Stenocereus pruinosus, a columnar cactus used for its edible fruit occurring in natural forests, silviculturally managed in milpa agroforestry systems, and agriculturally managed in homegardens of the Tehuacán Valley, Mexico. We aimed at analyzing criteria of artificial selection and their consequences on phenotypic diversity and differentiation, as well as documenting management of propagules at landscape level and their possible contribution to gene flow among populations.MethodsSemi-structured interviews were conducted to 83 households of the region to document perception of variation, criteria of artificial selection, and patterns of moving propagules among wild and managed populations. Morphological variation of trees from nine wild, silviculturally and agriculturally managed populations was analyzed for 37 characters through univariate and multivariate statistical methods. In addition, indexes of morphological diversity (MD) per population and phenotypic differentiation (PD) among populations were calculated using character states and frequencies.ResultsPeople recognized 15 pitaya varieties based on their pulp color, fruit size, form, flavor, and thorniness. On average, in wild populations we recorded one variety per population, in silviculturally managed populations 1.58 ± 0.77 varieties per parcel, and in agriculturally managed populations 2.19 ± 1.12 varieties per homegarden. Farmers select in favor of sweet flavor (71% of households interviewed) and pulp color (46%) mainly red, orange and yellow. Artificial selection is practiced in homegardens and 65% of people interviewed also do it in agroforestry systems. People obtain fruit and branches from different population types and move propagules from one another. Multivariate analyses showed morphological differentiation of wild and agriculturally managed populations, mainly due to differences in reproductive characters; however, the phenotypic differentiation indexes were relatively low among all populations studied. Morphological diversity of S. pruinosus (average MD = 0.600) is higher than in other columnar cacti species previously analyzed.ConclusionsArtificial selection in favor of high quality fruit promotes morphological variation and divergence because of the continual replacement of plant material propagated and introduction of propagules from other villages and regions. This process is counteracted by high gene flow influenced by natural factors (pollinators and seed dispersers) but also by human management (movement of propagules among populations), all of which determines relatively low phenotypic differentiation among populations. Conservation of genetic resources of S. pruinosus should be based on the traditional forms of germplasm management by local people.

Sequence variations inOsAGPasesignificantly associated with amylose content and viscosity properties in rice (Oryza sativaL.)

Sequence-based variations in starch synthesis-related genes (SSRGs) exert a basic influence on the determination of eating quality in rice (Oryza sativa L.). This study aimed to investigate the relationship between the sequence variations from parts of 10 SSRGs and the amylose content (AC) plus rapid viscosity analysis (RVA) profiles in a heuristic rice core set by association mapping (AM). In total, 86 sequence variations were found in 10 sequenced amplicons, including 79 single-nucleotide polymorphisms (SNPs), six insertion-deletions (InDels) and one polymorphic simple sequence repeat (SSR). Among them, 61 variations were exon-based, of which 41 should lead to amino acid changes. Four subpopulations were revealed by population structure analysis based on 170 genome-wide SSR genotypes. The final AM showed a sum of four significant associations between three phenotypic indices and three sequence variations. An ADP-glucose pyrophosphorylase small unit 1 (OsAGPS1) SNP (A-G) was significantly associated with increased AC (P<0·001, R(2)=15·6%), while a 12-bp deletion of AGPase large unit 4 (OsAGPL4) was significantly related to the decreased breakdown viscosity (BDV) (P<0·001, R(2)=16·6%) in both general linear model (GLM) and mixed linear model (MLM). This study provides a new perspective of allele mining for breeding strategies based on marker-assisted selection.

Cocktail Approach for In Vivo Phenotyping of 5 Major CYP450 Isoenzymes: Development of an Effective Sampling, Extraction, and Analytical Procedure and Pilot Study With Comparative Genotyping

In this study, the authors developed a phenotyping method for CYP1A2, 2C9, 2C19, 2D6, and 3A4 using a cocktail of 100 mg caffeine, 125 mg tolbutamide, 20 mg omeprazole, 30 mg dextromethorphan, and 2 mg midazolam. A simple sampling scheme was established collecting 3 blood samples at 0, 4, and 24 hours followed by solid-phase extraction and liquid chromatography/tandem mass spectrometry analysis. After addition of 8 deuterated internal standards and extraction, the analytes were separated using gradient elution with ammonium acetate and methanol. Data acquisition was performed on a triple quadrupole linear ion trap mass spectrometer in multiple-reaction monitoring mode with positive electrospray ionization. The assay was validated according to international guidelines: limits of quantification (LOQs) were between 0.25 and 1.0 ng/mL for all analytes, except for paraxanthine and caffeine (20 ng/mL). Extraction efficiencies ranged between 77% and 103% and matrix effects between 23% and 95%; precision and accuracy data fulfilled accepted criteria. Calibration curves from LOQ to 1000 ng/mL were established for undiluted and 1:10 diluted plasma (r > 0.998). The method was tested in a pilot study with 14 volunteers. Additional genotyping of the probands generally demonstrated good accordance with the measured phenotyping indices but also disclosed certain contradictory results.

Genetic analysis of familial hypercholesterolaemia in Western Australia

ObjectiveTo determine the spectrum of mutations associated with familial hypercholesterolaemia (FH) and their detection rate in the FH Western Australia (FHWA) Program. MethodsMutation testing of the LDLR gene, plus select regions in APOB and PCSK9, was performed in the first 343 patients considered to be phenotypic index cases of FH and classified on the basis of the Dutch Lipid Clinic Network Criteria (DLCNC) score as “possible”, “probable”, or “definite” FH. ResultsOverall, 86 different pathogenic (or likely pathogenic) mutations were identified in 129 patients, including four compound heterozygotes manifesting a more severe clinical phenotype. Fourteen of these mutations were novel and twelve (9.6%) were large deletions/duplications of the LDLR. The most common mutations were the familial defective apoB-100 mutation APOB p.Arg3527Gln (7.2%) and an LDLR intron 3 splice site mutation c.313 + 1G > A (4.8%). While 70% of ‘definite’ FH patients were found to carry a mutation, only 29% of ‘probable’ and 11% of ‘possible’ FH patients were mutation-positive. ConclusionThis information provides a useful DNA database on which to base ongoing cascade screening for FH and future research into the genetic aetiology of FH in Western Australia. These findings suggest genetic testing should be prioritised to those with high DLCNC scores and offers a cost-effective family screening method from FH index cases, leading to detection of other previously undiagnosed and younger family members, enabling early instigation of intervention and preventative measures for premature coronary heart disease.

Stability of yield and related traits in dual-purpose sorghum (Sorghum bicolor) across locations

The present study detected differential response in 10 dual-purpose sorghum genotypes over locations for fodder and biomass yields, which are very important agronomic traits. The G × E (linear) as well as pooled deviation mean squares were found significant for these traits indicating that the linear sensitivity of different genotypes is variable and performance of genotypes fluctuated significantly from their respective linear path of response to environments. The test hybrid ‘SPH 1467’ had the highest phenotypic index and was found stable for fodder and biomass yields. Among the varieties, ‘SPV 1750’ recorded the highest grain yield while ‘SPV 1716’ had the highest fodder and biomass yield, but were not stable across locations for these traits. The genotype ‘SPV 1616’ showed high adaptability for grain and fodder yields and biomass, and hence better suited as a dual purpose sorghum variety.

G x E Interaction on Yield Stability of Five Sweet Corn Hybrids Grown under Different Agricultural Systems

Yield stability in sweet corn and its dependence on G x E interaction were investigated in a series of two way experiments. Five Romanian sweet corn hybrids were tested in three years (2008-2010) in three locations of Central Transylvania in different soils and climatic conditions. The experiments were organized in a split plot design in which, on a general level of organic fertilization (40 t/ha manure), four levels of mineral N fertilization were applied (kg/ha, active matter): N0, typical for organic technologies; N50, corresponding to the low-input (sustainable) system; N100 and N150 customary with conventional system of agriculture. Based on ear yield data registered for hybrids in locations x years x cropping system, a phenotypic index (Pi) was computed for each sweet corn hybrid illustrating the stability of their cob yields, with and without husks. The share of genotypic and G x E effects in the total value of Pi have been estimated. In different agricultural systems the tested hybrids were classified differently based on their Pi values. It is concluded that, at least for the time being, the initiation of an organic breeding program for sweet corn, in Romania, is not economically justified since all semiearly and semilate tested hybrids yielded satisfactorily under organic agricultural practices. Moreover, among the recently released sweet corn hybrids one can find certain genotypes highly suitable to organic (i.e. ‘Deliciul verii’, ‘Estival’) or low input (‘Dulcin’, ‘Estival’) agricultural practices. These three hybrids recorded the highes ear yields (with and without husks) over years, locations and agricultural systems.

Abstract 2630: DNA repair single nucleotide polymorphisms interact with indoor tanning and melanoma

Abstract Development of melanoma has previously been associated with compromised DNA repair which can be analyzed by genotyping SNPs in DNA repair genes. The Minnesota Skin Health Study collected DNA samples to investigate the hypothesis that DNA repair SNPs are associated with increased risk for melanoma among tanning bed users. 92 SNPs, with minor allele frequencies greater than 0.05, were analyzed in 20 genes for 1659 samples_893 melanoma cases and 766 controls. The SNPs were genotyped on the Illumina BeadExpress GoldenGate platform. The SNPs were then analyzed for individual SNP associations with melanoma, haplotype associations with melanoma, individual SNP interactions with ever/never indoor tanning, and haplotype interactions with ever/never indoor tanning after adjustments for age, gender, and phenotypic index. There were several SNPs that had an association with melanoma including: six SNPs in three nucleotide excision repair genes ERCC4, ERCC6 (rs4253190, adjusted OR=1.19, 95%CI: 1.04-1.37; rs4838518, adjusted OR=0.86, 95%CI: 0.75-0.99; rs4253121, adjusted OR=0.84, 95%CI:0.71-0.99), and XPC, one SNP in base excision repair gene RFC1, one SNP in direct reversal DNA repair gene MGMT, and one SNP in a novel gene FBRSL1(rs4883571, adjusted OR=0.87, 95%CI: 0.75-1.00). There were four haplotype associations with melanoma including one ERCC6 block (rs10745261, rs6537537, rs4253121: GGA, adjusted OR: 0.84, 95%CI: 0.71-0.99), two MGMT blocks, and one XPC block. Additionally, there was one SNP in FBRSL1 (rs4883557, p=0.0056) and one SNP in ERCC6 (rs10745261, p=0.025) that had an interaction with indoor tanning along with two haplotypes including one block in ERCC6 (rs10745261, rs6537537, rs4253121: AAG, p=0.0355) and one block in MGMT. While the interaction analyses were suggestive, the study is limited because none of the SNPs or haplotypes were only significant (p&amp;lt;0.05) before Bonferroni correction. Further analyses of the function of these SNPs will be necessary, particularly for ERCC6, which had SNPs that were significant in every analysis, and FBRSL1, which is a novel gene whose function is unknown. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2630. doi:1538-7445.AM2012-2630

Abstract 2003: STAT3 is a critical mediator of the pro-survival effect of Bcl-2-Rac1 interaction in human cancer cells

Abstract We recently showed that Bcl-2 overexpression induced a pro-oxidant intracellular milieu resulting in an inhibition of apoptotic execution and that reversing the pro-oxidant milieu by inhibiting intracellular superoxide production sensitized Bcl-2-overexpressing cells to apoptotic stimuli. We provide evidence that the small GTPase Rac1 is functionally involved since gene silencing and functional inhibition of Rac1 blocked Bcl-2-mediated increase in intracellular superoxide production in tumor cells. A co-localization and physical interaction between the two proteins were observed, which could be blocked by the BH3 mimetics as well as by synthetic Bcl-2 BH3 domain peptides both in vitro and in vivo. The Bcl-2 BH3 peptides as well as silencing and functional inhibition of Rac1 reversed intracellular superoxide levels and overcame Bcl-2-mediated drug resistance in human leukemia and cervical cancer cells, demonstrating that this interaction is functionally relevant. Notably, the interaction was observed in primary cells from patients diagnosed with B-cell lymphoma with Bcl-2 overexpression but not in noncancerous tissue. Furthermore, computer simulation driven virtual predictive experiments based on the protein pathway dynamic network created by Cellworks Group Inc. were carried out to study the functional implication of this interaction. An HCT116 human colorectal cancer cell line with KRAS over-activation, PI3K overexpression, CDKN2A deletion, β-catenin overexpression and Bcl-2 overexpression was created as a base line. Phenotypic indices of angiogenesis, proliferation, viability, metastasis as well as tumor volume were all found to be amplified in a variant cell line when Rac1 was overexpressed based on the above computer modeled HCT116. Strikingly, the expression levels of both STAT3 and β-catenin were significantly upregulated in the variant cell line; however upon Rac1 or Bcl-2 knockdown in both the base and the variant cell lines, apoptotic markers such as Bax, caspase 3 and cleaved PARP1 were amplified while STAT3 and β-catenin were significantly down-regulated. Intrigued by these predictions, we set out to verify the correlation between STAT3 signaling and Bcl-2-Rac1 interaction. Interestingly, there is indeed a strong correlation between the activation status of STAT3 (pY705) and Bcl-2 expression as well as Rac1 activation status. Furthermore, STAT3 was found to be localized to mitochondria and our preliminary results suggest an association with Bcl-2. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2003. doi:1538-7445.AM2012-2003

Highly plastic response in morphological and physiological traits to light, soil-N and moisture in the model invasive plant, Phalaris arundinacea

The ability of an introduced species to thrive is often influenced by its capacity to cope with disturbance and resource fluctuation, and one way to cope is by being phenotypically plastic. The biomass and resource allocation of the invasive plant species, Phalaris arundinacea (reed canarygrass), to contrasting levels of light, soil-N and moisture was evaluated. We predicted that P. arundinacea would show a highly plastic response in important growth and physiological traits to treatment conditions (presence of three-way interactions and large phenotypic plasticity index (PI) values) because of its ability to persist in variable environments. MANOVA tests showed significant three-way interactions for each of the three groups of plant traits (aboveground (AGB) and belowground biomass (BGB), shoot C/N and root C/N ratios, leaf chlorophyll and soluble protein), demonstrating the complex correlated response to the treatment effects by pairs of response variables. There were significant three-way interactions for seven of nine plant traits (univariate analyses), including AGB and BGB, AGB per tiller, shoot/root ratio, shoot C/N ratio, root C/N ratio and leaf chlorophyll content. Total plasticity values, which represented the greatest possible plasticity for each plant trait, were larger than any of the PI values for the main effects. Understanding which traits show plasticity, as well as the magnitude of response expressed in common invasive species is an important area of research because aspects of their aggressive behavior may be explained by how they grow and allocate resources under variable environmental conditions, which in turn can be important when seeking to make predictions about the probability and degree of invasion success with species-specific invasion models.

A herbal-drug interaction study of keishi-bukuryo-gan, a traditional herbal preparation used for menopausal symptoms, in healthy female volunteers

Many patients use herbal medicines to relieve menopausal symptoms. Keishi-bukuryo-gan contains five herbal components, and has been used for treating hypermenorrhoea, dysmenorrhoea and menopausal symptoms in Asian countries. In this study, we investigated the potential herb-drug interactions of keishi-bukuryo-gan in healthy female subjects. Thirty-one healthy females (20-27 years) were studied to evaluate their baseline activity of cytochrome P450 (CYP) 1A2, CYP2D6, CYP3A, xanthine oxidase (XO) and N-acetyltransferase 2 (NAT2) based on the urinary metabolic indices of an 8-h urine sample collected after a 150-mg dose of caffeine and a 30-mg dose of dextromethorphan, and also the urinary excretion ratio of 6β-hydroxycortisol to cortisol. Thereafter, the subjects received 3.75g of keishi-bukuryo-gan twice daily for seven days, and underwent the same tests on post-dose day 7. The geometric mean phenotypic index for CYP1A2 significantly decreased by 16% on day 7 compared with the baseline (P=0.026). Keishi-bukuryo-gan did not alter the indices for CYP2D6, CYP3A, XO and NAT2. Keishi-bukuryo-gan may inhibit the activity of CYP1A2, which is predominantly involved in oestrogen metabolism. However, TJ-25 is unlikely to participate in herb-drug interactions involving medications predominantly metabolized by CYP2D6, CYP3A, XO and NAT2. K

EBV-Negative Primary Pulmonary Lymphoma in a Patient with AIDS

Abstract 5203AIDS-related primary pulmonary lymphoma (PPL) is defined as exclusive involvement of the lung by lymphoma with no evidence of extrapulmonary disease at the time of diagnosis and three months thereafter. It is an aggressive disease with a median survival time of four months. A 46 year old male patient with a seven year history of HIV/AIDS and CD4 count of 200/ul was hospitalized because of flank pain, hematuria and hemoptysis. Abdominal CT scan incidentally revealed multiple nodules in the lower lobes of both lungs. Serial chest CT scans demonstrated multiple nodular opacities in all lobes of the lungs that enlarged rapidly and coalesced together. Clinicians favored opportunistic infection due to rapid disease progression but included Wegener’s granulomatosis in the differential diagnosis because of hemoptysis. Open lung biopsy showed diffuse large B cell lymphoma (DLBCL), NOS, with an activated B cell phenotype (CD10−/BCL6−/MUM1+) and high proliferative index (Ki67 90%). CD79A expression confirmed B cell lineage. The diagnostic criteria for PPL were fulfilled because staging failed to detect extrapulmonary disease. Infarction due to the angiodestructive nature of the PPL and short doubling time accounted for hemoptysis and rapid disease progression, respectively. The patient died 45 days after admission because of shock, presumably due to superimposed infection. Unlike prior reports of AIDS-related PPL, our case was negative for CD19, CD20 and Epstein-Barr virus (EBV). Although PPL is a rare disease, it deserves consideration in the differential diagnosis of rapidly progressive lung nodules in AIDS patients. To the best of our knowledge, this is the first reported case of EBV-negative PPL. Disclosures:No relevant conflicts of interest to declare.

GENOTYPE SEEDLING AGE INTERACTION FOR HYBRID SEED YIELD OF RICE (Oryza sativa L.)

The experiment was carried out in Randomized Completely Block Design (RCBD) during the Boro season 2006-2007 (Mid October to mid May) at Bangabandhu Sheikh Mujibur Rahaman Agricultural University-Gazipur. Alok showed significant bi but its deviation from regression (S2di) invalided its linear prediction. Among the three CMS lines CMS-2 was stable for % OCR due to considerable mean, phenotypic index, regression coefficient near unity (bi ? 1) as well as insignificant deviation from regression (S2di ? 0) and CMS-1 was highly responsive to seedling ages due to significant bi and insignificant S2di. Although, Alok showed significant bi but its deviation from regression (S2di) invalided its linear prediction. Maximum out crossing rate was obtained from CMS-2 irrespective of seedling ages. On the other hand 43 days old seedling of CMS-1 gave the maximum out crossing rate. CMS-2 was highly responsive to yield over seedling ages. CMS-1 showed insignificant regression coefficient (bi) indicating stability over seedling ages but deviation from regression (S2di) was significant which invalided its linear prediction. Alok showed lower mean, significant regression coefficient (bi) and insignificant deviation from regression (S2di) indicating responsitive to favourable seedling ages with comparatively lower yield. 43 days old seedlings of CMS-2 gave the maximum hybrid seed production rate.DOI: http://dx.doi.org/10.3329/bjpbg.v24i1.16995