Development of certain novel N-(2-(2-(2-oxoindolin-3-ylidene)hydrazinecarbonyl)phenyl)-benzamides and 3-(2-oxoindolin-3-ylideneamino)-2-substituted quinazolin-4(3H)-ones as CFM-1 analogs: design, synthesis, QSAR analysis and anticancer activity.

The reaction of N-(2-(hydrazinecarbonyl)aryl)benzamides 2a, b with indoline-2,3-diones 4ae in acidified ethanolic solution furnished the corresponding N-(2-(2-(2-oxoindolin-3-ylidene)hydrazinecarbonyl)phenyl)benzamides 5aj, respectively. Furthermore, 3-(2-oxoindolin-3-ylideneamino)-2-substituted quinazolin-4(3H)-ones 6aj were prepared by the reaction of 3-amino-2-arylquinazolin-4(3H)-one 3a, b with 4ae. Six derivatives of the twenty newly synthesized compounds showed remarkable antitumor activity against most of the tested cell lines, Daoy, UW228-2, Huh-7, Hela and MDA-MB231. Although these six compounds were more potent than the standard drug (CFM-1), indeed compounds 5b, 5d and 6b were the best candidates with IC50 values in the range 1.866.87, 4.4210.89 and 1.468.60 μg/ml and percentage inhibition in the range 77.188.7, 59.4184.8 and 75.488.0%, respectively. QSAR analyses on the current series of derivatives also have been performed for all five cancer cell lines and thus 10 statistically significant models were developed and internally cross validated

Correlations among different stability parameters for grain yield in chickpea

The presence of Genotype x Environment (G x E) interaction in plant breeding experiments led to the development of several stability parameter in the put few decades. The interrelationships among different stability parameten available in the literature showed highly significant correlation between sf and bi, and among φ(i), ωi2, Wi2, Sdi2, ri2, and Si4. None of the parameten except CVi was consistently correlated with mean yield. Ranking of genotypes based on these stability parameten was different over different subsets of environments within each trial indicating their poor repeatabilit

Repeatability of different stability parameters for grain yield in chickpea

The presence of genotype × environment (GE) interactions in plant breeding experiments has led to the development of several stability parameters in the past few decades. The present study investigated the repeatability of these parameters for 16 chickpea (Cicer arietinum L.) genotypes by correlating their estimates obtained from extreme subsets of environments within a year and also over years. Based on the estimates of response and stability parameters within each trial, the ranking of genotypes in the low-yielding subset differed from that in the high-yielding subset. This indicates poor repeatability for response and stability parameters over the extreme environmental subsets. The estimates of mean yield and stability parameters represented by ecovalence, W2i, were consistent over years, whereas those of response parameters (bi, and S2i) showed poor repeatability. Our results suggest that single-year results for yield and stability can be used effectively for selecting cultivars with stable grain yield if tested in a wider range of environment

Two Allelic Variants of Aldo-Keto Reductase 1A1 Exhibit Reduced in Vitro Metabolism of Daunorubicin

ABSTRACT: Aldo-keto reductases (AKRs) are a class of NADPH-dependent oxidoreductases that have been linked to metabolism of the anthracyclines doxorubicin (DOX) and daunorubicin (DAUN). Although widely used, cardiotoxicity continues to be a serious side effect that may be linked to metabolites or reactive intermediates generated in their metabolism. In this study we examine the little known effects of nonsynonymous single nucleotide polymorphisms of human AKR1A1 on the metabolism of these drugs to their alcohol metabolites. Expressed and purified from bacteria using affinity chromatography, the AKR1A1 protein with a single histidine (6x-His) tag exhibited the greatest activity using two test substrates: p-nitrobenzaldehyde (5.09 ؎ 0.16 mol/min/mg of purified protein) and DL-glyceraldehyde (1.24 ؎ 0.17 mol/min/mg). These activities are in agreement with published literature values of nontagged human AKR1A1. The 6x-His-tagged AKR1A1 wild type and allelic variants, E55D and N52S, were subsequently examined for metabolic activity using DAUN and DOX. The tagged variants showed significantly reduced activities (1.10 ؎ 0.42 and 0.72 ؎ 0.47 nmol of daunorubicinol (DAUNol) formed/min/mg of purified protein for E55D and N52S, respectively) compared with the wild type (2.34 ؎ 0.71 nmol/min/mg). The wild type and E55D variant metabolized DOX to doxorubicinol (DOXol); however, the levels fell below the limit of quantitation (25 nM). The N52S variant yielded no detectable DOXol. A kinetic analysis of the DAUN reductase activities revealed that both amino acid substitutions lead to reduced substrate affinity, measured as significant increases in the measured K m for the reduction reaction by AKR1A1. Hence, it is possible that these allelic variants can act as genetic biomarkers for the clinical development of DAUN-induced cardiotoxicity

ESR1 mutant breast cancers show elevated basal cytokeratins and immune activation

Estrogen receptor alpha (ER/ESR1) is frequently mutated in endocrine resistant ER-positive (ER+) breast cancer and linked to ligand-independent growth and metastasis. Despite the distinct clinical features of ESR1 mutations, their role in intrinsic subtype switching remains largely unknown. Here we find that ESR1 mutant cells and clinical samples show a significant enrichment of basal subtype markers, and six basal cytokeratins (BCKs) are the most enriched genes. Induction of BCKs is independent of ER binding and instead associated with chromatin reprogramming centered around a progesterone receptor-orchestrated insulated neighborhood. BCK-high ER+ primary breast tumors exhibit a number of enriched immune pathways, shared with ESR1 mutant tumors. S100A8 and S100A9 are among the most induced immune mediators and involve in tumor-stroma paracrine crosstalk inferred by single-cell RNA-seq from metastatic tumors. Collectively, these observations demonstrate that ESR1 mutant tumors gain basal features associated with increased immune activation, encouraging additional studies of immune therapeutic vulnerabilities

A new approach for finding an appropriate combination of texture parameters for classification

This paper suggests an approach for finding an appropriate combination of various parameters for extracting texture features (e.g. choice of spectral band for extracting texture feature, size of the moving window, quantization level of the image, and choice of texture feature etc.) to be used in the classification process. Gray level co-occurrence matrix (GLCM) method has been used for extracting texture from remotely sensed satellite image. Results of the classification of an Indian urban environment using spatial property (texture), derived from spectral and multi-resolution wavelet decomposed images have also been reported. A multivariate data analysis technique called ‘conjoint analysis’ has been used in the study to analyze the relative importance of these parameters. Results indicate that the choice of texture feature and window size have higher relative importance in the classification process than quantization level or the choice of image band for extracting texture feature. In case of texture features derived using wavelet decomposed image, the parameter ‘decomposition level’ has almost equal relative importance as the size of moving window and the decomposition of images up to level one is sufficient and there is no need to go for further decomposition. It was also observed that the classification incorporating texture features improves the overall classification accuracy in a statistically significant manner in comparison to pure spectral classification

New Chickpea Varieties for Myanmar

New chickpea lines have been introduced into Myanmar from ICRISAT. Lines with high yields and resistance to diseases and pests have been selected for advanced multilocational trials. ICCV2, ICCV5 and ICCV88202 performed better than the local varieties (2.2, 2.51 and 1.52 t/ha, respectively, in 1992-93 compared with 1.36 and 1.47 t/ha for local varieties in multilocational tests). ICCC42 also produced a high yield, 1.0 t/ha compared with 0.69 t/ha from a local desi variety in farmers' fields in 1992-93. ICCV2 and ICCV88202 are very early maturing and so can make efficient use of limited soil moisture, and escape terminal drought and pod borer (Helicoverpa armigera) damage. ICCC42 and ICCV5 are of short to medium duration and efficiently use nutrients and soil moisture under irrigation. All the new varieties are resistant to wilt (Fusarium oxysporum f.sp. ciceris)