Selection Indices For Improvement Research Articles

Genetic parameters, correlation and path analysis for fodder and dual purpose sorghum [Sorghum bicolor (L.) Moench] genotypes

About 60 diverse sorghum genotypes were evaluated to assess the genetic parameters, association among fodder and grain yield component traits and their direct and indirect effects on grain yield. The experiment was conducted in randomized block design at Instructional Farm, Department of Genetics and Plant Breeding, Rajasthan College of Agriculture (MPUAT), Udaipur in collaboration with AICRP on Sorghum. Analysis of variance revealed highly significant differences among the genotypes for all 14 traits studied. In the present investigation range of the magnitudes of all genetic parameters for each trait was classified based on mean and standard deviation (SD) into three categories viz., high (> ), medium (in between ) and low (< ). Traits viz., total soluble solids (%), grain yield per plant (g), leaf breadth (cm) and dry fodder yield per plant (g) were the most approachable for selection as they had higher GCV, PCV, genetic gain and moderate to high heritability in a broad sense. Hence, simple selection could be effective for further improvement of these characters. Based on correlation and path analysis, the traits, dry fodder yield per plant, harvest index, green fodder yield per plant, leaf breadth, protein content and plant height might be considered as indirect selection indices for improvement in grain and fodder yields of sorghum.

Selection index for improvement of production and reproduction performance in southern Odisha goats

Selection index for improvement of production and reproduction performance in southern Odisha goats

Regio- and Stereoselective Synthesis of 2′-Deoxy-4′-thioguanine Nucleosides: Evaluation of Anti-Hepatitis B Virus Activity and ­Cytotoxicity Leading to Improved Selectivity Index by 4′-C-Cyanation

AbstractAn N 9-regio- and β-anomer-selective 4′-thioglycosidation of purine bases has been developed. The reaction between a 2-deoxy-2-iodo-4-thioribofuranosyl glycosyl donor and N-(6-chloro-9H-purin-2-yl)-2-methylpropanamide gave the corresponding 2′-deoxy-4′-thiopurine nucleoside in 87% yield along with its N 7-regioisomer in 6% yield, without the formation of the α-anomer. By using a derivative obtained from 17, a practical chemical synthesis of 2′-deoxy-4′-thioguanosine was developed. 4′-α-C-Cyano-2′-deoxy-4′-thioguanosine was synthesized, starting from a 4-(acetoxymethyl)-2-deoxy-2-iodo-4-thioribofuranose derivative as a glycosyl donor. An evaluation of the anti-hepatitis B virus (HBV) activity and the cytotoxicity toward the host cell revealed that 4'-C-cyano-2'-deoxy-4'-thioguanosine exhibited about 100 times more potent anti-HBV activity than 2′-deoxy-4′-thioguanosine with a comparative cytotoxicity, resulting in the identification of a novel molecule having better selectivity index value than that of 2′-deoxy-4′-thioguanosine. This finding might provide a guideline for the development of the next generation of anti-HBV agents.

Selection indices for oil content and oil yield improvement in low and high oleic acid content populations in sunflower (Helianthus annuus L.)

A F2 population was partitioned into low oleic and high oleic acid content groups using a high oleic allele-specific marker.  These low and high oleic acid content groups and pooled groups were subjected to variability and association analyses.  The variability parameters were similar in both high oleic and low oleic populations.  Traits viz., plant height, head diameter, 100-seed weight, seed yield and oil content are considered as selection indices for improving oil yield.   These selection indices can be followed to improve oil yield in both high oleic and low oleic populations.   However, separate selection indices to improve oil content viz., volume weight, plant height and head diameter for high oleic acid populations and volume weight, days to flowering and 100-seed weight for a low oleic populations may be followed.   These results indicated that similar selection indices could not be adopted to improve a trait in all populations. Keywords: Sunflower, high oleic acid content, oil yield, variability, correlation.

Naphthoquinone as a New Chemical Scaffold for Leishmanicidal Inhibitors of Leishmania GSK-3.

More than 1 billion people live in areas endemic for leishmaniasis, which is a relevant threat for public health worldwide. Due to the inadequate treatments, there is an urgent need to develop novel alternative drugs and to validate new targets to fight this disease. One appealing approach is the selective inhibition of protein kinases (PKs), enzymes involved in a wide range of processes along the life cycle of Leishmania. Several PKs, including glycogen synthase kinase 3 (GSK-3), have been validated as essential for this parasite by genetic or pharmacological methods. Recently, novel chemical scaffolds have been uncovered as Leishmania GSK-3 inhibitors with antiparasitic activity. In order to find new inhibitors of this enzyme, a virtual screening of our in-house chemical library was carried out on the structure of the Leishmania GSK-3. The virtual hits identified were experimentally assayed both for leishmanicidal activity and for in vitro inhibition of the enzyme. The best hits have a quinone scaffold. Their optimization through a medicinal chemistry approach led to a set of new compounds, provided a frame to establish biochemical and antiparasitic structure–activity relationships, and delivered molecules with an improved selectivity index. Altogether, this study paves the way for a systemic search of this class of inhibitors for further development as potential leishmanicidal drugs.

Enteroviral replication inhibition by N-Alkyl triazolopyrimidinone derivatives through a non-capsid binding mode

Small-molecule inhibitors exhibiting broad-spectrum enteroviral inhibition by targeting viral replication proteins are highly desirable in antiviral drug discovery. We used the previously identified antiviral compound 1 as the starting material to develop a novel compound series with high efficacy against human rhinovirus (hRV). Further optimization of N-substituted triazolopyrimidinone derivatives revealed that the N-alkyl triazolopyrimidinone derivatives (2) had more potent antiviral activity against hRVs than compound 1. The new compounds showed improved selectivity index values, and compound 2c (KR-25210) displayed broad anti-hRV activity, with half-maximal effective concentration values ≤ 2 µM against all tested hRVs. In addition, 2c showed notable activity against other enteroviruses. Drug-likeness elucidation showed that 2c exhibited reasonable human and rat liver microsomal phase-I stability and safe CYP inhibition. Replication studies revealed that 2c is not a capsid inhibitor, and a time-of-addition assay indicated that 2c targets the virus replication stages.

Development of Selection Indices for Improvement of Seed Yield and Lipid Composition in Bambara Groundnut (Vigna subterranea (L.) Verdc.).

The underutilised grain legume bambara groundnut (Vigna subterranea) has the potential to contribute significantly to nutritional security. However, the lack of commercial cultivars has hindered its wider adoption and utilisation as a food source. The development of competitive cultivars is impeded by (1) lack of systematic data describing variation in nutritional composition within the gene pool, and (2) a poor understanding of how concentrations of different nutritional components interact. In this study, we analysed seed lipid and protein concentration and lipid composition within a collection of 100 lines representing the global gene pool. Seed protein and lipid varied over twofold with a normal distribution, but no significant statistical correlation was detected between the two components. Seed lipid concentration (4.2–8.8 g/100 g) is primarily determined by the proportion of oleic acid (r2 = 0.45). Yield and composition data for a subset of 40 lines were then used to test selection parameters for high yielding, high lipid breeding lines. From five selection indices tested using 15 scenarios, an index based on the seed number, seed weight, and oleic acid yielded a >50% expected increase in each of the mean values of seed number, pod dry weight, seed dry weight, and seed size, as well as an expected 7% increase in seed lipid concentration.

Genetic variability, character association and path analysis of oil yield and its component characters in Cymbopogon sp.

Seeking an opportunity for genetic improvement in aromatic grasses lead to an explorative study on the aspects of genetic variability, character association and path analysis between essential oil yield/plot and its contributing traits in twenty five genotypes of Cymbopogon sp. collected from different agro-climatic zones of India, grown in RBD with three replicates. Highly significant differences between genotypes were recorded for the traits that were brought under study. High genotypic and phenotypic coefficients of variation coupled with high heritability and moderate to high genetic advance over mean were recorded in geraniol content, citral content and geranyl acetate content indicating predominance of additive gene effects controlling these traits. Correlation and path analysis revealed that oil content, herb yield/plot and geranyl acetate content are overriding traits among all other growth and yield parameters, therefore more emphasis should be laid upon them while designing selection indices for improvement of essential oil yield.

Rational Design of Hybrid SARS-CoV-2 Main Protease Inhibitors Guided by the Superimposed Cocrystal Structures with the Peptidomimetic Inhibitors GC-376, Telaprevir, and Boceprevir.

SARS-CoV-2 main protease (Mpro) is a cysteine protease that mediates the cleavage of viral polyproteins and is a validated antiviral drug target. Mpro is highly conserved among all seven human coronaviruses, with certain Mpro inhibitors having broad-spectrum antiviral activity. In this study, we designed two hybrid inhibitors UAWJ9-36-1 and UAWJ9-36-3 based on the superimposed X-ray crystal structures of SARS-CoV-2 Mpro with GC-376, telaprevir, and boceprevir. Both UAWJ9-36-1 and UAWJ9-36-3 showed potent binding and enzymatic inhibition against the Mpro’s from SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-OC43, HCoV-NL63, HCoV-229E, and HCoV-HKU1. Cell-based Flip-GFP Mpro assay results show that UAWJ9-36-1 and UAWJ9-36-3 inhibited the intracellular protease activity of SARS-CoV-2 Mpro. In addition, UAWJ9-36-1 and UAWJ9-36-3 had potent antiviral activity against SARS-CoV-2, HCoV-OC43, HCoV-NL63, and HCoV-229E, with UAWJ9-36-3 being more potent than GC-376 in inhibiting SARS-CoV-2. Selectivity profiling revealed that UAWJ9-36-1 and UAWJ9-36-3 had an improved selectivity index over that of GC-376 against host cysteine proteases calpain I and cathepsin L, but not cathepsin K. The X-ray crystal structures of SARS-CoV-2 Mpro with UAWJ9-36-1 and UAWJ9-36-3 were both solved at 1.9 Å, which validated our design hypothesis. Overall, hybrid inhibitors UAWJ9-36-1 and UAWJ9-36-3 are promising candidates to be further developed as broad-spectrum coronavirus antivirals.

Influence of 4'-Substitution on the Activity of Gemcitabine and Its ProTide Against VZV and SARS-CoV-2.

In addition to its therapeutic value as a chemotherapy drug, gemcitabine is of ongoing interest to the scientific community for its broad-spectrum antiviral activity. Herein the synthesis of 4′-methoxy- and 4′-fluoro-substituted gemcitabine analogues along with their phosphoramidate prodrugs is described. Among these derivatives, 4′-fluorogemcitabine proved to be active against varicella zoster virus (VZV, TK+ strain) with an EC50 of 0.042 μM and produced significant cytotoxicity (CC50 = 0.11 μM). Upon derivatization of this trifluoro nucleoside as its prodrug, decreased anti-VZV activity was observed, but with a concomitantly improved selectivity index (SI = 36). When this prodrug was tested against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its antiviral activity (EC50 = 0.73 μM) was comparable to or slightly lower than its cytotoxic concentration in measurements of cell growth and cell morphology, respectively.

Combining Ability of Early-Maturing Yellow Maize Inbreds under Combined Drought and Heat Stress and Well-Watered Environments

Grain-yield potential of maize (Zea mays L.) is limited by the harsh climatic conditions during dry seasons in the savanna of sub-Saharan Africa (SSA). One hundred and five hybrids derived from diallel crosses involving 15 early-maturing yellow maize inbreds were screened under combined drought and heat stress (CDHS) and well-watered (WW) conditions at four locations representative of the dry savannas of Niger, 2012–2014. The objective of the study was to examine the general combining ability (GCA) effects of the inbred lines and specific combining ability (SCA) of the crosses under CDHS and WW environments, assess yield and stability of the derived hybrids under contrasting environments and investigate inter-relationships among traits of the hybrids under contrasting environments. GCA and SCA effects for grain yield and other measured traits were significant, with preponderance of GCA effects over SCA effects under both the CDHS and WW environments. Inbred ENT 13 possessed positive and significant GCA effects for grain yield under both CDHS and WW environments indicating that the inbred could be used for developing outstanding hybrids with good levels of tolerance to CDHS. This also implied that the inbred line could serve as invaluable genetic resource for introgression of favorable alleles into tropical early-maturing maize populations for accelerated genetic gains from selection for improved grain yield. Hybrids ENT 13 × TZEI 167 and TZEI 157 × ENT 13 were the most stable and among the highest yielding hybrids across research environments. These outstanding hybrids could be tested extensively for commercialization in SSA to improve food security. Plant and ear aspects and days to 50% silking could be combined with grain yield in a selection index for improvement of yield under CDHS without yield penalties under WW environments.

Studies on character association among quality traits and yield components in Basmati rice (Oryza sativa L.)

Rice is most important food crop of India and grown in different regions with differential consumer preferences for grain size, shape, aroma and cooking qualities. Therefore, crop improvement in rice not only focused on yield but also to enhance quality. Hence the present investigation was carried out with an objective of assessing the character association among twenty-two morphological and quality characters of thirty basmati rice (Oryza sativa L) genotypes. Correlation analysis revealed that Seed yield was significantly and positively associated with days to maturity (0.330**), number of tillers per plant (0.434**), number of grains per panicle (0.358**), grain weight per panicle (0.410**), and flag leaf length (0.258*). The days to maturity exhibited a significant positive correlation with plant height, panicle length, grain weight per plant, kernel length before cooking, kernel length after cooking and L: B ratio. Tiller per plant reflected the positive and significant association with a number of grains per panicle, grain weight per panicle and grain weight per plant. Flag leaf length showed a significant positive correlation with a number of grains per panicle and grain weight per plant, while Grains per panicle was positively and significantly associated with grain weight per panicle, grain weight per plant and kernel breadth before cooking. Grain weight per panicle exhibited a significant positive association with grain yield per plant (0.410**), kernel breadth before cooking (0.381**), 100 grain weight (0.240*) and 100 kernel weight (0.210*). These characters could be utilized to form a selection index for improvement of the basmati rice.

Selection indices for improvement in body weights and fleece yield of chokla sheep

Data on 3714 Chokla sheep, maintained at ICAR-Central Sheep and Wool Research Institute (CSWRI), Avikanagar, Rajasthan, collected for a period of 18 years (1994 to 2011) were used in the study. Traits analyzed were body weights at birth (BWT), 3 months (3WT), 6 months (6WT), 9 months (9WT), 12 months (12WT) of age and first six monthly greasy fleece yield (GFY1). Genetic and phenotypic covariance between body weights increased with advancing age. The covariance among body weights at different ages and GFY1 also showed similar trends. A total of 59 selection indices was constructed by incorporating these traits in different combinations. The index I58 (0.0008 BWT + 0.0033 3WT + 0.2348 9WT +0.2257 12WT + 0.1803 GFYI) was considered most useful for its reliability (r IH = 0.4181) and genetic gain (ΔH = 2.3295). However, due to complexity of index I58, Index (I4) with single trait based on 9 months was considered as a best selection index (I4), due to its accuracy (rIH = 0.4289), positive b values and genetic gain (ΔH =0.8920). Preliminary selection at 9 months, followed by direct selection at 12 months age based on (9WT) was recommended as selection criteria. Usually breeding rams are used for breeding after 12 months age, so preliminary selection of ram at 9WT was recommended as selection criteria.

Qualitative and Quantitative Aspects of Teasle Gourd Genotypes

ABSTRACTPlant morphology is widely adaptive. Phenotypic differentiation among genotypes reflects a balance between natural selection in the local environment, migration of alleles via gene flow, and, at a lower frequency, the acquisition of novel traits through mutation. Teasle gourd [Momordica subangulata Blume subsp. renigera (G. Don) de Wilde] is a rich source of antioxidant vitamins and a raw material for commercial extraction of neutraceuticals. Extensive collection and characterization for evaluation of superior genotypes are important in improvement. The aim of the study was to evaluate genetic diversity of accessions through genetic components analyses, and genetic divergence by multivariate analysis and principal component analysis (PCA). Wide variation occurred for 13 qualitative and 19 quantitative characters. Number of fruit/plant and fruit weight was identified as the most important selection indices for improvement of yield. Based on determination of divergence, the 18 genotypes could be grouped into seven clusters. Geographical diversity was not adequate as an index of genetic diversity. Based on PCA and average values, genotypes “BCTG-1,” “BCTG-2,” and “BCTG-4” possessed optimum combinations of all variables. Inter-mating between these female clones by inducing staminate, or hermaphrodite, flowers with application of growth substances may be an alternative breeding method for teasle gourd. Desirable characters in hybrids as new varieties can be fixed indefinitely through clonal propagation within a short period of time.

Physicochemical, Stress Degradation Evaluation and Pharmacokinetic Study of AZGH102, a New Synthesized COX2 Inhibitors after I.V. and Oral Administration in Male and Female Rats.

Coxibs such as celecoxib, rofecoxib, and valdecoxib are introduced as selective COX-2 inhibitors to the market. It has been reported that inhibition of COX-2 beside traditional effects of NSAIDs, reduces the risk of colorectal, breast and lung cancers and also slow the progress of Alzheimer's disease. Zarghi et al. reported 8-benzoyl-2-(4-(methylsulfonyl)phenyl)quinoline-4-carboxylic acid (AZGH 102) as a novel compound with similar IC50 to celecoxib besides improved selectivity index (COX-1/COX-2 inhibitory potency) in comparison with celecoxib. In this study, the physicochemical properties of AZGH 102 such as solubility, log P, and stability were evaluated and the pharmacokinetic characteristics of this compound following intravenous (10 mg/Kg), and oral administration (20 mg/Kg), to male and female Wistar rats were investigated. As the data demonstrated, the AZGH 102 classified as lipophil compound and had suitable stability. This derivative absorbs and distributes faster in female than in male. The AUC 0-∞, absolute bioavailability, Cl and Vd were different in both sexes. According to the obtained data, the AZGH 102 has a sex dependent pharmacokinetic in Wistar rats.

Suppression of Adenovirus Replication by Cardiotonic Steroids.

Despite human adenoviruses being a common and, in some instances, life-threating pathogen in humans, there are few well-tolerated therapies. In this report, we demonstrate that two cardiotonic steroids already in use in humans, digoxin and digitoxin, are potent inhibitors of multiple adenovirus species. A synthetic derivative of the cardiotonic steroid convallotoxin was even more potent than digoxin and digitoxin when tested with HAdV-C5. These drugs alter the cascade of adenovirus gene expression, acting after initiation of early gene expression to block viral DNA replication and synthesis of viral structural proteins. These findings validate a novel approach to treating adenovirus infections through the modulation of host cell processes.

Response of maize hybrids from heterotrophic to autotrophic phase of development in cold conditions

Maize ( Zea mays L.) is a crop of a tropical region with sensitivity to low temperature. This study was conducted to evaluate the performance of experimental maize hybrids in winter months of northern India in field conditions. Data were recorded for survival rate, leaf length and width, seedling height and leaf colour. The analysis of pooled data from 3- leaf stage to 6-leaf stage showed hybrids131023 x 131026 and NS76B x EL-CML-1 as best performers. Hybrids with relatively high leaf appearance rate, less cold injury symptoms showed good level of cold tolerance in terms early seedling growth under cold stress. These secondary traits could be used in selection index for improvement of tropical maize for low temperature adaptation.

A comparative antimicrobial and toxicological study of gold(iii) and silver(i) complexes with aromatic nitrogen-containing heterocycles: synergistic activity and improved selectivity index of Au(iii)/Ag(i) complexes mixture

Combination therapy may be applied in the case of gold(iii) and silver(i) complexes with aromatic nitrogen-containing heterocycles to improve their antimicrobial activity and reduce toxic-side effects.

Structure-activity relationship of N-benzenesulfonyl matrinic acid derivatives as a novel class of coxsackievirus B3 inhibitors.

A novel series of N-benzenesulfonyl matrinic amine/amide and matrinic methyl ether analogues were designed, synthesized and evaluated for their in vitro anti-coxsackievirus B3 (CVB3) activities. The structure-activity relationship (SAR) studies revealed that introduction of a suitable amide substituent on position 4' could greatly enhance the antivirus potency. Compared to the lead compounds, the newly synthesized matrinic amide derivatives 21c-d and 21j exhibited stronger anti-CVB3 activities with lower micromolar IC50 from 2.5 μM to 2.7 μM, and better therapeutic properties with improved selectivity index (SI) from 63 to 67. The SAR results provided powerful information for further strategic optimization, and these top compounds were selected for the next evaluation as novel enterovirus inhibitors.

829 HEPATITIS C VIRUS AND LIPID DROPLETS: LIPIDOMIC PROFILING OF HCV CORE PROTEIN-EXPRESSING HEPATOMA CELLS

2.9 (±0.4) and 0.52 (±0.08) uM, respectively. The CC50 of NDGA and M4N was 54 and >150uM, respectively. At the ED50, the CI of M4N with telaprevir was 0.66 and with boceprevir was 0.58. The CI of M4N with simvastatin was 0.50 and with fluvastatin was 0.48. The CI of M4N with NS5B nucleoside inhibitor 2’-C-methyladenosine was 0.48. Conclusion: Based on the EC50s and CC50s, M4N is a more potent compound than NDGA, roughly 5-fold throughout the three assays and has an improved selectivity index. The CIs show M4N to have moderate synergistic interactions with NS3 PIs, a NS5b nucleoside inhibitor, and with HMG-CoA reductase inhibitors. In conclusion, M4N and NDGA not only exhibit anti-HCV activity but also interact synergistically with other HCV antivirals making them an attractive candidate for HCV therapy. Moreover, NDGA derivatives will be novel antivirals through their action on cellular targets involved with lipid metabolism. Beneficial aspects of indirectly targeting viral replication in this manner include an expected high barrier to resistance and broad genotype coverage.