Research on Oracle Technology Based on Multi-Threshold Aggregate Signature Algorithm and Enhanced Trustworthy Oracle Reputation Mechanism.

In the realm of IoT sensor data security, particularly in areas like agricultural product traceability, the challenges of ensuring product origin and quality are paramount. This research presents a novel blockchain oracle solution integrating an enhanced MTAS signature algorithm derived from the Schnorr signature algorithm. The key improvement lies in the automatic adaptation of flexible threshold values based on the current scenario, catering to diverse security and efficiency requirements. Utilizing the continuously increasing block height of the blockchain as a pivotal blinding parameter, our approach strengthens signature verifiability and security. By combining the block height with signature parameters, we devise a distinctive signing scheme reliant on a globally immutable timestamp. Additionally, this study introduces a reliable oracle reputation mechanism for monitoring and assessing oracle node performance, maintaining both local and global reputations. This mechanism leverages smart contracts to evaluate each oracle's historical service, penalizing or removing nodes engaged in inappropriate behaviors. Experimental results highlight the innovative contributions of our approach to enhancing on-chain efficiency and fortifying security during the on-chain process, offering promising advancements for secure and efficient IoT sensor data transmission.

Analysis of genetic diversity and genome-wide association study for drought tolerance related traits in Iranian bread wheat.

BACKGROUND: Drought is most likely the most significant abiotic stress affecting wheat yield. The discovery of drought-tolerant genotypes is a promising strategy for dealing with the world's rapidly diminishing water resources and growing population. A genome-wide association study (GWAS) was conducted on 298 Iranian bread wheat landraces and cultivars to investigate the genetic basis of yield, yield components, and drought tolerance indices in two cropping seasons (2018-2019 and 2019-2020) under rainfed and well-watered environments. RESULTS: A heatmap display of hierarchical clustering divided cultivars and landraces into four categories, with high-yielding and drought-tolerant genotypes clustering in the same group. The results of the principal component analysis (PCA) demonstrated that selecting genotypes based on the mean productivity (MP), geometric mean productivity (GMP), harmonic mean (HM), and stress tolerance index (STI) can help achieve high-yield genotypes in the environment. Genome B had the highest number of significant marker pairs in linkage disequilibrium (LD) for both landraces (427,017) and cultivars (370,359). Similar to cultivars, marker pairs on chromosome 4A represented the strongest LD (r2 = 0.32). However, the genomes D, A, and B have the highest LD, respectively. The single-locus mixed linear model (MLM) and multi-locus random-SNP-effect mixed linear model (mrMLM) identified 1711 and 1254 significant marker-trait association (MTAs) (-log10 P > 3) for all traits, respectively. A total of 874 common quantitative trait nucleotides (QTNs) were simultaneously discovered by both MLM and mrMLM methods. Gene ontology revealed that 11, 18, 6, and 11 MTAs were found in protein-coding regions (PCRs) for spike weight (SW), thousand kernel weight (TKW), grain number per spike (GN), and grain yield (GY), respectively. CONCLUSION: The results identified rich regions of quantitative trait loci (QTL) on Ch. 4A and 5A suggest that these chromosomes are important for drought tolerance and could be used in wheat breeding programs. Furthermore, the findings indicated that landraces studied in Iranian bread wheat germplasm possess valuable alleles, that are responsive to water-limited conditions. This GWAS experiment is one of the few types of research conducted on drought tolerance that can be exploited in the genome-mediated development of novel varieties of wheat.

Delineating Marker-Trait Associations for Fusarium Wilt in Chickpea Using the Axiom® CicerSNP Array.

Fusarium wilt (FW) caused by Fusarium oxysporum f. sp. ciceri is a devastating disease of chickpea (Cicer arietinum). To identify promising resistant genotypes and genomic loci for FW resistance, a core set of 179 genotypes of chickpea was tested for FW reactions at the seedling and reproductive stages under field conditions and controlled conditions in the greenhouse. Our results revealed that at the seedling stage, most of the genotypes were resistant, whereas at the reproductive stage, most of the genotypes were susceptible. Genotyping using a 50K Axiom® CicerSNP Array and trait data of FW together led to the identification of 26 significant (P ≤ E-05) marker-trait associations (MTAs) for FW resistance. Among the 26 MTAs, 12 were identified using trait data recorded in the field (three at the seedling and nine at the reproductive stage), and 14 were identified using trait data recorded under controlled conditions in the greenhouse (six at the seedling and eight at the reproductive stage). The phenotypic variation explained by these MTAs varied from 11.75 to 15.86%, with an average of 13.77%. Five MTAs were classified as major, explaining more than 15% of the phenotypic variation for FW, and two were declared stable, being identified in two environments. One of the promising stable and major MTAs (Affx_123280060) detected in field conditions at the reproductive stage was also detected in greenhouse conditions at the seedling and reproductive stages. The stable and major (>15% PVE) MTAs can be used in chickpea breeding programs.

Validation of Novel spot blotch disease resistance alleles identified in unexplored wheat (Triticum aestivum L.) germplasm lines through KASP markers.

BACKGROUND: During the last few decades, the diverse sources of resistance, several genes and QTLs for spot blotch resistance have been identified. However, a large set of germplasm lines are still unexplored that have the potential to develop highly resistant wheat cultivars for the target environments. Therefore, the identification of new sources of resistance to spot blotch is essential for breeding programmes to develop spot blotch resistant cultivars and sustain wheat production. The association mapping panel of 294 diverse bread wheat accessions was used to explore new sources of spot blotch disease resistance and to identify genomic regions using genome wide association analysis (GWAS). The genotypes were tested in replicated trials for spot blotch disease at three major hot spots in India (Varanasi in UP, Pusa in Bihar, and Cooch Behar in West Bengal). The area under the disease progress curve (AUDPC) was calculated to assess the level of resistance in each genotype. RESULTS: A total of 19 highly and 76 moderately resistant lines were identified. Three accessions (EC664204, IC534306 and IC535188) were nearly immune to spot blotch disease. The genotyping of all accessions resulted in a total of 16,787 high-quality polymorphic SNPs. The GWAS was performed using a Compressed Mixed Linear Model (CMLM) and a Mixed Linear Model (MLM). A total of seven significant MTAs, common in both the models and consistent across the environment, were further validated to develop KASP markers. Four MTAs (AX-94710084, AX-94865722, AX-95135556, and AX-94529408) on three chromosomes (2AL, 2BL, and 3BL) have been successfully validated through the KASP marker. CONCLUSIONS: The new source of resistance was identified from unexplored germplasm lines. The genomic regions identified through GWAS were validated through KASP markers. The marker information and the highly resistant sources are valuable resources to rapidly develop immune or near immune wheat varieties.

Identification of potential inhibitory analogs of metastasis tumor antigens (MTAs) using bioactive compounds: revealing therapeutic option to prevent malignancy.

The deeper understanding of metastasis phenomenon and detection of drug targets could be a potential approach to minimize cancer mortality. In this study, attempts were taken to unmask novel therapeutics to prevent metastasis and cancer progression. Initially, we explored the physiochemical, structural and functional insights of three metastasis tumor antigens (MTAs) and evaluated some plant-based bioactive compounds as potent MTA inhibitors. From 50 plant metabolites screened, isoflavone, gingerol, citronellal and asiatic acid showed maximum binding affinity with all three MTA proteins. The ADME analysis detected no undesirable toxicity that could reduce the drug likeness properties of top plant metabolites. Moreover, molecular dynamics studies revealed that the complexes were stable and showed minimum fluctuation at molecular level. We further performed ligand-based virtual screening to identify similar drug molecules using a large collection of 376,342 compounds from DrugBank. The results suggested that several structural analogs (e.g., tramadol, nabumetone, DGLA and hydrocortisone) may act as agonist to block the MTA proteins and inhibit cancer progression at early stage. The study could be useful to develop effective medications against cancer metastasis in future. Due to encouraging results, we highly recommend further in vitro and in vivo trials for the experimental validation of the findings.

The New Microtubule-Targeting Agent SIX2G Induces Immunogenic Cell Death in Multiple Myeloma.

Microtubule-targeting agents (MTAs) are effective drugs for cancer treatment. A novel diaryl [1,2]oxazole class of compounds binding the colchicine site was synthesized as cis-restricted-combretastatin-A-4-analogue and then chemically modified to have improved solubility and a wider therapeutic index as compared to vinca alkaloids and taxanes. On these bases, a new class of tricyclic compounds, containing the [1,2]oxazole ring and an isoindole moiety, has been synthetized, among which SIX2G emerged as improved MTA. Several findings highlighted the ability of some chemotherapeutics to induce immunogenic cell death (ICD), which is defined by the cell surface translocation of Calreticulin (CALR) via dissociation of the PP1/GADD34 complex. In this regard, we computationally predicted the ability of SIX2G to induce CALR exposure by interacting with the PP1 RVxF domain. We then assessed both the potential cytotoxic and immunogenic activity of SIX2G on in vitro models of multiple myeloma (MM), which is an incurable hematological malignancy characterized by an immunosuppressive milieu. We found that the treatment with SIX2G inhibited cell viability by inducing G2/M phase cell cycle arrest and apoptosis. Moreover, we observed the increase of hallmarks of ICD such as CALR exposure, ATP release and phospho-eIF2α protein level. Through co-culture experiments with immune cells, we demonstrated the increase of (i) CD86 maturation marker on dendritic cells, (ii) CD69 activation marker on cytotoxic T cells, and (iii) phagocytosis of tumor cells following treatment with SIX2G, confirming the onset of an immunogenic cascade. In conclusion, our findings provide a framework for further development of SIX2G as a new potential anti-MM agent.

Identification of genetic loci and candidate genes related to ß-glucan content in barley grain by genome-wide association study in International Barley Core Selected Collection.

ß-glucan is an important trait to be improved in barley breeding programs, as it greatly affects the quality of the end products when barley grains are used as raw material of feed or malt production or consumed as food for human. Although the genes associated with ß-glucan synthesis have been identified, genetic regulation of ß-glucan accumulation in barley grains is still completely unclear. In this study, 100 accessions from International Barley Core Selected Collection (BCS) were planted in two environments for two consecutive years to determine the genotypic variation of grain ß-glucan content. A genome-wide association study (GWAS) identified 14 stable marker-trait associations (MTAs) (-Log10(P)> 4) for grain ß-glucan content. Significantly positive correlation was found between grain ß-glucan content and the number of favorable alleles of 14 stable MTAs. Seven putative candidate genes encoding some enzymes in glucose metabolism were found to be associated with ß-glucan content. One of the putative genes, HORVU6Hr1G088380, could be an important gene controlling barely ß-glucan content, with the SNPs being closely linked in all tested accessions and divided into two haplotypes. High resolution melting (HRM) analysis of the first SNP suggested that the HRM-SNP marker is valid for marker-assisted selection in barley breeding. This study provides useful information for the genes and markers related to grain ß-glucan content in barley. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-020-01199-5.

The Role of Taste Receptor mTAS1R3 in Chemical Communication of Gametes.

Fertilization is a multiple step process leading to the fusion of female and male gametes and the formation of a zygote. Besides direct gamete membrane interaction via binding receptors localized on both oocyte and sperm surface, fertilization also involves gamete communication via chemical molecules triggering various signaling pathways. This work focuses on a mouse taste receptor, mTAS1R3, encoded by the Tas1r3 gene, as a potential receptor mediating chemical communication between gametes using the C57BL/6J lab mouse strain. In order to specify the role of mTAS1R3, we aimed to characterize its precise localization in testis and sperm using super resolution microscopy. The testis cryo-section, acrosome-intact sperm released from cauda epididymis and sperm which underwent the acrosome reaction (AR) were evaluated. The mTAS1R3 receptor was detected in late spermatids where the acrosome was being formed and in the acrosomal cap of acrosome intact sperm. AR is triggered in mice during sperm maturation in the female reproductive tract and by passing through the egg surroundings such as cumulus oophorus cells. This AR onset is independent of the extracellular matrix of the oocyte called zona pellucida. After AR, the relocation of mTAS1R3 to the equatorial segment was observed and the receptor remained exposed to the outer surroundings of the female reproductive tract, where its physiological ligand, the amino acid L-glutamate, naturally occurs. Therefore, we targeted the possible interaction in vitro between the mTAS1R3 and L-glutamate as a part of chemical communication between sperm and egg and used an anti-mTAS1R3-specific antibody to block it. We detected that the acrosome reacted spermatozoa showed a chemotactic response in the presence of L-glutamate during and after the AR, and it is likely that mTAS1R3 acted as its mediator.

Intrinsic and Extrinsic Factors Affecting Microtubule Dynamics in Normal and Cancer Cells.

Microtubules (MTs), highly dynamic structures composed of α- and ß-tubulin heterodimers, are involved in cell movement and intracellular traffic and are essential for cell division. Within the cell, MTs are not uniform as they can be composed of different tubulin isotypes that are post-translationally modified and interact with different microtubule-associated proteins (MAPs). These diverse intrinsic factors influence the dynamics of MTs. Extrinsic factors such as microtubule-targeting agents (MTAs) can also affect MT dynamics. MTAs can be divided into two main categories: microtubule-stabilizing agents (MSAs) and microtubule-destabilizing agents (MDAs). Thus, the MT skeleton is an important target for anticancer therapy. This review discusses factors that determine the microtubule dynamics in normal and cancer cells and describes microtubule-MTA interactions, highlighting the importance of tubulin isoform diversity and post-translational modifications in MTA responses and the consequences of such a phenomenon, including drug resistance development.

Genome-wide association study of agronomic traits in bread wheat reveals novel putative alleles for future breeding programs.

BACKGROUND: Identification of loci for agronomic traits and characterization of their genetic architecture are crucial in marker-assisted selection (MAS). Genome-wide association studies (GWAS) have increasingly been used as potent tools in identifying marker-trait associations (MTAs). The introduction of new adaptive alleles in the diverse genetic backgrounds may help to improve grain yield of old or newly developed varieties of wheat to balance supply and demand throughout the world. Landraces collected from different climate zones can be an invaluable resource for such adaptive alleles. RESULTS: GWAS was performed using a collection of 298 Iranian bread wheat varieties and landraces to explore the genetic basis of agronomic traits during 2016-2018 cropping seasons under normal (well-watered) and stressed (rain-fed) conditions. A high-quality genotyping by sequencing (GBS) dataset was obtained using either all original single nucleotide polymorphism (SNP, 10938 SNPs) or with additional imputation (46,862 SNPs) based on W7984 reference genome. The results confirm that the B genome carries the highest number of significant marker pairs in both varieties (49,880, 27.37%) and landraces (55,086, 28.99%). The strongest linkage disequilibrium (LD) between pairs of markers was observed on chromosome 2D (0.296). LD decay was lower in the D genome, compared to the A and B genomes. Association mapping under two tested environments yielded a total of 313 and 394 significant (-log10 P >3) MTAs for the original and imputed SNP data sets, respectively. Gene ontology results showed that 27 and 27.5% of MTAs of SNPs in the original set were located in protein-coding regions for well-watered and rain-fed conditions, respectively. While, for the imputed data set 22.6 and 16.6% of MTAs represented in protein-coding genes for the well-watered and rain-fed conditions, respectively. CONCLUSIONS: Our finding suggests that Iranian bread wheat landraces harbor valuable alleles that are adaptive under drought stress conditions. MTAs located within coding genes can be utilized in genome-based breeding of new wheat varieties. Although imputation of missing data increased the number of MTAs, the fraction of these MTAs located in coding genes were decreased across the different sub-genomes.

Association and genome analyses to propose putative candidate genes for malt quality traits.

BACKGROUND: We studied the genetics of nine malt quality traits using association genetics in a panel of North Dakota, ICARDA, and Ethiopian barley lines. Grain samples harvested from Bekoji in 2011 and 2012 were used. RESULTS: The mapping panel revealed strong population structure explained by inflorescence-type, geographic origin, and breeding history. North Dakota germplasm were superior in malt quality traits and they can be donors to improve malt quality properties. We identified 106 marker-trait associations (MTAs) for the nine traits, representing 81 genomic regions across all barley chromosomes. Chromosomes 3H, 5H, and 7H contained most of the MTAs (58.5%). Nearly 18.5% of these genomic regions contained two to three malt quality traits. Within ±250 kb of 81 genomic regions, we recovered 348 barley genes, with some potential impacting malt quality. These include invertase, ß-fructofuranosidase, α-glucosidase, serine carboxypeptidase, and bidirectional sugar transporter SWEET14-like protein. Eighteen of these genes were also previously reported in the Hordeum Toolbox, and 17 of them highly expressed during the germination process. CONCLUSION: The results from this study invite further follow-up functional characterization experiments to relate the genes with individual malt quality traits with higher confidence. It also provides germplasm resources for malt barley improvement. © 2018 Society of Chemical Industry.

Exploring the effect of end-binding proteins and microtubule targeting chemotherapy drugs on microtubule dynamic instability.

Microtubules (MTs) play a key role in normal cell development and are a primary target for many cancer chemotherapy MT targeting agents (MTAs). As such, understanding MT dynamics in the presence of such agents, as well as other proteins that alter MT dynamics, is extremely important. In general, MTs grow relatively slowly and shorten very fast (almost instantaneously), an event referred to as a catastrophe. These dynamics, referred to as dynamic instability, have been studied in both experimental and theoretical settings. In the presence of MTAs, it is well known that such agents work by suppressing MT dynamics, either by promoting MT polymerization or promoting MT depolymerization. However, recent in vitro experiments show that in the presence of end-binding proteins (EBs), low doses of MTAs can increase MT dynamic instability, rather than suppress it. Here, we develop a novel mathematical model, to describe MT and EB dynamics, something which has not been done in a theoretical setting. Our MT model is based on previous modeling efforts, and consists of a pair of partial differential equations to describe length distributions for growing and shortening MT populations, and an ordinary differential equation (ODE) system to describe the time evolution for concentrations of GTP- and GDP-bound tubulin. A new extension of our approach is the use of an integral term, rather than an advection term, to describe very fast MT shortening events. Further, we introduce an ODE system to describe the binding and unbinding of EBs with MTs. To compare simulation results with experiment, we define novel mathematical expressions for time- and distance-based catastrophe frequencies. These quantities help to define MT dynamics in in vivo and in vitro settings. Simulation results show that increasing concentrations of EBs work to increase time-based catastrophe while distance-based catastrophe is less affected by changes in EB concentration, a result that is consistent with experiment. We further describe how EBs and MTAs alter MT dynamics. In the context of this modeling framework, we show that it is likely that MTAs and EBs do not work independently from one another. Thus, we propose a mechanism for how EBs can work synergistically with MTAs to promote MT dynamic instability at low MTA dose.

Effects of Eribulin on the RNA Content of Extracellular Vesicles Released by Metastatic Breast Cancer Cells.

Extracellular vesicles (EVs) are small lipid particles secreted by almost all human cells into the extracellular space. They perform the essential function of cell-to-cell communication, and their role in promoting breast cancer progression has been well demonstrated. It is known that EVs released by triple-negative and highly aggressive MDA-MB-231 breast cancer cells treated with paclitaxel, a microtubule-targeting agent (MTA), promoted chemoresistance in EV-recipient cells. Here, we studied the RNA content of EVs produced by the same MDA-MB-231 breast cancer cells treated with another MTA, eribulin mesylate. In particular, we analyzed the expression of different RNA species, including mRNAs, lncRNAs, miRNAs, snoRNAs, piRNAs and tRNA fragments by RNA-seq. Then, we performed differential expression analysis, weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, and miRNA-target identification. Our findings demonstrate the possible involvement of EVs from eribulin-treated cells in the spread of chemoresistance, prompting the design of strategies that selectively target tumor EVs.

Genetic dissection of value-added quality traits and agronomic parameters through genome-wide association mapping in bread wheat (T. aestivum L.).

Bread wheat (T. aestivum) is one of the world's most widely consumed cereals. Since micronutrient deficiencies are becoming more common among people who primarily depend upon cereal-based diets, a need for better-quality wheat varieties has been felt. An association panel of 154 T. aestivum lines was evaluated for the following quality traits: grain appearance (GA) score, grain hardness (GH), phenol reaction (PR) score, protein percent, sodium dodecyl sulfate (SDS) sedimentation value, and test weight (TWt). In addition, the panel was also phenotyped for grain yield and related traits such as days to heading, days to maturity, plant height, and thousand kernel weight for the year 2017-18 at the Borlaug Institute for South Asia (BISA) Ludhiana and Jabalpur sites. We performed a genome-wide association analysis on this panel using 18,351 genotyping-by-sequencing (GBS) markers to find marker-trait associations for quality and grain yield-related traits. We detected 55 single nucleotide polymorphism (SNP) marker trait associations (MTAs) for quality-related traits on chromosomes 7B (10), 1A (9), 2A (8), 3B (6), 2B (5), 7A (4), and 1B (3), with 3A, 4A, and 6D, having two and the rest, 4B, 5A, 5B, and 1D, having one each. Additionally, 20 SNP MTAs were detected for yield-related traits based on a field experiment conducted in Ludhiana on 7D (4) and 4D (3) chromosomes, while 44 SNP MTAs were reported for Jabalpur on chromosomes 2D (6), 7A (5), 2A (4), and 4A (4). Utilizing these loci in marker-assisted selection will benefit from further validation studies for these loci to improve hexaploid wheat for better yield and grain quality.

mTOR inhibitor introduce disitamab vedotin (RC48-ADC) rechallenge microtubule-chemotherapy resistance in HER2-low MBC patients with PI3K mutation.

This study aimed to explore the efficacy and potential mechanisms of rechallenge therapy with microtubule-targeting agents (MTAs) in patients with HER2-low metastatic breast cancer (MBC). We performed a systematic review to investigate the rechallenge treatment concept in the field of HER2-low MBC treatment and utilized a series of cases identified in the literature to illustrate the concept. Here we reported two clinical cases of HER2-low MBC patients whose disease progressed after prior treatment with MTAs such as docetaxel and vincristine. When rechallenged with disitamab vedotin ((RC48-antibody-drug conjugate (ADC), a monomethyl auristatin (MMAE) MTA)), both patients achieved a partial response and the final progression-free survival (PFS) was 13.5 and 9 months, respectively. Genomic profiling detected a PIK3CA H1047R mutation in the patients. The patients were treated with everolimus before being rechallenged with RC48, which may lead to a better response. This study further summarizes and analyzes the potential mechanism of the PI3K-AKT signaling pathway in MTA resistance and reveals that the PIK3CA H1047R mutation may be a potential molecular marker for the efficacy prediction of mTOR inhibitors, providing new insights and potential therapeutic strategies for the application of MTAs to MBC patients.

Genetic and molecular analysis of stem rot (Sclerotinia sclerotiorum) resistance in Brassica napus (canola type).

Identifying the molecular and genetic basis of resistance to Sclerotinia stem rot (Sclerotinia sclerotiorum) is critical for developing long-term and cost-effective management of this disease in rapeseed/canola (Brassica napus). Current cultural or chemical management options provide, at best, only partial and/or sporadic control. Towards this, a B. napus breeding population (Mystic x Rainbow), including the parents, F1, F2, BC1P1 and BC1P2, was utilized in a field study to determine the inheritance pattern of Sclerotinia stem rot resistance (based on stem lesion length, SLL). Broad sense heritability was 0.58 for SLL and 0.44 for days to flowering (DTF). There was a significant negative correlation between SLL and stem diameter (SD) (r = -0.39) and between SLL and DTF (r = -0.28), suggesting co-selection of SD and DTF traits, along with SLL, should assist in improving overall resistance. Non-additive genetic variance was evident for SLL, DTF, and SD. In a genome wide association study (GWAS), a significant quantitative trait locus (QTL) was identified for SLL. Several putative candidate marker trait associations (MTA) were located within this QTL region. Overall, this study has provided valuable new understanding of inheritance of resistance to S. sclerotiorum, and has identified QTL, MTAs and transgressive segregants with high-level resistances. Together, these will foster more rapid selection for multiple traits associated with Sclerotinia stem rot resistance, by enabling breeders to make critical choices towards selecting/developing cultivars with enhanced resistance to this devastating pathogen.

Genome-Wide Association Study Reveals Novel Powdery Mildew Resistance Loci in Bread Wheat.

Powdery mildew (PM), caused by the fungal pathogen Blumeria graminis f. sp. tritici (Bgt), significantly threatens global bread wheat production. Although the use of resistant cultivars is an effective strategy for managing PM, currently available wheat cultivars lack sufficient levels of resistance. To tackle this challenge, we conducted a comprehensive genome-wide association study (GWAS) using a diverse panel of 286 bread wheat genotypes. Over three consecutive years (2020-2021, 2021-2022, and 2022-2023), these genotypes were extensively evaluated for PM severity under field conditions following inoculation with virulent Bgt isolates. The panel was previously genotyped using the Illumina 90K Infinium iSelect assay to obtain genome-wide single-nucleotide polymorphism (SNP) marker coverage. By applying FarmCPU, a multilocus mixed model, we identified a total of 113 marker-trait associations (MTAs) located on chromosomes 1A, 1B, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 6B, 7A, and 7B at a significance level of p ≤ 0.001. Notably, four novel MTAs on chromosome 6B were consistently detected in 2020-2021 and 2021-2022. Furthermore, within the confidence intervals of the identified SNPs, we identified 96 candidate genes belonging to different proteins including 12 disease resistance/host-pathogen interaction-related protein families. Among these, protein kinases, leucine-rich repeats, and zinc finger proteins were of particular interest due to their potential roles in PM resistance. These identified loci can serve as targets for breeding programs aimed at developing disease-resistant wheat cultivars.

Genome-wide association studies for a comprehensive understanding of the genetic architecture of culm strength and yield traits in rice.

Lodging resistance in rice is a complex trait determined by culm morphological and culm physical strength traits, and these traits are a major determinant of yield. We made a detailed analysis of various component traits with the aim of deriving optimized parameters for measuring culm strength. Genotyping by sequencing (GBS)-based genome-wide association study (GWAS) was employed among 181 genotypes for dissecting the genetic control of culm strength traits. The VanRaden kinship algorithm using 6,822 filtered single-nucleotide polymorphisms (SNPs) revealed the presence of two sub-groups within the association panel with kinship values concentrated at<0.5 level, indicating greater diversity among the genotypes. A wide range of phenotypic variation and high heritability for culm strength and yield traits were observed over two seasons, as reflected in best linear unbiased prediction (BLUP) estimates. The multi-locus model for GWAS resulted in the identification of 15 highly significant associations (p< 0.0001) for culm strength traits. Two novel major effect marker-trait associations (MTAs) for section modulus and bending stress were identified on chromosomes 2 and 12 with a phenotypic variance of 21.87% and 10.14%, respectively. Other MTAs were also noted in the vicinity of previously reported putative candidate genes for lodging resistance, providing an opportunity for further research on the biochemical basis of culm strength. The quantitative trait locus (QTL) hotspot identified on chromosome 12 with the synergistic association for culm strength trait (section modulus, bending stress, and internode breaking weight) and grain number can be considered a novel genomic region that can serve a dual purpose of enhancing culm strength and grain yield. Elite donors in the indica background with beneficial alleles of the identified major QTLs could be a valuable resource with greater significance in practical plant breeding programs focusing on improving lodging resistance in rice.

Recent Advances in Combretastatin A-4 Inspired Inhibitors of Tubulin Polymerization: An Update.

Cancer is one of the leading causes of fatality and mortality worldwide. Investigations on developing therapeutic strategies for cancer are supported throughout the world. The massive achievements in molecular sciences involving biochemistry, molecular chemistry, medicine, and pharmacy, and high throughput techniques such as genomics and proteomics have helped create new potential drug targets for cancer treatment. Microtubules are very attractive targets for cancer therapy because of the crucial roles they play in cell division. In recent years, lots of efforts have been put into the identification of new microtubule-targeting agents (MTAs) in anticancer therapy. Combretastatin A-4 (CA-4) is a natural compound that binds to microtubules' colchicine binding site and inhibits microtubule polymerization. Due to CA-4's structural simplicity, many analogs have been synthesized. This article summarises the new molecule development efforts to reach CA-4 analogues by pharmacophore group modifications, which have been reported since 2015.

Genome-Wide Association Study Reveals Marker-Trait Associations for Early Vegetative Stage Salinity Tolerance in Rice.

Rice germplasm is a rich resource for discovering genes associated with salt tolerance. In the current study, a set of 96 accessions were evaluated for seedling stage salinity tolerance and its component traits. Significant phenotypic variation was observed among the genotypes for all the measured traits and eleven accessions with high level of salt tolerance at seedling stage were identified. The germplasm set comprised of three sub-populations and genome-wide association study (GWAS) identified a total of 23 marker-trait associations (MTAs) for traits studied. These MTAs were located on rice chromosomes 1, 2, 5, 6, 7, 9, and 12 and explained the trait phenotypic variances ranging from 13.98 to 29.88 %. Twenty-one MTAs identified in this study were located either in or near the previously reported quantitative trait loci (QTLs), while two MTAs namely, qSDW2.1 and qSNC5 were novel. A total of 18 and 13 putative annotated candidate genes were identified in a genomic region spanning ~200 kb around the MTAs qSDW2.1 and qSNC5, respectively. Some of the important genes underlying the novel MTAs were OsFBA1,OsFBL7, and mTERF which are known to be associated with salinity tolerance in crops. These MTAs pave way for combining salinity tolerance with high yield in rice genotypes through molecular breeding.