Post liver transplant short term and survival outcomes in patients living with obesity.

The objectives of our study were to examine and compare patient and graft survival over a 5-year period across BMI groups, and examine immediate and short-term complications post-LT. This was a retrospective study that examined all liver transplants that occurred at our institution between January 2015-October 2022. Patients were divided into 4 BMI groups (n = 888): normal-overweight (BMI 18.5- 29.9 kg/m2), class I obesity (BMI 30-34.9 kg/m2), class II obesity (BMI 35-39.9 kg/m2), and class III obesity (BMI ≥40 kg/m2) patients. Kaplan Meier curves with the log rank test were created to assess survival outcomes and multivariate Cox regression analysis was performed. Patient and graft survival did not differ statistically between each BMI group. However, patient survival was significantly lower in patients with BMI ≥40 compared to patients with BMI <40. In multivariate analysis, BMI ≥40, admission to the ICU, and age were independent predictors of increased risk of mortality. Infection, arrhythmia, cardiac arrest, and myocardial infarction were more frequent immediate complications in the class III obesity group. Efforts to closely monitor patients with BMI ≥40 post LT to maximize survival are needed. Further studies are needed to improve post LT survival among patients with BMI ≥40.

Comparison of the genetic basis of salt tolerance at germination, seedling, and reproductive stages in an introgression line population of rice.

BACKGROUND: Salinity is a major limitation for rice farming due to climate change. Since salt stress adversely impact rice plants at germination, seedling, and reproductive stages resulting in poor crop establishment and reduced grain yield, enhancing salt tolerance at these vulnerable growth stages will enhance rice productivity in salinity prone areas. METHODS AND RESULTS: An introgression line (ILs) population from a cross between a high yielding cultivar 'Cheniere' and a salt tolerant donor 'TCCP' was evaluated to map quantitative trait loci (QTLs) for traits associated with salt tolerance at germination, seedling, and reproductive stages. Using a genotyping-by-sequencing based high density SNP linkage map, a total of 7, 16, and 30 QTLs were identified for five germination traits, seven seedling traits, and ten reproductive traits, respectively. There was overlapping of QTLs for some traits at different stages indicating the pleiotropic effects of these QTLs or clustering of linked genes. Candidate genes identified for salt tolerance were OsSDIR1 and SERF for the seedling stage, WRKY55 and OsUBC for the reproductive stage, and MYB family transcription factors for all three stages. Gene ontology analysis revealed significant GO terms related to nucleotide binding, protein binding, protein kinase activity, antiporter activity, active transmembrane transporter activity, calcium-binding protein, and F- box protein interaction domain containing protein. CONCLUSIONS: The colocalized QTLs for traits at different growth stages would be helpful to improve multiple traits simultaneously using marker-assisted selection. The salt tolerant ILs have the potential to be released as varieties or as pre-breeding lines for developing salt tolerant rice varieties.

The association of tibial vs. humeral intraosseous vascular access with patient outcomes in adult out-of-hospital cardiac arrests.

AIM: Humeral and tibial intraosseous (IO) vascular access can deliver resuscitative medications for out-of-hospital cardiac arrest (OHCA), however the optimal site is unclear. We examined the association between IO tibia vs. humerus as the first-attempted vascular access site with OHCA outcomes. METHODS: We used prospectively-collected data from the British Columbia Cardiac Arrest registry, including adult OHCAs treated with IO humerus or IO tibia as the first-attempted intra-arrest vascular access. We fit logistic regression models on the full study cohort and a propensity-matched cohort, to estimate the association between IO site and both favorable neurological outcomes (Cerebral Performance Category 1-2) and survival at hospital discharge. RESULTS: We included 1041 (43%) and 1404 (57%) OHCAs for whom IO humerus and tibia, respectively, were the first-attempted intra-arrest vascular access. Among humerus and tibia cases, 1010 (97%) and 1369 (98%) had first-attempt success, and the median paramedic arrival-to-successful access interval was 6.7 minutes (IQR 4.4-9.4) and 6.1 minutes (IQR 4.1-8.9), respectively. In the propensity-matched cohort (n = 2052), 31 (3.0%) and 44 (4.3%) cases had favourable neurological outcomes in the IO humerus and IO tibia groups, respectively; compared to IO humerus, we did not detect an association between IO tibia with favorable neurological outcomes (OR 1.44; 95% CI 0.90-2.29) or survival to hospital discharge (OR 1.29; 95% CI 0.83-2.01). Results using the full cohort were similar. CONCLUSIONS: We did not detect an association between the first-attempted intra-arrest IO site (tibia vs. humerus) and clinical outcomes. Clinical trials are warranted to test differences between vascular access strategies.

Einkorn genomics sheds light on history of the oldest domesticated wheat.

Einkorn (Triticum monococcum) was the first domesticated wheat species, and was central to the birth of agriculture and the Neolithic Revolution in the Fertile Crescent around 10,000 years ago1,2. Here we generate and analyse 5.2-Gb genome assemblies for wild and domesticated einkorn, including completely assembled centromeres. Einkorn centromeres are highly dynamic, showing evidence of ancient and recent centromere shifts caused by structural rearrangements. Whole-genome sequencing analysis of a diversity panel uncovered the population structure and evolutionary history of einkorn, revealing complex patterns of hybridizations and introgressions after the dispersal of domesticated einkorn from the Fertile Crescent. We also show that around 1% of the modern bread wheat (Triticum aestivum) A subgenome originates from einkorn. These resources and findings highlight the history of einkorn evolution and provide a basis to accelerate the genomics-assisted improvement of einkorn and bread wheat.

Genome-Wide Association Study Identified Candidate Genes for Alkalinity Tolerance in Rice.

Alkalinity stress is a major hindrance to enhancing rice production globally due to its damaging effect on plants' growth and development compared with salinity stress. However, understanding of the physiological and molecular mechanisms of alkalinity tolerance is limited. Therefore, a panel of indica and japonica rice genotypes was evaluated for alkalinity tolerance at the seedling stage in a genome-wide association study to identify tolerant genotypes and candidate genes. Principal component analysis revealed that traits such as alkalinity tolerance score, shoot dry weight, and shoot fresh weight had the highest contribution to variations in tolerance, while shoot Na+ concentration, shoot Na+:K+ ratio, and root-to-shoot ratio had moderate contributions. Phenotypic clustering and population structure analysis grouped the genotypes into five subgroups. Several salt-susceptible genotypes such as IR29, Cocodrie, and Cheniere placed in the highly tolerant cluster suggesting different underlying tolerance mechanisms for salinity and alkalinity tolerance. Twenty-nine significant SNPs associated with alkalinity tolerance were identified. In addition to three alkalinity tolerance QTLs, qSNK4, qSNC9, and qSKC10, which co-localized with the earlier reported QTLs, a novel QTL, qSNC7, was identified. Six candidate genes that were differentially expressed between tolerant and susceptible genotypes were selected: LOC_Os04g50090 (Helix-loop-helix DNA-binding protein), LOC_Os08g23440 (amino acid permease family protein), LOC_Os09g32972 (MYB protein), LOC_Os08g25480 (Cytochrome P450), LOC_Os08g25390 (Bifunctional homoserine dehydrogenase), and LOC_Os09g38340 (C2H2 zinc finger protein). The genomic and genetic resources such as tolerant genotypes and candidate genes would be valuable for investigating the alkalinity tolerance mechanisms and for marker-assisted pyramiding of the favorable alleles for improving alkalinity tolerance at the seedling stage in rice.

The Fusarium graminearum Transporters Abc1 and Abc6 Are Important for Xenobiotic Resistance, Trichothecene Accumulation, and Virulence to Wheat.

The plant pathogenic fungus Fusarium graminearum is the causal agent of Fusarium head blight (FHB) disease on small-grain cereals. F. graminearum produces trichothecene mycotoxins such as deoxynivalenol (DON) that are required for full virulence. DON must be exported outside the cell to cause FHB disease, a process that may require the involvement of membrane-bound transporters. In this study, we show that the deletion of membrane-bound transporters results in reduced DON accumulation as well as reduced FHB symptoms on wheat. Deletion of the ATP-binding cassette (ABC) transporter gene Abc1 results in the greatest reduction in DON accumulation and virulence. Deletion of another ABC transporter gene, Abc6, also reduces FHB symptoms to a lesser degree. Combining deletions fails to reduce DON accumulation or virulence in an additive fashion, even when a ∆abc1 deletion is included. Heterologous expression of F. graminearum transporters in a DON-sensitive strain of yeast confirms Abc1 as a major DON resistance mechanism; furthermore, it suggests that Abc1 is directly participating in DON transport rather than facilitating DON transport though other means. Yeast expression further indicates that multiple transporters, including Abc1, play an important role in resistance to the wheat phytoalexin 2-benzoxazolinone (BOA) and other xenobiotics. Thus, Abc1 may contribute to virulence on wheat both by facilitating export of DON and by providing resistance to the wheat phytoalexin BOA. This research provides useful information that may aid in designing novel management techniques of FHB or other destructive plant diseases.

Genetic diversity and population structure of bermudagrass (Cynodon spp.) revealed by genotyping-by-sequencing.

Bermudagrass (Cynodon spp.) breeding and cultivar development is hampered by limited information regarding its genetic and phenotypic diversity. To explore diversity in bermudagrass, a total of 206 Cynodon accessions consisting of 193 common bermudagrass (C. dactylon var. dactylon) and 13 African bermudagrass (C. transvaalensis) accessions of worldwide origin were assembled for genetic characterization. Genotyping-by-sequencing (GBS) was employed for genetic marker development. With a minor allele frequency of 0.05 and a minimum call rate of 0.5, a total of 37,496 raw single nucleotide polymorphisms (SNPs) were called de novo and were used in the genetic diversity characterization. Population structure analysis using ADMIXTURE revealed four subpopulations in this germplasm panel, which was consistent with principal component analysis (PCA) and phylogenetic analysis results. The first three principal components explained 15.6%, 10.1%, and 3.8% of the variance in the germplasm panel, respectively. The first subpopulation consisted of C. dactylon accessions from various continents; the second subpopulation was comprised mainly of C. transvaalensis accessions; the third subpopulation contained C. dactylon accessions primarily of African origin; and the fourth subpopulation represented C. dactylon accessions obtained from the Oklahoma State University bermudagrass breeding program. Genetic diversity parameters including Nei's genetic distance, inbreeding coefficient, and Fst statistic revealed substantial genetic variation in the Cynodon accessions, demonstrating the potential of this germplasm panel for further genetic studies and cultivar development in breeding programs.

Wheat Pore-Forming Toxin-Like Protein Confers Broad-Spectrum Resistance to Fungal Pathogens in Arabidopsis.

Fusarium head blight (FHB), caused by the hemibiotrophic fungus Fusarium graminearum, is one of the major threats to global wheat productivity. A wheat pore-forming toxin-like (PFT) protein was previously reported to underlie Fhb1, the most widely used quantitative trait locus in FHB breeding programs worldwide. In the present work, wheat PFT was ectopically expressed in the model dicot plant Arabidopsis. Heterologous expression of wheat PFT in Arabidopsis provided a broad-spectrum quantitative resistance to fungal pathogens including F. graminearum, Colletotrichum higginsianum, Sclerotinia sclerotiorum, and Botrytis cinerea. However, there was no resistance to bacterial or oomycete pathogens Pseudomonas syringae and Phytophthora capsici, respectively in the transgenic Arabidopsis plants. To explore the reason for the resistance response to, exclusively, the fungal pathogens, purified PFT protein was hybridized to a glycan microarray having 300 different types of carbohydrate monomers and oligomers. It was found that PFT specifically hybridized with chitin monomer, N-acetyl glucosamine (GlcNAc), which is present in fungal cell walls but not in bacteria or oomycete species. This exclusive recognition of chitin may be responsible for the specificity of PFT-mediated resistance to fungal pathogens. Transfer of the atypical quantitative resistance of wheat PFT to a dicot system highlights its potential utility in designing broad-spectrum resistance in diverse host plants. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Characterization of Leaf Rust Resistance in International Barley Germplasm Using Genome-Wide Association Studies.

A panel of 114 genetically diverse barley lines were assessed in the greenhouse and field for resistance to the pathogen Puccinia hordei, the causal agent of barley leaf rust. Multi-pathotype tests revealed that 16.6% of the lines carried the all-stage resistance (ASR) gene Rph3, followed by Rph2 (4.4%), Rph1 (1.7%), Rph12 (1.7%) or Rph19 (1.7%). Five lines (4.4%) were postulated to carry the gene combinations Rph2+9.am, Rph2+19 and Rph8+19. Three lines (2.6%) were postulated to carry Rph15 based on seedling rust tests and genotyping with a marker linked closely to this gene. Based on greenhouse seedling tests and adult-plant field tests, 84 genotypes (73.7%) were identified as carrying APR, and genotyping with molecular markers linked closely to three known APR genes (Rph20, Rph23 and Rph24) revealed that 48 of the 84 genotypes (57.1%) likely carry novel (uncharacterized) sources of APR. Seven lines were found to carry known APR gene combinations (Rph20+Rph23, Rph23+Rph24 and Rph20+Rph24), and these lines had higher levels of field resistance compared to those carrying each of these three APR genes singly. GWAS identified 12 putative QTLs; strongly associated markers located on chromosomes 1H, 2H, 3H, 5H and 7H. Of these, the QTL on chromosome 7H had the largest effect on resistance response to P. hordei. Overall, these studies detected several potentially novel genomic regions associated with resistance. The findings provide useful information for breeders to support the utilization of these sources of resistance to diversify resistance to leaf rust in barley and increase resistance durability.

Genetic Dissection of Alkalinity Tolerance at the Seedling Stage in Rice (Oryza sativa) Using a High-Resolution Linkage Map.

Although both salinity and alkalinity result from accumulation of soluble salts in soil, high pH and ionic imbalance make alkaline stress more harmful to plants. This study aimed to provide molecular insights into the alkalinity tolerance using a recombinant inbred line (RIL) population developed from a cross between Cocodrie and Dular with contrasting response to alkalinity stress. Forty-six additive QTLs for nine morpho-physiological traits were mapped on to a linkage map of 4679 SNPs under alkalinity stress at the seedling stage and seven major-effect QTLs were for alkalinity tolerance scoring, Na+ and K+ concentrations and Na+:K+ ratio. The candidate genes were identified based on the comparison of the impacts of variants of genes present in five QTL intervals using the whole genome sequences of both parents. Differential expression of no apical meristem protein, cysteine protease precursor, retrotransposon protein, OsWAK28, MYB transcription factor, protein kinase, ubiquitin-carboxyl protein, and NAD binding protein genes in parents indicated their role in response to alkali stress. Our study suggests that the genetic basis of tolerance to alkalinity stress is most likely different from that of salinity stress. Introgression and validation of the QTLs and genes can be useful for improving alkalinity tolerance in rice at the seedling stage and advancing understanding of the molecular genetic basis of alkalinity stress adaptation.

Integration of QTL Mapping and Whole Genome Sequencing Identifies Candidate Genes for Alkalinity Tolerance in Rice (Oryza sativa).

Soil alkalinity is an important stressor that impairs crop growth and development, resulting in reduced crop productivity. Unlike salinity stress, research efforts to understand the mechanism of plant adaptation to alkaline stress is limited in rice, a major staple food for the world population. We evaluated a population of 193 recombinant inbred lines (RIL) developed from a cross between Cocodrie and N22 under alkaline stress at the seedling stage. Using a linkage map consisting of 4849 SNP markers, 42 additive QTLs were identified. There were seven genomic regions where two or more QTLs for multiple traits colocalized. Three important QTL clusters were targeted, and several candidate genes were identified based on high impact variants using whole genome sequences (WGS) of both parents and differential expression in response to alkalinity stress. These genes included two expressed protein genes, the glucan endo-1,3-beta-glucosidase precursor, F-box domain-containing proteins, double-stranded RNA-binding motif-containing protein, aquaporin protein, receptor kinase-like protein, semialdehyde hydrogenase, and NAD-binding domain-containing protein genes. Tolerance to alkaline stress in Cocodrie was most likely due to the low Na+/K+ ratio resulting from reduced accumulation of Na+ ions and higher accumulation of K+ in roots and shoots. Our study demonstrated the utility of integrating QTL mapping with WGS to identify the candidate genes in the QTL regions. The QTLs and candidate genes originating from the tolerant parent Cocodrie should be targeted for introgression to improve alkalinity tolerance in rice and to elucidate the molecular basis of alkali tolerance.

Determination of Alteration in Micromeritic Properties of a Solid Dispersion: Brunauer-Emmett-Teller Based Adsorption and Other Structured Approaches.

The present study is focused on the use of solid dispersion technology to triumph over the solubility-related problems of bexarotene which is currently used for treating various types of cancer and has shown potential inhibitory action on COVID-19 main protease and human ACE2 receptors. It is based on comparison of green locust bean gum and synthetic poloxamer as polymers using extensive mechanistic methods to explore the mechanism behind solubility enhancement and to find suitable concentration of drug to polymer ratio to prepare porous 3rd generation solid dispersion. The prepared solid dispersions were characterized using different studies like X-ray diffraction (XRD), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET), differential scanning calorimetry (DSC), and particle size analysis in order to determine the exact changes occurred in the product which are responsible for enhancing solubility profiles of an insoluble drug. The results showed different profiles for particle size, solubility, dissolution rate, porosity, BET, and Langmuir specific surface area of prepared solid dispersions by using different polymers. In addition to the comparison of polymers, the BET analysis deeply explored the changes occurred in all dispersions when the concentration of polymer was increased. The optimized solid dispersion prepared with MLBG using lyophilization technique showed reduced particle size of 745.7±4.4 nm, utmost solubility of 63.97%, pore size of 211.597 Å, BET and Langmuir specific surface area of 5.6413 m2/g and 8.2757 m2/g, respectively.

Cloning of the broadly effective wheat leaf rust resistance gene Lr42 transferred from Aegilops tauschii.

The wheat wild relative Aegilops tauschii was previously used to transfer the Lr42 leaf rust resistance gene into bread wheat. Lr42 confers resistance at both seedling and adult stages, and it is broadly effective against all leaf rust races tested to date. Lr42 has been used extensively in the CIMMYT international wheat breeding program with resulting cultivars deployed in several countries. Here, using a bulked segregant RNA-Seq (BSR-Seq) mapping strategy, we identify three candidate genes for Lr42. Overexpression of a nucleotide-binding site leucine-rich repeat (NLR) gene AET1Gv20040300 induces strong resistance to leaf rust in wheat and a mutation of the gene disrupted the resistance. The Lr42 resistance allele is rare in Ae. tauschii and likely arose from ectopic recombination. Cloning of Lr42 provides diagnostic markers and over 1000 CIMMYT wheat lines carrying Lr42 have been developed documenting its widespread use and impact in crop improvement.

Current understanding of atypical resistance against fungal pathogens in wheat.

Pathogens and pests are a major challenge to global food security. Around one hundred different pests and pathogens challenge wheat, one of the most important food crops in the world. Traditional worldwide use of a few key resistance genes in wheat cultivars has necessitated a diversification of the toolbox of resistance genes in wheat varieties over the coming decades to meet the global production demands. Recent advances in gene discovery and functional characterization of genetic resistance mechanisms in wheat reveal great diversity in the types and effectiveness of the underlying resistance genes. This article summarizes the recent developments in the discovery of non-traditional "atypical" resistance genes in wheat against diverse fungal pathogens.

Validation of DNA marker-assisted selection for forage biomass productivity under deficit irrigation in alfalfa.

Drought and limited irrigation resources threaten agricultural sustainability in many regions of the world. Application of genomic-based breeding strategies may benefit crop variety development for these environments. Here, we provide a first report on the effect of deploying DNA marker-assisted selection (MAS) for the drought resilience quantitative trait in alfalfa (Medicago sativa L.). The goals of this study were to validate the effect of several quantitative trait loci (QTL) associated with alfalfa forage and crown-root (CR) biomass during drought and to determine their potential to improve forage yield of elite germplasm under water-limited conditions. Marker assisted selection was employed to introgress favorable or unfavorable DNA marker alleles affiliated with 10 biomass QTL into three elite backgrounds. Thirty-two populations were developed and evaluated for forage productivity over 3 yr under continuous deficit irrigation management in New Mexico, USA. Significant yield differences (ranging from -13 to 26%) were detected among some MAS-derived populations in all three elite backgrounds. Application of QTL MAS generally resulted in expected phenotypic responses within an elite genetic background that was similar to that in which the QTL were originally identified. However, relative performance of the populations varied substantially across the three genetic backgrounds. These outcomes indicate that QTL MAS can significantly affect forage productivity of elite alfalfa germplasm in drought-stressed environments. However, if biomass QTL are detected in donor germplasm that is genetically dissimilar to targeted elite populations, characterization of donor alleles may be warranted within elite backgrounds of interest to confirm their phenotypic effects prior to implementing MAS-based breeding.

Synthesis and antiplasmodial activity of regioisomers and epimers of second-generation dual acting ivermectin hybrids.

With its strong effect on vector-borne diseases, and insecticidal effect on mosquito vectors of malaria, inhibition of sporogonic and blood-stage development of Plasmodium falciparum, as well as in vitro and in vivo impairment of the P. berghei development inside hepatocytes, ivermectin (IVM) continues to represent an antimalarial therapeutic worthy of investigation. The in vitro activity of the first-generation IVM hybrids synthesized by appending the IVM macrolide with heterocyclic and organometallic antimalarial pharmacophores, against the blood-stage and liver-stage infections by Plasmodium parasites prompted us to design second-generation molecular hybrids of IVM. Here, a structural modification of IVM to produce novel molecular hybrids by using sub-structures of 4- and 8-aminoquinolines, the time-tested antiplasmodial agents used for treating the blood and hepatic stage of Plasmodium infections, respectively, is presented. Successful isolation of regioisomers and epimers has been demonstrated, and the evaluation of their in vitro antiplasmodial activity against both the blood stages of P. falciparum and the hepatic stages of P. berghei have been undertaken. These compounds displayed structure-dependent antiplasmodial activity, in the nM range, which was more potent than that of IVM, its aglycon or primaquine, highlighting the superiority of this hybridization strategy in designing new antiplasmodial agents.

Multipotentiality of Luliconazole against Various Fungal Strains: Novel Topical Formulations and Patent Review.

Luliconazole is a broad-spectrum antifungal agent with impactful fungicidal and fungistatic activity. It has shown exceptional potency against miscellaneous fungal strains like Candida, Aspergillus, Malassezia, Fusarium species and various dermatophytes. Luliconazole belongs to class II of the Biopharmaceutical Classification System with low aqueous solubility. Although it is available conventionally as 1% w/v topical cream, it has limitations of lower skin permeation and shorter skin retention. Therefore, nanoformulations based on various polymers and nanostructure carriers can be employed to overcome the impediments regarding topical delivery and efficacy of luliconazole. In this review, we have tried to provide insight into the literature gathered from authentic web resources and research articles regarding recent research conducted on the subject of formulation development, patents, and future research requisites of luliconazole. Nanoformulations can play a fundamental role in improving topical delivery by escalating dermal localization and skin penetration. Fabricating luliconazole into nanoformulations can overcome the drawbacks and can efficiently enhance its antimycotic activity. It has been concluded that luliconazole has exceptional potential in the treatment of various fungal infections, and therefore, it should be exploited to its maximum for its innovative application in the field of mycology.

Ivermectin: A Promising Therapeutic for Fighting Malaria. Current Status and Perspective.

Finding new chemotherapeutic interventions to treat malaria through repurposing of time-tested drugs and rigorous design of new drugs using tools of rational drug design remains one of the most sought strategies at the disposal of medicinal chemists. Ivermectin, a semisynthetic derivative of avermectin B1, is among the efficacious drugs used in mass drug administration drives employed against onchocerciasis, lymphatic filariasis, and several other parasitic diseases in humans. In this review, we present the prowess of ivermectin, a potent endectocide, in the control of malaria through vector control to reduce parasite transmission combined with efficacious chemoprevention to reduce malaria-related fatalities.

Screening of an Ethyl Methane Sulfonate Mutagenized Population of a Wheat Cultivar Susceptible to Fusarium Head Blight Identifies Resistant Variants.

Fusarium head blight (FHB) primarily caused by Fusarium graminearum is a key disease of small grains. Diseased spikes show symptoms of premature bleaching shortly after infection and have aborted or shriveled seeds, resulting in reduced yields. The fungus also deteriorates quality and safety of the grain because of production of mycotoxins, especially deoxynivalenol (DON), which can result in grain being docked or rejected at the point of sale. Genetic host resistance to FHB is quantitative, and no complete genetic resistance against this devastating disease is available. Alternative approaches to develop new sources of FHB resistance are needed. In this study, we performed extensive forward genetic screening of the M4 generation of an ethyl methane sulfonate-induced mutagenized population of cultivar Jagger to isolate variants with FHB resistance. In field testing, 74 mutant lines were found to have resistance against FHB spread, and 30 of these lines also had low DON content. Subsequent testing over 2 years in controlled greenhouse conditions revealed 10 M6 lines showing significantly lower FHB spread. Seven and 6 of those 10 lines also had reduced DON content and fewer Fusarium-damaged kernels, respectively. Future endeavors will include identification of the mutations that led to resistance in these variants.

Molecular Design and Synthesis of Ivermectin Hybrids Targeting Hepatic and Erythrocytic Stages of Plasmodium Parasites.

Ivermectin is a powerful endectocide, which reduces the incidence of vector-borne diseases. Besides its strong insecticidal effect on mosquito vectors of the disease, ivermectin inhibits Plasmodium falciparum sporogonic and blood stage development and impairs Plasmodium berghei development inside hepatocytes, both in vitro and in vivo. Herein, we present the first report on structural modification of ivermectin to produce dual-action molecular hybrids with good structure-dependent in vitro activity against both the hepatic and erythrocytic stages of P. berghei and P. falciparum infection, suggesting inclusion of ivermectin antimalarial hybrids in malaria control strategies. The most active hybrid displayed over threefold and 10-fold higher in vitro activity than ivermectin against hepatic and blood stage infections, respectively. Although an overwhelming insecticidal effect against Anopheles stephensi mosquitoes in laboratory conditions was not noticed, in silico docking analysis supports allosteric binding to glutamate-gated chloride channels similar to ivermectin.