Combining ability analysis of fusarium head blight resistance in European winter wheat varieties

The aims of the present study were to estimate the general combining ability (GCA) and the specific combining ability (SCA) effects controlling type II FHB resistance across environments in a set of European winter wheat varieties and, for purposes of future selection, to identify potential combinations of parents with suitable levels of FHB resistance. Parental varieties as well as F1 generations were evaluated under both field and greenhouse conditions in two years. The results of the present study indicate that in the F1 generation mean DON content was relatively lowest after crossing of moderately resistant parents (Sakura/Bakfis, Sakura/Federer, Petrus/Bakfis, and Sakura/Petrus), and mean DON content is low also after crossing the moderately resistant Bakfis variety with the susceptible Biscay and Cubus varieties. Evaluation of crosses in the F1 generation was followed by evaluation of selected crosses (derived from the Bakfis and Sakura varieties) in the F2 generation. Correlations between F1 and F2 were highly significant in relation both to their DON content and visual symptom score (VSS), as well as between the individual experiments (and in the different years). The only exception was in the case of the 2014 field experiment, when inoculation was successful but conditions were not optimal for the disease to progress and DON to accumulate. The selection of a suitable parental variety (with a high GCA) can markedly influence the success rate of breeding for resistance to FHB. Detection of high SCA in the F1 generation is important for directing breeders to promising combinations for achieving FHB resistance. It was demonstrated here that low DON content may be achieved even after crossing a moderately resistant variety with susceptible varieties. Another possibility is to make use of heterosis directly for acquiring resistance in hybrid wheat (for decreasing DON content and manifestation of symptoms)

Exploring the effects of topoisomerase II inhibitor XK469 on anthracycline cardiotoxicity and DNA damage

Anthracyclines, such as doxorubicin (adriamycin), daunorubicin, or epirubicin, rank among the most effective agents in classical anticancer chemotherapy. However, cardiotoxicity remains the main limitation of their clinical use. Topoisomerase IIβ has recently been identified as a plausible target of anthracyclines in cardiomyocytes. We examined the putative topoisomerase IIβ selective agent XK469 as a potential cardioprotective and designed several new analogues. In our experiments, XK469 inhibited both topoisomerase isoforms (α and β) and did not induce topoisomerase II covalent complexes in isolated cardiomyocytes and HL-60, but induced proteasomal degradation of topoisomerase II in these cell types. The cardioprotective potential of XK469 was studied on rat neonatal cardiomyocytes, where dexrazoxane (ICRF-187), the only clinically approved cardioprotective, was effective. Initially, XK469 prevented daunorubicin-induced toxicity and p53 phosphorylation in cardiomyocytes. However, it only partially prevented the phosphorylation of H2AX and did not affect DNA damage measured by Comet Assay. It also did not compromise the daunorubicin antiproliferative effect in HL-60 leukemic cells. When administered to rabbits to evaluate its cardioprotective potential in vivo, XK469 failed to prevent the daunorubicin induced cardiac toxicity in either acute or chronic settings. In the following in vitro analysis, we found that prolonged and continuous exposure of rat neonatal cardiomyocytes to XK469 led to significant toxicity. In conclusion, this study provides important evidence on the effects of XK469 and its combination with daunorubicin in clinically relevant doses in cardiomyocytes. Despite its promising characteristics, long-term treatments and in vivo experiments have not confirmed its cardioprotective potential

Neurodevelopmental and Epilepsy Phenotypes in Individuals With Missense Variants in the Voltage-Sensing and Pore Domains of KCNH5

Background and Objectives KCNH5 encodes the voltage-gated potassium channel EAG2/Kv10.2. We aimed to delineate the neurodevelopmental and epilepsy phenotypic spectrum associated with de novo KCNH5 variants.Methods We screened 893 individuals with developmental and epileptic encephalopathies for KCNH5 variants using targeted or exome sequencing. Additional individuals with KCNH5 variants were identified through an international collaboration. Clinical history, EEG, and imaging data were analyzed; seizure types and epilepsy syndromes were classified. We included 3 previously published individuals including additional phenotypic details.Results We report a cohort of 17 patients, including 9 with a recurrent de novo missense variant p.Arg327His, 4 with a recurrent missense variant p.Arg333His, and 4 additional novel missense variants. All variants were located in or near the functionally critical voltage-sensing or pore domains, absent in the general population, and classified as pathogenic or likely pathogenic using the American College of Medical Genetics and Genomics criteria. All individuals presented with epilepsy with a median seizure onset at 6 months. They had a wide range of seizure types, including focal and generalized seizures. Cognitive outcomes ranged from normal intellect to profound impairment. Individuals with the recurrent p.Arg333His variant had a self-limited drug-responsive focal or generalized epilepsy and normal intellect, whereas the recurrent p.Arg327His variant was associated with infantile-onset DEE. Two individuals with variants in the pore domain were more severely affected, with a neonatal-onset movement disorder, early-infantile DEE, profound disability, and childhood death.Discussion We describe a cohort of 17 individuals with pathogenic or likely pathogenic missense variants in the voltage-sensing and pore domains of Kv10.2, including 14 previously unreported individuals. We present evidence for a putative emerging genotype-phenotype correlation with a spectrum of epilepsy and cognitive outcomes. Overall, we expand the role of EAG proteins in human disease and establish KCNH5 as implicated in a spectrum of neurodevelopmental disorders and epilepsy.</p

Ultra-Rare Genetic Variation in the Epilepsies : A Whole-Exome Sequencing Study of 17,606 Individuals

Sequencing-based studies have identified novel risk genes associated with severe epilepsies and revealed an excess of rare deleterious variation in less-severe forms of epilepsy. To identify the shared and distinct ultra-rare genetic risk factors for different types of epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals and 8,436 controls of European ancestry. We focused on three phenotypic groups: severe developmental and epileptic encephalopathies (DEEs), genetic generalized epilepsy (GGE), and non-acquired focal epilepsy (NAFE). We observed that compared to controls, individuals with any type of epilepsy carried an excess of ultra-rare, deleterious variants in constrained genes and in genes previously associated with epilepsy; we saw the strongest enrichment in individuals with DEEs and the least strong in individuals with NAFE. Moreover, we found that inhibitory GABA(A) receptor genes were enriched for missense variants across all three classes of epilepsy, whereas no enrichment was seen in excitatory receptor genes. The larger gene groups for the GABAergic pathway or cation channels also showed a significant mutational burden in DEEs and GGE. Although no single gene surpassed exome-wide significance among individuals with GGE or NAFE, highly constrained genes and genes encoding ion channels were among the lead associations; such genes included CACNAIG, EEF1A2, and GABRG2 for GGE and LGI1, TRIM3, and GABRG2 for NAFE. Our study, the largest epilepsy WES study to date, confirms a convergence in the genetics of severe and less-severe epilepsies associated with ultra-rare coding variation, and it highlights a ubiquitous role for GABAergic inhibition in epilepsy etiology.Peer reviewe

Photosynthesis and biochemical characterization of the green alga Chlamydopodium fusiforme (Chlorophyta) grown in a thin-layer cascade

Photosynthesis, growth and biochemical composition of the biomass of the freshwater microalga Chlamydopodium fusiforme cultures outdoors in a thin-layer cascade were investigated. Gross oxygen production measured off-line in samples taken from the outdoor cultures was correlated with the electron transport rate estimated from chlorophyll a fluorescence measurements. According to photosynthesis measurements, a mean of 38.9 ± 10.3 mol of photons were required to release one mole of O2, which is 4.86 times higher than the theoretical value (8 photons per 1 O2). In contrast, according to the fluorescence measurements, a mean of 11.7 ± 0.74 mol of photons were required to release 1 mol of O2. These findings indicate that fluorescence-based photosynthesis rates may not be fully replace oxygen measurements to evaluate the performance of an outdoor culture. Daily gross biomass productivity was 0.3 g DW L−1 day−1 consistently for 4 days. Biomass productivity was strongly affected by the suboptimal concentration at which the culture was operated and by the respiration rate, as the substantial volume of culture was kept in the dark (about 45% of the total volume). As the cells were exposed to excessive light, the photosynthetic activity was mainly directed to the synthesis of carbohydrates in the biomass. In the morning, carbohydrate content decreased because of the dark respiration. Per contra, protein content in the biomass was lower at the end of the day and higher in the morning due to carbohydrate consumption by respiration. The data gathered in these trials are important for the future exploitation of Chlamydopodium fusiforme as a potential novel species in the field of microalgae for the production of bio-based compounds.Fil: Torzillo, Giuseppe. Consiglio Nazionale delle Ricerche; Italia. Universidad de Costa Rica; Costa RicaFil: Álvarez Gómez, Félix. Universidad de Málaga; EspañaFil: Celis Plá, Paula S. M.. Universidad de Playa Ancha; ChileFil: Rearte, Tomás Agustín. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gómez Serrano, Cintia. Universidad de Almería; EspañaFil: Silva Benavides, Ana Margarita. Universidad de Costa Rica; Costa RicaFil: Štěrbová, Karolína. Czech Academy of Sciences. Institute of Botany; República Checa. University of South Bohemia; República ChecaFil: Caporgno, Martín. Czech Academy of Sciences. Institute of Botany; República ChecaFil: Touloupakis, Eleftherios. Consiglio Nazionale delle Ricerche; ItaliaFil: Masojídek, Ji?í. University of South Bohemia; República Checa. Czech Academy of Sciences. Institute of Botany; República ChecaFil: Figueroa, Felix L.. Universidad de Málaga; Españ