Genetic yield control in sugar beet hybrids obtained by diallel crosses

Purpose. The aim of our study was to determine the combination ability of the studied pollinators and identify the genetic control of the yield sign in interline diallel hybrids of sugar beet. Methods. The source material was homozygous as a result self-pollination. The combination ability and genetic control of quantitative traits were determined by the Hayman model. Results. Genetic analysis revealed that sugar beet pollinator line demonstrated genetic control of yield in diallel sugar beet hybrids by 14 genes and gene groups. Lines (BZ 1 and BZ 4) with high general combination ability demonstrated a significant additive effect of genes were selected. The effects of specific combination ability, which significantly affected the yield of heterosis hybrids, were revealed. Their share of influence was 36.4 and 23.8%, respectively. High-yielding hybrid combinations of parent genotypes were selected. They are transferred to reproduction and testing for ecological plasticity. Conclusions. Genetic control of the yield sign in diallel hybrids is found based on the Hаyman model. The influence of the combination ability of sugar beet pollinators was determined and the best parent genotype pairs were selected. According to the effects of specific gene interaction, the best combinations have been identified that can be used as sources of economically valuable traits.

Nifedipine Potentiates Susceptibility of Salmonella Typhimurium to Different Classes of Antibiotics

The calcium channel blocker nifedipine induces cellular iron export, thereby limiting the availability of the essential nutrient iron for intracellular pathogens, resulting in bacteriostatic activity. To study if nifedipine may exert a synergistic anti-microbial activity when combined with antibiotics, we used the mouse macrophage cell line RAW267.4, infected with the intracellular bacterium Salmonella Typhimurium, and exposed the cells to varying concentrations of nifedipine and/or ampicillin, azithromycin and ceftriaxone. We observed a significant additive effect of nifedipine in combination with various antibiotics, which was not observed when using Salmonella, with defects in iron uptake. Of interest, increasing intracellular iron levels increased the bacterial resistance to treatment with antibiotics or nifedipine or their combination. We further showed that nifedipine increases the expression of the siderophore-binding peptide lipocalin-2 and promotes iron storage within ferritin, where the metal is less accessible for bacteria. Our data provide evidence for an additive effect of nifedipine with conventional antibiotics against Salmonella, which is partly linked to reduced bacterial access to iron.

Genetic Parameters and QTLs for Total Phenolic Content and Yield of Wheat Mapping Population of CSDH Lines under Drought Stress

A doubled haploid population of 94 lines from the Chinese Spring × SQ1 wheat cross (CSDH) was used to evaluate additive and epistatic gene action effects on total phenolic content, grain yield of the main stem, grain number per plant, thousand grain weight, and dry weight per plant at harvest based on phenotypic and genotypic observations of CSDH lines. These traits were evaluated under moderate and severe drought stress and compared with well-watered plants. Plants were grown in pots in an open-sided greenhouse. Genetic parameters, such as additive and epistatic effects, affecting total phenolic content, were estimated for eight year-by-drought combinations. Twenty-one markers showed a significant additive effect on total phenolic content in all eight year-by-drought combinations. These markers were located on chromosomes: 1A, 1B, 2A, 2B, 2D, 3A, 3B, 3D, 4A, and 4D. A region on 4AL with a stable QTL controlling the phenolic content, confirmed by various statistical methods is particularly noteworthy. In all years and treatments, three markers significantly linked to QTLs have been identified for both phenols and yield. Thirteen markers were coincident with candidate genes. Our results indicated the importance of both additive and epistatic gene effects on total phenolic content in eight year-by-drought combinations.

Estimation of additive and epistatic gene effects for phenotypic and biochemical traits in double hyploid lines of winter rape seed ,(Brassica napus L.)

In this paper 60 doubled haploid lines of winter oilseed rape (Brassica napus L.) were studied. Genetic parameters as additive and epistatic effects were estimated for 24 traits. The results indicate the importance of both these effects for number of branches per plant, number of siliques per plant, linoleic acid, total of glucosinolates, total of alkenyl glucosinolates, gluconapin, glucobrassicanapin, progoitryn, napoleiferin and indolyl in both years of this study. Statistically significant epistatic effect and non-significant additive effect for thousand seed weight means that this trait was determined by genes with small individual effects but strong gene by gene interaction effects. Confounding epistatic effects in models suggested that inheritance of this trait is complex and polygenic.

Integrative Approach to Facilitate Fracture Healing: Topical Chinese Herbal Paste with Oral Strontium Ranelate

Strontium ranelate (SrR) is one of the pharmaceutical agents reported to be effective on the promotion of fracture healing. This study aimed to evaluate the integrative effect of the oral SrR with a topical Chinese herbal paste, namely, CDR, on facilitation of bone healing. The in vivo efficacy was evaluated using rats with tibial fracture. They were treated with either CDR topically, or SrR orally, or their combined treatments. The in vivo results illustrated a significant additive effect of CDR on SrR in increasing the yield load of the fractured tibia. The in vitro results showed that neither SrR nor CDR exhibited a cytotoxic effect on UMR106 and bone-marrow stem cell (BMSC), but both of them increased the proliferation of BMSC at low concentrations. The combination of CDR at 200 μg/mL with SrR at 200 or 400 μg/ml also showed an additive effect on increasing the ALP activity of BMSC. Both SrR and CDR alone reduced osteoclast formation, and the effective concentration of SrR to inhibit osteoclastogenesis was reduced in the presence of CDR. This integrative approach by combining oral SrR and topical CDR is effective in promoting fracture healing properly due to their additive effects on proosteogenic and antiosteoclastogenic properties.

Genetic analysis of quantitative traits in cowpea [vigna unguiculata (L.) walp.] using six parameter genetic model

Generation Mean Analysis was carried out using six basic generations in 3 different crosses of cowpea to determine suitable breeding methods. For most of the studied traits, additive, dominance, additive x additive, additive x dominance and dominance x dominance effects were significant. Additive effect significantly contributed for days to 1st flowering and seed yield per plant. Dominance effect was significant for the incidence of cowpea mosaic virus in family 1, while for pod maturity in family 2. Additive x dominance type of interaction contributed significantly for days to 1st flowering, days to pod maturity and seed yield per hectare. Duplicate type of epistasis was observed for days to 1st flowering and incidence of cowpea mosaic virus in family 1, number of pods per plant and pod length in family 2 and 3. The findings suggested that pureline, pedigree and recurrent selection could be followed in cowpea improvement.

Strong Gender-Specific Additive Effects of the NYD-SP18 and FTO Variants on BMI Values

The role of the FTO gene in obesity development is well established in populations around the world. The NYD-SP18 variant has been suggested to have a similar effect on BMI, but the role of this gene in determining BMI has not yet been verified. The objective of our study was to confirm the association between NYD-SP18 rs6971019 SNP and BMI in the Slavic population and to analyze i) the gender-specific effects of NYD-SP18 on BMI and ii) the simultaneous effect of FTO rs17817449 and NYD-SP18 on BMI. We analyzed a sample of a large adult population based on the post-MONICA study (1,191 males and 1,368 females). Individuals were analyzed three times over 9 years. NYD-SP18 rs6971019 SNP is related to BMI in males (2000/1 GG 28.3±3.7 kg/m2 vs. +A 27.5±3.7 kg/m2 P<0.0005; in other examinations P<0.05 and <0.005), but not in females (all P values over 0.48 in all three examinations). Further analysis revealed the significant additive effect (but not the interaction) of FTO and NYD-SP18 SNPs on BMI in males (all P<0.01). These results suggest that association between NYD-SP18 rs6971019 SNP and BMI may be restricted to males. Furthermore, variants within NYD-SP18 and FTO genes revealed a significant additive effect on BMI values in males.

The use of roflumilast in COPD: a review

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Chronic inflammation and exacerbations play a central role in the progression of the disease. Currently, treatment options for COPD have been shown to improve the progressive decline in lung-function and/or decrease mortality rates. Roflumilast, a phosphodiesterase- 4 inhibitor, is an anti-inflammatory drug which has been licensed as an add-on therapy for COPD patients with forced expiratory volume in the first second &lt;50% and frequent exacerbations. Clinical trials have demonstrated that roflumilast improves lung function and reduces exacerbation frequency. Roflumilast has a mechanism of action which allows it to obtain a significant additive effect to current therapeutic options for COPD patients. It is generally well tolerated, although the most common adverse effects include diarrhea, nausea, weight loss, and headache. This review article provides an overview of the positive effects of roflumilast on lung function, exacerbation frequency and glucose metabolism, and its interaction with concomitant inhaled treatments.

Genetic interactions contribute less than additive effects to quantitative trait variation in yeast

Genetic mapping studies of quantitative traits typically focus on detecting loci that contribute additively to trait variation. Genetic interactions are often proposed as a contributing factor to trait variation, but the relative contribution of interactions to trait variation is a subject of debate. Here, we use a very large cross between two yeast strains to accurately estimate the fraction of phenotypic variance due to pairwise QTL-QTL interactions for 20 quantitative traits. We find that this fraction is 9% on average, substantially less than the contribution of additive QTL (43%). Statistically significant QTL-QTL pairs typically have small individual effect sizes, but collectively explain 40% of the pairwise interaction variance. We show that pairwise interaction variance is largely explained by pairs of loci at least one of which has a significant additive effect. These results refine our understanding of the genetic architecture of quantitative traits and help guide future mapping studies.

Combined blockade of signalling pathways shows marked anti-tumour potential in phaeochromocytoma cell lines

Currently, there is no completely effective therapy available for metastatic phaeochromocytomas (PCCs) and paragangliomas. In this study, we explore new molecular targeted therapies for these tumours, using one more benign (mouse phaeochromocytoma cell (MPC)) and one more malignant (mouse tumour tissue (MTT)) mouse PCC cell line – both generated from heterozygous neurofibromin 1 knockout mice. Several PCC-promoting gene mutations have been associated with aberrant activation of PI3K/AKT, mTORC1 and RAS/RAF/ERK signalling. We therefore investigated different agents that interfere specifically with these pathways, including antagonism of the IGF1 receptor by NVP-AEW541. We found that NVP-AEW541 significantly reduced MPC and MTT cell viability at relatively high doses but led to a compensatory up-regulation of ERK and mTORC1 signalling at suboptimal doses while PI3K/AKT inhibition remained stable. We subsequently investigated the effect of the dual PI3K/mTORC1/2 inhibitor NVP-BEZ235, which led to a significant decrease of MPC and MTT cell viability at doses down to 50 nM but again increased ERK signalling. Accordingly, we next examined the combination of NVP-BEZ235 with the established agent lovastatin, as this has been described to inhibit ERK signalling. Lovastatin alone significantly reduced MPC and MTT cell viability at therapeutically relevant doses and inhibited both ERK and AKT signalling, but increased mTORC1/p70S6K signalling. Combination treatment with NVP-BEZ235 and lovastatin showed a significant additive effect in MPC and MTT cells and resulted in inhibition of both AKT and mTORC1/p70S6K signalling without ERK up-regulation. Simultaneous inhibition of PI3K/AKT, mTORC1/2 and ERK signalling suggests a novel therapeutic approach for malignant PCCs.