Learning Bayesian Networks with Heterogeneous Agronomic Data Sets via Mixed-Effect Models and Hierarchical Clustering

Research involving diverse but related data sets, where associations between covariates and outcomes may vary, is prevalent in various fields including agronomic studies. In these scenarios, hierarchical models, also known as multilevel models, are frequently employed to assimilate information from different data sets while accommodating their distinct characteristics. However, their structure extend beyond simple heterogeneity, as variables often form complex networks of causal relationships. Bayesian networks (BNs) provide a powerful framework for modelling such relationships using directed acyclic graphs to illustrate the connections between variables. This study introduces a novel approach that integrates random effects into BN learning. Rooted in linear mixed-effects models, this approach is particularly well-suited for handling hierarchical data. Results from a real-world agronomic trial suggest that employing this approach enhances structural learning, leading to the discovery of new connections and the improvement of improved model specification. Furthermore, we observe a reduction in prediction errors from 28\% to 17\%. By extending the applicability of BNs to complex data set structures, this approach contributes to the effective utilisation of BNs for hierarchical agronomic data. This, in turn, enhances their value as decision-support tools in the field.Comment: 28 pages, 5 figure

Signal transduction in the Sertoli cell: serum modulation of the response to FSH

Immature Sertoli cells of the testicular seminiferous tubule maintain the expression of their differentiated phenotype when cultured in unsupplemented medium. In preliminary experiments we observed that foetal bovine serum (FBS) stimulates polyphosphoinositides (PI) hydrolysis in Sertoli cells. We then evaluated the effect of serum on the function of the immature Sertoli cell in culture, in terms of cAMP and estrogen production. Treatment of Sertoli cells for 30 min with 1–10% FBS had no effect on basal cAMP accumulation but abolished the response to FSH. The serum concentration producing half-maximal inhibition of the FSH-dependent cAMP accumulation was 0.5–1%. Comparison of the FSH-dose-response in the absence or presence of serum showed a decreased maximal response when serum was present. Sertoli cells exposed to serum were also less responsive to the β-adrenergic agonist isoproterenol, to cholera toxin, and to forskolin. The serum inhibition was rapidly reversed upon removal of serum or incubating the cells with the phosphodiesterase inhibitor MIX (methyl-isobutyl-xanthine). Similarly to what observed with cAMP, serum affected androgen aromatization stimulated by FSH, isoproterenol, cholera toxin, forskolin and dibutyryl cAMP. These data indicate that factors present in serum can act as modulators of the Sertoli cell function in vitro by rapidly and reversibly inhibiting the cAMP and steroidogenic response of the Sertoli cell to FSH

Breeding for black rot resistance in grapevine: advanced approaches for germplasm screening

Crop improvement by means of traditional or molecular breeding is a key strategy to accomplish the European Green Deal target of reducing pesticides by 50% by 2030. Regarding viticulture, this is exacerbated by the massive use of chemicals to control pathogen infections. Black rot is an emergent disease caused by the ascomycete Phyllosticta ampelicida, and its destructiveness is alarming vine growers. Implementing and improving effective phenotyping strategies are fundamental preliminary steps to breed disease resistant varieties and this work suggests good practices adopted for this purpose. Primarily, the pedigree of black rot resistance donors was reconstructed based on the collection of phenotypic historical data, highlighting unexplored sources of black rot resistance. Strains used for artificial infections were isolated, genetically characterized and mixed to avoid race-specific resistance selection. A new inoculation protocol based on the use of leaf mature lesions was developed. Ex vivo inoculation on detached leaves was effective for the evaluation of conidia germination and hyphal growth, but not for disease progression. Finally, the pedigree was used for the identification of 23 genotypes to be tested. Two breeding selections (NY39 and NY24) resulted symptomless in all assessments and a third one (F25P52) also showed very high resistance, although with a greater variability. Other two genotypes (F12P19 and ‘Charvir’) fell within the medium resistance category, making them good candidates in a regime of well-timed preventive treatments. In conclusion, this work was effective to a comprehensive parental line characterization and preparatory towards grapevine breeding programs for black rot resistanc

Seedling Establishment of Tall Fescue Exposed to Long-Term Starvation Stress

In germinating seeds under unfavorable environmental conditions, the mobilization of stores in the cotyledons is delayed, which may result in a different modulation of carbohydrates balance and a decrease in seedling vigor. Tall fescue (Festuca arundinacea Schreb.) caryopses grown at 4˚C in the dark for an extended period in complete absence of nutrients, showed an unexpected ability to survive. Seedlings grown at 4˚C for 210 days were morphologically identical to seedlings grown at 23˚C for 21 days. After 400 days, seedlings grown at 4˚C were able to differentiate plastids to chloroplast in just few days once transferred to the light and 23˚C. Tall fescue exposed to prolonged period at 4˚C showed marked anatomical changes: cell wall thickening, undifferentiated plastids, more root hairs and less xylem lignification. Physiological modifications were also observed, in particular related to sugar content, GA and ABA levels and amylolytic enzymes pattern. The phytohormones profiles exhibited at 4 and 23˚C were comparable when normalized to the respective physiological states. Both the onset and the completion of germination were linked to GA and ABA levels, as well as to the ratio between these two hormones. All plants showed a sharp decline in carbohydrate content, with a consequent onset of gradual sugar starvation. This explained the slowed then full arrest in growth under both treatment regimes. The analysis of amylolytic activity showed that Ca2+ played a central role in the stabilization of several isoforms. Overall, convergence of starvation and hormone signals meet in crosstalk to regulate germination, growth and development in tall fescue

Resistance to Plasmopara viticola in a grapevine segregating population is associated with stilbenoid accumulation and with specific host transcriptional responses

<p>Abstract</p> <p>Background</p> <p>Downy mildew, caused by the oomycete <it>Plasmopara viticola</it>, is a serious disease in <it>Vitis </it><it>vinifera</it>, the most commonly cultivated grapevine species. Several wild <it>Vitis </it>species have instead been found to be resistant to this pathogen and have been used as a source to introgress resistance into a <it>V. vinifera </it>background. Stilbenoids represent the major phytoalexins in grapevine, and their toxicity is closely related to the specific compound. The aim of this study was to assess the resistance response to <it>P. viticola </it>of the Merzling × Teroldego cross by profiling the stilbenoid content of the leaves of an entire population and the transcriptome of resistant and susceptible individuals following infection.</p> <p>Results</p> <p>A three-year analysis of the population's response to artificial inoculation showed that individuals were distributed in nine classes ranging from total resistance to total susceptibility. In addition, quantitative metabolite profiling of stilbenoids in the population, carried out using HPLC-DAD-MS, identified three distinct groups differing according to the concentrations present and the complexity of their profiles. The high producers were characterized by the presence of <it>trans</it>-resveratrol, <it>trans</it>-piceid, <it>trans</it>-pterostilbene and up to thirteen different viniferins, nine of them new in grapevine.</p> <p>Accumulation of these compounds is consistent with a resistant phenotype and suggests that they may contribute to the resistance response.</p> <p>A preliminary transcriptional study using cDNA-AFLP selected a set of genes modulated by the oomycete in a resistant genotype. The expression of this set of genes in resistant and susceptible genotypes of the progeny population was then assessed by comparative microarray analysis.</p> <p>A group of 57 genes was found to be exclusively modulated in the resistant genotype suggesting that they are involved in the grapevine-<it>P. viticola </it>incompatible interaction. Functional annotation of these transcripts revealed that they belong to the categories defense response, photosynthesis, primary and secondary metabolism, signal transduction and transport.</p> <p>Conclusions</p> <p>This study reports the results of a combined metabolic and transcriptional profiling of a grapevine population segregating for resistance to <it>P. viticola</it>. Some resistant individuals were identified and further characterized at the molecular level. These results will be valuable to future grapevine breeding programs.</p

Secondary and primary metabolites reveal putative resistance-associated biomarkers against Erysiphe necator in resistant grapevine genotypes

Numerous fungicide applications are required to control Erysiphe necator, the causative agent of powdery mildew. This increased demand for cultivars with strong and long-lasting field resistance to diseases and pests. In comparison to the susceptible cultivar 'Teroldego', the current study provides information on some promising disease-resistant varieties (mono-locus) carrying one E. necator-resistant locus: BC4 and 'Kishmish vatkana', as well as resistant genotypes carrying several E. necator resistant loci (pyramided): 'Bianca', F26P92, F13P71, and NY42. A clear picture of the metabolites' alterations in response to the pathogen is shown by profiling the main and secondary metabolism: primary compounds and lipids; volatile organic compounds and phenolic compounds at 0, 12, and 48 hours after pathogen inoculation. We identified several compounds whose metabolic modulation indicated that resistant plants initiate defense upon pathogen inoculation, which, while similar to the susceptible genotype in some cases, did not imply that the plants were not resistant, but rather that their resistance was modulated at different percentages of metabolite accumulation and with different effect sizes. As a result, we discovered ten up-accumulated metabolites that distinguished resistant from susceptible varieties in response to powdery mildew inoculation, three of which have already been proposed as resistance biomarkers due to their role in activating the plant defense response

Mono-locus and pyramided resistant grapevine cultivars reveal early putative biomarkers upon artificial inoculation with Plasmopara viticola

10openInternationalBothOne of the most economically important grapevine diseases is Downy mildew (DM) caused by the oomycete Plasmopara viticola. A strategy to reduce the use of fungicides to compensate for the high susceptibility of V. vinifera is the selection of grapevine varieties showing pathogen-specific resistance. We applied a metabolomics approach to evaluate the metabolic modulation in mono-locus resistant genotypes carrying one locus associated with P. viticola resistance (Rpv) (BC4- Rpv1, Bianca- Rpv3-1, F12P160- Rpv12, Solaris- Rpv10), as well as in pyramided resistant genotypes carrying more than one Rpv (F12P60- Rpv3-1; Rpv12 and F12P127- Rpv3-1, Rpv3-3; Rpv10) taking as a reference the susceptible genotype Pinot Noir. In order to understand if different sources of resistance are associated with different degrees of resistance and, implicitly, with different responses to the pathogen, we considered the most important classes of plant metabolite primary compounds, lipids, phenols and volatile organic compounds at 0, 12, 48, and 96 h post-artificial inoculation (hpi). We identified 264 modulated compounds; among these, 22 metabolites were found accumulated in significant quantities in the resistant cultivars compared to Pinot Noir. In mono-locus genotypes, the highest modulation of the metabolites was noticed at 48 and 96 hpi, except for Solaris, that showed a behavior similar to the pyramided genotypes in which the changes started to occur as early as 12 hpi. Bianca, Solaris and F12P60 showed the highest number of interesting compounds accumulated after the artificial infection and with a putative effect against the pathogen. In contrast, Pinot Noir showed a less effective defense response in containing DM growth.openCiubotaru, R.M.; Franceschi, P.; Zulini, L.; Stefanini, M.; Skrab, D.; Rossarolla, M.D.; Robatscher, P.; Oberhuber, M.; Vrhovsek, U.; Chitarrini, G.Ciubotaru, R.M.; Franceschi, P.; Zulini, L.; Stefanini, M.; Skrab, D.; Rossarolla, M.D.; Robatscher, P.; Oberhuber, M.; Vrhovsek, U.; Chitarrini, G

Proton Pump Inhibitors Reduce Pancreatic Adenocarcinoma Progression by Selectively Targeting H⁺, K⁺-ATPases in Pancreatic Cancer and Stellate Cells

Pancreatic duct cells are equipped with acid/base transporters important for exocrine secretion. Pancreatic ductal adenocarcinoma (PDAC) cells may utilize such transporters to acidify extracellular tumor microenvironment, creating a niche favoring cell proliferation, fibrosis and resistance to chemotherapy&mdash;all contributing to the notoriously bad prognosis of this disease. Here, we report that gastric and non-gastric H+, K+-ATPases (coded by ATP4A and ATP12A) are overexpressed in human and murine pancreatic cancer and that we can target them specifically with proton pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) in in vitro models of PDAC. Focusing on pantoprazole, we show that it significantly reduced human cancer cell proliferation by inhibiting cellular H+ extrusion, increasing K+ conductance and promoting cyclin D1-dependent cell cycle arrest and preventing STAT3 activation. Pantoprazole also decreased collagen secretion from pancreatic stellate cells. Importantly, in vivo studies show that pantoprazole treatment of tumor-bearing mice reduced tumor size, fibrosis and expression of angiogenic markers. This work provides the first evidence that H+, K+-ATPases contribute to PDAC progression and that these can be targeted by inhibitors of these pumps, thus proving a promising therapeutic strategy

The Brazilian grapevine variety called ‘Peverella’ corresponds to the ‘Boschera’ variety

Through fingerprinting analysis using reference microsatellite markers and comparing with the Vitis International Variety Catalogue (VIVC) database, it was possible to discover that in Brazil, the wine grape variety cultivated for over 70 years, called 'Peverella' (Variety number VIVC = 12963; National Register of Vine Varieties (Italy), code: 254) is actually the grape variety called 'Boschera' (Variety number VIVC = 1576;National Register of Vine Varieties (Italy), code: 326). This discovery makes wines produced in Brazil even rarer (with only approximately 10 hectares planted worldwide), presenting an additional means to promote and market this historic variety