Anticancer Activity, Reduction Mechanism and G-Quadruplex DNA Binding of a Redox-Activated Platinum(IV)–Salphen Complex

Aiming at reducing the unselective cytotoxicity of Pt(II) chemotherapeutics, a great deal of effort has been concentrated into the design of metal‐containing drugs with different anticancer mechanisms of action. Inert Pt(IV) prodrugs have been proposed to be a valid alternative as they are activated by reduction directly into the cell releasing active Pt(II) species. On the other hand, a promising strategy for designing metallodrugs is to explore new potential biological targets rather than canonical B‐DNA. G‐quadruplex nucleic acid, obtained by self‐assembly of guanine‐rich nucleic acid sequences, has recently been considered an attractive target for anticancer drug design. Therefore, compounds capable of binding and stabilizing this type of DNA structure would be greatly beneficial in anticancer therapy. Here, computational analysis reports the mechanism of action of a recently synthesized Pt(IV)–salphen complex conjugating the inertness of Pt(IV) prodrugs with the ability to bind G‐quadruplexes of the corresponding Pt(II) complex. The reduction mechanism of the Pt(IV) complex with a biological reducing agent was investigated in depth by means of DFT, whereas classical MD simulations were carried out to shed light into the binding mechanism of the released Pt(II) complex. The results show that the Pt(IV) prodrug may be reduced by both inner‐ and outer‐sphere mechanisms, and the active Pt(II) complex, as a function of its protonation state, stabilizes the G‐quadruplex DNA prevalently, either establishing π‐stacking nteractions with the terminal G‐tetrad or through electrostatic interactions along with H‐bonds formation

Investigating the impact of pedoclimatic conditions on the oenological performance of two red cultivars grown throughout southern Italy

The cultivated grapevine, Vitis vinifera subsp. vinifera, possesses a rich biodiversity with numerous varieties. Each variety adapts differently to varying pedoclimatic conditions, which greatly influence the terroir expression of wine regions. These conditions impact vine growth, physiology, and berry composition, ultimately shaping the unique characteristics and typicity of the wines produced. Nowadays, the potential of the different adaptation capacities of grape varieties has not yet been thoroughly investigated. We addressed this issue by studying two grape varieties, Aglianico and Cabernet Sauvignon, in two different pedoclimatic conditions of Southern Italy. We evaluated and compared the effect of different pedoclimatic conditions on plant physiology, the microbial quality of grapes using Next-Generation Sequencing (NGS) technology, the expression trends of key genes in ripe berries and the concentration of phenolic compounds in grapes and wines by HPLC-MS, HPLC-DAD, NMR and spectrophotometric analyses. Metabolomic and microbiome data were integrated with quantitative gene expression analyses to examine varietal differences and plasticity of genes involved in important oenological pathways. The data collected showed that the phenotypic response of studied grapes in terms of vigor, production, and fruit quality is strongly influenced by the pedoclimatic conditions and, in particular, by soil physical properties. Furthermore, Aglianico grape variety was more influenced than the Cabernet Sauvignon by environmental conditions. In conclusion, the obtained findings not only reinforce the terroir concept and our comprehension of grape’s ability to adapt to climate variations but can also have implications for the future usage of grape genetic resources

Genetic and Morpho-Agronomic Characterization of Sicilian Tetraploid Wheat Germplasm

Cereal landraces are a very valuable resource in contemporary agriculture. A renewed focus for breeding purposes could ameliorate some negative consequences of modern agriculture and conventional breeding, such as the loss of genetic diversity. One strategy combining molecular genotyping and characterization of morpho-agronomic traits related to productivity is proposed to assess a group of tetraploid wheat landraces named Bufala, historically cultivated in the mountain areas of Sicily and characterized by adaptability in terms of cold tolerance, ability to grow in marginal soils, weed competitiveness and resistance to diseases. A total of 55 SSR molecular markers were used to detect patterns of diversity in 30 rivet and durum wheat genotypes. Furthermore, phenotyping was then conducted for 8 morpho-agronomic traits. Discriminant analysis of principal components (DAPC), STRUCTURE and phylogenetical analysis allowed to identify three groups, two of them genetically close and including both Bufala and Bufala-related rivet landraces. To the third group, old and more recent durum wheat varieties, constituting the outgroup, were assigned. Clustering was confirmed by Principal Component Analysis (PCA). Finally, a correlation analysis showed that Bufala genotypes are characterized by lower ear density, major ear length and later earing time compared with the other studied genotypes. The levels of diversity and population structure could be an important contribution to parent selection in tetraploid wheat breeding programs, as well as to germplasm conservation and management

Control Patterns in Contracting-Out Relationships: It Matters What You Do, Not Who You Are

The contracting-out of public services has often been accompanied by a strong academic focus on the emergence of new governance forms, and a general neglect of the processes and practices through which contracted-out services are controlled and monitored. To fill this gap, we draw on contracting-out and inter-organizational control literatures to explore the adoption of control mechanisms for public service provision at the municipal level and the variables that can explain their choice. Our results, based on a survey of Italian municipalities, show that in the presence of contracting-out, market-, hierarchy- and trust-based controls display different intensities, can co-exist and are explained by different variables. Service characteristics are more effective in explaining market- and hierarchy-based controls than relationship characteristics. Trust-based controls are the most widespread, but cannot be explained by the variables traditionally identified in contracting-out and inter-organizational control studies

Inter-organizational Processes: Requirements for Securing Data

Supply chains, built by the flow of goods and money between firms, are changing their nature into value networks, built on strategic and knowledge-based relationships. This phenomenon characterizes mainly complex product industries, i.e. aerospace, requiring long research and development projects. Strategic relationships are implemented by processes crossing organizational boundaries. To carry them out, data exchange is required, but this introduces risks, too. These risks can be faced by defining more accurate privacy management techniques and functionalities of inter-organizational platforms. In this paper some inter-organizational processes characterizing the aero-engine supply chains are discussed focusing on their security and privacy issues. They were explored thanks to the Italian aerospace company Avio. One of them, the supply chain planning process, involving high classified data exchange among all the firms in the value network, will be faced by the SecureSCM research project through cryptography and secure multiparty computation technology

Hub Genes and Pathways Related to Lemon (<i>Citrus limon</i>) Leaf Response to <i>Plenodomus tracheiphilus</i> Infection and Influenced by <i>Pseudomonas mediterranea</i> Biocontrol Activity

The lemon industry in the Mediterranean basin is strongly threatened by “mal secco” disease (MSD) caused by the fungus Plenodomus tracheiphlilus. Leaf pretreatments with Pseudomonas mediterranea 3C have been proposed as innovative tools for eco-sustainable interventions aimed at controlling the disease. In this study, by exploiting the results of previously performed RNAseq analysis, WCGNA was conducted among gene expression patterns in both inoculated (Pt) and pretreated and fungus-inoculated lemon plants (Citrus limon L.) (3CPt), and two indicators of fungal infection, i.e., the amount of fungus DNA measured in planta and the disease index (DI). The aims of this work were (a) to identify gene modules significantly associated with those traits, (b) to construct co-expression networks related to mal secco disease; (c) to define the effect and action mechanisms of P. mediterranea by comparing the networks. The results led to the identification of nine hub genes in the networks, with three of them belonging to receptor-like kinases (RLK), such as HERK1, CLAVATA1 and LRR, which play crucial roles in plant–pathogen interaction. Moreover, the comparison between networks indicated that the expression of those receptors is not induced in the presence of P. mediterranea, suggesting how powerful WCGNA is in discovering crucial genes that must undergo further investigation and be eventually knocked out

Fungal Infection Induces Anthocyanin Biosynthesis and Changes in DNA Methylation Configuration of Blood Orange [<i>Citrus sinensis</i> L. (Osbeck)]

The biosynthesis of sweet orange anthocyanins is triggered by several environmental factors such as low temperature. Much less is known about the effect of biotic stress on anthocyanin production in sweet orange, although in other species anthocyanins are often indicated as “defense molecules”. In this work, citrus fruits were inoculated with Penicillium digitatum, the causal agent of green mold, and the amount of anthocyanins and the expression of genes related to their biosynthesis was monitored by RT-real time PCR after 3 and 5 days from inoculation (DPI). Moreover, the status of cytosine methylation of DFR and RUBY promoter regions was investigated by McrBC digestion followed in real-time. Our results highlight that fungal infection induces anthocyanin production by activating the expression of several genes in the biosynthetic pathway. The induction of gene expression is accompanied by maintenance of high levels of methylation at the DFR and RUBY promoters in the inoculated fruits, thus suggesting that DNA methylation is not a repressive mark of anthocyanin related gene expression in sweet orange subjected to biotic stress. Finally, by measuring the expression levels of the Citrus DNA demethylase genes, we found that none of them is up-regulated in response to fungal infection, this result being in accordance with the observed maintenance of high-level DFR and Ruby promoter regions methylation

Do environmental and task characteristics matter? Unveiling the relevance of relational factors in the control of local public services

No abstract availabl