Enhancing stakeholder networks in wine tourism – evidence from Italian small municipalities

Purpose – The purpose of this paper is to explore validity and reliability of a possible collaboration model for wine tourism with a “public” basis, i.e. from the point of view of the municipality engaged in promoting the wine tourism industry insisting on the territory. Design/methodology/approach – The survey, proposing a theoretical/empirical framework, has investigated, through an electronic platform, the municipalities belonging to the National Association of “Wine Cities.” Findings – The research has demonstrated a substantial trustworthiness of the model, with further evidence about the underestimation of stakeholder networks on behalf of Italian small municipalities. A clear difference of perception between non-small municipalities and small municipalities has emerged with regard to the perceived relevance of the collaboration with the territorial wine tourism players/stakeholders. Practical implications – A recent legislation in Italy, just focused on small municipalities, might help overcome these gaps, between non-small municipalities and small municipalities, releasing in the territories new energies for the development of wine tourism, from both planning and financing points of view. Originality/value – Italy as country is the largest producer of wine in the world. Similarly, wine tourism, as additional wine business opportunity, is a successful phenomenon in Italy, even though with great margins of development (especially with comparison to the New World of Wine). One of the main limits of this delay is the lack of public-private collaboration, at widespread level, among the players/stakeholders of the sector. The model that has been proposed in this research contributes scientifically and practically to fill this gaps

Itaconate modulates tricarboxylic acid and redox metabolism to mitigate reperfusion injury.

ObjectivesCerebral ischemia/reperfusion (IR) drives oxidative stress and injurious metabolic processes that lead to redox imbalance, inflammation, and tissue damage. However, the key mediators of reperfusion injury remain unclear, and therefore, there is considerable interest in therapeutically targeting metabolism and the cellular response to oxidative stress.MethodsThe objective of this study was to investigate the molecular, metabolic, and physiological impact of itaconate treatment to mitigate reperfusion injuries in in vitro and in vivo model systems. We conducted metabolic flux and bioenergetic studies in response to exogenous itaconate treatment in cultures of primary rat cortical neurons and astrocytes. In addition, we administered itaconate to mouse models of cerebral reperfusion injury with ischemia or traumatic brain injury followed by hemorrhagic shock resuscitation. We quantitatively characterized the metabolite levels, neurological behavior, markers of redox stress, leukocyte adhesion, arterial blood flow, and arteriolar diameter in the brains of the treated/untreated mice.ResultsWe demonstrate that the "immunometabolite" itaconate slowed tricarboxylic acid (TCA) cycle metabolism and buffered redox imbalance via succinate dehydrogenase (SDH) inhibition and induction of anti-oxidative stress response in primary cultures of astrocytes and neurons. The addition of itaconate to reperfusion fluids after mouse cerebral IR injury increased glutathione levels and reduced reactive oxygen/nitrogen species (ROS/RNS) to improve neurological function. Plasma organic acids increased post-reperfusion injury, while administration of itaconate normalized these metabolites. In mouse cranial window models, itaconate significantly improved hemodynamics while reducing leukocyte adhesion. Further, itaconate supplementation increased survival in mice experiencing traumatic brain injury (TBI) and hemorrhagic shock.ConclusionsWe hypothesize that itaconate transiently inhibits SDH to gradually "awaken" mitochondrial function upon reperfusion that minimizes ROS and tissue damage. Collectively, our data indicate that itaconate acts as a mitochondrial regulator that controls redox metabolism to improve physiological outcomes associated with IR injury

Sc substitution for Mg in MgB2: effects on Tc and Kohn anomaly

Here we report synthesis and characterization of Mg_{1-x}Sc_{x}B_{2} (0.12T_{c}>6 K. We find that the Sc doping moves the chemical potential through the 2D/3D electronic topological transition (ETT) in the sigma band where the ``shape resonance" of interband pairing occurs. In the 3D regime beyond the ETT we observe a hardening of the E_{2g} Raman mode with a significant line-width narrowing due to suppression of the Kohn anomaly over the range 0<q<2k_{F}.Comment: 8 pages, 4 EPS figures, to be published in Phys. Rev.

Inhibition of the mitochondrial pyruvate carrier protects from excitotoxic neuronal death.

Glutamate is the dominant excitatory neurotransmitter in the brain, but under conditions of metabolic stress it can accumulate to excitotoxic levels. Although pharmacologic modulation of excitatory amino acid receptors is well studied, minimal consideration has been given to targeting mitochondrial glutamate metabolism to control neurotransmitter levels. Here we demonstrate that chemical inhibition of the mitochondrial pyruvate carrier (MPC) protects primary cortical neurons from excitotoxic death. Reductions in mitochondrial pyruvate uptake do not compromise cellular energy metabolism, suggesting neuronal metabolic flexibility. Rather, MPC inhibition rewires mitochondrial substrate metabolism to preferentially increase reliance on glutamate to fuel energetics and anaplerosis. Mobilizing the neuronal glutamate pool for oxidation decreases the quantity of glutamate released upon depolarization and, in turn, limits the positive-feedback cascade of excitotoxic neuronal injury. The finding links mitochondrial pyruvate metabolism to glutamatergic neurotransmission and establishes the MPC as a therapeutic target to treat neurodegenerative diseases characterized by excitotoxicity

Oncogenic R132 IDH1 Mutations Limit NADPH for De Novo Lipogenesis through (D)2-Hydroxyglutarate Production in Fibrosarcoma Sells.

Neomorphic mutations in NADP-dependent isocitrate dehydrogenases (IDH1 and IDH2) contribute to tumorigenesis in several cancers. Although significant research has focused on the hypermethylation phenotypes associated with (D)2-hydroxyglutarate (D2HG) accumulation, the metabolic consequences of these mutations may also provide therapeutic opportunities. Here we apply flux-based approaches to genetically engineered cell lines with an endogenous IDH1 mutation to examine the metabolic impacts of increased D2HG production and altered IDH flux as a function of IDH1 mutation or expression. D2HG synthesis in IDH1-mutant cells consumes NADPH at rates similar to de novo lipogenesis. IDH1-mutant cells exhibit increased dependence on exogenous lipid sources for in&nbsp;vitro growth, as removal of medium lipids slows growth more dramatically in IDH1-mutant cells compared with those expressing wild-type or enzymatically inactive alleles. NADPH regeneration may be limiting for lipogenesis and potentially redox homeostasis in IDH1-mutant cells, highlighting critical links between cellular biosynthesis and redox metabolism

Neutron Diffraction Study of Heavy Water Intercalation in Superconducting Deuterated Sodium Cobaltate Na\u3csub\u3e0.35\u3c/sub\u3eCoO\u3csub\u3e2\u3c/sub\u3e1.4D\u3csub\u3e2\u3c/sub\u3eO

When Na-deficient NaxCoO2 is intercalated with water1 or heavy water2, it becomes a superconductor. The maximum critical temperature of 4.5 K is found for the composition NaxCoO2yD2O (x= 0.3 and y=1.4). In spite of its low transition temperature, several similarities with high temperature superconducting cuprates have raised interest in this compound. Nevertheless, up to now, a clear understanding of the role of water has not been achieved. Since superconductivity appears only when water is inserted in the parent compound, the goal of this research work was to understand what kind of effect water intercalation has in terms of electron conduction and superconductivity. Neutron scattering played a crucial role in this study because of its ability to determine the accurate positions of light elements such as hydrogen or deuterium. We have focused our attention on the intra-molecular range of D2O, studying the structural changes that take place within the (heavy) water molecules themselves. In order to do this the distance correlations D-D, D-O, and O-O have been studied. Powder neutron diffraction data of the deuterated sodium cobaltate have been analyzed using the Pair Density Function (PDF) technique, which gives information about the local structure of the water molecules. The peaks of the PDF of the neutron diffraction data, in fact, give directly in real space the distances between pair of atoms, in this case the distances D-D, D-O, and O-O. If a peak shifts to a lower (or higher) value of r (Å) it means that the bond between that particular pair of atoms has become shorter (or longer). In this way it was possible to determine any change in the geometry of the water molecules. The results obtained show that the D-D distance and the D-O-D angle in Na0.35CoO21.4D2O are significantly different from those of ordinary water (D2O). Two coexisting distributions of possible D-O-D bond angles are observed. We speculate that the altered geometry of the intercalated water molecules is due to a modification of the dynamics of the hydrogen bond. In this case, water may be embedded in an electronically active environment and indirectly participate in electronic conduction

The Impact of Genetic and Environmental Factors on Phytonutrient Concentrations within Leafy Specialty Crops in Controlled Environments

Specialty leafy greens are excellent sources of antioxidants, vitamins, and minerals. Many of these metabolites are influenced by microclimate environmental conditions and genotype. The objective of this thesis was to measure the impacts of abiotic factors on plant growth and development along with nutritional content of specialty leafy greens in controlled environments. Chapter one looks at changes in biomass and nutritional content of different microgreen cultivars grown in a greenhouse over four growing seasons. Chapter two looks at the influence of light-emitting diode (LED) treatments on the growth and nutritional content of hydroponically grown kale. The morphology and nutritional content of hydroponically grown kale plants were significantly impacted by LED treatment. LED treatments with higher proportion of blue light had significantly shorter plants and greater fresh mass (FM) as compared to all other LED treatments. Environmental and genetic factors influenced the growth and development, as well as impacted the nutritional content of the different microgreen cultivars. Brassica microgreens had the highest FM and shortest production times throughout all seasons, as compared to the herb and lettuce microgreens. Whereas, the herb microgreens had the highest concentrations of shoot tissue carotenoids and minerals, as compared to brassica and lettuce microgreens. Results from this thesis provides valuable production data for producers who grow specialty leafy greens in controlled environments. Nutritional data among microgreen species may contribute to consumer knowledge for healthy eating choices

Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models.

Continuous de novo fatty acid synthesis is a common feature of cancer that is required to meet the biosynthetic demands of a growing tumor. This process is controlled by the rate-limiting enzyme acetyl-CoA carboxylase (ACC), an attractive but traditionally intractable drug target. Here we provide genetic and pharmacological evidence that in preclinical models ACC is required to maintain the de novo fatty acid synthesis needed for growth and viability of non-small-cell lung cancer (NSCLC) cells. We describe the ability of ND-646-an allosteric inhibitor of the ACC enzymes ACC1 and ACC2 that prevents ACC subunit dimerization-to suppress fatty acid synthesis in vitro and in vivo. Chronic ND-646 treatment of xenograft and genetically engineered mouse models of NSCLC inhibited tumor growth. When administered as a single agent or in combination with the standard-of-care drug carboplatin, ND-646 markedly suppressed lung tumor growth in the Kras;Trp53-/- (also known as KRAS p53) and Kras;Stk11-/- (also known as KRAS Lkb1) mouse models of NSCLC. These findings demonstrate that ACC mediates a metabolic liability of NSCLC and that ACC inhibition by ND-646 is detrimental to NSCLC growth, supporting further examination of the use of ACC inhibitors in oncology