The Emerging Role of Altered D-Aspartate Metabolism in Schizophrenia: New Insights From Preclinical Models and Human Studies

Besides D-serine, another D-amino acid with endogenous occurrence in the mammalian brain, D-aspartate, has been recently shown to influence NMDA receptor (NMDAR)-mediated transmission. D-aspartate is present in the brain at extracellular level in nanomolar concentrations, binds to the agonist site of NMDARs and activates this subclass of glutamate receptors. Along with its direct effect on NMDARs, D-aspartate can also evoke considerable L-glutamate release in specific brain areas through the presynaptic activation of NMDA, AMPA/kainate and mGlu5 receptors. D-aspartate is enriched in the embryonic brain of rodents and humans and its concentration strongly decreases after birth, due to the post-natal expression of the catabolising enzyme D-aspartate oxidase (DDO). Based on the hypothesis of NMDAR hypofunction in schizophrenia pathogenesis, recent preclinical and clinical studies suggested a relationship between perturbation of D-aspartate metabolism and this psychiatric disorder. Consistently, neurophysiological and behavioral characterization of Ddo knockout (Ddo−/−) and D-aspartate-treated mice highlighted that abnormally higher endogenous D-aspartate levels significantly increase NMDAR-mediated synaptic plasticity, neuronal spine density and memory. Remarkably, increased D-aspartate levels influence schizophrenia-like phenotypes in rodents, as indicated by improved fronto-hippocampal connectivity, attenuated prepulse inhibition deficits and reduced activation of neuronal circuitry induced by phencyclidine exposure. In healthy humans, a genetic polymorphism associated with reduced prefrontal DDO gene expression predicts changes in prefrontal phenotypes including greater gray matter volume and enhanced functional activity during working memory. Moreover, neurochemical detections in post-mortem brain of schizophrenia-affected patients have shown significantly reduced D-aspartate content in prefrontal regions, associated with increased DDO mRNA expression or DDO enzymatic activity. Overall, these findings suggest a possible involvement of dysregulated embryonic D-aspartate metabolism in schizophrenia pathophysiology and, in turn, highlight the potential use of free D-aspartate supplementation as a new add-on therapy for treating the cognitive symptoms of this mental illness

Experimental Evidence on Tax Salience and Tax Incidence

While a basic theoretical principle in public economics assumes that individuals’ behaviour is fully-optimizer with respect to the introduction of a tax, an increasing body of research is presenting evidence that agents decision making is often affected by non-negligible cognitive biases, which could be responsible for lower market performance as well as for deviations from standard theoretical predictions. This paper extends the latter strand of research focusing on two trend topics in public economics: tax salience and tax incidence. While the former refers to the prominence of the tax, the latter places emphasis on the statutory vs. factual division of tax payments. Is market performance affected by the salience of the tax? Is the incidence of a tax independent of which side of the market it is levied on (Liability Side Equivalence Principle, LES)? We address these questions through a laboratory experiment in which one unit of a fictitious good is traded through a double-auction market institution. Based on a panel data analysis, our contribution shows that a non-salient tax reduces both the allocational and informational efficiency of the market with respect to the instance in which the tax is salient. Moreover, we show that the Liability Side Equivalence Principle does not hold in practice

Start up of biological sequencing batch reactor (SBR) and short-term biomass acclimation for polyhydroxyalkanoates production

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Experimental Evidence on Tax Salience and Tax Incidence

While a basic theoretical principle in public economics assumes that individuals’ behaviour is fully-optimizer with respect to the introduction of a tax, an increasing body of research is presenting evidence that agents decision making is often affected by non-negligible cognitive biases, which could be responsible for lower market performance as well as for deviations from standard theoretical predictions. This paper extends the latter strand of research focusing on two trend topics in public economics: tax salience and tax incidence. While the former refers to the prominence of the tax, the latter places emphasis on the statutory vs. factual division of tax payments. Is market performance affected by the salience of the tax? Is the incidence of a tax independent of which side of the market it is levied on (Liability Side Equivalence Principle, LES)? We address these questions through a laboratory experiment in which one unit of a fictitious good is traded through a double-auction market institution. Based on a panel data analysis, our contribution shows that a non-salient tax reduces both the allocational and informational efficiency of the market with respect to the instance in which the tax is salient. Moreover, we show that the Liability Side Equivalence Principle does not hold in practice

Parenteral Nutrition in Liver Resection

Albeit a very large number of experiments have assessed the impact of various substrates on liver regeneration after partial hepatectomy, a limited number of clinical studies have evaluated artificial nutrition in liver resection patients. This is a peculiar topic because many patients do not need artificial nutrition, while several patients need it because of malnutrition and/or prolonged inability to feeding caused by complications. The optimal nutritional regimen to support liver regeneration, within other postoperative problems or complications, is not yet exactly defined. This short review addresses relevant aspects and potential developments in the issue of postoperative parenteral nutrition after liver resection

Innovation in grapevine water status monitoring and drought adaptation: leaf angle and temperature regulation

Increase of frequency, duration, and intensity of drought and heatwave and related water and heat crops stress are among the principal effects of climate change. This paper reports: (i) the effect of calcite particle film (CaPF) as a mitigation strategy against heat stress in well-watered (WW) or in drought-stress (D) conditions; and (ii) response of leaf angle variation to stomatal conductance changes induced by drought stress of Aleatico grapevine cultivar. Results have showed that CaPF, under WW conditions, reduced leaf temperature, and increased gas exchange, but, under very severe water stress, CaPF treatment was ineffective. Leaf angle ranged from 70° (WW vines) to 100° (drought stressed vines) and showed a good fit (R2 =0.81) with stomatal conductance within the range of 0.25 – 0.05 mol m-2 s–1 proving it might be a reliable proxy of vine water status

Old age: biologic versus chronologic

We read with great interest the article by Goldberg et al1 reporting the results of a “Pooled Analysis of Safety and Efficacy of Oxaliplatin Plus Fluorouracil/Leucovorin Administered Bimonthly in Elderly Patients With Colorectal Cancer” published in the September 1, 2006, issue of the Journal of Clinical Oncology. The elderly population represents a heterogeneous group of patients frequently undertreated due to their age, although benefits of therapy could be overlapped with their younger counterpart

Insulin Resistance as Common Molecular Denominator Linking Obesity to Alzheimer's Disease

Alzheimer's disease (AD) is an aging-related multi-factorial disorder to which metabolic factors contribute at what has canonically been considered a centrally mediated process. Although the exact underlying mechanisms are still unknown, obesity is recognized as a risk factor for AD and the condition of insulin resistance seems to be the link between the two pathologies. Using mice with high fat diet (HFD) obesity we dissected the molecular mechanisms shared by the two disorders. Brains of HFD fed mice showed elevated levels of APP and Aβ40/Aβ42 together with BACE, GSK3β and Tau proteins involved in APP processing and Aβ accumulation. Immunofluorescence, Thioflavin T staining experiments, confirmed increased Aβ generation, deposition in insoluble fraction and plaques formation in both the hippocampus and the cerebral cortex of HFD mice. Presence of Aβ40/Aβ42 in the insoluble fraction was also shown by ELISA assay. Brain insulin resistance was demonstrated by reduced presence of insulin receptor (IRs) and defects in Akt-Foxo3a insulin signaling. We found reduced levels of phospho-Akt and increased levels of Foxo3a in the nuclei of neurons where proapototic genes were activated. Dysregulation of different genes related to insulin resistance, especially those involved in inflammation and adipocytokines synthesis were analyzed by Profiler PCR array. Further, HFD induced oxidative stress, mitochondrial dysfunction and dynamics as demonstrated by expression of biomarkers involved in these processes. Here, we provide evidence that obesity and AD markers besides insulin resistance are associated with inflammation, adipokine dyshomeostasis, oxidative stress and mitochondrial dysfunction, all mechanisms leading to neurodegeneration

Protective, Antioxidant and Antiproliferative Activity of Grapefruit IntegroPectin on SH-SY5Y Cells

Tested in vitro on SH-SY5Y neuroblastoma cells, grapefruit IntegroPectin is a powerful protective, antioxidant and antiproliferative agent. The strong antioxidant properties of this new citrus pectin, and its ability to preserve mitochondrial membrane potential and morphology, severely impaired in neurodegenerative disorders, make it an attractive therapeutic and preventive agent for the treatment of oxidative stress-associated brain disorders. Similarly, the ability of this pectic polymer rich in RG-I regions, as well as in naringin, linalool, linalool oxide and limonene adsorbed at the outer surface, to inhibit cell proliferation or even kill, at high doses, neoplastic cells may have opened up new therapeutic strategies in cancer research. In order to take full advantage of its vast therapeutic and preventive potential, detailed studies of the molecular mechanism involved in the antiproliferative and neuroprotective of this IntegroPectin are urgently needed