N-Methyl-D-aspartic Acid (NMDA) in the nervous system of the amphioxus Branchiostoma lanceolatum

<p>Abstract</p> <p>Background</p> <p>NMDA (<it>N</it>-methyl-D-aspartic acid) is a widely known agonist for a class of glutamate receptors, the NMDA type. Synthetic NMDA elicits very strong activity for the induction of hypothalamic factors and hypophyseal hormones in mammals. Moreover, endogenous NMDA has been found in rat, where it has a role in the induction of GnRH (Gonadotropin Releasing Hormone) in the hypothalamus, and of LH (Luteinizing Hormone) and PRL (Prolactin) in the pituitary gland.</p> <p>Results</p> <p>In this study we show evidence for the occurrence of endogenous NMDA in the amphioxus <it>Branchiostoma lanceolatum</it>. A relatively high concentration of NMDA occurs in the nervous system of this species (3.08 ± 0.37 nmol/g tissue in the nerve cord and 10.52 ± 1.41 nmol/g tissue in the cephalic vesicle). As in rat, in amphioxus NMDA is also biosynthesized from D-aspartic acid (D-Asp) by a NMDA synthase (also called D-aspartate methyl transferase).</p> <p>Conclusion</p> <p>Given the simplicity of the amphioxus nervous and endocrine systems compared to mammalian, the discovery of NMDA in this protochordate is important to gain insights into the role of endogenous NMDA in the nervous and endocrine systems of metazoans and particularly in the chordate lineage.</p

Looking at Socially Integrative Cities through the Educating City: The Example of Educational Museums in Europe and China

This contribution aims to show how the idea of an educating city can help to find effective ways of social integration capable of promoting the well-being of individuals and the community. In this direction, the concept of an educating city is adopted as a key to re-read the concept of a socially integrative city through an eminently educational perspective. The education channel, rethought through multiple learning initiatives capable of following alternative paths to those of school and university experiences (formal education), allows enhancing the human potential and wealth of knowledge and skills of the city, making all citizens protagonists and participants. In addressing this issue, a specific case study will be analyzed: educational museums. The aim is to show how the museum, as a non-formal education space and an expression of collective identity, can play an important role in connoting a city as an educating city. Specifically, both the European and Chinese realities will be examined to offer one of the possible insights into how the city is a reality in progress to be explored, which can grow and improve together with its citizens if you work in the direction of community education (Dewey) by rediscovering a place that, like museums, can contribute to enrich the social capital of a community. ULTERIORI INFORMAZIONI: lo scrivente, F. d'Aniello, è autore del paragrafo Introduction: the Educating City: pp. 175-177

Simultaneous onset of infantile spasms in monozygotic twins.

The clinical, electroencephalographic, and genetic findings are reported for three pairs of monozygotic twins who developed infantile spasms in their first year. In all three pairs, the spasms started on the same day in each member of the pair. Neither sequencing of the ARX and CDKL5 (alias STK9) genes nor array comparative genomic hybridization assessment revealed any abnormalities. The long-term outcome was poor in all twins, although with different severity in individual pairs. These findings suggest that genes other than those currently known likely play a role in predisposition to infantile spasms, and that genetic susceptibility is linked to a variable phenotypic expression, ranging from quite benign to very severe, in monozygotic twins with no other apparent risk factors

Induction of Cytotoxic Oxidative Stress by d-Alanine in Brain Tumor Cells Expressing Rhodotorula gracilis d-Amino Acid Oxidase: A Cancer Gene Therapy Strategy

Overview summary Gene-directed enzyme prodrug therapy (GDEPT) is an antineoplastic treatment strategy designed to overcome the systemic toxicity of chemotherapy by specifically expressing a foreign enzyme in malignant cells that converts a nontoxic prodrug into a cytotoxic metabolite. The relative inefficiency of current in situ gene transfer methodology suggests that enzyme/prodrug combinations that produce membrane permeable metabolites will elicit a more favorable therapeutic response. Ideally, the agent produced by the transduced cell “factories” would be cytotoxic toward both proliferating and quiescent cells. We describe a novel GDEPT approach using d-amino acid oxidase from the red yeast Rhodotorula gracilis and d-alanine as a substrate that generates hydrogen peroxide, a reactive metabolite of oxygen that has both these characteristics. We also demonstrate the ability to sensitize tumor cells to this GDEPT protocol by manipulating cellular antioxidant pathways.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63220/1/hum.1998.9.2-185.pd

Individual differences and knockout in zebrafish reveal similar cognitive effects of BDNF between teleosts and mammals

The remarkable similarities in cognitive performance between teleosts and mammals suggest that the underlying cognitive mechanisms might also be similar in these two groups. We tested this hypothesis by assessing the effects of the brain-derived neurotrophic factor (BDNF), which is critical for mammalian cognitive functioning, on fish's cognitive abilities. We found that individual differences in zebrafish's learning abilities were positively correlated with bdnf expression. Moreover, a CRISPR/Cas9 mutant zebrafish line that lacks the BDNF gene (bdnf(-/-)) showed remarkable learning deficits. Half of the mutants failed a colour discrimination task, whereas the remaining mutants learned the task slowly, taking three times longer than control bdnf(+/+) zebrafish. The mutants also took twice as long to acquire a T-maze task compared to control zebrafish and showed difficulties exerting inhibitory control. An analysis of habituation learning revealed that cognitive impairment in mutants emerges early during development, but could be rescued with a synthetic BDNF agonist. Overall, our study indicates that BDNF has a similar activational effect on cognitive performance in zebrafish and in mammals, supporting the idea that its function is conserved in vertebrates

Numerical modelling of masonry infill walls in existing steel frames

It is now widely recognised that masonry infill plays an essential role in the seismic behaviour of existing steel buildings; however, there is still a lack of clear guidance on the modelling of masonry infill in the current Eurocode 8-Part 3. Several methods for the numerical modelling of masonry infills have been proposed in literature over the past few decades, which either adopt a detailed approach (micro-model) or a simplified approach (macromodel). In the former case, bricks are individually modelled, taking into account the brickmortar cohesive interface, which is able to provide detailed insights of the behaviour of masonry infills and the frame-wall interaction but usually at a high computational cost. On the other hand, a simplified model can be easily built within finite element software, most of which replace the infill wall panel with one or more equivalent struts in the diagonal direction. It has been demonstrated that the strut models can simulate RC infilled structures’ global response with acceptable accuracy; however, there are still no adequate recommendations for their modelling within steel frames. Besides, these models are generally incapable of capturing the interactions between the infills and the frame members. To this end, the present paper numerically investigates an Abaqus macro-model of the infilled steel frame, which was experimentally tested as part of the recent SERA HITFRAMES project. The preliminary re-sults shows that the different detailing of steel frames could lead to different damage patterns in the infill walls when compared to RC frames. In particular, instead of a single diagonal strut, at most three struts were observed in this study. The results also suggested that the number and geometry of struts could change with increasing displacement demands, hence it might not be appropriate to use the same strut model for infill walls on different floors

Zebrafish, a novel model system to study uremic toxins: The case for the sulfur amino acid lanthionine

The non-proteinogenic amino acid lanthionine is a byproduct of hydrogen sulfide biosynthesis: the third endogenous vasodilator gas, after nitric oxide and carbon monoxide. While hydrogen sulfide is decreased in uremic patients on hemodialysis, lanthionine is increased and has been proposed as a new uremic toxin, since it is able to impair hydrogen sulfide production in hepatoma cells. To characterize lanthionine as a uremic toxin, we explored its effects during the early development of the zebrafish (Danio rerio), a widely used model to study the organ and tissue alterations induced by xenobiotics. Lanthionine was employed at concentrations reproducing those previously detected in uremia. Light-induced visual motor response was also studied by means of the DanioVision system. Treatment of zebrafish embryos with lanthionine determined acute phenotypical alterations, on heart organogenesis (disproportion in cardiac chambers), increased heart beating, and arrhythmia. Lanthionine also induced locomotor alterations in zebrafish embryos. Some of these effects could be counteracted by glutathione. Lanthionine exerted acute effects on transsulfuration enzymes and the expression of genes involved in inflammation and metabolic regulation, and modified microRNA expression in a way comparable with some alterations detected in uremia. Lanthionine meets the criteria for classification as a uremic toxin. Zebrafish can be successfully used to explore uremic toxin effects

Valproic acid and phenobarbital blood levels during the first month of treatment with the ketogenic diet.

Objective – The aim of this study was to assess how the ketogenic diet influences the blood levels of antiepileptic drugs in the first month of treatment in a pediatric population with drug-resistant epilepsy. Methods – The plasma concentrations of antiepileptic drugs were investigated in an open study on 36 consecutive children and adolescents (20 males), aged between 6 months and 16 years (mean age 4.7 years), who were put on the ketogenic diet because of medically refractory epilepsy. The plasma levels of antiepileptic drugs were determined 30 days and immediately before the diet and on days 8, 15, 22 and 29 after the start of the diet. The daily dose of each drug was not changed during the first month of treatment, while the daily dose of benzodiazepines was reduced by up to 30% if excessive sedation or drowsiness occurred. Results – While plasma concentrations of phenobarbital did not change in the first month on the ketogenic diet (mean increase of 2.3 mg ⁄ l 1.0), valproic acid showed a slight but not significant decrease (mean decresase of 6.7 mg ⁄ l 3.2), 2 weeks after the start of the diet. Conclusions – Adjustments in the daily dose of either drug before the start of the diet do not however appear to be justified

Dynamic response of existing steel frames with masonry infills under multiple earthquakes

Existing steel moment-resisting frames in several seismic regions worldwide are often characterised by high vulnerability to earthquakes due to insufficient local and/or global ductility. Therefore, it is of paramount importance to assess their response under strong motions and provide cost-effective retrofitting remedies. However, the current code-based assessment framework utilized in Europe for assessing existing structures is inadequate and requires improvement, especially to account for the contribution of masonry infills as they significantly influence the seismic response of steel buildings. To this end, the H2020-INFRAIA-SERA project HITFRAMES (i.e., Hybrid Testing of an Existing Steel Frame with Infills under Multiple Earthquakes) aims at experimental evaluation of a case study building representative of non-seismically designed European steel frames. This paper presents the dynamic response analyses of the case study building and serves as a theoretical prediction of the experimental results for HTTFRAMES. The case study building is analysed as a bare, an infilled and a retrofitted frame with buckling restrained braces (BRBs), respectively. It is subjected to the natural seismic sequence recorded during the 2016-2017 Central Italy earthquakes. The modal properties of the case study building are determined first, followed by the investigation of its non-linear dynamic response. The dynamic tests are performed with the earthquake records scaled to different intensity levels to simulate the structural performance under different limit states according to Eurocode 8-Part 3. The impact of masonry infills and BRB-retrofit is also investigated by comparing the response of models with different configurations. It can be concluded that appropriately-designed BRBs are effective in protecting steel frames from experiencing critical damage during earthquakes and reducing significantly the transient and residual drift

Brain Proteome and Behavioural Analysis in Wild Type, BDNF+/− and BDNF−/− Adult Zebrafish (Danio rerio) Exposed to Two Different Temperatures

Experimental evidence suggests that environmental stress conditions can alter the expression of BDNF and that the expression of this neurotrophin influences behavioural responses in mammalian models. It has been recently demonstrated that exposure to 34 degrees C for 21 days alters the brain proteome and behaviour in zebrafish. The aim of this work was to investigate the role of BDNF in the nervous system of adult zebrafish under control and heat treatment conditions. For this purpose, zebrafish from three different genotypes (wild type, heterozygous BDNF+/- and knock out BDNF-/-) were kept for 21 days at 26 degrees C or 34 degrees C and then euthanized for brain molecular analyses or subjected to behavioural tests (Y-maze test, novel tank test, light and dark test, social preference test, mirror biting test) for assessing behavioural aspects such as boldness, anxiety, social preference, aggressive behaviour, interest for the novel environment and exploration. qRT-PCR analysis showed the reduction of gene expression of BDNF and its receptors after heat treatment in wild type zebrafish. Moreover, proteomic analysis and behavioural tests showed genotype- and temperature-dependent effects on brain proteome and behavioural responding. Overall, the absent expression of BDNF in KO alters (1) the brain proteome by reducing the expression of proteins involved in synapse functioning and neurotransmitter-mediated transduction; (2) the behaviour, which can be interpreted as bolder and less anxious and (3) the cellular and behavioural response to thermal treatment