Interactions between fibroblast growth factors and Notch regulate neuronal differentiation

The differentiation of precursor cells into neurons has been shown to be influenced by both the Notch signaling pathway and growth factor stimulation. In this study, the regulation of neuronal differentiation by these mechanisms was examined in the embryonic day 10 neuroepithelial precursor (NEP) population. By downregulating Notch1 expression and by the addition of a Delta1 fusion protein (Delta Fc), it was shown that signaling via the Notch pathway inhibited neuron differentiation in the NEP cells, in vitro. The expression of two of the Notch receptor homologs, Notch1 and Notch3, and the ligand Delta1 in these NEP cells was found to be influenced by a number of different growth factors, indicating a potential interaction between growth factors and Notch signaling. Interestingly, none of the growth factors examined promoted neuron differentiation; however, the fibroblast growth factors (FGFs) 1 and 2 potently inhibited differentiation. FGF1 and FGF2 upregulated the expression of Notch and decreased expression of Delta1 in the NEP cells. In addition, the inhibitory response of the cells to the FGFs could be overcome by downregulating Notch1 expression and by disrupting Notch cleavage and signaling by the ablation of the Presenilin1 gene. These results indicate that FGF1 and FGF2 act via the Notch pathway, either directly or indirectly, to inhibit differentiation. Thus, signaling through the Notch receptor may be a common regulator of neuronal differentiation within the developing forebrain

Schools and the legacy of hybrid buildings

Learning from the past, collecting data on the Italian condition of school buildings, our R&D work aimed to question the design process of school buildings in Italy introducing an innovative model of school, which turned the conventional and isolated, mono-functional and rigid school buildings into interior urban public spaces and porous community hubs to empower the communities around them and to become manifestos of sustainability. Through some built examples of school buildings designed in Italy, the paper discusses the outputs and impact of the introduction of new design layouts, participation projects with different stakeholders and sustainability. The research has guided the introduction of the new Italian guide-lines for school building design, approved in 2013. A future perspective to be explored is the reconsideration of exporting the strategy in different contexts and to design reconsider other public infrastructures turning the mono-functional use of public buildings into hybrid and multifunctional ones

Bioleaching of Valuable Elements from Red Mud: A Study on the Potential of Non-Enriched Biomass

Red mud (RM) is the main residue produced by the alkaline extraction of alumina (Al2O3) from bauxite, and it contains valuable metals such as iron (Fe), aluminium (Al), titanium (Ti), magnesium (Mg), manganese (Mn), rare earth elements, etc. This research aimed to investigate the biologically induced leaching of some valuable elements from raw RM without preliminary biomass enrichment and inoculum, simultaneously reducing RM polluting potential and extracting metals for their subsequent recovery within a circular economy-based approach. In addition to the missing inoculum, such an approach is challenging since high RM alkalinity and pH, as well as the absence of any sulphides, constrain the use of the most common biohydrometallurgical techniques. Red Muds from two European locations were tested (RM-I and RM-II, respectively). Bioleaching tests were performed at different temperatures (T = 22 & DEG;C and 28 & DEG;C; and also 15 & DEG;C for RM-II) and solid-to-liquid ratios (S/L = 2%, 5%). A sudden drop in pH from alkaline to constant neutral/acidic values was observed in almost all tests, and such results were attributed to biological activity since abiotic tests did not show any pH decrease. The best results in terms of extraction were achieved with RM-II, in particular for Al, Mg and Mn (17%, 42% and 47%, respectively). At 2% S/L, the highest temperature allowed for a better metal release, while at 5% S/L, the highest extraction of Al, Mg and Ti was observed at 22 & DEG;C. As expected, iron was less available to leach at the achieved pH values, as it was mostly present as hematite in both RMs. Finally, the first microbiological characterisation of the autochthonous biomass selected during the bioleaching treatment of RM was provided

Fatal hyalohyphomycosis with cutaneous involvement caused by purpureocillium lilacinum in an immunocompromised patient with bullous pemphigoid

Emergent pathogen as Purpureocillium lilacinum are becoming cause of morbidity and mortality in our population, especially in immunocompromised patients. We describe a case of hyalohyphomycosis in a diabetic man under systemic steroid treatment for a bullous pemphigoid. Treatment with different antimycotic drugs were ineffective and infection spread diffusely, leading to deterioration of general conditions and ultimately death. The aim of this article is to increase awareness of clinicians about this uncommon, but frequently fatal refractory mycotic infection

A review on coordination properties of thiol-containing chelating agents towards mercury, cadmium, and lead

The present article reviews the clinical use of thiol-based metal chelators in intoxications and overexposure with mercury (Hg), cadmium (Cd), and lead (Pb). Currently, very few commercially available pharmaceuticals can successfully reduce or prevent the toxicity of these metals. The metal chelator meso-2,3-dimercaptosuccinic acid (DMSA) is considerably less toxic than the classical agent British anti-Lewisite (BAL, 2,3-dimercaptopropanol) and is the recommended agent in poisonings with Pb and organic Hg. Its toxicity is also lower than that of DMPS (dimercaptopropane sulfonate), although DMPS is the recommended agent in acute poisonings with Hg salts. It is suggested that intracellular Cd deposits and cerebral deposits of inorganic Hg, to some extent, can be mobilized by a combination of antidotes, but clinical experience with such combinations are lacking. Alpha-lipoic acid (alpha-LA) has been suggested for toxic metal detoxification but is not considered a drug of choice in clinical practice. The molecular mechanisms and chemical equilibria of complex formation of the chelators with the metal ions Hg2+, Cd2+, and Pb2+ are reviewed since insight into these reactions can provide a basis for further development of therapeutics

Opposite Structural Effects of Epigallocatechin-3-gallate and Dopamine Binding to α-Synuclein

The intrinsically disordered and amyloidogenic protein α-synuclein (AS) has been linked to several neurodegenerative states, including Parkinson's disease. Here, nanoelectrospray-ionization mass spectrometry (nano-ESI-MS), ion mobility (IM), and native top-down electron transfer dissociation (ETD) techniques are employed to study AS interaction with small molecules known to modulate its aggregation, such as epigallocatechin-3-gallate (EGCG) and dopamine (DA). The complexes formed by the two ligands under identical conditions reveal peculiar differences. While EGCG engages AS in compact conformations, DA preferentially binds to the protein in partially extended conformations. The two ligands also have different effects on AS structure as assessed by IM, with EGCG leading to protein compaction and DA to its extension. Native top-down ETD on the protein-ligand complexes shows how the different observed modes of binding of the two ligands could be related to their known opposite effects on AS aggregation. The results also show that the protein can bind either ligand in the absence of any covalent modifications, such as oxidation

Impacts of Anthropogenic Pollutants on Benthic Prokaryotic Communities in Mediterranean Touristic Ports

Ports and marinas are central nodes in transport network and play a strategic role in coastal development. They receive pollution from land-based sources, marine traffic and port infrastructures on one side and constitute a potential pollution source for the adjacent coastal areas on the other. The aim of the present study was to evaluate the effects of organic and inorganic co-contamination on the prokaryotic communities in sediments from three Mediterranean ports. The structure and composition of the bacterial and archaeal communities were assessed by targeted metagenomic analysis of the 16S rRNA gene, and the links of prokaryotic communities with environmental and pollution variables were investigated. The harbors presented pronounced site-specificity in the environmental properties and pollution status. Consistently, the structure of archaeal and bacterial communities in surface sediments exhibited a strong spatial variation among the three investigated ports. On the contrary, a wide overlap in composition of prokaryotic assemblages among sites was found, but local variation in the community composition and loss of prokaryotic diversity was highlighted in a heavily impacted port sector near a shipyard. We provided evidences that organic matter, metals and PAHs as well as temperature and salinity play a strong role in structuring benthic bacterial communities significantly contributing to the understanding of their responses to anthropogenic perturbations in marine coastal areas. Among metals, copper was recognized as strongly associated with the observed changes in bacterial assemblages. Overall, this study provides the first assessment of the effects exerted by multiple organic and inorganic contaminations on benthic prokaryotes in ports over a large spatial scale and designates bacterial community as a candidate tool for the monitoring of the sediment quality status in harbors

Formation of citrazinic acid ions and their contribution to optical and magnetic features of carbon nanodots: A combined experimental and computational approach

The molecular model is one of the most appealing to explain the peculiar optical properties of Carbon nanodots (CNDs) and was proven to be successful for the bottom up synthesis, where a few molecules were recognized. Among the others, citrazinic acid is relevant for the synthesis of citric acid-based CNDs. Here we report a combined experimental and computational approach to discuss the formation of different protonated and deprotonated species of citrazinic acid and their contribution to vibrational and magnetic spectra. By computing the free energy formation in water solution, we selected the most favoured species and we retrieved their presence in the experimental surface enhanced Raman spectra. As well, the chemical shifts are discussed in terms of tautomers and rotamers of most favoured species. The expected formation of protonated and de-protonated citrazinic acid ions under extreme pH conditions was proven by evaluating specific interactions with H2 SO4 and NaOH molecules. The reported results confirm that the presence of citrazinic acid and its ionic forms should be considered in the interpretation of the spectroscopic features of CNDs

A family of kojic acid derivatives aimed to remediation of Pb2+ and Cd2+

The present work analyzes the complex formation ability towards Pb2+ and Cd2+ of a series of kojic acid derivatives that join the chelating properties of the pyrone molecules and those of polyamines, with the aim of evaluating how the different effects of oxygen and nitrogen coordinating groups act on the stability of metal complexes. Experimental research is carried out using potentiometric and spectrophotometric techniques supported by 1H and 13C NMR spectroscopy and DFT calculations. Actually, a different coordination mechanism toward Pb2+ and Cd2+ was proved: in the case of Pb2+, coordination takes place exclusively via the oxygen atoms, while the contribute of the nitrogen atoms appears relevant in the case of Cd2+. Lead complexes of all the studied ligands are characterized by significantly stronger stability than those of cadmium. Finally, on the basis of the measured complex formation stabilities, some of the proposed molecules seems promising effective ligands for lead and cadmium ion decorporation from polluted soils or waste waters