Effect of substituents on complex stability aimed at designing new iron(III) and aluminum(III) chelators

The solution equilibria of iron(III) and aluminum(III) with two classes of hard ligands (catechol, salicylic acid and their nitro-derivatives) have been reliably studied by potentiometric, spectrophotometric and NMR spectroscopy. The effect of the nitro substituent on the binding properties of catechol and salicylic acid has been examined thoroughly. The inductive and resonance properties of the substituent that, as expected, lower the basicity of the phenolic and carboxylic groups, lead to a general decrease in both protonation and complex formation constants. This decrease causes an increase in pM of between 0.2 and 1.1 pM units for the nitro-substituted salicylates and of about 4 units for 4-nitrocatechol, with a significantly higher chelating efficacy. The influence of the substituent on catechol and salicylic acid is discussed in detail on the basis of conditional constants at pH 7.4.     

Effects of denzimol on benzodiazepine receptors in the CNS: Relationship between the enhancement of diazepam activity and benzodiazepine binding sites induced by denzimol in the rat

Denzimol, a new anticonvulsant drug with a pharmacological profile similar to that of phenytoin, enhances the ataxic and antimetrazol activity of diazepam in rats without affecting its activity against picrotoxin-induced seizures. $\text{In vivo}$ and $\text{ex vivo}$ denzimol enhances the binding of ³H-flunitrazepam in cortex and in hippocampus but not in cerebellum.The possibility of this increase in the number of benzodiazepine binding sites contributing in some way to enhancement of the depressive and anticonvulsant activity of diazepam is discussed.     

Benzodiazepine receptors': Correlation with pharmacological responses in living animals

The data relating the pharmacological activities of benzodiazepines to $\text{in vivo}$ occupancy of their receptor sites is reviewed, in the light of the complexity of evaluating pharmacodynamic parameters in living animals. Methodological problems in the measurement of $\text{in vivo}$ receptor occupancy and species differences in benzodiazepine metabolism are considered in detail.     

The tongue morphology and lingual gland histochemistry of Ligurian Sea odontocetes

The morphology and histomorphology of the tongue and the histochemistry of the lingual glands of eight specimens from four species of Ligurian Sea odontocetes (Stenella coeruleoalba, Tursiops truncatus, Grampus griseus, and Ziphius cavirostris) were studied. The shape of tongues and the appearance of their dorsal surfaces differed between species. The lingual glands differed in size, distribution, and histochemistry by species. In S. coeruleoalba and G. griseus, a strong alcianophilic mucous material was detected in the lingual glands, while neutral and acidic mucous substances were observed in the most proximal secretory acini. In G. griseus, small simple alveolar apocrine glands were also found, and the duct of the serous lingual glands in Z. cavirostris is of apocrine type. Numerous mechanoreceptors were observed. Only the tongue of the young specimens showed marginal papillae: their histomorphological composition is consistent with the hypothesis that they create a tight seal between the tongue and the roof of the cavity in order to create suction. This comparative study suggests that differences in tongue morphology and in the morphology and histochemistry of lingual glands might be related to feeding habits.     

Proteomics contributions to epigenetic drug discovery

The combined activity of epigenetic features, which include histone post-translational modifications, DNA methylation, and nucleosome positioning, regulates gene expression independently from changes in the DNA sequence, defining how the shared genetic information of an organism is used to generate different cell phenotypes. Alterations in epigenetic processes have been linked with a multitude of diseases, including cancer, fueling interest in the discovery of drugs targeting the proteins responsible for writing, erasing, or reading histone and DNA modifications. Mass spectrometry (MS)-based proteomics has emerged as a versatile tool that can assist drug discovery pipelines from target validation, through target deconvolution, to monitoring drug efficacy in vivo. Here, we provide an overview of the contributions of MS-based proteomics to epigenetic drug discovery, describing the main approaches that can be used to support different drug discovery pipelines and highlighting how they contributed to the development and characterization of epigenetic drugs.     

The impact of human trampling on a threatened coastal Mediterranean plant: The case of Anchusa littorea Moris (Boraginaceae)

In a 5-period study (2007–2011) we examined the effects of human trampling on the last remaining population of Anchusa littorea on its sandy coastal habitat in Sardinia. This species, considered extinct in the wild for several years, was casually rediscovered in a small population at Is Arenas (SW Sardinia). We monthly monitored six trampled and six un-trampled permanent plots, mapping individuals and recording their size and reproductive variables. Trampled and un-trampled plots showed significant differences with respect to plant density, plant size and reproductive performance (flowers and fruits production) of A. littorea. This study demonstrated that human trampling represents a severe threat to the conservation of this species that can be appreciated as a keystone species with concern to human trampling effects on coastal dune plants. In case of A. littorea urgent measures should be undertaken to protect this unique remnant population in the dune system of Is Arenas. In particular, tourist paths should be redirected and confined to others areas in order to promote the natural expansion of A. littorea in its original habitat. A possible integrated strategy for the conservation and management of the species consists in a combination of in situ and ex situ measures.     

Scheffersomyces stipitis ability to valorize different residual biomasses for vitamin B9 production

Sugar beet pulp (SBP), sugar beet molasses (SBM) and unfermented grape marcs (UGM) represent important waste in the agro-food sector. If suitably pre-treated, hexose and pentose sugars can be released in high quantities and can subsequently be used by appropriate cell factories as growth media and for the production of (complex) biomolecules, accomplishing the growing demand for products obtained from sustainable resources. One example is vitamin B₉ or folate, a B-complex vitamin currently produced by chemical synthesis, almost exclusively in the oxidized form of folic acid (FA). It is therefore desirable to develop novel competitive strategies for replacing its current fossil-based production with a sustainable bio-based process. In this study, we assessed the production of natural folate by the yeast Scheffersomyces stipitis, investigating SBM, SBP and UGM as potential growth media. Pre-treatment of SBM and SBP had previously been optimized in our laboratory; thus, here we focused only on UGM pre-treatment and hydrolysis strategies for the release of fermentable sugars. Then, we optimized the growth of S. stipitis on the three media formulated from those biomasses, working on inoculum pre-adaptation, oxygen availability and supplementation of necessary nutrients to support the microorganism. Folate production, measured with a microbiological assay, reached 188.2 ± 24.86 μg/L on SBM, 130.6 ± 1.34 μg/L on SBP and 101.9 ± 6.62 μg/L on UGM. Here, we demonstrate the flexibility of S. stipitis in utilizing different residual biomasses as growth media. Moreover, we assessed the production of folate from waste, and to the best of our knowledge, we obtained the highest production of folate from residual biomasses ever reported, providing the first indications for the future development of this microbial production process.