Design, Synthesis and Catalytic Activity of (Cyclopentadienone)iron Complexes Containing a Stereogenic Plane and a Stereogenic Axis

Herein, we report the synthesis and characterization of several chiral (cyclopentadienone)iron complexes (CICs) featuring either two (R)-BINOL-derived stereoaxes or a combination of one (R)-BINOL-derived stereoaxis and a stereogenic plane. The stereoplane-containing CICs were obtained as epimer mixtures, which were separated by flash column chromatography and assigned an absolute configuration based on XRD analysis, NMR and order of elution. The library was tested in the asymmetric hydrogenation of ketones showing good catalytic activity and a moderate stereoselectivity which, notably, is mostly imparted by the stereogenic plane. Indeed, the two epimers of each CIC possessing a stereoplane show opposite and equally strong stereochemical preference.Winning plane: chiral (cyclopentadienone)iron complexes (CICs) featuring a combination of an (R)-BINOL-derived stereoaxis and a stereogenic plane were synthesized in diastereoisomerically pure form, characterized and tested in the asymmetric hydrogenation of ketones. The new CICs showed good catalytic activity and, remarkably, the stereoplane epimers displayed similar and opposite stereochemical preference

A combined fragment-based virtual screening and STD-NMR approach for the identification of E-cadherin ligands

Cadherins promote cell-cell adhesion by forming homophilic interactions via their N-terminal extracellular domains. Hence, they have broad-ranging physiological effects on tissue organization and homeostasis. When dysregulated, cadherins contribute to different aspects of cancer progression and metastasis; therefore, targeting the cadherin adhesive interface with small-molecule antagonists is expected to have potential therapeutic and diagnostic value. Here, we used molecular docking simulations to evaluate the propensity of three different libraries of commercially available drug-like fragments (nearly 18,000 compounds) to accommodate into the Trp2 binding pocket of E-cadherin, a crucial site for the orchestration of the protein's dimerization mechanism. Top-ranked fragments featuring five different aromatic chemotypes were expanded by means of a similarity search on the PubChem database (Tanimoto index >90%). Of this set, seven fragments containing an aromatic scaffold linked to an aliphatic chain bearing at least one amine group were finally selected for further analysis. Ligand-based NMR data (Saturation Transfer Difference, STD) and molecular dynamics simulations suggest that these fragments can bind E-cadherin mostly through their aromatic moiety, while their aliphatic portions may also diversely engage with the mobile regions of the binding site. A tetrahydro-β-carboline scaffold functionalized with an ethylamine emerged as the most promising fragment

Short communication: Characterization of Staphylococcus aureus from bulk tank milk of dairy cattle in Lombardy (northern Italy).

ABSTRACT Staphylococcus aureus is one of the most important pathogens causing mastitis in cattle, and it is responsible for economic losses in dairy herds worldwide. The PCR amplification of the 16S-23S rRNA intergenic spacer (ribosomal spacer PCR, RS-PCR) allows a rapid classification of the strains in genotypes and genotypic clusters (CL), which are characterized by different epidemiological and clinical properties. Both RS-PCR and multi-locus sequence typing (MLST) were performed on strains isolated from bovine bulk tank milk (BTM) collected from dairy herds located in the Lombardy region (northern Italy), to outline the distribution of Staph. aureus genotypes in this geographical area. Out of 844 examined samples, 398 were positive for Staph. aureus, with a variable count (cfu/mL) Up to 8 colonies from each sample were genotyped. A total of 1,101 Staph. aureus strains were analyzed with RS-PCR, and only a selection of them (n = 86), in relation to their frequency and geographical origin, underwent MLST. This study revealed 8 major genotypic clusters (CLB, CLC, CLR, CLS, CLI, CLF, CLAO, and CLZ), of which Staph. aureus CLB (29.3%) was the most common. Samples of BTM positive for CLB had a Staph. aureus cfu/mL count significantly higher than the non-CLB positive ones. Our MLST analysis showed genotypes already known as bovine-associated in literature, such as clonal complexes CC8, CC97, and CC151. The same selection of 86 strains was also analyzed for the presence of the adlb gene, which was recently proposed as a possible marker of contagiousness. Most Staph. aureus belonging to CLB or CC8 carried the adlb gene (85%), whereas this gene was detected in only 9% of non-CLB strains (CLAA, CLBI, CLBJ, CLS). In conclusion, the present study confirms that Staph. aureus CLB, which is recognized as a contagious genotype, is a particularly relevant agent of intramammary infection in dairy cows in Lombardy, and indirectly supports the idea that adlb can be a possible marker of contagiousness of isolates

Conformational switch and multiple supramolecular structures of a newly identified self-assembling protein-mimetic peptide from Pseudomonas aeruginosa YeaZ protein

Protein-mimetic peptides (PMPs) are shorter sequences of self-assembling proteins, that represent remarkable building blocks for the generation of bioinspired functional supramolecular structures with multiple applications. The identification of novel aminoacidic sequences that permit the access to valuable biocompatible materials is an attractive area of research. In this work, in silico analysis of the Pseudomonas aeruginosa YeaZ protein (PaYeaZ) led to the identification of a tetradecapeptide that represents the shortest sequence responsible for the YeaZ-YeaZ dimer formation. Based on its sequence, an innovative 20-meric peptide, called PMP-2, was designed, synthesized, and characterized in terms of secondary structure and self-assembly properties. PMP-2 conserves a helical character and self-assembles into helical nanofibers in non-polar solvents (DMSO and trifluoroethanol), as well as in dilute (0.5 mM) aqueous solutions. In contrast, at higher concentrations (> 2 mM) in water, a conformational transition from alpha-helix to beta-sheet occurs, which is accompanied by the Protein-mimetic peptide aggregation into 2D-sheets and formation supramolecular gel in aqueous environment. Our findings reveal a newly identified Protein-mimetic peptide that could turn as a promising candidate for future material applications

A Common Anterior Insula Representation of Disgust Observation, Experience and Imagination Shows Divergent Functional Connectivity Pathways

Similar brain regions are involved when we imagine, observe and execute an action. Is the same true for emotions? Here, the same subjects were scanned while they (a) experience, (b) view someone else experiencing and (c) imagine experiencing gustatory emotions (through script-driven imagery). Capitalizing on the fact that disgust is repeatedly inducible within the scanner environment, we scanned the same participants while they (a) view actors taste the content of a cup and look disgusted (b) tasted unpleasant bitter liquids to induce disgust, and (c) read and imagine scenarios involving disgust and their neutral counterparts. To reduce habituation, we inter-mixed trials of positive emotions in all three scanning experiments. We found voxels in the anterior Insula and adjacent frontal operculum to be involved in all three modalities of disgust, suggesting that simulation in the context of social perception and mental imagery of disgust share a common neural substrates. Using effective connectivity, this shared region however was found to be embedded in distinct functional circuits during the three modalities, suggesting why observing, imagining and experiencing an emotion feels so different

When Ears Drive Hands: The Influence of Contact Sound on Reaching to Grasp

Background Most research on the roles of auditory information and its interaction with vision has focused on perceptual performance. Little is known on the effects of sound cues on visually-guided hand movements. Methodology/Principal Findings We recorded the sound produced by the fingers upon contact as participants grasped stimulus objects which were covered with different materials. Then, in a further session the pre-recorded contact sounds were delivered to participants via headphones before or following the initiation of reach-to-grasp movements towards the stimulus objects. Reach-to-grasp movement kinematics were measured under the following conditions: (i) congruent, in which the presented contact sound and the contact sound elicited by the to-be-grasped stimulus corresponded; (ii) incongruent, in which the presented contact sound was different to that generated by the stimulus upon contact; (iii) control, in which a synthetic sound, not associated with a real event, was presented. Facilitation effects were found for congruent trials; interference effects were found for incongruent trials. In a second experiment, the upper and the lower parts of the stimulus were covered with different materials. The presented sound was always congruent with the material covering either the upper or the lower half of the stimulus. Participants consistently placed their fingers on the half of the stimulus that corresponded to the presented contact sound. Conclusions/Significance Altogether these findings offer a substantial contribution to the current debate about the type of object representations elicited by auditory stimuli and on the multisensory nature of the sensorimotor transformations underlying action

Distinct Olfactory Cross-Modal Effects on the Human Motor System

BACKGROUND: Converging evidence indicates that action observation and action-related sounds activate cross-modally the human motor system. Since olfaction, the most ancestral sense, may have behavioural consequences on human activities, we causally investigated by transcranial magnetic stimulation (TMS) whether food odour could additionally facilitate the human motor system during the observation of grasping objects with alimentary valence, and the degree of specificity of these effects. METHODOLOGY/PRINCIPAL FINDINGS: In a repeated-measure block design, carried out on 24 healthy individuals participating to three different experiments, we show that sniffing alimentary odorants immediately increases the motor potentials evoked in hand muscles by TMS of the motor cortex. This effect was odorant-specific and was absent when subjects were presented with odorants including a potentially noxious trigeminal component. The smell-induced corticospinal facilitation of hand muscles during observation of grasping was an additive effect which superimposed to that induced by the mere observation of grasping actions for food or non-food objects. The odour-induced motor facilitation took place only in case of congruence between the sniffed odour and the observed grasped food, and specifically involved the muscle acting as prime mover for hand/fingers shaping in the observed action. CONCLUSIONS/SIGNIFICANCE: Complex olfactory cross-modal effects on the human corticospinal system are physiologically demonstrable. They are odorant-specific and, depending on the experimental context, muscle- and action-specific as well. This finding implies potential new diagnostic and rehabilitative applications