Аntimicrobial and anticancer activity of new poly(propyleneamine) metallodendrimers

The synthesis, EPR characterisation and biological evaluation of two new metallodendrimers, i.e. a poly(propyleneamine) dendrimer functionalized at the external surface with 4-bromo-1,8-naphthalimide and conjugated with Cu(II) and Zn(II), was performed with the aim to evaluate their antimicrobial and anticancer activity. The antimicrobial activity was investigated in meat-peptone broth against bacteria B. subtilis and P. aeruginosa, and the yeast C. lipolytica. The results showed that the compounds inhibited effectively the tested pathogens even after their deposition on a textile fabric. Anticancer activity was investigated against three human permanent cell lines from non-small cell lung cancer (A549), triple negative breast cancer (MDA-MB-231) and carcinoma of the uterine cervix (HeLa) in the c?=?0.01–30 μM concentration range. The results suggest that these compounds are promising for application in biomedicine as anticancer drugs in the design of new effective preparations. The antimicrobial and anticancer activity may be related to the peculiar structural and dynamical properties revealed for the Cu(II) complexes, by a computer aided analysis of the electron paramagnetic resonance (EPR) spectra. This analysis indicated the formation, at the lowest Cu(II) concentrations, of a flexible rhombic Cu-N4 coordination with the internal amino groups of the dendrimer, which transformed into a Cu2-N4 coordination already at 0.25 equiv. of Cu(II).     

Unusual Lipid A from a Cold‐Adapted Bacterium: Detailed Structural Characterization

Colwellia psychrerythraea 34H is a Gram‐negative cold‐adapted microorganism that adopts many strategies to cope with the limitations associated with the low temperatures of its habitat. In this study, we report the complete characterization of the lipid A moiety from the lipopolysaccharide of Colwellia. Lipid A and its partially deacylated derivative were completely characterized by high‐resolution mass spectrometry, NMR spectroscopy, and chemical analysis. An unusual structure with a 3‐hydroxy unsaturated tetradecenoic acid as a component of the primary acylation pattern was identified. In addition, the presence of a partially acylated phosphoglycerol moiety on the secondary acylation site at the 3‐position of the reducing 2‐amino‐2‐deoxyglucopyranose unit caused tremendous natural heterogeneity in the structure of lipid A. Biological‐activity assays indicated that C. psychrerythraea 34H lipid A did not show an agonistic or antagonistic effect upon testing in human macrophages.     

An evaluative baseline for geo-semantic relatedness and similarity

In geographic information science and semantics, the computation of semantic similarity is widely recognised as key to supporting a vast number of tasks in information integration and retrieval. By contrast, the role of geo-semantic relatedness has been largely ignored. In natural language processing, semantic relatedness is often confused with the more specific semantic similarity. In this article, we discuss a notion of geo-semantic relatedness based on Lehrer’s semantic fields, and we compare it with geo-semantic similarity. We then describe and validate the Geo Relatedness and Similarity Dataset (GeReSiD), a new open dataset designed to evaluate computational measures of geo-semantic relatedness and similarity. This dataset is larger than existing datasets of this kind, and includes 97 geographic terms combined into 50 term pairs rated by 203 human subjects. GeReSiD is available online and can be used as an evaluation baseline to determine empirically to what degree a given computational model approximates geo-semantic relatedness and similarity.     

Expression of α-amylase inhibitors in diploid Triticum species

The aim of the work was to characterize the expression of various α-amylase inhibitors (αAIs), well known anti-nutritional compounds, for the development of healthier diploid wheat-based functional foods.     

Editorial: Special Issue on Computing Frontiers

Journal of Signal Processing Systems -     

Dysregulation of Muscle-Specific MicroRNAs as Common Pathogenic Feature Associated with Muscle Atrophy in ALS,SMA and SBMA: Evidence from Animal Models and Human Patients

Motor neuron diseases (MNDs) are neurodegenerative disorders characterized by upper and/or lower MN loss. MNDs include amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and spinal and bulbar muscular atrophy (SBMA). Despite variability in onset, progression, and genetics, they share a common skeletal muscle involvement, suggesting that it could be a primary site for MND pathogenesis. Due to the key role of muscle-specific microRNAs (myomiRs) in skeletal muscle development, by real-time PCR we investigated the expression of miR-206, miR-133a, miR-133b, and miR-1, and their target genes, in G93A-SOD1 ALS, Δ7SMA, and KI-SBMA mouse muscle during disease progression. Further, we analyzed their expression in serum of SOD1-mutated ALS, SMA, and SBMA patients, to demonstrate myomiR role as noninvasive biomarkers. Our data showed a dysregulation of myomiRs and their targets, in ALS, SMA, and SBMA mice, revealing a common pathogenic feature associated with muscle impairment. A similar myomiR signature was observed in patients’ sera. In particular, an up-regulation of miR-206 was identified in both mouse muscle and serum of human patients. Our overall findings highlight the role of myomiRs as promising biomarkers in ALS, SMA, and SBMA. Further investigations are needed to explore the potential of myomiRs as therapeutic targets for MND treatment.     

Identification of Potential Leukocyte Biomarkers Related to Drug Recovery of CFTR: Clinical Applications in Cystic Fibrosis

The aim of this study was the identification of specific proteomic profiles, related to a restored cystic fibrosis transmembrane conductance regulator (CFTR) activity in cystic fibrosis (CF) leukocytes before and after ex vivo treatment with the potentiator VX770. We used leukocytes, isolated from CF patients carrying residual function mutations and eligible for Ivacaftor therapy, and performed CFTR activity together with proteomic analyses through micro-LC–MS. Bioinformatic analyses of the results obtained revealed the downregulation of proteins belonging to the leukocyte transendothelial migration and regulation of actin cytoskeleton pathways when CFTR activity was rescued by VX770 treatment. In particular, we focused our attention on matrix metalloproteinase 9 (MMP9), because the high expression of this protease potentially contributes to parenchyma lung destruction and dysfunction in CF. Thus, the downregulation of MMP9 could represent one of the possible positive effects of VX770 in decreasing the disease progression, and a potential biomarker for the prediction of the efficacy of therapies targeting the defect of Cl⁻ transport in CF.     

Molecular Modeling Studies on the Human Neuropeptide S Receptor and Its Antagonists

Neuropeptide S (NPS) is a 20‐residue peptide of great interest due to its potential involvement in several biological processes such as arousal, anxiety, and food intake. The NPS receptor belongs to the rhodopsin‐like G‐protein‐coupled receptor superfamily, and several polymorphisms and isoforms of this receptor are associated with asthma, allergies, and bronchial hyper‐responsiveness, in particular the Asn 107 Ile mutation. Limited structural information is available for this peptide–receptor system, particularly regarding the NPS receptor structure, its nonpeptide ligands, and the molecular aspects of agonist and antagonist binding processes. In this work, rhodopsin‐based homology models of the NPS receptor and its Asn 107 Ile variant were built and refined in a membrane bilayer model, and binding modes for nonpeptide antagonists were simulated. This study provides the first structural study of the human NPS receptor, and the results provide a starting point for further characterization of the binding modes of its antagonists, and for the rational design of new NPS receptor ligands.     

Depressive personality styles, dysphoria, and social comparisons in everyday life.

"Sociotropic" people are supposedly vulnerable to dysphoria after negative interpersonal events, whereas "autonomous" people are supposedly vulnerable to achievement-related failures. The present study examined whether these personality styles are borne out in social comparison processes. For 3 weeks, 27 sociotropic and 35 autonomous undergraduates completed records of their social comparisons. Depressive personality style moderated comparison frequency and the affective consequences of comparisons, especially for dysphoric individuals: Dysphoric respondents were especially likely to make comparisons in domains that were congruent with their personalities, and comparisons in congruent domains were associated with greater mood change than comparisons in other domains, perhaps especially for dysphoric respondents. These results have implications for the literatures on social comparison and on depressive personality styles. (PsycINFO Database Record (c) 2010 APA, all rights reserved)