Role of Metal Ions and Hydrogen Bond Acceptors in the Tautomeric Equilibrium of Nitro-9[(Alkylamino)Amino]-Acridine Drugs

3-nitro-9-[2-(dialkylamino)ethyl)]aminoacridines (alkyl = methyl or ethyl) have been used as ligands towards platinum(If). The end product is a complex in which the acridine acts as a tridentate ligand contributing the two exocyclic nitrogen atoms and one of the two peri carbons. The metallation takes place predominantly at the peri position of the unsubstituted ring. The coordinated acridine is in the imino tautomeric form although, in the free state, it occurs exclusively in the amino form (both in the solid state and in solution). The imino tautomer is considered to be the biologically active form. In the platinated species the N(10)H of the acridine can be involved in strong hydrogen bonding with a chloride ion leading to formation of an association complex, the formation constant has been found to be 1.4±103 M−1. The N(10)H┄CI interaction can influence the tautomeric equilibrium of the acridine dye also in the uncoordinated species, however, the shift in favor of the imino tautomer is not complete

Use of Electrical Coductivity Sensors to monitor Health Status and Quality of Milk in Dairy Goats

Intramammary infection (IMI) can adversely affect, in dairy goats, milk quality and milk yield leading to high economical losses. Although somatic cell count (SCC) and microbiological tests could be valid approaches to detect IMI, other methods of IMI early detection may be useful to detect infected animals and to improve milk quality.The aim of this study was to test a new multivariate model developed with the fuzzy logic technology and based on the milk EC - acquired on-line for each gland by dedicated sensors - and on new qualitative and quantitative indexes derived from the spectrum of the recorded signals.Results obtained showed that the fuzzy logic model tested could achive better results than those already reached in dairy goat research. Nevertheless, further experiment and more field data could be useful to reach the best possible accuracy that this multivariate approach could show

APRESENTAÇÃO

O reconhecimento e a valorização da formação de professores, inicial e contínua, como objeto de pesquisa acadêmica é relativamente recente e transversal aos contextos nacional e internacional. A constituição do campo de estudos da formação de professores tem sido fortemente impulsionada pelos movimentos de profissionalização docente; pelos questionamentos sobre a pouca relevância da preparação dos professores para a realidade da prática quotidiana nas escolas; pelas demandas das denominadas “sociedades do conhecimento”. Assim, a investigação sobre a formação de professores mobiliza esforços para produzir conhecimentos capazes de dar respostas às complexidades presentes na educação como um todo e especialmente na formação de professores

Sintesi di nuove strutture macrocicliche a ridotta libertà conformazionale

L'obiettivo della nostra ricerca consiste nella creazione di nuove strutture macrocicliche a ridotta libertà conformazionale che incorporino la sequenza consensus RGD per mezzo di una funzione γ-amminoacidica supportata da anelli ciclopentanici (Acpca), ossidrilati e non. Tali scaffold amminoacidici possono essere visti di fatto come mimetici dell’acido γ- amminobutanoico bloccato in una conformazione a W da un ponte α,γ-etilene o idrossietilene. La valutazione biologica in vitro dei ciclo-pseudopeptidi mediante test di binding verso i recettori αvβ3 e αvβ5 isolati, l’approfondito studio strutturale in soluzione via NMR e, infine, studi di docking eseguiti sulla struttura a raggi X del segmento extracellulare dell’integrina αvβ3 complessata con il composto di riferimento EMD121974 hanno completato il nostro studio

Comparative 454 pyrosequencing of transcripts from two olive genotypes during fruit development

<p>Abstract</p> <p>Background</p> <p>Despite its primary economic importance, genomic information on olive tree is still lacking. 454 pyrosequencing was used to enrich the very few sequence data currently available for the <it>Olea europaea </it>species and to identify genes involved in expression of fruit quality traits.</p> <p>Results</p> <p>Fruits of <it>Coratina</it>, a widely cultivated variety characterized by a very high phenolic content, and <it>Tendellone</it>, an oleuropein-lacking natural variant, were used as starting material for monitoring the transcriptome. Four different cDNA libraries were sequenced, respectively at the beginning and at the end of drupe development. A total of 261,485 reads were obtained, for an output of about 58 Mb. Raw sequence data were processed using a four step pipeline procedure and data were stored in a relational database with a web interface.</p> <p>Conclusion</p> <p>Massively parallel sequencing of different fruit cDNA collections has provided large scale information about the structure and putative function of gene transcripts accumulated during fruit development. Comparative transcript profiling allowed the identification of differentially expressed genes with potential relevance in regulating the fruit metabolism and phenolic content during ripening.</p

Lysozyme–Mineral Clay Systems: Comparison of Interaction for Controlled Release in Feed Application

A synthetic approach to bond lysozyme (LY) to commercial natural carriers, namely clay minerals (bentonite, BN; and sepiolite, SP) and commercial zeolite (Phil 75((R)), PH), already in use in feed formulation, is proposed. The synthetic route, which implies solid-liquid adsorption, is a simple and effective way for preparing hybrid materials characterized by LY loadings up to 37 mg(LY)/g(carrier). By operating at pH 4.3, initial LY content of 37.5 mg(LY)/g(carrier), and reaction time of 90 min, hybrid materials with LY loadings of 37, 35, and 12 mg(LY)/g(carrier) for LY-SP, LY-BN, and LY-PH, respectively were obtained. The LY initial concentration and pH, as well as the physico-chemical properties of the carries were found to be the parameters that govern the synthesis of the materials. The driving force for an effective LY adsorption and interaction is the combined Zero Point Charge (ZPC) of the carriers, always negative (in the range between 4 and 170 mV) and the positive ZPC of LY, as well as the carrier morphology, characterized by mesoporosity (pore dimensions in the range of 5-12 nm). However, it is the interaction of charges of opposite sign that mainly affects LY loadings and bond strength. Based on SEM-EDX analysis, LY molecules are quite homogeneously spread onto the carriers' surface. TG-DTG analyses showed that the LY-carrier interaction in the hybrid materials is stronger than that in a simple mechanical mixture of the components. Specifically, in the hybrid materials, the phenomenon at 300 degrees C, associated to LY decomposition, is broadened and slightly shifted towards higher temperatures (320-350 degrees C), whereas in a mechanical mixture of the same composition, it occurs at temperatures closer to those of free LY, as if there were no or very weak interactions. At pH 3, a very little LY release, 0.03 and 0.01 mg(LY)/g(carrier), was found for LY-BN and LY-PH, respectively. The latter became larger at pH 7, 0.06 mg(LY)/g(carrier) for both BN and PH carriers, suggesting that BN and PH are better modulators of LY release. The paper provides insights for the study and the development of new optimized feed formulations for the targeted delivery of natural compounds with antimicrobial activity, alternatives to antibiotics, and vaccinal antigens

CD38 and ZAP-70 are functionally linked and mark CLL cells with high migratory potential

AbstractOur interest in chronic lymphocytic leukemia (CLL) derives primarily from the exploitation of human diseases as strategic models for defining the in vivo biological roles of CD38. Using this model, we showed that CD38 triggers robust proliferation/survival signals modulated through the interactions with the CD31 ligand expressed by nurselike cells and by the stromal/endothelial components. By analyzing a cohort of 56 patients with clinically and molecularly characterized CLL, we show that (1) patients with CD38+/ZAP-70+ are characterized by enhanced migration toward Stromal derived factor-1α (SDF-1α)/CXCL12; (2) CD38 ligation leads to tyrosine phosphorylation of ZAP-70, showing that these markers are functionally linked; (3) ZAP-70 represents a limiting factor for the CD38 pathway in the CLL context, as shown by studying CD38-mediated signal transduction in 26 molecularly characterized patients; and (4) the CLL subgroup of patients defined on the basis of migratory potential is marked by a specific genetic signature, with a significant number of differentially expressed genes being involved in cell-cell interactions and movement. Altogether, the results of this work provide biological evidence for why the combined analysis of CD38 and ZAP-70 expression as determined in several clinical trials results in more dependable identification of patients with CLL who have aggressive disease

A Feasible Methodological Approach to Estimate the Burden of Autism Spectrum Disorder: Results from the EPI-ASD Study in the Province of Lecce (Southern Italy)

Diagnoses of Autism Spectrum Disorder (ASD) have rapidly increased globally. However, the lack of comprehensive epidemiological surveys and surveillance systems, able to provide official data at a national or European level is one of the main issues in the monitoring of this condition. The present study aimed to estimate the prevalence of ASD in children and adolescents aged 3-18 years old living in the province of Lecce (Southern Italy) through official data provided by the Local Health Authority of Lecce (ASL/LE) up to 31 October 2020, and compare it with school-based data concerning the number of students needing support for ASD. Based on data provided by the ASL/LE, in 2020 there were 509 cases of ASD among children and adolescents aged 3-18 years old, corresponding to a prevalence of 0.46%. A total of 408 (80.2%) were boys and 101 (19.8%) were girls. In relation to their age, 155 ASD cases (0.90%) were diagnosed in the 3-5 age group, while 222 (0.55%) in the 6-11 age group and 132 (0.25%) in the 12-18 age group. Prevalence of ASD assessed by school-based dataset was underestimated in the 3-5 age group, while the 6-11 and 12-18 age groups were consistent with the official data provided by the ASL/LE

The societal burden of chronic liver diseases: results from the COME study.

OBJECTIVE: Chronic liver diseases (CLDs) impose a significant socioeconomic burden on patients and the healthcare system, but to what extent remains underexplored. We estimated costs and health-related-quality-of-life (HRQoL) among patients with CLDs at different stages and with different aetiologies. DESIGN: A cost-of-illness study was conducted. Direct costs, productivity loss and HRQoL were estimated in patients with chronic hepatitis, cirrhosis hepatocellular carcinoma (HCC) or where orthotopic liver transplantation (OLT) had been performed, for hepatitis C virus (HCV) infection, hepatitis B virus (HBV) infection, or in those with liver disease from other causes. Patients were retrospectively observed for 6 months. The societal perspective was adopted to calculate costs. RESULTS: In total, 1088 valid patients (median age=59.5 years, 60% men) were enrolled. 61% had chronic hepatitis, 20% cirrhosis, 8% HCC and 12% underwent OLT. HCV infection was identified in 52% and HBV infection in 29% of the patients. Adjusted mean direct costs increased from €3000/patient-month in HBV infected patients with OLT. Antiviral treatment was the cost driver in patients with hepatitis, while hospital costs were the driver in the other subgroups. Absenteeism increased from HBV-infected patients with hepatitis (0.7 day/patient-month) to patients with OLT with other aetiologies (3.7 days/patient-month). HRQoL was on average more compromised in cirrhosis and patients with HCC, than in hepatitis and patients with OLT. HBV-infected patients generated higher direct costs, patients with other aetiologies generated the highest productivity loss and HCV-infected patients reported the worst HRQoL levels. CONCLUSIONS: The present study can be considered a benchmark for future research and to guide policies aimed at maximising the cost-effective of the interventions

Targeted activation of the SHP-1/PP2A signaling axis elicits apoptosis of chronic lymphocytic leukemia cells

Lyn, a member of the Src family of kinases, is a key factor in the dys-regulation of survival and apoptotic pathways of malignant B cells in chronic lymphocytic leukemia. One of the effects of Lyn's action is spatial and functional segregation of the tyrosine phosphatase SHP-1 into two pools, one beneath the plasma membrane in an active state promoting pro-survival signals, the other in the cytosol in an inhibited conformation and unable to counter the elevated level of cytosolic tyrosine phosphorylation. We herein show that SHP-1 activity can be elicited directly by nintedanib, an agent also known as a triple angiokinase inhibitor, circumventing the phospho-S591-dependent inhibition of the phosphatase, leading to the dephosphorylation of pro-apoptotic players such as procaspase-8 and serine/threonine phosphatase 2A, eventually triggering apoptosis. Furthermore, the activation of PP2A by using MP07-66, a novel FTY720 analog, stimulated SHP-1 activity via dephosphorylation of phospho-S591, which unveiled the existence of a positive feedback signaling loop involving the two phosphatases. In addition to providing further insights into the molecular basis of this disease, our findings indicate that the PP2A/SHP-1 axis may emerge as an attractive, novel target for the development of alternative strategies in the treatment of chronic lymphocytic leukemia