P2Y11 Agonism Prevents Hypoxia/Reoxygenation- and Angiotensin II-Induced Vascular Dysfunction and Intimal Hyperplasia Development

Vascular dysfunction in cardiovascular diseases includes vasomotor response impairments, endothelial cells (ECs) activation, and smooth muscle cells (SMCs) proliferation and migration to the intima. This results in intimal hyperplasia and vessel failure. We previously reported that activation of the P2Y11 receptor (P2Y11R) in human dendritic cells, cardiofibroblasts and cardiomyocytes was protective against hypoxia/reoxygenation (HR) lesions. In this study, we investigated the role of P2Y11R signaling in vascular dysfunction. P2Y11R activity was modulated using its pharmacological agonist NF546 and antagonist NF340. Rat aortic rings were exposed to angiotensin II (AngII) and evaluated for their vasomotor response. The P2Y11R agonist NF546 reduced AngII-induced vascular dysfunction by promoting EC-dependent vasorelaxation, through an increased nitric oxide (NO) bioavailability and reduced AngII-induced H₂O₂ release; these effects were prevented by the use of the P2Y11R antagonist NF340. Human vascular SMCs and ECs were subjected to AngII or H/R simulation in vitro. P2Y11R agonist modulated vasoactive factors in human ECs, that is, endothelial nitric oxide synthase (eNOS) and endothelin-1, reduced SMC proliferation and prevented the switch towards a synthetic phenotype. H/R and AngII increased ECs secretome-induced SMC proliferation, an effect prevented by P2Y11R activation. Thus, our data suggest that P2Y11R activation may protect blood vessels from HR-/AngII-induced injury and reduce vascular dysfunctions. These results open the way for new vasculoprotective interventions.     

Carotenoid Composition and Vitamin A Values of Oils from Four Brazilian Palm Fruits

In oils extracted from fresh and sterilized palm fruits (Elaeis guineensis, Jacq. tenera, dura dumpy and psifera and E. oleifera), cis-phytofluene, 13-cis-α-carotene, α-carotene, 13-cis-β-carotene, β-carotene, 9-cis-β-carotene, σ-carotene, zeaxanthin, --cryptoxanthin, poly-cis-lycopene, mono-lycopene and lycopene, were identified and quantified by normal phase open column chromatography (stepwise-elution), TLC, UV/Vis spectroscopy and specific chemical reactions. The sum of α- and β-carotene in all samples analysed was higher than 80% of the total carotenoid content, while the α/β-carotene ratios were W.9, 1/11.1, 1/22 and V2.6 for oils extracted from fresh fruits of dura dumpy, psifera, tenera and E. oleifera, respectively. Total carotenoid contents (pg/g) and vitamin A values (R. E./100 g) of these samples were 1 120.7 and 12 404 for dura dumpy, 283.2 and 3612 for psifera, 660.5 and 7630 for tenera and 1576.8 and 21691 for E. oleifera. The sterilization of fruits (127°C × 35 min.) resulted in isomerization of pigments and reduction of vitamin A values of approximately 45% and 25%, respectively.     

Biosynthesis of fatty acids byTrypanosoma cruzi

The incorporation of [1-¹⁴C] acetate into fatty acids by cultured epimastigotes ofTrypanosoma cruzi was studied. After 8, 24, and 48 hr incubation with labeled precursor, up to 2.8% of the initial radioactivity added to the medium was found in theT. cruzi long chain fatty acids. Saturated (16∶0 and 18∶0), monounsaturated (18∶1ω9), and diunsaturated (18∶2ω6) fatty acids were synthesized. Both the pattern of incorporation of labeled acetate into the fatty acids and the decarboxylation ratios found suggest that de novo synthesis of fatty acids has taken place.     

A prismoid framework for languages with resources

Inspired by the Multiplicative Exponential fragment of Linear Logic, we define a framework called the prismoid of resources where each vertex is a language which refines the λ-calculus by using a different choice to make explicit or implicit (meta-level) the definition of the contraction, weakening, and substitution operations. For all the calculi in the prismoid we show simulation of β-reduction, confluence, preservation of β-strong normalisation and strong normalisation for typed terms. Full composition also holds for all the calculi of the prismoid handling explicit substitutions. The whole development of the prismoid is done by making the set of resources a parameter of the formalism, so that all the properties for each vertex are obtained as a particular case of the general abstract proofs.     

Evaluating evolution: Naturalistic inquiry and the Perseus Project

Delia Neuman is an assistant professor in the College of Library and Information Services at the University of Maryland, College Park. She has written several articles on the use of naturalistic inquiry to study electronic environments, including two published in Educational Technology Research and Development: Naturalistic Inquiry and Computer-Based Instruction: Rationale, Procedures and Potential (Spring 1989) and Learning Disabled Students' Interactions with Commercial Courseware: A Naturalistic Study (Spring 1991). She is currently involved in a study funded by the American Library Association to use naturalistic methods to investigate high school students' use of CD-ROM and online databases.     

Synthesis of AlN nanopowder coated with a thin layer of C,using a thermal plasma reactor

High-purity nanocrystalline aluminum nitride powders were synthesized by using a 12?kW non-transferred arc plasma. The synthesis was conducted in a versatile, new designed, one-chamber thermal plasma reactor (TPR). The novel experimental assembly incorporated better working conditions like: high temperature gradient between the crucible and reactor's wall, and high super-saturation of the system by nitrogen and carbon. Thermodynamic modelling of the synthesis was conducted in order to achieve the best conditions for AlN formation. In this study, aluminum discs of Al 1100 were used as precursor material and pure nitrogen was the only gas used as reagent and plasmogenic gas.Nanopowders collected from reactor's wall were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-Ray diffraction (XRD). Synthesized h-AlN nano-powders were found to be free of oxides and aluminum metal. A thin carbon-layer around the particles was detected. TEM results indicated that the carbon-layer was around 5 and 10?nm. This outcome could make a significant difference with other synthesis reported in the literature since the occurrence of the carbon-layer, could delay AlN oxidation, prevent hydration, and could avoid the agglomeration of the particles.     

N‐Benzyl‐4‐((heteroaryl)methyl)benzamides: A New Class of Direct NADH‐Dependent 2‐trans Enoyl–Acyl Carrier Protein Reductase (InhA) Inhibitors with Antitubercular Activity

Isoniazid (INH) remains one of the cornerstones of antitubercular chemotherapy for drug‐sensitive strains of M. tuberculosis bacteria. However, the increasing prevalence of multidrug‐resistant (MDR) and extensively drug‐resistant (XDR) strains containing mutations in the KatG enzyme, which is responsible for the activation of INH into its antitubercular form, have rendered this drug of little or no use in many cases of drug‐resistant tuberculosis. Presented herein is a novel family of antitubercular direct NADH‐dependent 2‐trans enoyl–acyl carrier protein reductase (InhA) inhibitors based on an N‐benzyl‐4‐((heteroaryl)methyl)benzamide template; unlike INH, these do not require prior activation by KatG. Given their direct InhA target engagement, these compounds should be able to circumvent KatG‐related resistance in the clinic. The lead molecules were shown to be potent inhibitors of InhA and showed activity against M. tuberculosis bacteria. This new family of inhibitors was found to be chemically tractable, as exemplified by the facile synthesis of analogues and the establishment of structure–activity relationships. Furthermore, a co‐crystal structure of the initial hit with the enzyme is disclosed, providing valuable information toward the design of new InhA inhibitors for the treatment of MDR/XDR tuberculosis.     

The Role of IL-22 in Wound Healing. Potential Implications in Clinical Practice

Wound healing is a complex process that is mediated and influenced by several cytokines, chemokines, and growth factors. Interleukin-22 (IL-22) is a cytokine that plays a critical role in tissue regeneration. Our study is a systematic review that addressed the implications of IL-22 in the healing of wounds caused by external factors. Thirteen studies were included in our review, most of them being experimental studies. Three clinical studies underlined the potential role of IL-22 in day-to-day clinical practice. IL-22 plays a central role in wound healing, stimulating the proliferation, migration, and differentiation of the cells involved in tissue repair. However, overexpression of IL-22 can cause negative effects, such as keloid scars or peritoneal adhesions. The results of the presented studies are promising, but further research that validates the roles of IL-22 in clinical practice and analyzes its potential implication in surgical healing is welcomed.