Determination of tartaric acid in wines by FIA with tubular tartrate-selective electrodes

A flow injection analysis (FIA) system comprising a tartrate- (TAT) selective electrode has been developed for determination of tartaric acid in wines. Several electrodes constructed for this purpose had a PVC membrane with a complex of quaternary ammonium and TAT as anion exchanger, a phenol derivative as additive, and a more or less polar mediator solvent. Characterization of the electrodes showed behavior was best for membranes with o-nitrophenyl octyl ether as solvent. On injection of 500 μL into a phosphate buffer carrier (pH = 3.1; ionic strength 10–2 mol/L) flowing at 3 mL/min, the slope was 58.06 ± 0.6 with a lower limit of linear range of 5.0 × 10–4 mol/L TAT and R2 = 0.9989. The interference of several species, e.g. chloride, bromide, iodide, nitrate, gallic acid, tannin, sucrose, glucose, fructose, acetate, and citrate, was evaluated in terms of potentiometric selectivity coefficients. The Hofmeister series was followed for inorganic species and the most interfering organic ion was citrate. When red and white wines were analyzed and the results compared with those from an independent method they were found to be accurate, with relative standard deviations below 5.0%

Thermochemical and Theoretical Studies of 2-Hydroxyquinoxaline, 2,3-Dihydroxyquinoxaline, and 2-Hydroxy-3-methylquinoxaline

The standard (p° = 0.1 MPa) molar enthalpies of formation for crystalline 2-hydroxyquinoxaline, 2,3-dihydroxyquinoxaline, and 2-hydroxy-3-methylquinoxaline were derived from the standard molar enthalpies of combustion, in oxygen, at T = 298.15 K, measured by static bomb combustion calorimetry. The standard molar enthalpies of sublimation, at T = 298.15 K, of the three compounds were measured by Calvet microcalorimetry. The derived standard molar enthalpies of formation in the gaseous phase are 45.9 ± 4.3 kJ·mol-1 for 2-hydroxyquinoxaline, −(179.2 ± 5.3) kJ·mol-1 for 2,3-dihydroxyquinoxaline, and −(8.8 ± 4.9) kJ·mol-1 for 2-hydroxy-3-methylquinoxaline. In addition, theoretical calculations using the density functional theory and the B3LYP/6-311G** hybrid exchange-correlation energy functional were performed for these molecules in order to obtain the most stable geometries and to access their relative stability. The theoretical results are in general good agreement with experimental findings

A thermochemical and theoretical study of the phenylpyridine isomers

The standard (p° = 0.1 MPa) molar enthalpies of formation for 2-, 3-, and 4-phenylpyridine in the gas phase were derived from the standard molar enthalpies of combustion, in oxygen, at 298.15 K, measured by static bomb combustion calorimetry. The standard molar enthalpies of vaporization for 2-, 3-, and 4-phenylpyridine at T = 298.15 K were measured by correlation-gas chromatography. The enthalpy of sublimation of 4-phenylpyridine was obtained as a weighted mean of the value derived from the vaporization and fusion enthalpy values and the value measured directly by Calvet microcalorimetry. The following enthalpies of formation were then derived:  2-phenylpyridine, g = 228.3 ± 5.8 kJ·mol-1; 3-phenylpyridine, g = 240.9 ± 5.5 kJ·mol-1; 4-phenylpyridine, g = 240.0 ± 3.3 kJ·mol-1. The most stable geometries of all phenylpyridine isomers were obtained using both restricted Hartree−Fock (RHF) and density functional theory (DFT/B3LYP) methods. The resulting geometries were then used to obtain estimates of enthalpies of formation of the three isomers of phenylpyridine, which are in good agreement with the experimental values. A theoretical interpretation of the effect of the phenyl ring has on the relative stabilities of the three molecules is presented

Hypoglycemic and anti-lipemic effects of the aqueous extract from Cissus sicyoides

BACKGROUND: Cissus sicyoides (Vitaceae) is a medicinal plant popularly known in Brazil as "cipó-pucá, anil-trepador, cortina, and insulina". The plant is used in several diseases, including rheumatism, epilepsy, stroke and also in the treatment of diabetes. In the present work, we studied the hypoglycemic and anti-lipemic effects of the aqueous extract prepared from fresh leaves of the plant (AECS), in the model of alloxan-induced diabetes in rats. In addition, hepatic enzyme levels were also determined. RESULTS: Results showed that the daily treatment of diabetic rats with AECS for 7 days (100 and 200 mg/kg, p.o.) significantly decreased blood glucose levels in 25 and 22% respectively, as compared to the same groups before AECS treatment. No significant changes were seen in control diabetic rats before (48 h after alloxan administration) and after distilled water treatment. While no changes were seen in total cholesterol levels, a significant decrease was observed in plasma triglyceride levels, in the alloxan-induced diabetic rats after AECS treatment with both doses, as compared to the same groups before treatment. Significant decreases in blood glucose (25%) and triglyceride levels (48%) were also observed in the alloxan-induced diabetic rats after 4 days treatment with AECS (200 mg/kg, p.o.). Aspartate (AST) and alanine (ALT) aminotransferases levels, in diabetic controls and AECS-treated rats, were in the range of reference values presented by normal rats. CONCLUSIONS: The results justify the popular use of C. sicyoides, pointing out to the potential benefit of the plant aqueous extract (AECS) in alternative medicine, in the treatment of type 2 diabetes mellitus

Novel scFv against Notch Ligand JAG1 Suitable for Development of Cell Therapies toward JAG1-Positive Tumors

Funding Information: This research was funded by the Fundação para a Ciência e Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior (FCT/MCTES, Portugal) grant PTDC/BBB-BMD/4497/2014 (to A.B.), through national funds to iNOVA4Health (UIDB/04462/2020 and UIDP/04462/2020), and the Associate Laboratory LS4FUTURE (LA/P/0087/2020). Publisher Copyright: © 2023 by the authors.The Notch signaling ligand JAG1 is overexpressed in various aggressive tumors and is associated with poor clinical prognosis. Hence, therapies targeting oncogenic JAG1 hold great potential for the treatment of certain tumors. Here, we report the identification of specific anti-JAG1 single-chain variable fragments (scFvs), one of them endowing chimeric antigen receptor (CAR) T cells with cytotoxicity against JAG1-positive cells. Anti-JAG1 scFvs were identified from human phage display libraries, reformatted into full-length monoclonal antibodies (Abs), and produced in mammalian cells. The characterization of these Abs identified two specific anti-JAG1 Abs (J1.B5 and J1.F1) with nanomolar affinities. Cloning the respective scFv sequences in our second- and third-generation CAR backbones resulted in six anti-JAG1 CAR constructs, which were screened for JAG1-mediated T-cell activation in Jurkat T cells in coculture assays with JAG1-positive cell lines. Studies in primary T cells demonstrated that one CAR harboring the J1.B5 scFv significantly induced effective T-cell activation in the presence of JAG1-positive, but not in JAG1-knockout, cancer cells, and enabled specific killing of JAG1-positive cells. Thus, this new anti-JAG1 scFv represents a promising candidate for the development of cell therapies against JAG1-positive tumors.publishersversionpublishe

In the matter of the request of Liberty Mutual Fire Insurance Company, a Massachusetts domestic stock insurance company, to redomesticate to the state of Wisconsin

Submitted by Nuzia Santos ([email protected]) on 2018-08-24T16:36:28Z No. of bitstreams: 1 Phosphatidyl Inositol 3 Kinase-Gamma Balances.pdf: 10035595 bytes, checksum: 5a61fb2c618990d4314d36db3868ee2e (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2018-08-24T16:44:27Z (GMT) No. of bitstreams: 1 Phosphatidyl Inositol 3 Kinase-Gamma Balances.pdf: 10035595 bytes, checksum: 5a61fb2c618990d4314d36db3868ee2e (MD5)Made available in DSpace on 2018-08-24T16:44:27Z (GMT). No. of bitstreams: 1 Phosphatidyl Inositol 3 Kinase-Gamma Balances.pdf: 10035595 bytes, checksum: 5a61fb2c618990d4314d36db3868ee2e (MD5) Previous issue date: 2018Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, Brazil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Laboratório de Imunologia e Mecânica Pulmonar. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brazil / UNIFRANZ. Coordinación Nacional de Investigación. La Paz, Bolivia.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil / Universidade de São Paulo. Departamento de Farmacologia. Laboratório de Inflamação e Dor. Universidade de São Paulo. Ribeirão Preto, SP, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil / Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunologia de Doenças Virais. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia Geral. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de RNA de Interferência Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunologia de Doenças Virais. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil / Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Laboratório de Imunologia e Mecânica Pulmonar. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil.Influenza A virus (IAV) infection causes severe pulmonary disease characterized by intense leukocyte infiltration. Phosphoinositide-3 kinases (PI3Ks) are central signaling enzymes, involved in cell growth, survival, and migration. Class IB PI3K or phosphatidyl inositol 3 kinase-gamma (PI3Kγ), mainly expressed by leukocytes, is involved in cell migration during inflammation. Here, we investigated the contribution of PI3Kγ for the inflammatory and antiviral responses to IAV. PI3Kγ knockout (KO) mice were highly susceptible to lethality following infection with influenza A/WSN/33 H1N1. In the early time points of infection, infiltration of neutrophils was higher than WT mice whereas type-I and type-III IFN expression and p38 activation were reduced in PI3Kγ KO mice resulting in higher viral loads when compared with WT mice. Blockade of p38 in WT macrophages infected with IAV reduced levels of interferon-stimulated gene 15 protein to those induced in PI3Kγ KO macrophages, suggesting that p38 is downstream of antiviral responses mediated by PI3Kγ. PI3Kγ KO-derived fibroblasts or macrophages showed reduced type-I IFN transcription and altered pro-inflammatory cytokines suggesting a cell autonomous imbalance between inflammatory and antiviral responses. Seven days after IAV infection, there were reduced infiltration of natural killer cells and CD8+ T lymphocytes, increased concentration of inflammatory cytokines in bronchoalveolar fluid, reduced numbers of resolving macrophages, and IL-10 levels in PI3Kγ KO. This imbalanced environment in PI3Kγ KO-infected mice culminated in enhanced lung neutrophil infiltration, reactive oxygen species release, and lung damage that together with the increased viral loads, contributed to higher mortality in PI3Kγ KO mice compared with WT mice. In humans, we tested the genetic association of disease severity in influenza A/H1N1pdm09-infected patients with three potentially functional PIK3CG single-nucleotide polymorphisms (SNPs), rs1129293, rs17847825, and rs2230460. We observed that SNPs rs17847825 and rs2230460 (A and T alleles, respectively) were significantly associated with protection from severe disease using the recessive model in patients infected with influenza A(H1N1)pdm09. Altogether, our results suggest that PI3Kγ is crucial in balancing antiviral and inflammatory responses to IAV infection

Rarity of monodominance in hyperdiverse Amazonian forests.

Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors