Single-Ion Magnets Based on Mononuclear Cobalt(II) Complexes with Sulfadiazine

The already reported monomeric complex Co(SDZ)2bpy (1) and the new ternary complex Co(SDZ)2(6MQ)2 (2) (SDZ = sulfadiazine, bpy = 2,2′‐bipyridine, and 6MQ = 6‐methoxyquinoline) have been synthesized in order to study their magnetic properties. X‐ray diffraction studies indicate that in both compounds the SDZ acts as a bidentate ligand coordinating through the sulfonamide and the pyrimidine N atoms giving rise to a CoN6 coordination sphere. The complexes have been characterized based on elemental analyses, FTIR, UV/Vis spectroscopy, and thermogravimetric analysis (TGA, only for 2). Compounds 1 and 2 have been characterized magnetically, and they show slow relaxation of the magnetization below 9 and 6 K, respectively.Centro de Química InorgánicaInstituto de Física La Plat

Conservación de variabilidad genética en líneas de ratones CF1 endocriadas y seleccionadas por peso

Fil: Renny, M. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Fil: Julio, N.B. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Bernardi, S.F. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.FIL: Gardenal, Cristina Noemí. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Diversidad y Ecología Animal; Argentina.Fil: Oyarzabal, M.I. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Como un modelo experimental para aportar información sobre caracteres de interés económico en animales productivos, se fundaron líneas de Mus musculus. A partir de una población testigo de la cepa CF1 (t) se originaron dos pares de líneas de selección divergente para peso a los 49 días de edad: s (bajo peso) y s´ (alto peso); estas líneas son endocriadas por limitación del número y cuentan con 60 generaciones.Fil: Renny, M. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Fil: Julio, N.B. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Bernardi, S.F. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.FIL: Gardenal, Cristina Noemí. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Diversidad y Ecología Animal; Argentina.Fil: Oyarzabal, M.I. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Genética y Herencia (Genética Médica va en 3 "Ciencias Médicas y de la Salud”

Dietary total antioxidant capacity and obesity in children and adolescents

Dietary antioxidant intake has been suggested to protect against oxidative damage and related clinical complications. The aim of this study was to assess the potential relationships between the dietary total antioxidant capacity (TAC) and obesity-related features in children and adolescents. Anthropometric variables from 369 children and adolescents were measured (184 obese and 185 control). A validated food-frequency questionnaire was used to calculate the TAC and the daily nutrient and energy intake. Dietary TAC showed positive associations with fiber, folic acid, magnesium, and vitamins A, C and E. BMI, SDS-BMI and total body fat were inversely associated with dietary TAC only in obese subjects. These data suggest that dietary TAC may be a potential indicator of the risk to develop obesity-related features and could be considered as a useful method in assessing antioxidant intake

CHEMDNER: The drugs and chemical names extraction challenge

Natural language processing (NLP) and text mining technologies for the chemical domain (ChemNLP or chemical text mining) are key to improve the access and integration of information from unstructured data such as patents or the scientific literature. Therefore, the BioCreative organizers posed the CHEMDNER (chemical compound and drug name recognition) community challenge, which promoted the development of novel, competitive and accessible chemical text mining systems. This task allowed a comparative assessment of the performance of various methodologies using a carefully prepared collection of manually labeled text prepared by specially trained chemists as Gold Standard data. We evaluated two important aspects: one covered the indexing of documents with chemicals (chemical document indexing - CDI task), and the other was concerned with finding the exact mentions of chemicals in text (chemical entity mention recognition - CEM task). 27 teams (23 academic and 4 commercial, a total of 87 researchers) returned results for the CHEMDNER tasks: 26 teams for CEM and 23 for the CDI task. Top scoring teams obtained an F-score of 87.39% for the CEM task and 88.20% for the CDI task, a very promising result when compared to the agreement between human annotators (91%). The strategies used to detect chemicals included machine learning methods (e.g. conditional random fields) using a variety of features, chemistry and drug lexica, and domain-specific rules. We expect that the tools and resources resulting from this effort will have an impact in future developments of chemical text mining applications and will form the basis to find related chemical information for the detected entities, such as toxicological or pharmacogenomic properties

Expression of USP18 and IL2RA is increased in individuals receiving latent tuberculosis treatment with isoniazid

Background. The treatment of latent tuberculosis infection (LTBI) in individuals at risk of reactivation is essential for tuberculosis control. However, blood biomarkers associated with LTBI treatment have not been identified. Methods. Blood samples from tuberculin skin test (TST) reactive individuals were collected before and after one and six months of isoniazid (INH) therapy. Peripheral mononuclear cells (PBMC) were isolated, and an in-house interferon-γ release assay (IGRA) was performed. Expression of chemokine ligand 4 (CCL4), chemokine ligand 10 (CXCL10), chemokine ligand 11 (CXCL11), interferon alpha (IFNA), radical S-adenosyl methionine domain-containing 2 (RSAD2), ubiquitin-specific peptidase 18 (USP18), interferon-induced protein 44 (IFI44), interferon-induced protein 44 like (IFI44L), interferon-induced protein tetratricopeptide repeats 1(IFIT1), and interleukin 2 receptor subunit alpha (IL2RA) mRNA levels were assessed by qPCR before, during, and after INH treatment. Results. We observed significantly lower relative abundances of USP18, IFI44L, IFNA, and IL2RA transcripts in PBMC from IGRA-positive individuals compared to levels in IGRA-negative individuals before INH therapy. Also, relative abundance of CXCL11 was significantly lower in IGRA-positive than in IGRA-negative individuals before and after one month of INH therapy. However, the relative abundance of CCL4, CXCL10, and CXCL11 mRNA was significantly decreased and that of IL2RA and USP18 significantly increased after INH therapy, regardless of the IGRA result. Our results show that USP18, IFI44L, IFIT1, and IL2RA relative abundances increased significantly, meanwhile the relative abundance of CCL4, CXCL11, and IFNA decreased significantly after six months of INH therapy in TST-positive individuals. Conclusions. Changes in the profiles of USP18, IL2RA, IFNA, CCL4, and CXCL11 expressions during INH treatment in TST-positive individuals, regardless of IGRA status, are potential tools for monitoring latent tuberculosis treatment

Dual Pharmacological Targeting of HDACs and PDE5 Inhibits Liver Disease Progression in a Mouse Model of Biliary Inflammation and Fibrosis

Liver fibrosis, a common hallmark of chronic liver disease (CLD), is characterized by the accumulation of extracellular matrix secreted by activated hepatic fibroblasts and stellate cells (HSC). Fibrogenesis involves multiple cellular and molecular processes and is intimately linked to chronic hepatic inflammation. Importantly, it has been shown to promote the loss of liver function and liver carcinogenesis. No effective therapies for liver fibrosis are currently available. We examined the anti-fibrogenic potential of a new drug (CM414) that simultaneously inhibits histone deacetylases (HDACs), more precisely HDAC1, 2, and 3 (Class I) and HDAC6 (Class II) and stimulates the cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) pathway activity through phosphodiesterase 5 (PDE5) inhibition, two mechanisms independently involved in liver fibrosis. To this end, we treated Mdr2-KO mice, a clinically relevant model of liver inflammation and fibrosis, with our dual HDAC/PDE5 inhibitor CM414. We observed a decrease in the expression of fibrogenic markers and collagen deposition, together with a marked reduction in inflammation. No signs of hepatic or systemic toxicity were recorded. Mechanistic studies in cultured human HSC and cholangiocytes (LX2 and H69 cell lines, respectively) demonstrated that CM414 inhibited pro-fibrogenic and inflammatory responses, including those triggered by transforming growth factor β (TGFβ). Our study supports the notion that simultaneous targeting of pro-inflammatory and fibrogenic mechanisms controlled by HDACs and PDE5 with a single molecule, such as CM414, can be a new disease-modifying strateg

Diagnóstico inicial do nível de boas práticas agropecuárias nas UPL do Programa Leite Seguro.

O objetivo desse trabalho é apresentar o diagnóstico das práticas adotadas e o nível de conformidade frente aos indicadores de BPA utilizados na Ferramenta Protambo na etapa inicial do acompanhamento das UPL participantes do Programa Leite Seguro

Diagnóstico inicial do nível de boas práticas agropecuárias nas UPL do Programa Leite Seguro.

O objetivo desse trabalho é apresentar o diagnóstico das práticas adotadas e o nível de conformidade frente aos indicadores de BPA utilizados na Ferramenta Protambo na etapa inicial do acompanhamento das UPL participantes do Programa Leite Seguro

Epigenetic mechanisms and metabolic reprogramming in fibrogenesis: dual targeting of G9a and DNMT1 for the inhibition of liver fibrosis

OBJECTIVE: Hepatic stellate cells (HSC) transdifferentiation into myofibroblasts is central to fibrogenesis. Epigenetic mechanisms, including histone and DNA methylation, play a key role in this process. Concerted action between histone and DNA-mehyltransferases like G9a and DNMT1 is a common theme in gene expression regulation. We aimed to study the efficacy of CM272, a first-in-class dual and reversible G9a/DNMT1 inhibitor, in halting fibrogenesis. DESIGN: G9a and DNMT1 were analysed in cirrhotic human livers, mouse models of liver fibrosis and cultured mouse HSC. G9a and DNMT1 expression was knocked down or inhibited with CM272 in human HSC (hHSC), and transcriptomic responses to transforming growth factor-β1 (TGFβ1) were examined. Glycolytic metabolism and mitochondrial function were analysed with Seahorse-XF technology. Gene expression regulation was analysed by chromatin immunoprecipitation and methylation-specific PCR. Antifibrogenic activity and safety of CM272 were studied in mouse chronic CCl4 administration and bile duct ligation (BDL), and in human precision-cut liver slices (PCLSs) in a new bioreactor technology. RESULTS: G9a and DNMT1 were detected in stromal cells in areas of active fibrosis in human and mouse livers. G9a and DNMT1 expression was induced during mouse HSC activation, and TGFβ1 triggered their chromatin recruitment in hHSC. G9a/DNMT1 knockdown and CM272 inhibited TGFβ1 fibrogenic responses in hHSC. TGFβ1-mediated profibrogenic metabolic reprogramming was abrogated by CM272, which restored gluconeogenic gene expression and mitochondrial function through on-target epigenetic effects. CM272 inhibited fibrogenesis in mice and PCLSs without toxicity. CONCLUSIONS: Dual G9a/DNMT1 inhibition by compounds like CM272 may be a novel therapeutic strategy for treating liver fibrosis

Total antioxidant capacity and oxidative stress after a 10-week dietary intervention program in obese children

Dietary and serum total antioxidant capacity (TAC) are considered appropriate tools for investigating the potential healthy effects of dietary antioxidants consumed in mixed diets. The aim was to analyse the impact of a dietary intervention on macronutrient intakes and to evaluate the improvement on oxidative status after weight loss (WL) by measuring dietary and serum TAC, and urinary F2-isoprostane levels as markers of oxidative stress. Forty-four overweight/obese children (mean age 11.5yr) were enrolled to undergo a 10-week WL program. They were dichotomized at the median of Body Mass Index-Standard Deviation Score (BMI-SDS) change, as high (HR) and low responders (LR) after intervention. Subjects were prescribed a fixed full-day meal diet, calculated according to their basal metabolic rate and physical activity levels. A validated food-frequency questionnaire was used to retrospectively calculate TAC and daily nutrient intake. The HR subjects were able to reduce anthropometric indices and to improve lipid and glucose profile. They also significantly diminished fat intake (p=0.013). Moreover, baseline serum TAC values did significantly predict the reduction in urinary F2 isoprostane [B= -0.236 (-0.393 to -0.078); p=0.014] in the HR group after the WL program. Notably, changes in dietary TAC after the treatment were associated with a decrease in body weight after the 10-week intervention [B=-2.815 (-5.313 to -0.318), p=0.029] in the HR group. The -SerumTAC/DietaryTAC and the -F2Isoprostane/DietaryTAC ratios revealed that the relationships between oxidative markers and antioxidants dietary intake were more favourable in the HR than in the LR group. Conclusion: Our study showed that a 10-week WL program was able to reduce adiposity indices in obese children. Moreover, after the intervention changes in dietary TAC and WL were significantly associated. Our result suggests that specific food with a high TAC content (such as fruits, vegetables and legumes) could be recommended to improve WL