Differential role of cyclooxygenase 1 and 2 isoforms in the modulation of colonic neuromuscular function in experimental inflammation

This study examines the role played by cyclooxygenase (COX) isoforms (COX-1 and -2) in the regulation of colonic neuromuscular function in normal rats and after induction of colitis by 2,4-dinitrobenzenesulfonic acid (DNBS). The expression of COX-1 and COX-2 in the colonic neuromuscular layer was assessed by reverse transcription-polymerase chain reaction and immunohistochemistry. The effects of COX inhibitors on in vitro motility were evaluated by studying electrically induced and carbachol-induced contractions of the longitudinal muscle. Both COX isoforms were constitutively expressed in normal colon; COX-2 was up-regulated in the presence of colitis. In normal and inflamed colon, both COX isoforms were mainly localized in neurons of myenteric ganglia. In the normal colon, indomethacin (COX-1/COX-2 inhibitor), SC-560 [5-(4-chloro-phenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole] (COX-1 inhibitor), or DFU [5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone] (COX-2 inhibitor) enhanced atropine-sensitive electrically evoked contractions. The most prominent effects were observed with indomethacin or SC-560 plus DFU. In the inflamed colon, SC-560 lost its effect, whereas indomethacin and DFU maintained their enhancing actions. These results were more evident after blockade of noncholinergic pathways. In rats with colitis, in vivo treatment with superoxide dismutase or S-methylisothiourea (inhibitor of inducible nitric-oxide synthase) restored the enhancing motor effect of SC-560. COX inhibitors had no effect on carbachol-induced contractions in normal or DNBS-treated rats. In conclusion, in the normal colon, both COX isoforms act at the neuronal level to modulate the contractile activity driven by excitatory cholinergic pathways. In the presence of inflammation, COX-1 activity is hampered by oxidative stress, and COX-2 seems to play a predominant role in maintaining an inhibitory control of colonic neuromuscular function

Universidad y mercado : Transformaciones institucionales y discursivas en la Universidad Nacional del Litoral

El objetivo del presente trabajo es dar cuenta de los procesos de transformación en la relación entre Universidad y mercado, iniciados a mediados del siglo XX y profundizados en los albores del siglo XXI, según los cuales la universidad se ha constituido paulatinamente en un agente clave del crecimiento económico, la innovación y la transferencia de conocimientos especializados.Facultad de Humanidades y Ciencias de la Educació

Variation of morphological descriptors for the evaluation of tomato germplasm and their stability across different growing conditions

[EN] Germplasm and breeding materials are usually characterized using morphological and agronomic descriptors, which should have a high heritability. Despite the widespread use of tomato (Solanum lycopersicum) standardized descriptors, little information exists on environmental effects on descriptor values and their heritability. We have evaluated 12 tomato accessions from seven cultivar groups in three different environments (open-field conventional, open-field organic, and greenhouse) and characterized them with 36 descriptors. A wide range of variation was found for most descriptors, demonstrating their utility for describing tomato materials and their diversity and relationships. The analysis of descriptors variation reveals that while for some descriptors with a simple genetic control the accession effect accounts for 100% of the variation, for others like yield per plant only 10.83% of the variation observed is due to the accession effect. Although significant differences were found among environments for most descriptors, including a much higher yield in the open-field conventional environment than in the two others, the environmental effect was low for most traits. However, the genotype×environment effect generally had an important contribution to the structure of variation for many descriptors, and for three traits it had the highest contribution to the percentage of the sum of squares. As a result of the variation structure, the heritability values are high (> 0.7) for only 10 descriptors, while for five is low (< 0.3). Principal components analysis (PCA) reveals that projections in the PCA graph of a same accession grown in different environments plot together in the same area of the PCA graph. Although cultivar groups are generally clearly separated in the PCA graph, accessions from the same cultivar group in some cases are intermixed. These results have important implications for detecting tomato duplicates and establishing core collections, as well as for analyzing germplasm and breeding results, when using data sets containing data of accessions grown in different environments.This work has been partially funded by the TRADITOM (Traditional tomato varieties and cultural practices: a case for agricultural diversification with impacto n food security and health of European population) and G2P-SOL (Linking genetic resources, genomes and phenotypes of Solanaceous crops) projects. These projects have received funding from the European Union's Horizon 2020 research and innovation programme under grant agreements No 634561 (TRADITOM) and No 677379 (G2P-SOL). Authors are grateful to Mr. Jonatan Cerdan for his technical help.Figás-Moreno, MDR.; Prohens Tomás, J.; Casanova-Calancha, C.; Fernández De Córdova Martínez, PJ.; Soler Aleixandre, S. (2018). Variation of morphological descriptors for the evaluation of tomato germplasm and their stability across different growing conditions. Scientia Horticulturae. 238:107-115. https://doi.org/10.1016/j.scienta.2018.04.039S10711523

Interlaboratory comparison study of the Colony Forming Efficiency assay for assessing cytotoxicity of nanomaterials

Nanotechnology has gained importance in the past years as it provides opportunities for industrial growth and innovation. However, the increasing use of manufactured nanomaterials (NMs) in a number of commercial applications and consumer products raises also safety concerns and questions regarding potential unintended risks to humans and the environment. Since several years the European Commission’s Joint Research Centre (JRC) is putting effort in the development, optimisation and harmonisation of in vitro test methods suitable for screening and hazard assessment of NMs. Work is done in collaboration with international partners, in particular the Organisation for Economic Co-operation and Development (OECD). This report presents the results from an interlaboratory comparison study of the in vitro Colony Forming Efficiency (CFE) cytotoxicity assay performed in the frame of OECD's Working Party of Manufactured Nanomaterials (WPMN). Twelve laboratories from European Commission, France, Italy, Japan, Poland, Republic of Korea, South Africa and Switzerland participated in the study coordinated by JRC. The results show that the CFE assay is a suitable and robust in vitro method to assess cytotoxicity of NMs. The assay protocol is well defined and is easily and reliably transferable to other laboratories. The results obtained show good intra and interlaboratory reproducibility of the assay for both the positive control and the tested nanomaterials. In conclusion the CFE assay can be recommended as a building block of an in vitro testing battery for NMs toxicity assessment. It could be used as a first choice method to define dose-effect relationships for other in vitro assays.JRC.I.4-Nanobioscience

PESQUISAS DESENVOLVIDAS NO PROGRAMA DE PÓS-GRADUAÇÃO EM GERONTOLOGIA DA UNIVERSIDADE FEDERAL DE SÃO CARLOS E SUA IMPORTÂNCIA NO CONTEXTO DO ENVELHECIMENTO

Esta revisão narrativa tem como objetivo apresentar e discutir a relevância dos estudos desenvolvidos no Programa de Pós-Graduação em Gerontologia da Universidade Federal de São Carlos (PPGGero/UFSCar). Os dados foram coletados na disciplina “Seminários Avançados em Gerontologia”, em que os docentes autores apresentaram suas linhas de pesquisa, as quais foram compiladas pelos discentes autores. Os resultados desta revisão apresentam os estudos realizados em um programa interdisciplinar de mestrado acadêmico que possui duas linhas de pesquisa denominadas: 1) Saúde, Biologia e Envelhecimento; e 2) Gestão, Tecnologia e Inovação em Gerontologia. Os estudos se inserem em diversas temáticas da área do envelhecimento, que se articulam entre ambas as linhas de pesquisa do programa. Na linha 1 destacam-se estudos relacionados à cognição, à demência e suas consequências aos pacientes e cuidadores, bem como a pesquisas relacionadas ao seu diagnóstico e cuidado. Destacam-se também pesquisas epidemiológicas e aquelas relacionadas a condições ou doenças comuns no envelhecimento, como dor crônica, osteoartrite e, mais recentemente, a infecções em idosos, incluindo a COVID-19. Na linha 2 destacam-se pesquisas relacionadas a tecnologias assistivas voltadas aos idosos, bem como estratégias de marketing e políticas de atenção para esse público. É notório que a multidimensionalidade de abordagens das questões do envelhecimento exige enfoque multidisciplinar sobre um contexto de excelência acadêmica. Assim, conclui-se que as pesquisas do PPGGero/UFSCar, ao abrangerem várias áreas do conhecimento – as quais permeiam as ciências humanas, biológicas, sociais e exatas no contexto de tecnologia e inovação –, promovem a formação de mestres e pesquisadores que contribuem para a produção de conhecimento em Gerontologia no país

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Role of HIF-1 and NF-κB Transcription Factors in the Modulation of Transferrin Receptor by Inflammatory and Anti-inflammatory Signals*

Inflammation generates various changes in body iron homeostasis, including iron sequestration in the reticuloendothelial system with ensuing hypoferremia and anemia of chronic disease. Increased iron accumulation is caused by hepcidin-mediated down-regulation of the iron export protein ferroportin and higher iron uptake. However, enhanced iron acquisition by macrophages cannot be accounted for by the previously reported transferrin receptor (TfR1) down-regulation in macrophages exposed to lipopolysaccharide (LPS)/interferon γ (IFNγ) because it impairs a major iron uptake mechanism. Because TfR1 is up-regulated by the hypoxia-inducible factor (HIF-1), we investigated the effect of inflammatory and anti-inflammatory signals on HIF-1-mediated TfR1 gene expression. Exposure of mouse macrophages (RAW 264.7 and J774A.1 cells or peritoneal macrophages) to LPS/IFNγ up-regulated NF-κB, which in turn rapidly and transiently activated HIF-1-dependent TfR1 expression and iron uptake. Activation of an anti-inflammatory pathway by pre-exposure to the adenosine A2A receptor agonist CGS21680 prevented the inducing effect of LPS/IFNγ on HIF-1 and TfR1 expression by inhibiting NF-κB activity, whereas treatment with CGS21680 alone increased HIF-1-mediated TfR1 expression by means of an NF-κB-independent signaling pathway. In conclusion, an interplay of the HIF-1 and NF-κB pathways controls TfR1 transcription in inflammation. The consequent changes in TfR1 expression may be involved in modulating iron retention in inflammatory macrophages, thus possibly contributing to the development of hypoferremia in the early phases preceding the down-regulation of macrophage ferroportin by hepcidin