The role of the EP receptors for prostaglandin E2 in skin and skin cancer

One of the most common features of exposure of skin to ultraviolet (UV) light is the induction of inflammation, a contributor to tumorigenesis, which is characterized by the synthesis of cytokines, growth factors and arachidonic acid metabolites, including the prostaglandins (PGs). Studies on the role of the PGs in non-melanoma skin cancer (NMSC) have shown that the cyclooxygenase-2 (COX-2) isoform of the cyclooxygenases is responsible for the majority of the pathological effects of PGE2. In mouse skin models, COX-2 deficiency significantly protects against chemical carcinogen- or UV-induced NMSC while overexpression confers endogenous tumor promoting activity. Current studies are focused on identifying which of the G protein-coupled EP receptors mediate the tumor promotion/progression activities of PGE2 and the signaling pathways involved. As reviewed here, the EP1, EP2, and EP4 receptors, but not the EP3 receptor, contribute to NMSC development, albeit through different signaling pathways and with somewhat different outcomes. The signaling pathways activated by the specific EP receptors are context specific and likely depend on the level of PGE2 synthesis, the differential levels of expression of the different EP receptors, as well as the levels of expression of other interacting receptors. Understanding the role and mechanisms of action of the EP receptors potentially offers new targets for the prevention or therapy of NMSCs

Metagenomic investigation of ticks from Kenyan wildlife reveals diverse microbial pathogens and new country pathogen records

Focusing on the utility of ticks as xenosurveillance sentinels to expose circulating pathogens in Kenyan drylands, host-feeding ticks collected from wild ungulates [buffaloes, elephants, giraffes, hartebeest, impala, rhinoceros (black and white), zebras (Grévy’s and plains)], carnivores (leopards, lions, spotted hyenas, wild dogs), as well as regular domestic and Boran cattle were screened for pathogens using metagenomics. A total of 75 host-feeding ticks [Rhipicephalus (97.3%) and Amblyomma (2.7%)] collected from 15 vertebrate taxa were sequenced in 46 pools. Fifty-six pathogenic bacterial species were detected in 35 pools analyzed for pathogens and relative abundances of major phyla. The most frequently observed species was Escherichia coli (62.8%), followed by Proteus mirabilis (48.5%) and Coxiella burnetii (45.7%). Francisella tularemia and Jingmen tick virus (JMTV) were detected in 14.2 and 13% of the pools, respectively, in ticks collected from wild animals and cattle. This is one of the first reports of JMTV in Kenya, and phylogenetic reconstruction revealed significant divergence from previously known isolates and related viruses. Eight fungal species with human pathogenicity were detected in 5 pools (10.8%). The vector-borne filarial pathogens (Brugia malayi, Dirofilaria immitis, Loa loa), protozoa (Plasmodium spp., Trypanosoma cruzi), and environmental and water-/food-borne pathogens (Entamoeba histolytica, Encephalitozoon intestinalis, Naegleria fowleri, Schistosoma spp., Toxoplasma gondii, and Trichinella spiralis) were detected. Documented viruses included human mastadenovirus C, Epstein-Barr virus and bovine herpesvirus 5, Trinbago virus, and Guarapuava tymovirus-like virus 1. Our findings confirmed that host-feeding ticks are an efficient sentinel for xenosurveillance and demonstrate clear potential for wildlife-livestock-human pathogen transfer in the Kenyan landscape

Crescimento vegetativo e produção de cafeeiros (Coffea arabica L.) recepados em duas épocas, conduzidos em espaçamentos crescentes Vegetative growth and yield of coffee plants (Coffea arabica L.) in two different pruning times, conducted at different spacings

O experimento foi instalado na Fazenda Experimental da Empresa de Pesquisa Agropecuária de Minas Gerais - EPAMIG em Machado, Sul de Minas Gerais, em 1992, com o objetivo de avaliar as conseqüências da redução dos espaçamentos entre as linhas e entre as plantas na linha de plantio sobre a produção e a fenologia do cafeeiro(Coffea arabica L.). O delineamento experimental foi o blocos casualizados - DBC, em um arranjo fatorial 4 x 3 com parcela subdividida, sendo quatro distâncias entre as linhas (2,0; 2,5; 3,0 e 3,5 m) e três distâncias entre as plantas na linha de plantio (0,5; 0,75; 1,0 m), e duas épocas de poda (uma precoce feita logo após a colheita em de julho 2002 e a outra tardia em de janeiro de 2003), totalizando 24 tratamentos com três repetições. Em julho de 2002 e em janeiro de 2003 foi realizada a poda tipo "recepa", na qual foram conduzidas duas brotações por planta. Em agosto de 2004, avaliou-se o crescimento dos componentes vegetativos e a produção das parcelas. Os espaçamentos adotados não influenciaram o crescimento de nenhum dos componentes vegetativos das brotações no período avaliado. Todas as características vegetativas foram influenciadas positivamente pela adoção da poda precoce, assim como a produtividade da primeira colheita realizada após a poda, que foi também influenciada positivamente pela adoção de espaçamentos mais adensados. Os cafeeiros que foram submetidos à poda tardia não produziram, em julho de 2004, como aqueles podados precocemente.<br>The experiment was established in the Empresa de Pesquisa Agropecuária de Minas Gerais - Epamig Experiment Station, located in the city of Machado, south of the Minas Gerais state, Brazil, in the year of 1992, with the objective of evaluating the consequences of the reduction on planting spaces among rows and among plants, upon beans yield and plant phenology (Coffea arabica L.). The experimental design used was a 4x 3 factorial with split plot at four distances between planting rows (2,0; 2,5; 3,0 e 3,5 m) and three distances among plants in the row (0,5; 0,75 e 1,0 m), and two different pruning times (one precociously conducted just after the harvest, on july 2002, and the other latter on january 2003), making a total 24 treatments arranged in randomized blocks with three replicates. In july 2002 and january 2003 a drastic pruning was clone and conducing two sprouts per plant. Vegetative growth and beans yield were evaluated in august 2004. Coffee plant spacing did not affected growth of any of the vegetative components of sprouting, during the evaluated period. All the vegetative characteristics were positively affected by the early pruning procedure, as well as the beans yield of the first harvest after pruning, which also showed to be positively influenced by the adoption of a narrower spacing plant. The coffee plants which were submitted to late prunning, had lancer bean yield in july 2004 as those precociously prunned

The 3T3 neutral red uptake phototoxicity test:practical experience and implications for phototoxicity testing - the report of an ECVAM-EFPIA workshop

This is the report from the “ECVAM-EFPIA workshop on 3T3 NRU Phototoxicity Test: Practical Experience and Implications for Phototoxicity Testing”, jointly organized by ECVAM and EFPIA and held on the 25-27 October 2010 in Somma Lombardo, Italy. The European Centre for the Validation of Alternative Methods (ECVAM) was established in 1991 within the European Commission Joint Research, based on a Communication from the European Commission1. The main objective of ECVAM is to promote the scientific and regulatory acceptance of alternative methods which are of importance to the biosciences and which reduce, refine and replace the use of laboratory animals. The European Federation of Pharmaceuticals Industries and Association (EFPIA) represent the pharmaceutical industry operating in Europe. Through its direct membership of 31 national associations and 40 leading pharmaceutical companies, EFPIA is the voice on the EU scene of 2,200 companies committed to researching, developing and bringing to patients new medicines that improve health and the quality of life around the world. The workshop, co-chaired by Joachim Kreysa (ECVAM) and Phil Wilcox (GSK, EFPIA) involved thirty-five experts from academia, regulatory authorities and industry that were invited to contribute with their experiences in the field. The main objectives of the workshop were: - to present 'in use' experience of the pharmaceutical industry with the 3T3 Neutral Red Uptake Phototoxicity Test (3T3 NRU-PT), - to discuss why it differs from the results in the original validation exercise, - to discuss technical issues and - consider ways to improve the usability of the 3T3 NRU-PT for (non-topical) pharmaceuticals, e.g. by modifying technical aspects of the assay or adjusting the criteria used to classify for a positive response. During the workshop, the assay methodology was reviewed by comparing the OECD Test Guideline with the actual protocol used, data from EFPIA and JPMA ‘surveys’ were presented and possible reasons for the outcomes were discussed. Experts from cosmetics and pharmaceutical industries presented their experience with the 3T3 NRU-PT and evidence was presented for phototoxic clinical symptoms that could be linked to certain relevant molecules. Brainstorming sessions discussed if the 3T3 NRU-PT needed to be improved and whether alternatives to the 3T3 NRU-PT exist. Finally, the view point from EU and US regulators was also presented. In the final session, the conclusions of the meeting were summarised with action points. It was concluded that the 3T3 NRU-PT is a hazard-based assay with a high level of sensitivity. It is relevant and an accepted test that correctly identifies non-phototoxic materials. However, positive results in the 3T3 NRU-PT often do not translate into a clinical phototoxicity risk. Possible ways to improve the practical use of this assay include: (i.) implementation of absorption criteria as a means to reduce the number of materials tested, (ii.) limit the highest concentration tested, and (iii.) consider modifying the criteria used to identify “positives” in the test.JRC.I.5-Systems Toxicolog