Understanding the mutagenicity of atmospheric particulate air samples

Orientador: Gisela de Aragão UmbuzeiroDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de TecnologiaResumo: O fracionamento de uma mistura complexa, como o extrato orgânico do material particulado de ar, com base nas diferentes características físicas e químicas dos seus componentes acoplada a testes de mutagenicidade e análises cromatográficas, vem sendo um procedimento útil na elucidação de quais substâncias está presentes na mistura. Este trabalho foi realizado em colaboração com outro grupo de pesquisa em um projeto temático financiado pela FAPESP, e seu objetivo foi estudar a mutagenicidade de frações de extratos orgânicos de material particulado de ar, utilizando ensaio Salmonella/microssoma em microssuspensão com os pares de linhagens TA98/YG1041, TA98/TA1538 e TA1538/YG5161 de Salmonella typhimurium que apresentam diferentes sensibilidades para grupos específicos de compostos. Também foi objetivo do trabalho comparar as potências mutagênicas obtidas para cada uma das frações com os níveis de hidrocarbonetos policíclicos aromáticos analisados pelos pesquisadores do projeto temático. Foram avaliadas três frações, Nitro-HPA, Oxi-HPA e HPA utilizando o método Salmonella/microssoma em microssuspensão na presença e ausência de ativação metabólica (mistura S9) em experimentos de dose-resposta, com quantidade máxima de 10 m³ por placa; também foi avaliada a contribuição na mutagenicidade dos hidrocarbonetos policíclicos aromáticos analisados para cada fração. De acordo com a contribuição na mutagenicidade dos compostos identificados, foi possível inferir que esses não explicam totalmente a mutagenicidade observada para algumas linhagens, e que outros compostos podem estar causando esse efeito. A comparação dos perfis observados entre as frações analisadas e os compostos químicos encontrados na literatura utilizando os pares de linhagens foi capaz de fornecer alguns grupos que podem justificar a mutagenicidade observada, porém, faltam estudos com compostos químicos puros. Um estudo utilizando os pares de linhagens com compostos químicos pode ajudar a identificar e entender o perfil das respostas observadas em amostras ambientais de material particulado de ar, bem como em outras amostras ambientais, especialmente em análises químicas direcionadas pelo efeito biológico (ADEB)Abstract: The fractionation of a complex mixture based on different physical and chemical characteristics of its components coupled to mutagenicity testing and chromatographic analyzes have been useful in elucidating what substances are present in the mixture. This work was performed in collaboration with another research group in a broad thematic project funded by FAPESP. Samples were collected extracted and prepared by the participants and in this work the objective was to study the mutagenicity of fractions of organic extracts of air particulate matter using Salmonella/microsome microsuspension in combination with selective pair of strains TA98/YG1041, TA98/TA1538 and TA1538/YG5161 of Salmonella typhimurium which have different sensitivities to specific types of compounds. Another objective was to compare the mutagenic potencies obtained for each of the fractions with the levels of polycyclic aromatic hydrocarbons analyzed by the researchers of the thematic project. We evaluated three fractions, named as Nitro-PAH, Oxy-PAH and PAH, using the Salmonella/microsome microsuspension protocol in the presence and absence of metabolic activation (S9) in dose-response experiments, with maximum of 10 m³ per plate, was also evaluated the contribution of mutagenicity in polycyclic aromatic hydrocarbons for each fraction analyzed. According to the contribution in the mutagenicity of the compounds identified, it was possible to infer that these do not fully explain the mutagenicity observed for some strains, and that other compounds may be causing this effect. The comparison of the profiles observed between fractions and analyzed the chemical compounds found in the literature using the pairs of strains was able to provide some groups which may justify the mutagenicity observed, however, there are few studies with pure chemicals. A study using pairs of strains with single chemicals could help in the identification and understanding of the profile of the responses seen atmospheric air particulate samples as well as in other environmental samples, and so assist chemical analysis studies in effect directed analysis (EDA)MestradoTecnologia e InovaçãoMestre em Tecnologi

Waterless Dyeing and In Vitro Toxicological Properties of Biocolorants from Cortinarius sanguineus

As a part of an ongoing interest in identifying environmentally friendly alternatives to synthetic dyes and in using liquid CO2 as a waterless medium for applying the resulting colorants to textiles, our attention turned to yellow-to-red biocolorants produced by Cortinarius sanguineus fungus. The three principal target anthraquinone colorants (emodin, dermocybin, and dermorubin) were isolated from the fungal bodies using a liquid–liquid separation method and characterized using 700 MHz NMR and high-resolution mass spectral analyses. Following structure confirmations, the three colorants were examined for dyeing synthetic polyester (PET) textile fibers in supercritical CO2. We found that all three biocolorants were suitable for dyeing PET fibers using this technology, and our attention then turned to determining their toxicological properties. As emodin has shown mutagenic potential in previous studies, we concentrated our present toxicity studies on dermocybin and dermorubin. Both colorants were non-mutagenic, presented low cellular toxicity, and did not induce skin sensitization. Taken together, our results indicate that dermocybin and dermorubin possess the technical and toxicological properties needed for consideration as synthetic dye alternatives under conditions that are free of wastewater production

Biological predictors of chemotherapy-induced peripheral neuropathy (CIPN): MASCC neurological complications working group overview.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating condition associated with a number of chemotherapeutic agents. Drugs commonly implicated in the development of CIPN include platinum agents, taxanes, vinca alkaloids, bortezomib, and thalidomide analogues. As a drug response can vary between individuals, it is hypothesized that an individual's specific genetic variants could impact the regulation of genes involved in drug pharmacokinetics, ion channel functioning, neurotoxicity, and DNA repair, which in turn affect CIPN development and severity. Variations of other molecular markers may also affect the incidence and severity of CIPN. Hence, the objective of this review was to summarize the known biological (molecular and genomic) predictors of CIPN and discuss the means to facilitate progress in this field

Role of GUCA1C in Primary Congenital Glaucoma and in the Retina: Functional Evaluation in Zebrafish

Primary congenital glaucoma (PCG) is a heterogeneous, inherited, and severe optical neuropathy caused by apoptotic degeneration of the retinal ganglion cell layer. Whole-exome sequencing analysis of one PCG family identified two affected siblings who carried a low-frequency homozygous nonsense GUCA1C variant (c.52G > T/p.Glu18Ter/rs143174402). This gene encodes GCAP3, a member of the guanylate cyclase activating protein family, involved in phototransduction and with a potential role in intraocular pressure regulation. Segregation analysis supported the notion that the variant was coinherited with the disease in an autosomal recessive fashion. GCAP3 was detected immunohistochemically in the adult human ocular ciliary epithelium and retina. To evaluate the ocular effect of GUCA1C loss-of-function, a guca1c knockout zebrafish line was generated by CRISPR/Cas9 genome editing. Immunohistochemistry demonstrated the presence of GCAP3 in the non-pigmented ciliary epithelium and retina of adult wild-type fishes. Knockout animals presented up-regulation of the glial fibrillary acidic protein in Müller cells and evidence of retinal ganglion cell apoptosis, indicating the existence of gliosis and glaucoma-like retinal damage. In summary, our data provide evidence for the role of GUCA1C as a candidate gene in PCG and offer new insights into the function of this gene in the ocular anterior segment and the retina.This research was funded by research grants from the “Instituto de Salud Carlos III/European Regional Development Fund (ERDF)” (PI15/01193, PI19/00208 and RD16/0008/0019, OFTARED), the Regional Ministry of Science and Technology of the Board of the Communities of “Castilla-La Mancha” (SBPLY/17/180501/000404; http://www.educa.jccm.es/idiuniv/es). SA-M was sponsored by the Regional Ministry of Science and Technology of the Board of the Communities of “Castilla-La Mancha” (PREJCCM2016/28)

Assessing the effect of prophylactic ankle taping on ankle and knee biomechanics during landing tasks in healthy individuals: A cross-sectional observational study

ABSTRACT BACKGROUND: Current research supports the fact that prophylactic ankle taping (AT) is effective in preventing ankle injuries in amateur and elite sports athletes. OBJECTIVE: This study aimed to investigate the effect of AT on balance, knee valgus during drop jump and single-leg countermovement jump (SL-CMJ) landings, and ankle range of motion (ROM) restriction in healthy participants. DESIGN AND SETTING: A cross-sectional observational study was conducted at the Universidad Europea de Madrid, Madrid, Spain. METHODS: Participants: Thirty-nine healthy individuals participated in this study and performed the movements under two conditions (with and without tape). Outcome measurements: ankle ROM, balance, SL-CMJ height, flight time, ground time, and knee valgus. Before any intervention, a random process was developed with a 1:1 allocation ratio, and the participants were assigned to groups A (tape-no tape) and B (no tape-tape). RESULTS: Significant differences between tape and no-tape moments were observed for drop jump knee valgus flexion (P = 0.007), with an increase in knee valgus in participants with ankle taping. Similarly, the Y-balance testshowed a significant decrease in all variables (P = 0.001 and), ankle dorsiflexion (P = 0.001) in participants with ankle taping. CONCLUSIONS: AT is effective for immediate ankle ROM restriction. However, an increase in knee valgus during drop jump task and a decrease in lower limb balance were observed during drop jump task. Based on these results, it can be concluded that AT application in healthy individuals should not be recommended as it results in increase in injury risk factors

Relatório de estágio profissional

O presente Relatório foi realizado no âmbito do Estágio Profissional I e II. Trata-se de um trabalho elaborado com base na observação de aulas e na experimentação didática; os materiais obtidos (como, por exemplo, horários, dados sobre as turmas, fichas, etc.) foram submetidos a uma análise documental

CPAMD8 loss-of-function underlies non-dominant congenital glaucoma with variable anterior segment dysgenesis and abnormal extracellular matrix

Abnormal development of the ocular anterior segment may lead to a spectrum of clinical phenotypes ranging from primary congenital glaucoma (PCG) to variable anterior segment dysgenesis (ASD). The main objective of this study was to identify the genetic alterations underlying recessive congenital glaucoma with ASD (CG-ASD). Next-generation DNA sequencing identified rare biallelic CPAMD8 variants in four patients with CG-ASD and in one case with PCG. CPAMD8 is a gene of unknown function and recently associated with ASD. Bioinformatic and in vitro functional evaluation of the variants using quantitative reverse transcription PCR and minigene analysis supported a loss-of-function pathogenic mechanism. Optical and electron microscopy of the trabeculectomy specimen from one of the CG-ASD cases revealed an abnormal anterior chamber angle, with altered extracellular matrix, and apoptotic trabecular meshwork cells. The CPAMD8 protein was immunodetected in adult human ocular fluids and anterior segment tissues involved in glaucoma and ASD (i.e., aqueous humor, non-pigmented ciliary epithelium, and iris muscles), as well as in periocular mesenchyme-like cells of zebrafish embryos. CRISPR/Cas9 disruption of this gene in F0 zebrafish embryos (96 hpf) resulted in varying degrees of gross developmental abnormalities, including microphthalmia, pharyngeal maldevelopment, and pericardial and periocular edemas. Optical and electron microscopy examination of these embryos showed iridocorneal angle hypoplasia (characterized by altered iris stroma cells, reduced anterior chamber, and collagen disorganized corneal stroma extracellular matrix), recapitulating some patients’ features. Our data support the notion that CPAMD8 loss-of-function underlies a spectrum of recessive CG-ASD phenotypes associated with extracellular matrix disorganization and provide new insights into the normal and disease roles of this gene

Coefficient shifts in geographical ecology: an empirical evaluation of spatial and non-spatial regression

Copyright © 2009 The Authors. Copyright © ECOGRAPHY 2009.A major focus of geographical ecology and macro ecology is to understand the causes of spatially structured ecological patterns. However, achieving this understanding can be complicated when using multiple regressions, because the relative importance of explanatory variables, as measured by regression coefficients, can shift depending on whether spatially explicit or non-spatial modelling is used. However, the extent to which coefficients may shift and why shifts occur are unclear. Here, we analyze the relationship between environmental predictors and the geographical distribution of species richness, body size, range size and abundance in 97 multi-factorial data sets. Our goal was to compare standardized partial regression coefficients of non-spatial ordinary least squares regressions (i.e. models fitted using ordinary least squares without taking autocorrelation into account; “OLS models” hereafter) and eight spatial methods to evaluate the frequency of coefficient shifts and identify characteristics of data that might predict when shifts are likely. We generated three metrics of coefficient shifts and eight characteristics of the data sets as predictors of shifts. Typical of ecological data, spatial autocorrelation in the residuals of OLS models was found in most data sets. The spatial models varied in the extent to which they minimized residual spatial autocorrelation. Patterns of coefficient shifts also varied among methods and datasets, although the magnitudes of shifts tended to be small in all cases. We were unable to identify strong predictors of shifts, including the levels of autocorrelation in either explanatory variables or model residuals. Thus, changes in coefficients between spatial and non-spatial methods depend on the method used and are largely idiosyncratic, making it difficult to predict when or why shifts occur. We conclude that the ecological importance of regression coefficients cannot be evaluated with confidence irrespective of whether spatially explicit modelling is used or not. Researchers may have little choice but to be more explicit about the uncertainty of models and more cautious in their interpretation

Multicentre, randomised, single-blind, parallel group trial to compare the effectiveness of a Holter for Parkinson's symptoms against other clinical monitoring methods: study protocol

Introduction In recent years, multiple studies have aimed to develop and validate portable technological devices capable of monitoring the motor complications of Parkinson's disease patients (Parkinson's Holter). The effectiveness of these monitoring devices for improving clinical control is not known. Methods and analysis This is a single-blind, cluster-randomised controlled clinical trial. Neurologists from Spanish health centres will be randomly assigned to one of three study arms (1:1:1): (a) therapeutic adjustment using information from a Parkinson?s Holter that will be worn by their patients for 7 days, (b) therapeutic adjustment using information from a diary of motor fluctuations that will be completed by their patients for 7 days and (c) therapeutic adjustment using clinical information collected during consultation. It is expected that 162 consecutive patients will be included over a period of 6 months. The primary outcome is the efficiency of the Parkinson?s Holter compared with traditional clinical practice in terms of Off time reduction with respect to the baseline (recorded through a diary of motor fluctuations, which will be completed by all patients). As secondary outcomes, changes in variables related to other motor complications (dyskinesia and freezing of gait), quality of life, autonomy in activities of daily living, adherence to the monitoring system and number of doctor?patient contacts will be analysed. The noninferiority of the Parkinson's Holter against the diary of motor fluctuations in terms of Off time reduction will be studied as the exploratory objective. Ethics and dissemination approval for this study has been obtained from the Hospital Universitari de Bellvitge Ethics Committee. The results of this study will inform the practical utility of the objective information provided by a Parkinson's Holter and, therefore, the convenience of adopting this technology in clinical practice and in future clinical trials. We expect public dissemination of the results in 2022.Funding This work is supported by AbbVie S.L.U, the Instituto de Salud Carlos III [DTS17/00195] and the European Fund for Regional Development, 'A way to make Europe'

Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe