553 research outputs found

    Different genomic changes underlie adaptive evolution in populations of contrasting history

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    Funding Information: This work was supported by Portuguese National Funds through “Fundacžão para a CiĂȘncia e a Tecnologia” (projects PTDC/ BIA-BEC/098213/2008, PTDC/BIA-BIC/2165/2012 and cE3c Unit FCT funding UID/BIA/00329/2013, grants SFRH/BD/ 60734/2009 to I.F. and SFRH/BPD/86186/2012 to P.S.). We thank Miguel Lopes-Cunha for help in the laboratory, Francisco Pina-Martins for help with computing, Josiane Santos and Ana Sofia Quina for discussions, and Mauro Santos and Anthony Long for advice on the study and comments on the manuscript. We also thank the three anonymous reviewers for their constructive suggestions.Experimental evolution is a powerful tool to understand the adaptive potential of populations under environmental change. Here, we study the importance of the historical genetic background in the outcome of evolution at the genomewide level. Using the natural clinal variation of Drosophila subobscura, we sampled populations from two contrasting latitudes (Adraga, Portugal and Groningen, Netherlands) and introduced them in a new common environment in the laboratory. We characterized the genome-wide temporal changes underlying the evolutionary dynamics of these populations, which had previously shown fast convergence at the phenotypic level, but not at chromosomal inversion frequencies. We found that initially differentiated populations did not converge either at genome-wide level or at candidate SNPs with signs of selection. In contrast, populations from Portugal showed convergence to the control population that derived from the same geographical origin and had been long-established in the laboratory. Candidate SNPs showed a variety of different allele frequency change patterns across generations, indicative of an underlying polygenic basis. We did not detect strong linkage around candidate SNPs, but rather a small but long-ranging effect. In conclusion, we found that history played a major role in genomic variation and evolution, with initially differentiated populations reaching the same adaptive outcome through different genetic routes.publishersversionpublishe

    The effects of death and post-mortem cold ischemia on human tissue transcriptomes

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    Post-mortem tissues samples are a key resource for investigating patterns of gene expression. However, the processes triggered by death and the post-mortem interval (PMI) can significantly alter physiologically normal RNA levels. We investigate the impact of PMI on gene expression using data from multiple tissues of post-mortem donors obtained from the GTEx project. We find that many genes change expression over relatively short PMIs in a tissue-specific manner, but this potentially confounding effect in a biological analysis can be minimized by taking into account appropriate covariates. By comparing ante- and post-mortem blood samples, we identify the cascade of transcriptional events triggered by death of the organism. These events do not appear to simply reflect stochastic variation resulting from mRNA degradation, but active and ongoing regulation of transcription. Finally, we develop a model to predict the time since death from the analysis of the transcriptome of a few readily accessible tissues.Peer ReviewedPostprint (published version

    METHYLPHENIDATE: PROCONVULSANT EFFECT AND ACTION ON ACETYL CHOLINESTERASE ACTIVITY IN YOUNG AND ADULT MICE

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    Objective: Methylphenidate (MPH) is a derivative of piperidine, structurally related to amphetamine. It is the most widely psychostimulant used in Brazil for treating attention deficit disorder and hyperactivity. This drug was investigated in an epilepsy model induced by pilocarpine and on acetylcholinesterase (AChE) activity in young and adult mice. Methods: The control group was treated with saline. The treated groups received MPH (2.5, 5, 10 or 20 mg/kg) in single dose, followed by pilocarpine (400mg/Kg). The groups were observed for1h after treatment. Results: MPH, in all doses, was efficacious in decreasing both the latency to first seizures and the survival percentage in young and adult animals. Determination of AChE activity in the hippocampus and striatum of young and adult animals, after pilocarpine-induced status epilepticus, demonstrated that pretreatment with MPH reduced AChE activity only in the striatum. Conclusion: Our findings suggest that MPH has proconvulsant action and cholinergic neurotransmission system can play a role in this effect

    Secondary crystalline phases identification in Cu2ZnSnSe4 thin films: contributions from Raman scattering and photoluminescence

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    In this work, we present the Raman peak positions of the quaternary pure selenide compound Cu2ZnSnSe4 (CZTSe) and related secondary phases that were grown and studied under the same conditions. A vast discussion about the position of the X-ray diffraction (XRD) reflections of these compounds is presented. It is known that by using XRD only, CZTSe can be identified but nothing can be said about the presence of some sec- ondary phases. Thin films of CZTSe, Cu2SnSe3, ZnSe, SnSe, SnSe2, MoSe2 and a-Se were grown, which allowed their investigation by Raman spectroscopy (RS). Here we present all the Raman spectra of these phases and discuss the similarities with the spectra of CZTSe. The effective analysis depth for the common back-scattering geometry commonly used in RS measurements, as well as the laser penetration depth for photoluminescence (PL) were esti- mated for different wavelength values. The observed asymmetric PL band on a CZTSe film is compatible with the presence of CZTSe single-phase and is discussed in the scope of the fluctuating potentials’ model. The estimated bandgap energy is close to the values obtained from absorption measurements. In general, the phase identifica- tion of CZTSe benefits from the contributions of RS and PL along with the XRD discussion.info:eu-repo/semantics/acceptedVersio

    An apoplastic fluid extraction method for the characterization of grapevine leaves proteome and metabolome from a single sample

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    The analysis of complex biological systems keeps challenging researchers. The main goal of systems biology is to decipher interactions within cells, by integrating datasets from large scale analytical approaches including transcriptomics, proteomics and metabolomics andmore specialized ‘OMICS’ such as epigenomics and lipidomics. Studying different cellular compartments allows a broader understanding of cell dynamics. Plant apoplast, the cellular compartment external to the plasma membrane including the cell wall, is particularly demanding to analyze. Despite our knowledge on apoplast involvement on several processes from cell growth to stress responses, its dynamics is still poorly known due to the lack of efficient extraction processes adequate to each plant system.Analyzing woody plants such as grapevine raises even more challenges. Grapevine is among the most important fruit crops worldwide and awider characterization of its apoplast is essential for a deeper understanding of its physiology and cellular mechanisms. Here, we describe, for the first time, a vacuum-infiltrationcentrifugationmethod that allows a simultaneous extraction of grapevine apoplastic proteins and metabolites from leaves on a single sample, compatible with high-throughput mass spectrometry analyses. The extracted apoplast from two grapevine cultivars, Vitis vinifera cv ‘Trincadeira’ and ‘Regent’, was directly used for proteomics and metabolomics analysis. The proteome was analyzed by nanoLC-MS/MS and more than 700 common proteinswere identified, with highly diverse biological functions. The metabolome profile through FT-ICR-MS allowed the identification of 514 unique putative compounds revealing a broad spectrum of molecular classesinfo:eu-repo/semantics/publishedVersio

    Preoperative toxoplasma gondii serostatus does not affect long-term survival of cardiac transplant recipients: analysis of the Spanish Heart Transplantation Registry

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    [Abstract] Background. It's unclear whether pre-transplant T. gondii seropositivity is associated with impaired survival in heart transplant recipients. Objectives. To test the above-mentioned hypothesis in the Spanish Heart Transplantation Registry. Methods. Post-transplant outcomes of 4048 patients aged > 16 years who underwent first, single-organ heart transplantation in 17 Spanish institutions from 1984 to 2014 were studied. Long-term post-transplant survival and survival free of cardiac death or retransplantation of 2434 (60%) T. gondii seropositive recipients and 1614 (40%) T. gondii seronegative recipients were compared. Results. T. gondii seropositive recipients were older, had higher body mass index, and presented higher prevalence of hypertension, hypercholesterolemia, COPD and Cytomegalovirus seropositivity than T. gondii seronegative recipients. In univariable analysis, pre-transplant T. gondii seropositivity was associated with increased post-transplant all-cause mortality (non-adjusted HR 1.15; 95% CI 1.04–1.26). However, this effect was no longer statistically significant after multivariable adjustment by recipient's age and sex (adjusted HR 1.01, 95% CI 0.92–1.11). Extended multivariable adjustment by other potential confounders showed similar results (adjusted HR 0.99, 95% CI 0.89–1.11). T. gondii seropositivity had no significant effect on the composite outcome cardiac death or retransplantation (non-adjusted HR 1.08, 95% CI 0.95–1.24, p = 0.235). The distribution of the causes of death was comparable in T. gondii seropositive and T. gondii seronegative recipients. No statistically significant impact of donor's T. gondii serostatus or donor-recipient T. gondii serostatus matching on post-transplant survival was observed. Conclusions. Our analysis did not show a significant independent effect of preoperative T. gondii serostatus on long-term outcomes after heart transplantation

    Optimization of Time-Course Experiments for Kinetic Model Discrimination

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    Systems biology relies heavily on the construction of quantitative models of biochemical networks. These models must have predictive power to help unveiling the underlying molecular mechanisms of cellular physiology, but it is also paramount that they are consistent with the data resulting from key experiments. Often, it is possible to find several models that describe the data equally well, but provide significantly different quantitative predictions regarding particular variables of the network. In those cases, one is faced with a problem of model discrimination, the procedure of rejecting inappropriate models from a set of candidates in order to elect one as the best model to use for prediction

    Case report: Urbanized non-human primates as sentinels for human zoonotic diseases: a case of acute fatal toxoplasmosis in a free-ranging marmoset in coinfection with yellow fever virus

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    Free-ranging non-human primates (NHP) can live in anthropized areas or urban environments in close contact with human populations. This condition can enable the emergence and transmission of high-impact zoonotic pathogens. For the first time, we detected a coinfection of the yellow fever (YF) virus with Toxoplasma gondii in a free-ranging NHP in a highly urbanized area of a metropolis in Brazil. Specifically, we observed this coinfection in a black-tufted marmoset found dead and taken for a necropsy by the local health surveillance service. After conducting an epidemiological investigation, characterizing the pathological features, and performing molecular assays, we confirmed that the marmoset developed an acute fatal infection caused by T. gondii in coinfection with a new YF virus South American-1 sub-lineage. As a result, we have raised concerns about the public health implications of these findings and discussed the importance of diagnosis and surveillance of zoonotic agents in urbanized NHPs. As competent hosts of zoonotic diseases such as YF and environmental sentinels for toxoplasmosis, NHPs play a crucial role in the One Health framework to predict and prevent the emergence of dangerous human pathogens

    Secondary crystalline phases identification in Cu2ZnSnSe4 thin films: contributions from Raman scattering and photoluminescence

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    In this work, we present the Raman peak positions of the quaternary pure selenide compound Cu2ZnSnSe4 (CZTSe) and related secondary phases that were grown and studied under the same conditions. A vast discussion about the position of the X-ray diffraction (XRD) reflections of these compounds is presented. It is known that by using XRD only, CZTSe can be identified but nothing can be said about the presence of some secondary phases. Thin films of CZTSe, Cu2SnSe3, ZnSe, SnSe, SnSe2, MoSe2 and a-Se were grown, which allowed their investigation by Raman spectroscopy (RS). Here we present all the Raman spectra of these phases and discuss the similarities with the spectra of CZTSe. The effective analysis depth for the common back-scattering geometry commonly used in RS measurements, as well as the laser penetration depth for photoluminescence (PL) were estimated for different wavelength values. The observed asymmetric PL band on a CZTSe film is compatible with the presence of CZTSe single-phase and is discussed in the scope of the fluctuating potentials’ model. The estimated bandgap energy is close to the values obtained from absorption measurements. In general, the phase identification of CZTSe benefits from the contributions of RS and PL along with the XRD discussion.info:eu-repo/semantics/publishedVersio
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