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Variations on a theme: diversification of cuticular hydrocarbons in a clade of cactophilic Drosophila
No full textAbstract
Background
We characterized variation and chemical composition of epicuticular hydrocarbons (CHCs) in the seven species of the Drosophila buzzatii cluster with gas chromatography/mass spectrometry. Despite the critical role of CHCs in providing resistance to desiccation and involvement in communication, such as courtship behavior, mating, and aggregation, few studies have investigated how CHC profiles evolve within and between species in a phylogenetic context. We analyzed quantitative differences in CHC profiles in populations of the D. buzzatii species cluster in order to assess the concordance of CHC differentiation with species divergence.
Results
Thirty-six CHC components were scored in single fly extracts with carbon chain lengths ranging from C29 to C39, including methyl-branched alkanes, n-alkenes, and alkadienes. Multivariate analysis of variance revealed that CHC amounts were significantly different among all species and canonical discriminant function (CDF) analysis resolved all species into distinct, non-overlapping groups. Significant intraspecific variation was found in different populations of D. serido suggesting that this taxon is comprised of at least two species. We summarized CHC variation using CDF analysis and mapped the first five CHC canonical variates (CVs) onto an independently derived period (per) gene + chromosome inversion + mtDNA COI gene for each sex. We found that the COI sequences were not phylogenetically informative due to introgression between some species, so only per + inversion data were used. Positive phylogenetic signal was observed mainly for CV1 when parsimony methods and the test for serial independence (TFSI) were used. These results changed when no outgroup species were included in the analysis and phylogenetic signal was then observed for female CV3 and/or CV4 and male CV4 and CV5. Finally, removal of divergent populations of D. serido significantly increased the amount of phylogenetic signal as up to four out of five CVs then displayed positive phylogenetic signal.
Conclusions
CHCs were conserved among species while quantitative differences in CHC profiles between populations and species were statistically significant. Most CHCs were species-, population-, and sex-specific. Mapping CHCs onto an independently derived phylogeny revealed that a significant portion of CHC variation was explained by species' systematic affinities indicating phylogenetic conservatism in the evolution of these hydrocarbon arrays, presumptive waterproofing compounds and courtship signals as in many other drosophilid species
Improving total saccharification yield of Arabidopsis plants by vessel-specific complementation of caffeoyl shikimate esterase (cse) mutants
No full textAbstract\ud
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Background\ud
Caffeoyl shikimate esterase (CSE) was recently characterized as an enzyme central to the lignin biosynthetic pathway in Arabidopsis thaliana. The cse-2 loss-of-function mutant shows a typical phenotype of lignin-deficient mutants, including collapsed vessels, reduced lignin content, and lignin compositional shift, in addition to a fourfold increase in cellulose-to-glucose conversion when compared to the wild type. However, this mutant exhibits a substantial developmental arrest, which might outweigh the gains in fermentable sugar yield. To restore its normal growth and further improve its saccharification yield, we investigated a possible cause for the yield penalty of the cse-2 mutant. Furthermore, we evaluated whether CSE expression is under the same multi-leveled transcriptional regulatory network as other lignin biosynthetic genes and analyzed the transcriptional responses of the phenylpropanoid pathway upon disruption of CSE.\ud
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Results\ud
Transactivation analysis demonstrated that only second-level MYB master switches (MYB46 and MYB83) and lignin-specific activators (MYB63 and MYB85), but not top-level NAC master switches or other downstream transcription factors, effectively activate the CSE promoter in our protoplast-based system. The cse-2 mutant exhibited transcriptional repression of genes upstream of CSE, while downstream genes were mainly unaffected, indicating transcriptional feedback of CSE loss-of-function on monolignol biosynthetic genes. In addition, we found that the expression of CSE under the control of the vessel-specific VND7 promoter in the cse-2 background restored the vasculature integrity resulting in improved growth parameters, while the overall lignin content remained relatively low. Thus, by restoring the vascular integrity and biomass parameters of cse-2, we further improved glucose release per plant without pretreatment, with an increase of up to 36 % compared to the cse-2 mutant and up to 154 % compared to the wild type.\ud
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Conclusions\ud
Our results contribute to a better understanding of how the expression of CSE is regulated by secondary wall-associated transcription factors and how the expression of lignin genes is affected upon CSE loss-of-function in Arabidopsis. Moreover, we found evidence that vasculature collapse is underlying the yield penalty found in the cse-2 mutant. Through a vessel-specific complementation approach, vasculature morphology and final stem weight were restored, leading to an even higher total glucose release per plant.The authors thank Andreas Pallidis, Rebecca Van Acker, and Bartel Vanholme\ud
for technical assistance. This work has been supported by the European Commission’s\ud
Directorate General for Research within the 7th Framework Program\ud
[Grant 270089 (MULTIBIOPRO)], by the Multidisciplinary Research Partnership\ud
‘Biotechnology for a Sustainable Economy’ (01MRB510W) of Ghent University\ud
and the Stanford University Global Climate and Energy Project (‘Lignin management:\ud
optimizing yield and composition in lignin-modified plants’). Ruben\ud
Vanholme is indebted to the Research Foundation Flanders for a postdoctoral\ud
fellowship. Igor Cesarino acknowledges the Foundation for Research of the\ud
State of São Paulo (FAPESP) for the BIOEN Young Investigators Awards research\ud
fellowship (Grant 2015/02527-1). Lívia Vargas and Marina de Lyra Soriano\ud
Saleme acknowledge the Program Ciência Sem Fronteiras for postdoctoral\ud
(Grant 248535/2013-7) and pre-doctoral (Grant 206863/2014-4) fellowships,\ud
respectivel
Smoking cessation and bronchial epithelial remodelling in COPD: a cross-sectional study
No full textAbstract
Background
Chronic Obstructive Pulmonary Disease (COPD) is associated with bronchial epithelial changes, including squamous cell metaplasia and goblet cell hyperplasia. These features are partially attributed to activation of the epidermal growth factor receptor (EGFR). Whereas smoking cessation reduces respiratory symptoms and lung function decline in COPD, inflammation persists. We determined epithelial proliferation and composition in bronchial biopsies from current and ex-smokers with COPD, and its relation to duration of smoking cessation.
Methods
114 COPD patients were studied cross-sectionally: 99 males/15 females, age 62 ± 8 years, median 42 pack-years, no corticosteroids, current (n = 72) or ex-smokers (n = 42, median cessation duration 3.5 years), postbronchodilator FEV1 63 ± 9% predicted. Squamous cell metaplasia (%), goblet cell (PAS/Alcian Blue+) area (%), proliferating (Ki-67+) cell numbers (/mm basement membrane), and EGFR expression (%) were measured in intact epithelium of bronchial biopsies.
Results
Ex-smokers with COPD had significantly less epithelial squamous cell metaplasia, proliferating cell numbers, and a trend towards reduced goblet cell area than current smokers with COPD (p = 0.025, p = 0.001, p = 0.081, respectively), but no significant difference in EGFR expression. Epithelial features were not different between short-term quitters (<3.5 years) and current smokers. Long-term quitters (≥3.5 years) had less goblet cell area than both current smokers and short-term quitters (medians: 7.9% vs. 14.4%, p = 0.005; 7.9% vs. 13.5%, p = 0.008; respectively), and less proliferating cell numbers than current smokers (2.8% vs. 18.6%, p < 0.001).
Conclusion
Ex-smokers with COPD had less bronchial epithelial remodelling than current smokers, which was only observed after long-term smoking cessation (>3.5 years).
Trial registration
NCT0015884
TNF-α induces vascular insulin resistance via positive modulation of PTEN and decreased Akt/eNOS/NO signaling in high fat diet-fed mice
No full textAbstract\ud
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Background\ud
High fat diet (HFD) induces insulin resistance in various tissues, including the vasculature. HFD also increases plasma levels of TNF-α, a cytokine that contributes to insulin resistance and vascular dysfunction. Considering that the enzyme phosphatase and tension homologue (PTEN), whose expression is increased by TNF-α, reduces Akt signaling and, consequently, nitric oxide (NO) production, we hypothesized that PTEN contributes to TNF-α-mediated vascular resistance to insulin induced by HFD. Mechanisms underlying PTEN effects were determined.\ud
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Methods\ud
Mesenteric vascular beds were isolated from C57Bl/6J and TNF-α KO mice submitted to control or HFD diet for 18 weeks to assess molecular mechanisms by which TNF-α and PTEN contribute to vascular dysfunction.\ud
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Results\ud
Vasodilation in response to insulin was decreased in HFD-fed mice and in ex vivo control arteries incubated with TNF-α. TNF-α receptors deficiency and TNF-α blockade with infliximab abolished the effects of HFD and TNF-α on insulin-induced vasodilation. PTEN vascular expression (total and phosphorylated isoforms) was increased in HFD-fed mice. Treatment with a PTEN inhibitor improved insulin-induced vasodilation in HFD-fed mice. TNF-α receptor deletion restored PTEN expression/activity and Akt/eNOS/NO signaling in HFD-fed mice.\ud
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Conclusion\ud
TNF-α induces vascular insulin resistance by mechanisms that involve positive modulation of PTEN and inhibition of Akt/eNOS/NO signaling. Our findings highlight TNF-α and PTEN as potential targets to limit insulin resistance and vascular complications associated with obesity-related conditions.This work was supported by grants from Fundação de Amparo à Pesquisa\ud
do Estado de São Paulo (FAPESP 2013/08216-2-CRID), Coordenação de Aper‑\ud
feiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de\ud
Desenvolvimento Científico e Tecnológico (CNPq), Brazil
One-class to multi-class model update using the class-incremental optimum-path forest classifier
No full textIncremental learning capabilities of classifiers is a relevant topic, specially when dealing with scenarios such as data stream mining, concept drift and active learning. We investigate the capabilities of an incremental version of the Optimum-Path Forest classifier (OPF-CI) in the context of learning new classes and compare its behavior against Support Vector Machines and k Nearest Neighbours classifiers. The OPF-CI classifier is a parameter-free, graphbased approach to incremental training that runs in linear time with respect to the number of instances. Our results show OPF-CI keeps the running time low while producing an accuracy behavior similar to the other classifiers for increments of instances. Also, it is robust to variations on the order of the learned classes, demonstrating the applicability of the method.FAPESP (grants #11/22749-8, #14/04889-5, #15/24217-4 and #15/13504-2
Aprendizado multi-instâncias e redes convolucionais aplicados a recuperação de imagens baseada em conteúdo e rascunhos
No full textA recuperação de imagens baseada em conteúdo (CBIR) permite a busca e indexação de imagens com base diretamente no seu conteúdo visual. A recuperação de imagens baseada em rascunhos (SBIR) é uma variação que utiliza como consulta um rascunho de um objeto, o que adiciona diversos desafios. Nesses cenários propomos duas abordagens: o aprendizado multi-instâncias ao representar imagens para CBIR e redes convolucionais com função de custo triplet na obtenção de descritores para SBIR, em particular versões compactas desses descritores. Os resultados apontam melhorias com relação aos métodos base e do estado da arte, demonstrando o potencial das abordagens propostas.Content based image rerieval (CBIR) allows for querying and indexing of image datasets based on the visual content of those images. Sketch based image retrieval (SBIR) is a variation that uses object sketches as queries, adding complexity to the retrieval challenge. To solve this problem we came up with two proposed approaches: Multiple Instance Learning (MIL) methods to represent images for CBIR and Convolutional Neural Networks with a triplet loss function to generate descriptors for SBIR, particularly, compact versions of such descriptors. The results show improvements when compared with base methods and the state of the art, demonstrating the potential of the shown approaches.FAPESP (processos #2014/14557-0, #2015/26050-0 e #15/13504-2
On the effect of endpoints on dynamic time warping
No full textWhile there exist a plethora of classification algorithms for most data types, there is an increasing acceptance that the unique properties of time series mean that the combination of nearest neighbor classifiers and Dynamic Time Warping (DTW) is very competitive across a host of domains, from medicine to astronomy to environmental sensors. While there has been significant progress in improving the efficiency and effectiveness of DTW in recent years, in this work we demonstrate that an underappreciated issue can significantly degrade the accuracy of DTW in real-world deployments. This issue has probably escaped the attention of the very active time series research community because of its reliance on static highly contrived benchmark datasets, rather than real world dynamic datasets where the problem tends to manifest itself. In essence, the issue is that DTW’s eponymous invariance to warping is only true for the main “body” of the two time series being compared. However, for the “head” and “tail” of the time series, the DTW algorithm affords no warping invariance. The effect of this is that tiny differences at the beginning or end of the time series (which may be either consequential or simply the result of poor “cropping”) will tend to contribute disproportionally to the estimated similarity, producing incorrect classifications. In this work, we show that this effect is real, and reduces the performance of the algorithm. We further show that we can fix the issue with a subtle redesign of the DTW algorithm, and that we can learn an appropriate setting for the extra parameter we introduced. We further demonstrate that our generalization is amiable to all the optimizations that make DTW tractable for large datasets
The effect of malaria and anti-malarial drugs on skeletal and cardiac muscles
No full textAbstract\ud
Malaria remains one of the most important infectious diseases in the world, being a significant public health problem associated with poverty and it is one of the main obstacles to the economy of an endemic country. Among the several complications, the effects of malaria seem to target the skeletal muscle system, leading to symptoms, such as muscle aches, muscle contractures, muscle fatigue, muscle pain, and muscle weakness. Malaria cause also parasitic coronary artery occlusion. This article reviews the current knowledge regarding the effect of malaria disease and the anti-malarial drugs on skeletal and cardiac muscles. Research articles and case report publications that addressed aspects that are important for understanding the involvement of malaria parasites and anti-malarial therapies affecting skeletal and cardiac muscles were analysed and their findings summarized. Sequestration of red blood cells, increased levels of serum creatine kinase and reduced muscle content of essential contractile proteins are some of the potential biomarkers of the damage levels of skeletal and cardiac muscles. These biomarkers might be useful for prevention of complications and determining the effectiveness of interventions designed to protect cardiac and skeletal muscles from malaria-induced damage