2,672 research outputs found

    BiGGEsTS: integrated environment for biclustering analysis of time series gene expression data

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    <p>Abstract</p> <p>Background</p> <p>The ability to monitor changes in expression patterns over time, and to observe the emergence of coherent temporal responses using expression time series, is critical to advance our understanding of complex biological processes. Biclustering has been recognized as an effective method for discovering local temporal expression patterns and unraveling potential regulatory mechanisms. The general biclustering problem is NP-hard. In the case of time series this problem is tractable, and efficient algorithms can be used. However, there is still a need for specialized applications able to take advantage of the temporal properties inherent to expression time series, both from a computational and a biological perspective.</p> <p>Findings</p> <p>BiGGEsTS makes available state-of-the-art biclustering algorithms for analyzing expression time series. Gene Ontology (GO) annotations are used to assess the biological relevance of the biclusters. Methods for preprocessing expression time series and post-processing results are also included. The analysis is additionally supported by a visualization module capable of displaying informative representations of the data, including heatmaps, dendrograms, expression charts and graphs of enriched GO terms.</p> <p>Conclusion</p> <p>BiGGEsTS is a free open source graphical software tool for revealing local coexpression of genes in specific intervals of time, while integrating meaningful information on gene annotations. It is freely available at: <url>http://kdbio.inesc-id.pt/software/biggests</url>. We present a case study on the discovery of transcriptional regulatory modules in the response of <it>Saccharomyces cerevisiae </it>to heat stress.</p

    Wireless interface for sensors in smart textiles

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    This paper describes a smart suit with sensors and electronics for monitoring patients at hydrotherapy sessions in swimming-pools. The smart suit allows the monitoring of the heart rate, patient posture and activity level. The sensors input are converted in a PWM using a V-F converter. A robust, low-voltage (3.0 V) and low-power electronic wireless CMOS RF interface was implemented at 433 MHz using ASK modulation.Fundação para a Ciência e a Tecnologia (FCT) - (SFRH/BD/4717/2001, POCTI/ESE/38468/2001)

    Weakly-supervised classification of HER2 expression in breast cancer haematoxylin and eosin stained slides

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    Human epidermal growth factor receptor 2 (HER2) evaluation commonly requires immunohistochemistry (IHC) tests on breast cancer tissue, in addition to the standard haematoxylin and eosin (H&E) staining tests. Additional costs and time spent on further testing might be avoided if HER2 overexpression could be effectively inferred from H&E stained slides, as a preliminary indication of the IHC result. In this paper, we propose the first method that aims to achieve this goal. The proposed method is based on multiple instance learning (MIL), using a convolutional neural network (CNN) that separately processes H&E stained slide tiles and outputs an IHC label. This CNN is pretrained on IHC stained slide tiles but does not use these data during inference/testing. H&E tiles are extracted from invasive tumour areas segmented with the HASHI algorithm. The individual tile labels are then combined to obtain a single label for the whole slide. The network was trained on slides from the HER2 Scoring Contest dataset (HER2SC) and tested on two disjoint subsets of slides from the HER2SC database and the TCGA-TCIA-BRCA (BRCA) collection. The proposed method attained 83.3% classification accuracy on the HER2SC test set and 53.8% on the BRCA test set. Although further efforts should be devoted to achieving improved performance, the obtained results are promising, suggesting that it is possible to perform HER2 overexpression classification on H&E stained tissue slides.publishersversionpublishe

    Perioperative Challenges of Heroin Addiction: A Case Report of Opioid-Free Anesthesia in Tongue Carcinoma Excision With Free-Flap Reconstruction

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    Anesthesia for major head and neck surgery is historically heavily reliant on opioids with deleterious consequences. We reported a case of a patient with a history of heroin abuse submitted to a tongue carcinoma excision, followed by free-flap reconstruction under opioid-free anesthesia. We used a propofol total intravenous anesthesia and perfusions of ketamine, dexmedetomidine, lidocaine, and magnesium sulfate for analgesia, complemented by boluses of dexamethasone, acetaminophen, parecoxib, and metamizole. Hemodynamic needs of the procedure were addressed by titrating perfusions of sodium nitroprusside or dobutamine. The patient was weaned from the ventilator at the end of the surgery. Surgical outcomes were achieved and opioid-free analgesia allowed early reestablishment of bodily functions without compromise of adequate pain control. Anesthesia protocols for free-flap surgery still lack scientific evidence, especially in the context of substance abuse: opioid-sparing approaches seem a viable option, which requires further studies and familiarity by health care professionalsinfo:eu-repo/semantics/publishedVersio

    Mitochondrial superoxide generation induces a parkinsonian phenotype in zebrafish and huntingtin aggregation in human cells.

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    Superoxide generation by mitochondria respiratory complexes is a major source of reactive oxygen species (ROS) which are capable of initiating redox signaling and oxidative damage. Current understanding of the role of mitochondrial ROS in health and disease has been limited by the lack of experimental strategies to selectively induce mitochondrial superoxide production. The recently-developed mitochondria-targeted redox cycler MitoParaquat (MitoPQ) overcomes this limitation, and has proven effective in vitro and in Drosophila. Here we present an in vivo study of MitoPQ in the vertebrate zebrafish model in the context of Parkinson's disease (PD), and in a human cell model of Huntington's disease (HD). We show that MitoPQ is 100-fold more potent than non-targeted paraquat in both cells and in zebrafish in vivo. Treatment with MitoPQ induced a parkinsonian phenotype in zebrafish larvae, with decreased sensorimotor reflexes, spontaneous movement and brain tyrosine hydroxylase (TH) levels, without detectable effects on heart rate or atrioventricular coordination. Motor phenotypes and TH levels were partly rescued with antioxidant or monoaminergic potentiation strategies. In a HD cell model, MitoPQ promoted mutant huntingtin aggregation without increasing cell death, contrasting with the complex I inhibitor rotenone that increased death in cells expressing either wild-type or mutant huntingtin. These results show that MitoPQ is a valuable tool for cellular and in vivo studies of the role of mitochondrial superoxide generation in redox biology, and as a trigger or co-stressor to model metabolic and neurodegenerative disease phenotypes

    Lifestyle, metabolic disorders and male hypogonadism - a one-way ticket?

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    Hypogonadism is more frequent among men with common metabolic diseases, notably obesity and type 2 diabetes. Indeed, endocrine disruption caused by metabolic diseases can trigger the onset of hypogonadism, although the underlying molecular mechanisms are not entirely understood. Metabolic diseases are closely related to unhealthy lifestyle choices, such as dietary habits and sedentarism. Therefore, hypogonadism is part of a pathological triad gathering unhealthy lifestyle, metabolic disease and genetic background. Additionally, hypogonadism harbors the potential to aggravate underlying metabolic disorders, further sustaining the mechanisms leading to disease. To what extent does lifestyle intervention in men suffering from these metabolic disorders can prevent, improve or reverse hypogonadism, is still controversial. Moreover, recent evidence suggests that the metabolic status of the father is related to the risk of inter and transgenerational inheritance of hypogonadism. In this review, we will address the proposed mechanisms of disease, as well as currently available interventions for hypogonadism.publishe

    Antibodies to Toxoplasma gondii and Leishmania spp. in domestic cats from Luanda, Angola

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    Toxoplasma gondii and Leishmania spp. are zoonotic protozoa of importance to animal and public health. The present study aimed to assess for the first time the seroprevalence of these zoonotic parasites in a domestic feline population living in Luanda, Angola. One hundred and two cats were sampled at a veterinary medical centre, from May 2014 to February 2016. The age of the cats ranged from 2.5 to 143 months (median: 12 months; interquartile range: 7.5–24). Serum samples were tested for immunoglobulin (Ig) G antibodies to T. gondii at two-fold dilutions of 1:20 to 1:2560 with a modified agglutination test (MAT) commercial kit. The direct agglutination test (DAT) for titration of IgG antibodies specific to Leishmania spp. used a standard freeze-dried antigen at a concentration of 5 × 10 7 promastigotes per milliliter, following a predefined protocol. Two-fold dilution series ranging from 1:25 to 1:800 were tested, with a cut-off titre of 100 chosen for seropositivity. Four out of 102 cats (3.9%; 95% confidence interval [CI]: 1.1–9.7) had antibodies to T. gondii: one had a titer of 20, one a titer of 160, and two had a titer ≥ 2560. No cat (0.0%; CI: 0.0–3.5) was found seropositive for Leishmania spp. A statistically significant difference was found between T. gondii seroprevalence and Leishmania spp. seroprevalence (p = 0.043). The odds of a cat being seropositive to T. gondii increased by an average factor of 1.58 for each 1-year increase in age (p = 0.003). The sampled cats were well-cared animals and may not represent the overall feline population of Angola at the national and city levels. The fact that only 12 out of the 102 sampled cats ate or had access to raw or undercooked meat and/or viscera may have reduced the likelihood of finding seropositive results. Under these circumstances, additional studies, including a larger number of cats, are necessary for a more comprehensive assessment of the zoonotic risk posed by these animals in Angola.The authors would like to express their gratitude to Hugo Vilhena for his logistic support. This work was sponsored by the Foundation for Science and Technology (FCT), Ministry of Education and Science, Portugal, under the Projects UID/CVT/00772/2013 and UID/CVT/ 0772/2016.info:eu-repo/semantics/publishedVersio

    Hydrophobic DES Based on Menthol and Natural Organic Acids for Use in Antifouling Marine Coatings

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    Publisher Copyright: © 2023 The Authors. Published by American Chemical Society.Marine biofouling negatively impacts industries with off-shore infrastructures, such as naval, oil, and aquaculture. To date, there are no ideal sustainable, economic, and environmentally benign solutions to deal with this phenomenon. The advances achieved in green solvents, as well as its application in different industries, such as pharmaceutical and biotechnology, have promoted the emergence of deep eutectic systems (DES). These eutectic systems have applications in various fields and can be revolutionary in the marine-based industrial sector. In this study, the main objective was to investigate the potential use of hydrophobic DES (HDES) based on menthol and natural organic acids for their use as marine antifouling coatings. Our strategy encompassed the physicochemical characterization of different formulations, which allowed us to identify the most appropriate molar ratio and intermolecular interactions for HDES formations. The miscibility of the resulting HDES with the marine coating has been evaluated and proven to be successful. The Men/OL (1:1) system proved to be the most promising in terms of cost-production and thus was the one used in subsequent antifouling tests. The cytotoxicity of this HDES was evaluated using an in vitro cell model (HaCat cells) showing no significant toxicity. Furthermore, the application of this system incorporated into coatings that are used in marine structures was also studied using marine species (Mytilus edulis mussels and Patella vulgata limpets) to evaluate both their antifouling and ecotoxicity effects. HDES Men/OL (1:1) incorporated in marine coatings was promising in reducing marine macrofouling and also proved to be effective at the level of microfouling without viability impairment of the tested marine species. It was revealed to be more efficient than using copper oxide, metallic copper, or ivermectin as antifouling agents. Biochemical assays performed on marine species showed that this HDES does not induce oxidative stress in the tested species. These results are a strong indication of the potential of this HDES to be sustainable and efficiently used in marine fouling control technologies.publishersversionpublishe
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