629 research outputs found

    Model Reduction on the Wnt Pathway Leads to Biological Adaptation

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    Complex systems are an unavoidable problem in the field of biology. One of the ways that scientists have tried to overcome this problem is by building mathematical models—manageable representations designed to look at specific physical phenomena. The Wnt Signaling Pathway is a complex system known to regulate cell-to-cell interactions, play a crucial role in Embryonic Development, and has been implicated in the study of cancer. Typically, the Wnt signal is observed through the behavior of a protein called beta-Catenin (β-Catenin). In 2003, Lee et al. built a model of the Wnt pathway which caused β-Catenin to increase over time. However, in 2010, Jensen et al. built a different model of the Wnt pathway which caused β-Catenin to oscillate over time. This project called for model reduction on the Jensen et al. model to identify the phenomenological parameter combinations that determined features of the Wnt oscillations. The method used to reduce the model is called the Manifold Boundary Approximation Method, which is a geometric, parameter-independent method of reducing the model one parameter at a time. Reduction of the model showed that there were 5 variables and 8 parameters which drove the oscillating behavior of the system. After comparing our results to the Lee et al. reduced model of the Wnt pathway done by student Dane Bjork, a minimal model was constructed which predicted a novel class behavior of the Wnt system: biological adaptation

    Association Between Interleukin 6 -174 G/c Promoter Gene Polymorphism And Runners’ Responses To The Dietary Ingestion Of Antioxidant Supplementation Based On Pequi (caryocar Brasiliense Camb.) Oil: A Before-after Study

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    Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Exercise is a double-edged sword: when practiced in moderation, it increases the expression of antioxidant enzymes, but when practiced strenuously it causes oxidative stress and cell damage. In this context, polymorphisms in the interleukin (IL)-6 gene should be investigated better because they can influence performance, at least in exercise that generates oxidative stress and leads to muscular injuries with consequent inflammation. In this work, we investigated the influence of IL-6 –174 G/C polymorphism on tissue damage and inflammation markers, lipid peroxidation, hemogram and lipid profile of runners before and after ingestion of 400 mg of pequi oil in capsules supplied daily for 14 consecutive days. The IL-6 genotypes were associated with significant differences in lipid peroxidation, with the CC mutant having lower values. There were also significant differences among these genotypes in the response to supplementation with pequi oil, exercise-induced damage and C-reactive protein (CRP) levels. The best protection against damage was observed with the heterozygous genotype. Although the CC genotype showed an increase in CRP levels after supplementation, the lack of a positive correlation between triglycerides and high-sensitivity CRP in this mutant genotype after supplementation indicated a protective effect of pequi. These findings deserve further investigation, particularly with regard to the quantification of circulating IL-6 concentrations. © 2016, Sociedade Brasileira de Genética.394554566CNPq, Conselho Nacional de Desenvolvimento Científico e TecnológicoUnB, Universidade de BrasíliaConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

    Immunotherapy for pancreatic cancer: chasing the light at the end of the tunnel

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    Background Checkpoint blockade immunotherapy has had a significant impact on the survival of a subset of patients with advanced cancers. It has been particularly effective in immunogenic cancer types that present large numbers of somatic mutations in their genomes. To date, all conventional immunotherapies have failed to produce significant clinical benefits for patients diagnosed with pancreatic cancer, probably due to its poor immunogenic properties, including low numbers of neoantigens and highly immune-suppressive microenvironments. Conclusions Herein, we discuss advances that have recently been made in cancer immunotherapy and the potential of this field to deliver effective treatment options for pancreatic cancer patients. Preclinical investigations, combining different types of therapies, highlight possibilities to enhance anti-tumor immunity and to generate meaningful clinical responses in pancreatic cancer patients. Results from completed and ongoing (pre)clinical trials are discussed.Surgical oncolog

    Zooplankton composition and distribution off the coast of Galicia, Spain

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    During June and September 1984, zooplankton samples were collected with other hydrographic and biological data along the Galician coast (NW of Spain). In June copepods contributed -60% to the total zooplankton community, with larvaceans, siphonophores and cladocerans also abundant. In September >90% of the zooplankton sampled were copepods. The dominant species of copepods in both June and September were Acartia e/ausi, Paracalanus parvus and Temora longicornis. The meroplankton was dominated by echinoderms, bryozoans, barnacle larvae and bivalve larvae. In June the average zooplankton biomass was 31.08 mg e m-3; the September average was 41.69 mg e m-3 The relationship between the slopes of the regression equations (biomass versus abundance) suggests that the zooplankton assemblage in June was composed by larger animals than in September. The major concentration of zooplankton was between O and SO m, with both June and September daytime surface samples having 6-7 times the amount of organisms than the lower water column (50-100 m). There were no distinct differences in total zooplankton abundances at the inshore and offshore stations; however, the inshore stations often had a higher percentage of meroplankton than the offshore stations. In June zooplankton abundance at the northern transects and the western transects was similar. In September there were greater concentrations of zooplankton in the western Galician shelf as compared with the northern shelf. These differences in the horizontal distribution of the zooplankton were related to upwelling events.Postprin

    Synthesizing attractors of Hindmarsh-Rose neuronal systems

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    In this paper a periodic parameter switching scheme is applied to the Hindmarsh-Rose neuronal system to synthesize certain attractors. Results show numerically, via computer graphic simulations, that the obtained synthesized attractor belongs to the class of all admissible attractors for the Hindmarsh-Rose neuronal system and matches the averaged attractor obtained with the control parameter replaced with the averaged switched parameter values. This feature allows us to imagine that living beings are able to maintain vital behavior while the control parameter switches so that their dynamical behavior is suitable for the given environment.Comment: published in Nonlinear Dynamic

    The potential of induced pluripotent stem cells to advance the treatment of pancreatic ductal adenocarcinoma

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    Simple Summary:& nbsp;Despite improvements in the treatment of several cancer types, the extremely poor prognosis of pancreatic cancer patients has remained unchanged over the last decades. Therefore, new therapeutic regimens for pancreatic cancer are highly needed. In this review, we will discuss the potential of induced pluripotent stem cells (iPSCs) to generate representative pancreatic cancer models that can aid the development of novel diagnostics and therapeutic strategies. Furthermore, the potential of iPSCs as pancreatic cancer vaccines or as a basis for cellular therapies will be discussed. With promising preclinical results and ongoing clinical trials, the potential of iPSCs to further the treatment of pancreatic cancer is being explored and, in turn, will hopefully provide additional therapies to increase the poor survival rates of this patient population.Advances in the treatment of pancreatic ductal adenocarcinoma (PDAC) using neoadjuvant chemoradiotherapy, chemotherapy, and immunotherapy have had minimal impact on the overall survival of patients. A general lack of immunogenic features and a complex tumor microenvironment (TME) are likely culprits for therapy refractoriness in PDAC. Induced pluripotent stem cells (iPSCs) should be explored as a means to advance the treatment options for PDAC, by providing representative in vitro models of pancreatic cancer development. In addition, iPSCs could be used for tailor-made cellular immunotherapies or as a source of tumor-associated antigens in the context of vaccination.Surgical oncolog

    Chronological age when healthcare transition skills are mastered in adolescents/young adults with inflammatory bowel disease

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    To describe the longitudinal course of acquisition of healthcare transition skills among adolescents and young adults with inflammatory bowel diseases

    Which psychological factors exacerbate irritable bowel syndrome? Development of a comprehensive model

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    There is evidence that psychological factors affect the onset, severity and duration of Irritable Bowel Syndrome (IBS). However, it is not clear which psychological factors are the most important and how they interact. The aims of the current study are to identify the most important psychological factors predicting IBS symptom severity and to investigate how these psychological variables are related to each other

    At the tip of an iceberg: citizen science and active surveillance collaborating to broaden the known distribution of Aedes japonicus in Spain

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    Background: Active surveillance aimed at the early detection of invasive mosquito species is usually focused on seaports and airports as points of entry, and along road networks as dispersion paths. In a number of cases, however, the first detections of colonizing populations are made by citizens, either because the species has already moved beyond the implemented active surveillance sites or because there is no surveillance in place. This was the case of the first detection in 2018 of the Asian bush mosquito, Aedes japonicus, in Asturias (northern Spain) by the citizen science platform Mosquito Alert. Methods: The collaboration between Mosquito Alert, the Ministry of Health, local authorities and academic researchers resulted in a multi-source surveillance combining active field sampling with broader temporal and spatial citizen-sourced data, resulting in a more flexible and efficient surveillance strategy. Results: Between 2018 and 2020, the joint efforts of administrative bodies, academic teams and citizen-sourced data led to the discovery of this species in northern regions of Spain such as Cantabria and the Basque Country. This raised the estimated area of occurrence of Ae. japonicus from < 900 km2 in 2018 to > 7000 km2 in 2020. Conclusions: This population cluster is geographically isolated from any other population in Europe, which raises questions about its origin, path of introduction and dispersal means, while also highlighting the need to enhance surveillance systems by closely combining crowd-sourced surveillance with public health and mosquito control agencies’ efforts, from local to continental scales. This multi-actor approach for surveillance (either passive and active) shows high potential efficiency in the surveillance of other invasive mosquito species, and specifically the major vector Aedes aegypti which is already present in some parts of Europe. Graphical abstract: [Figure not available: see fulltext.] © 2021, The Author(s)
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