101 research outputs found

    Analysis of DRD2 Gene Polymorphism in the Context of Personality Traits in a Group of Athletes

    Get PDF
    The presented study showed the relationship between dopamine receptor gene polymorphism and personality traits in athletes training in martial arts. Behavioral modulation resulting from a balance of the neurotransmitters dopamine and norepinephrine to inactivation of the dorsolateral prefrontal cortex and dysregulation of various pathways involved in attention and impulse control processes; Methods: The study was conducted among martial arts athletes. The study group included 258 volunteers and 284 controls. The genetic test was performed using the real-time PCR method; psychological tests were performed using standardized TCI questionnaires. All analyses were performed using STATISTICA 13. Results: Interaction between martial arts and DRD2 rs1799732 (manual) G/-(VIC/FAM)-ins/del and RD- Harm avoidance and Reward Dependence scale were demonstrated. In athletes, a lower Reward Dependence scale score was associated with the DRD2 rs1799732 (manual)-/-polymorphism compared to the control group. Conclusions: It seems justified to study not only genetic aspects related to brain transmission dopamine in martial arts athletes. In the studied athletes, the features related to reward addiction and harm avoidance are particularly important in connection with the dopaminergic reward system in the brai

    Construction and validation of a low-cost system for indoor air quality measurements in livestock facilities

    Get PDF
    In recent years, there has been an increase in demand for food of ani-mal origin. The number of intensive production systems such as pig and poultry farming has been increasing more and more and exerting great impacts on the environment, due to a large amount of particulate material and gaseous pollutants that are generated within these facilities. Thus, low-cost devices emerge as a cheap alternative that provides farmers with information on indoor air quality in its facilities. However, it is important that these devices make precise and accu-rate measurements, providing reliable concentration readings. Therefore, the ob-jective of this study is the construction and validation of a low-cost system capa-ble of measuring, storing and sending, via the mobile network, the concentrations of hydrogen sulfide, ammonia, carbon dioxide, PM2.5, PM10, temperature, and relative humidity. Preliminary inter-comparison tests showed that the built sys-tem had a reliable behavior in relation to all variables, even though the CO2 sen-sor was the one with the highest determination coefficient. The built device is able to provide continuous monitoring of atmospheric pollutants concentrations, at low cost and with simple handling.This study was supported by the Fundação para a Ciência e Tecnologia (FCT, Portugal) and FEDER under the PT2020 Program through financial support to CIMO (UID/AGR/00690/2013) and by the bilateral project established between the Polytechnic Institute of Bragança (Portugal) and the Federal University of Technology – Paraná (Brazil).info:eu-repo/semantics/publishedVersio

    Exploring hypotheses of the actions of TGF-beta 1 in epidermal wound healing using a 3D computational multiscale model of the human epidermis

    Get PDF
    In vivo and in vitro studies give a paradoxical picture of the actions of the key regulatory factor TGF-beta 1 in epidermal wound healing with it stimulating migration of keratinocytes but also inhibiting their proliferation. To try to reconcile these into an easily visualized 3D model of wound healing amenable for experimentation by cell biologists, a multiscale model of the formation of a 3D skin epithelium was established with TGF-beta 1 literature-derived rule sets and equations embedded within it. At the cellular level, an agent-based bottom-up model that focuses on individual interacting units ( keratinocytes) was used. This was based on literature-derived rules governing keratinocyte behavior and keratinocyte/ECM interactions. The selection of these rule sets is described in detail in this paper. The agent-based model was then linked with a subcellular model of TGF-beta 1 production and its action on keratinocytes simulated with a complex pathway simulator. This multiscale model can be run at a cellular level only or at a combined cellular/subcellular level. It was then initially challenged ( by wounding) to investigate the behavior of keratinocytes in wound healing at the cellular level. To investigate the possible actions of TGF-beta 1, several hypotheses were then explored by deliberately manipulating some of these rule sets at subcellular levels. This exercise readily eliminated some hypotheses and identified a sequence of spatial-temporal actions of TGF-beta 1 for normal successful wound healing in an easy-to-follow 3D model. We suggest this multiscale model offers a valuable, easy-to-visualize aid to our understanding of the actions of this key regulator in wound healing, and provides a model that can now be used to explore pathologies of wound healing

    Enhanced neuronal Met signalling levels in ALS mice delay disease onset

    Get PDF
    Signalling by receptor tyrosine kinases (RTKs) coordinates basic cellular processes during development and in adulthood. Whereas aberrant RTK signalling can lead to cancer, reactivation of RTKs is often found following stress or cell damage. This has led to the common belief that RTKs can counteract degenerative processes and so strategies to exploit them for therapy have been extensively explored. An understanding of how RTK stimuli act at cellular levels is needed, however, to evaluate their mechanism of therapeutic action. In this study, we genetically explored the biological and functional significance of enhanced signalling by the Met RTK in neurons, in the context of a neurodegenerative disease. Conditional met-transgenic mice, namely Rosa26LacZ−stop−Met, have been engineered to trigger increased Met signalling in a temporal and tissue-specific regulated manner. Enhancing Met levels in neurons does not affect either motor neuron (MN) development or maintenance. In contrast, increased neuronal Met in amyotrophic lateral sclerosis (ALS) mice prolongs life span, retards MN loss, and ameliorates motor performance, by selectively delaying disease onset. Thus, our studies highlight the properties of RTKs to counteract toxic signals in a disease characterized by dysfunction of multiple cell types by acting in MNs. Moreover, they emphasize the relevance of genetically assessing the effectiveness of agents targeting neurons during ALS evolution

    Characterization and structural determination of a new anti-MET function-blocking antibody with binding epitope distinct from the ligand binding domain

    Get PDF
    The growth and motility factor Hepatocyte Growth Factor/Scatter Factor (HGF/SF) and its receptor, the product of the MET proto-oncogene, promote invasion and metastasis of tumor cells and have been considered potential targets for cancer therapy. We generated a new Met-blocking antibody which binds outside the ligand-binding site, and determined the crystal structure of the Fab in complex with its target, which identifies the binding site as the Met Ig1 domain. The antibody, 107_A07, inhibited HGF/SF-induced cell migration and proliferation in vitro and inhibited growth of tumor xenografts in vivo. In biochemical assays, 107_A07 competes with both HGF/SF and its truncated splice variant NK1 for MET binding, despite the location of the antibody epitope on a domain (Ig1) not reported to bind NK1 or HGF/SF. Overlay of the Fab-MET crystal structure with the InternalinB-MET crystal structure shows that the 107_A07 Fab comes into close proximity with the HGF/SF-binding SEMA domain when MET is in the “compact”, InternalinB-bound conformation, but not when MET is in the “open” conformation. These findings provide further support for the importance of the “compact” conformation of the MET extracellular domain, and the relevance of this conformation to HGF/SF binding and signaling

    Development of a Three Dimensional Multiscale Computational Model of the Human Epidermis

    Get PDF
    Transforming Growth Factor (TGF-β1) is a member of the TGF-beta superfamily ligand-receptor network. and plays a crucial role in tissue regeneration. The extensive in vitro and in vivo experimental literature describing its actions nevertheless describe an apparent paradox in that during re-epithelialisation it acts as proliferation inhibitor for keratinocytes. The majority of biological models focus on certain aspects of TGF-β1 behaviour and no one model provides a comprehensive story of this regulatory factor's action. Accordingly our aim was to develop a computational model to act as a complementary approach to improve our understanding of TGF-β1. In our previous study, an agent-based model of keratinocyte colony formation in 2D culture was developed. In this study this model was extensively developed into a three dimensional multiscale model of the human epidermis which is comprised of three interacting and integrated layers: (1) an agent-based model which captures the biological rules governing the cells in the human epidermis at the cellular level and includes the rules for injury induced emergent behaviours, (2) a COmplex PAthway SImulator (COPASI) model which simulates the expression and signalling of TGF-β1 at the sub-cellular level and (3) a mechanical layer embodied by a numerical physical solver responsible for resolving the forces exerted between cells at the multi-cellular level. The integrated model was initially validated by using it to grow a piece of virtual epidermis in 3D and comparing the in virtuo simulations of keratinocyte behaviour and of TGF-β1 signalling with the extensive research literature describing this key regulatory protein. This research reinforces the idea that computational modelling can be an effective additional tool to aid our understanding of complex systems. In the accompanying paper the model is used to explore hypotheses of the functions of TGF-β1 at the cellular and subcellular level on different keratinocyte populations during epidermal wound healing

    The Met oncogene and basal-like breast cancer: another culprit to watch out for?

    Get PDF
    Recent findings suggest the involvement of the MET oncogene, encoding the tyrosine kinase receptor for hepatocyte growth factor, in the onset and progression of basal-like breast carcinoma. The expression profiles of basal-like tumors - but not those of other breast cancer subtypes - are enriched for gene sets that are coordinately over-represented in transcriptional signatures regulated by Met. Consistently, tissue microarray analyses have revealed that Met immunoreactivity is much higher in basal-like cases of human breast cancer than in other tumor types. Finally, mouse models expressing mutationally activated forms of Met develop a high incidence of mammary tumors, some of which exhibit basal characteristics. The present review summarizes current knowledge on the role and activity of Met in basal-like breast cancer, with a special emphasis on the correlation between this tumor subtype and the cellular hierarchy of the normal mammary gland

    Ockham’s razor for the MET-driven invasive growth linking idiopathic pulmonary fibrosis and cancer

    Full text link

    A new hypothesis for the cancer mechanism

    Full text link

    Hybrid power system using hydrogen and renewable energy sources

    No full text
    Prezentowany referat, jak i wykonane prace wstępne pokażą, że możliwa jest budowa quasiatonomicznego, cichego i bezemisyjnego systemu zasilania, bazującego na technologii wodorowej i odnawialnych źródłach energii, przystosowanego do pracy w warunkach rzeczywistych (wysokie i niskie temperatury otoczenia) i mogącego zastąpić funkcjonalnie tradycyjny, spalinowy zespół prądotwórczy. Efekt ten uzyskano poprzez doświadczalne badania zaprezentowanych w pracy podzespołów systemu i analityczne zintegrowanie różnych źródeł energii elektrycznej tak, aby wytworzyć hybrydowy układ źródeł prądu, zdolny do zasilania środków wspomagających akcje prowadzone przez sztaby zarządzania kryzysowego podczas klęsk żywiołowych itp. W pracy przedstawiony jest sposób doświadczalnego doboru poszczególnych elementów każdego z podsystemów oraz układów zarządzania ich pracą, który w efekcie powinien pozwolić na wskazanie, że jest możliwa autonomiczna praca urządzenia w przypadku konieczności długiego samodzielnego działania bez kontaktu z zapleczem logistycznym. Praca prezentuje możliwości wykorzystania odnawialnych źródeł energii elektrycznej do jednoczesnej pracy systemu z pełnym obciążeniem i magazynowania energii do regeneracji systemu wodorowego (wytworzenia wodoru do samodzielnego cyklu pracy) i podtrzymywania gotowości urządzenia. Przedstawiona w pracy propozycja urządzenia integruje kluczowe technologie, takie jak: nowoczesne baterie akumulatorów, niekonwencjonalne źródła energii – ogniwa paliwowe, odnawialne źródła energii – ogniwa fotowoltaiczne, generator wiatrowy oraz blok systemu zarządzania energią optymalizujący współpracę wszystkich komponentów.The paper presented and preliminary work show that is possible to build quasiautonomic, silent and emission-free power system based on hydrogen technology and renewable energy sources, adapted to work in real conditions (high and low ambient temperatures) and likely functionally replace traditional, combustion generator. This effect was obtained by experimental studies of the working components of the system presented in the paper and the analytical integration of different sources of energy, so as to produce a hybrid system of power source capable of powering equipment used by the crisis management staff during natural disasters , etc. The work will present experimental means for selection of individual elements of each of the subsystems, as described below, and systems to manage their work, which in effect should allow to demonstrate that autonomous operation of the unit in case of a necessity long, independent operation without contact with logistics facilities is possible. The paper will present the possibilities of using renewable energy sources for simultaneous operation of the system with a full load and energy storage system for the regeneration of hydrogen (hydrogen to produce a self-cycle) and maintaining the state of readiness. The device presented integrates essential technologies, such as modern batteries, unconventional energy sources – fuel cells, renewable energy – photovoltaic cells (PV), wind power generator and block energy management system which optimizes the cooperation of all the components
    corecore