150 research outputs found

    Effects of anisotropic interactions on the structure of animal groups

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    This paper proposes an agent-based model which reproduces different structures of animal groups. The shape and structure of the group is the effect of simple interaction rules among individuals: each animal deploys itself depending on the position of a limited number of close group mates. The proposed model is shown to produce clustered formations, as well as lines and V-like formations. The key factors which trigger the onset of different patterns are argued to be the relative strength of attraction and repulsion forces and, most important, the anisotropy in their application.Comment: 22 pages, 9 figures. Submitted. v1-v4: revised presentation; extended simulations; included technical results. v5: added a few clarification

    The semisynthetic flavonoid monoHER sensitises human soft tissue sarcoma cells to doxorubicin-induced apoptosis via inhibition of nuclear factor-κB

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    Background:Despite therapeutic advances, the prognosis of patients with metastatic soft tissue sarcoma (STS) remains extremely poor. The results of a recent clinical phase II study, evaluating the protective effects of the semisynthetic flavonoid 7-mono-O-(beta-hydroxyethyl)-rutoside (monoHER) on doxorubicin-induced cardiotoxicity, suggest that monoHER enhances the antitumour activity of doxorubicin in STSs.Methods:To molecularly explain this unexpected finding, we investigated the effect of monoHER on the cytotoxicity of doxorubicin, and the potential involvement of glutathione (GSH) depletion and nuclear factor-kappaB (NF-kappaB) inactivation in the chemosensitising effect of monoHER.Results:MonoHER potentiated the antitumour activity of doxorubicin in the human liposarcoma cell line WLS-160. Moreover, the combination of monoHER with doxorubicin induced more apoptosis in WLS-160 cells compared with doxorubicin alone. MonoHER did not reduce intracellular GSH levels. On the other hand, monoHER pretreatment significantly reduced doxorubicin-induced NF-kappaB activation.Conclusion:These results suggest that reduction of doxorubicin-induced NF-kappaB activation by monoHER, which sensitises cancer cells to apoptosis, is involved in the chemosensitising effect of monoHER in human liposarcoma cells

    'Asking the right question'. A comparison of two approaches to gathering data on 'herbals' use in survey based studies

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    BACKGROUND:Over the last decade academic interest in the prevalence and nature of herbal medicines use by pregnant women has increased significantly. Such data are usually collected by means of an administered questionnaire survey, however a key methodological limitation using this approach is the need to clearly define the scope of 'herbals' to be investigated. The majority of published studies in this area neither define 'herbals' nor provide a detailed checklist naming specific 'herbals' and CAM modalities, which limits inter-study comparison, generalisability and the potential for meta-analyses. The aim of this study was to compare the self-reported use of herbs, herbal medicines and herbal products using two different approaches implemented in succession. METHODS:Cross-sectional questionnaire surveys of women attending for their mid-trimester scan or attending the postnatal unit following live birth at the Royal Aberdeen Maternity Hospital, North-East Scotland. The questionnaire utilised two approaches to collect data on 'herbals' use, a single closed yes/no answer to the question "have you used herbs, herbal medicines and herbal products in the last three months"; and a request to tick which of a list of 40 'herbals' they had used in the same time period. RESULTS:A total of 889 responses were obtained of which 4.3% (38) answered 'yes' to herbal use via the closed question. However, using the checklist 39% (350) of respondents reported the use of one or more specific 'herbals' (p<0.0001). The 312 respondents who reported 'no' to 'herbals' use via the closed question but "yes" via the checklist consumed a total of 20 different 'herbals' (median 1, interquartile range 1-2, range 1-6). CONCLUSIONS:This study demonstrates that the use of a single closed question asking about the use of 'herbals', as frequently reported in published studies, may not yield valid data resulting in a gross underestimation of actual use

    Auditory stimulation of opera music induced prolongation of murine cardiac allograft survival and maintained generation of regulatory CD4+CD25+ cells

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    <p>Abstract</p> <p>Background</p> <p>Interactions between the immune response and brain functions such as olfactory, auditory, and visual sensations are likely. This study investigated the effect of sounds on alloimmune responses in a murine model of cardiac allograft transplantation.</p> <p>Methods</p> <p>Naïve CBA mice (H2<sup>k</sup>) underwent transplantation of a C57BL/6 (B6, H2<sup>b</sup>) heart and were exposed to one of three types of music--opera (<it>La Traviata</it>), classical (Mozart), and New Age (Enya)--or one of six different single sound frequencies, for 7 days. Additionally, we prepared two groups of CBA recipients with tympanic membrane perforation exposed to opera for 7 days and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment). An adoptive transfer study was performed to determine whether regulatory cells were generated in allograft recipients. Immunohistochemical, cell-proliferation, cytokine, and flow cytometry assessments were also performed.</p> <p>Results</p> <p>CBA recipients of a B6 cardiac graft that were exposed to opera music and Mozart had significantly prolonged allograft survival (median survival times [MSTs], 26.5 and 20 days, respectively), whereas those exposed to a single sound frequency (100, 500, 1000, 5000, 10,000, or 20,000 Hz) or Enya did not (MSTs, 7.5, 8, 9, 8, 7.5, 8.5 and 11 days, respectively). Untreated, CBA mice with tympanic membrane perforations and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment) rejected B6 cardiac grafts acutely (MSTs, 7, 8 and 8 days, respectively). Adoptive transfer of whole splenocytes, CD4<sup>+ </sup>cells, or CD4<sup>+</sup>CD25<sup>+ </sup>cells from opera-exposed primary allograft recipients resulted in significantly prolonged allograft survival in naive secondary recipients (MSTs, 36, 68, and > 100 days, respectively). Proliferation of splenocytes, interleukin (IL)-2 and interferon (IFN)-γ production was suppressed in opera-exposed mice, and production of IL-4 and IL-10 from opera-exposed transplant recipients increased compared to that from splenocytes of untreated recipients. Flow cytometry studies showed an increased CD4<sup>+</sup>CD25<sup>+ </sup>Forkhead box P3 (Foxp3)<sup>+ </sup>cell population in splenocytes from those mice.</p> <p>Conclusion</p> <p>Our findings indicate that exposure to opera music, such as La traviata, could affect such aspects of the peripheral immune response as generation of regulatory CD4<sup>+</sup>CD25<sup>+ </sup>cells and up-regulation of anti-inflammatory cytokines, resulting in prolonged allograft survival.</p

    Oral squamous cell cancer: early detection and the role of alcohol and smoking

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    Objective: Oral squamous cell carcinoma has a remarkable incidence worldwide and a fairly onerous prognosis, encouraging further research on factors that might modify disease outcome. Data sources: A web-based search for all types of articles published was initiated using Medline/Pub Med, with the key words such as oral cancer, alcohol consumption, genetic polymorphisms, tobacco smoking and prevention. The search was restricted to articles published in English, with no publication date restriction (last update 2010). Review Methods: In this review article, we approach the factors for a cytologic diagnosis during OSCC development and the markers used in modern diagnostic technologies as well. We also reviewed available studies of the combined effects of alcohol drinking and genetic polymorphisms on alcohol-related cancer risk. Results: The interaction of smoking and alcohol significantly increases the risk for aero-digestive cancers. The interaction between smoking and alcohol consumption seems to be responsible for a significant amount of disease. Conclusion: Published scientific data show promising pathways for the future development of more effective prognosis. There is a clear need for new prognostic indicators, which could be used in diagnostics and, therefore a better selection of the most effective treatment can be achieved

    Vasa-Like DEAD-Box RNA Helicases of Schistosoma mansoni

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    Genome sequences are available for the human blood flukes, Schistosoma japonicum, S. mansoni and S. haematobium. Functional genomic approaches could aid in identifying the role and importance of these newly described schistosome genes. Transgenesis is established for functional genomics in model species, which can lead to gain- or loss-of-functions, facilitate vector-based RNA interference, and represents an effective forward genetics tool for insertional mutagenesis screens. Progress toward routine transgenesis in schistosomes might be expedited if germ cells could be reliably localized in cultured schistosomes. Vasa, a member of the ATP-dependent DEAD-box RNA helicase family, is a prototypic marker of primordial germ cells and the germ line in the Metazoa. Using bioinformatics, 33 putative DEAD-box RNA helicases exhibiting conserved motifs that characterize helicases of this family were identified in the S. mansoni genome. Moreover, three of the helicases exhibited vasa-like sequences; phylogenetic analysis confirmed the three vasa-like genes—termed Smvlg1, Smvlg2, and Smvlg3—were members of the Vasa/PL10 DEAD-box subfamily. Transcripts encoding Smvlg1, Smvlg2, and Smvlg3 were cloned from cDNAs from mixed sex adult worms, and quantitative real time PCR revealed their presence in developmental stages of S. mansoni with elevated expression in sporocysts, adult females, eggs, and miracidia, with strikingly high expression in the undeveloped egg. Whole mount in situ hybridization (WISH) analysis revealed that Smvlg1, Smvlg2 and Smvlg3 were transcribed in the posterior ovary where the oocytes mature. Germ cell specific expression of schistosome vasa-like genes should provide an informative landmark for germ line transgenesis of schistosomes, etiologic agents of major neglected tropical diseases

    Adenovirus-5-Vectored P. falciparum Vaccine Expressing CSP and AMA1. Part B: Safety, Immunogenicity and Protective Efficacy of the CSP Component

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    Background: A protective malaria vaccine will likely need to elicit both cell-mediated and antibody responses. As adenovirus vaccine vectors induce both these responses in humans, a Phase 1/2a clinical trial was conducted to evaluate the efficacy of an adenovirus serotype 5-vectored malaria vaccine against sporozoite challenge.\ud \ud Methodology/Principal Findings: NMRC-MV-Ad-PfC is an adenovirus vector encoding the Plasmodium falciparum 3D7 circumsporozoite protein (CSP). It is one component of a two-component vaccine NMRC-M3V-Ad-PfCA consisting of one adenovector encoding CSP and one encoding apical membrane antigen-1 (AMA1) that was evaluated for safety and immunogenicity in an earlier study (see companion paper, Sedegah et al). Fourteen Ad5 seropositive or negative adults received two doses of NMRC-MV-Ad-PfC sixteen weeks apart, at 1x1010 particle units per dose. The vaccine was safe and well tolerated. All volunteers developed positive ELISpot responses by 28 days after the first immunization (geometric mean 272 spot forming cells/million[sfc/m]) that declined during the following 16 weeks and increased after the second dose to levels that in most cases were less than the initial peak (geometric mean 119 sfc/m). CD8+ predominated over CD4+ responses, as in the first clinical trial. Antibody responses were poor and like ELISpot responses increased after the second immunization but did not exceed the initial peak. Pre-existing neutralizing antibodies (NAb) to Ad5 did not affect the immunogenicity of the first dose, but the fold increase in NAb induced by the first dose was significantly associated with poorer antibody responses after the second dose, while ELISpot responses remained unaffected. When challenged by the bite of P. falciparum-infected mosquitoes, two of 11 volunteers showed a delay in the time to patency compared to infectivity controls, but no volunteers were sterilely protected.\ud \ud Significance: The NMRC-MV-Ad-PfC vaccine expressing CSP was safe and well tolerated given as two doses, but did not provide sterile protection

    Myocardial tagging by Cardiovascular Magnetic Resonance: evolution of techniques--pulse sequences, analysis algorithms, and applications

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    Cardiovascular magnetic resonance (CMR) tagging has been established as an essential technique for measuring regional myocardial function. It allows quantification of local intramyocardial motion measures, e.g. strain and strain rate. The invention of CMR tagging came in the late eighties, where the technique allowed for the first time for visualizing transmural myocardial movement without having to implant physical markers. This new idea opened the door for a series of developments and improvements that continue up to the present time. Different tagging techniques are currently available that are more extensive, improved, and sophisticated than they were twenty years ago. Each of these techniques has different versions for improved resolution, signal-to-noise ratio (SNR), scan time, anatomical coverage, three-dimensional capability, and image quality. The tagging techniques covered in this article can be broadly divided into two main categories: 1) Basic techniques, which include magnetization saturation, spatial modulation of magnetization (SPAMM), delay alternating with nutations for tailored excitation (DANTE), and complementary SPAMM (CSPAMM); and 2) Advanced techniques, which include harmonic phase (HARP), displacement encoding with stimulated echoes (DENSE), and strain encoding (SENC). Although most of these techniques were developed by separate groups and evolved from different backgrounds, they are in fact closely related to each other, and they can be interpreted from more than one perspective. Some of these techniques even followed parallel paths of developments, as illustrated in the article. As each technique has its own advantages, some efforts have been made to combine different techniques together for improved image quality or composite information acquisition. In this review, different developments in pulse sequences and related image processing techniques are described along with the necessities that led to their invention, which makes this article easy to read and the covered techniques easy to follow. Major studies that applied CMR tagging for studying myocardial mechanics are also summarized. Finally, the current article includes a plethora of ideas and techniques with over 300 references that motivate the reader to think about the future of CMR tagging
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