677 research outputs found

    Objective effect manifestation of pectus excavatum on load-stressed pulmonary function testing: a case report

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    Abstract Introduction Pectus excavatum is the most common congenital deformity of the anterior chest wall that, under certain conditions, may pose functional problems due to cardiopulmonary compromise and exercise intolerance. Case presentation We present the case of an otherwise physically-adept 21-year-old Chinese sportsman with idiopathic pectus excavatum, whose symptoms manifested only on bearing a loaded body vest and backpack during physical exercise. Corroborative objective evidence was obtained via load-stressed pulmonary function testing, which demonstrated restrictive lung function. Conclusion This report highlights the possible detrimental synergism of thoracic load stress and pectus excavatum on cardiopulmonary function. Thoracic load-stressed pulmonary function testing provides objective evidence in support of such a synergistic relationship.</p

    Ferritins: furnishing proteins with iron

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    Ferritins are a superfamily of iron oxidation, storage and mineralization proteins found throughout the animal, plant, and microbial kingdoms. The majority of ferritins consist of 24 subunits that individually fold into 4-α-helix bundles and assemble in a highly symmetric manner to form an approximately spherical protein coat around a central cavity into which an iron-containing mineral can be formed. Channels through the coat at inter-subunit contact points facilitate passage of iron ions to and from the central cavity, and intrasubunit catalytic sites, called ferroxidase centers, drive Fe2+ oxidation and O2 reduction. Though the different members of the superfamily share a common structure, there is often little amino acid sequence identity between them. Even where there is a high degree of sequence identity between two ferritins there can be major differences in how the proteins handle iron. In this review we describe some of the important structural features of ferritins and their mineralized iron cores and examine in detail how three selected ferritins oxidise Fe2+ in order to explore the mechanistic variations that exist amongst ferritins. We suggest that the mechanistic differences reflect differing evolutionary pressures on amino acid sequences, and that these differing pressures are a consequence of different primary functions for different ferritins

    WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

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    Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Î’-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Î’-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe

    Veratridine produces distinct calcium response profiles in mouse Dorsal Root Ganglia neurons.

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    Nociceptors are a subpopulation of dorsal root ganglia (DRG) neurons that detect noxious stimuli and signal pain. Veratridine (VTD) is a voltage-gated sodium channel (VGSC) modifier that is used as an "agonist" in functional screens for VGSC blockers. However, there is very little information on VTD response profiles in DRG neurons and how they relate to neuronal subtypes. Here we characterised VTD-induced calcium responses in cultured mouse DRG neurons. Our data shows that the heterogeneity of VTD responses reflects distinct subpopulations of sensory neurons. About 70% of DRG neurons respond to 30-100 μM VTD. We classified VTD responses into four profiles based upon their response shape. VTD response profiles differed in their frequency of occurrence and correlated with neuronal size. Furthermore, VTD response profiles correlated with responses to the algesic markers capsaicin, AITC and α, β-methylene ATP. Since VTD response profiles integrate the action of several classes of ion channels and exchangers, they could act as functional "reporters" for the constellation of ion channels/exchangers expressed in each sensory neuron. Therefore our findings are relevant to studies and screens using VTD to activate DRG neurons

    First serological evidence of West Nile virus in human rural populations of Gabon

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    To investigate West Nile virus (WNV) circulation in rural populations in Gabon, we undertook a large serological survey focusing on human rural populations, using two different ELISA assays. A sample was considered positive when it reacted in both tests. A total of 2320 villagers from 115 villages were interviewed and sampled. Surprisingly, the WNV-specific IgG prevalence was high overall (27.2%) and varied according to the ecosystem: 23.7% in forested regions, 21.8% in savanna, and 64.9% in the lakes region. The WNV-specific IgG prevalence rate was 30% in males and 24.6% in females, and increased with age. Although serological cross-reactions between flaviviruses are likely and may be frequent, these findings strongly suggest that WNV is widespread in Gabon. The difference in WNV prevalence among ecosystems suggests preferential circulation in the lakes region. The linear increase with age suggests continuous exposure of Gabonese populations to WNV. Further investigations are needed to determine the WNV cycle and transmission patterns in Gabon

    Constraints on Nucleon Decay via "Invisible" Modes from the Sudbury Neutrino Observatory

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    Data from the Sudbury Neutrino Observatory have been used to constrain the lifetime for nucleon decay to ``invisible'' modes, such as n -> 3 nu. The analysis was based on a search for gamma-rays from the de-excitation of the residual nucleus that would result from the disappearance of either a proton or neutron from O16. A limit of tau_inv > 2 x 10^{29} years is obtained at 90% confidence for either neutron or proton decay modes. This is about an order of magnitude more stringent than previous constraints on invisible proton decay modes and 400 times more stringent than similar neutron modes.Comment: Update includes missing efficiency factor (limits change by factor of 2) Submitted to Physical Review Letter

    Managing obesity through mobile phone applications: a state-of-the-art review from a user-centred design perspective

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    Evidence has shown that the trend of increasing obesity rates has continued in the last decade. Mobile phone applications, benefiting from their ubiquity, have been increasingly used to address this issue. In order to increase the applications’ acceptance and success, a design and development process that focuses on users, such as User-Centred Design, is necessary. This paper reviews reported studies that concern the design and development of mobile phone applications to prevent obesity, and analyses them from a User-Centred Design perspective. Based on the review results, strengths and weaknesses of the existing studies were identified. Identified strengths included: evidence of the inclusion of multidisciplinary skills and perspectives; user involvement in studies; and the adoption of iterative design practices. Weaknesses included the lack of specificity in the selection of end-users and inconsistent evaluation protocols. The review was concluded by outlining issues and research areas that need to be addressed in the future, including: greater understanding of the effectiveness of sharing data between peers; privacy; and guidelines for designing for behavioural change through mobile phone applications

    Koilocytes indicate a role for human papilloma virus in breast cancer

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    Background: High-risk human papilloma viruses (HPVs) are candidates as causal viruses in breast cancer. The scientific challenge is to determine whether HPVs are causal and not merely passengers or parasites. Studies of HPV-related koilocytes in breast cancer offer an opportunity to address this crucial issue. Koilocytes are epithelial cells characterised by perinuclear haloes surrounding condensed nuclei and are commonly present in cervical intraepithelial neoplasia. Koilocytosis is accepted as pathognomonic (characteristic of a particular disease) of HPV infection. The aim of this investigation is to determine whether putative koilocytes in normal and malignant breast tissues are because of HPV infection. Methods: Archival formalin-fixed normal and malignant breast specimens were investigated by histology, in situ PCR with confirmation of the findings by standard PCR and sequencing of the products, plus immunohistochemistry to identify HPV E6 oncoproteins. Results: human papilloma virus-associated koilocytes were present in normal breast skin and lobules and in the breast skin and cancer tissue of patients with ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDCs). Interpretation: As koilocytes are known to be the precursors of some HPV-associated cervical cancer, it follows that HPVs may be causally associated with breast cancer.6 page(s

    Selective Induction of Cell Death in Melanoma Cell Lines through Targeting of Mcl-1 and A1

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    Melanoma is an often fatal form of skin cancer which is remarkably resistant against radio- and chemotherapy. Even new strategies that target RAS/RAF signaling and display unprecedented efficacy are characterized by resistance mechanisms. The targeting of survival pathways would be an attractive alternative strategy, if tumor-specific cell death can be achieved. Bcl-2 proteins play a central role in regulating survival of tumor cells. In this study, we systematically investigated the relevance of antiapoptotic Bcl-2 proteins, i.e., Bcl-2, Bcl-xL, Bcl-w, Mcl-1, and A1, in melanoma cell lines and non-malignant cells using RNAi. We found that melanoma cells required the presence of specific antiapoptotic Bcl-2 proteins: Inhibition of Mcl-1 and A1 strongly induced cell death in some melanoma cell lines, whereas non-malignant cells, i.e., primary human fibroblasts or keratinocytes were not affected. This specific sensitivity of melanoma cells was further enhanced by the combined inhibition of Mcl-1 and A1 and resulted in 60% to 80% cell death in all melanoma cell lines tested. This treatment was successfully combined with chemotherapy, which killed a substantial proportion of cells that survived Mcl-1 and A1 inhibition. Together, these results identify antiapoptotic proteins on which specifically melanoma cells rely on and, thus, provide a basis for the development of new Bcl-2 protein-targeting therapies
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