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931.
Esther Wehrle Astrid Liedert Aline Heilmann Tim Wehner Ronny Bindl Lena Fischer Melanie Haffner-Luntzer Franz Jakob Thorsten Schinke Michael Amling Anita Ignatius 《Disease models & mechanisms》2015,8(1):93-104
Fracture healing is impaired in aged and osteoporotic individuals. Because adequate mechanical stimuli are able to increase bone formation, one therapeutical approach to treat poorly healing fractures could be the application of whole-body vibration, including low-magnitude high-frequency vibration (LMHFV). We investigated the effects of LMHFV on fracture healing in aged osteoporotic mice. Female C57BL/6NCrl mice (n=96) were either ovariectomised (OVX) or sham operated (non-OVX) at age 41 weeks. When aged to 49 weeks, all mice received a femur osteotomy that was stabilised using an external fixator. The mice received whole-body vibrations (20 minutes/day) with 0.3 g peak-to-peak acceleration and a frequency of 45 Hz. After 10 and 21 days, the osteotomised femurs and intact bones (contra-lateral femurs, lumbar spine) were evaluated using bending-testing, micro-computed tomography (μCT), histology and gene expression analyses. LMHFV disturbed fracture healing in aged non-OVX mice, with significantly reduced flexural rigidity (−81%) and bone formation (−80%) in the callus. Gene expression analyses demonstrated increased oestrogen receptor β (ERβ, encoded by Esr2) and Sost expression in the callus of the vibrated animals, but decreased β-catenin, suggesting that ERβ might mediate these negative effects through inhibition of osteoanabolic Wnt/β-catenin signalling. In contrast, in OVX mice, LMHFV significantly improved callus properties, with increased flexural rigidity (+1398%) and bone formation (+637%), which could be abolished by subcutaneous oestrogen application (0.025 mg oestrogen administered in a 90-day-release pellet). On a molecular level, we found an upregulation of ERα in the callus of the vibrated OVX mice, whereas ERβ was unaffected, indicating that ERα might mediate the osteoanabolic response. Our results indicate a major role for oestrogen in the mechanostimulation of fracture healing and imply that LMHFV might only be safe and effective in confined target populations.KEY WORDS: Whole-body vibration, LMHFV, Fracture healing, Oestrogen receptor signalling, Wnt signalling 相似文献
932.
MicroRNA and mRNA expression profiling in metastatic melanoma reveal associations with BRAF mutation and patient prognosis 下载免费PDF全文
Ellis Patrick Vivek Jayaswal Yue Hang Tang Andrew Barbour Nicholas K. Hayward John F. Thompson Richard A. Scolyer Yee Hwa Yang Graham J. Mann 《Pigment cell & melanoma research》2015,28(3):254-266
The role of microRNAs (miRNAs) in melanoma is unclear. We examined global miRNA expression profiles in fresh‐frozen metastatic melanomas in relation to clinical outcome and BRAF mutation, with validation in independent cohorts of tumours and sera. We integrated miRNA and mRNA information from the same samples and elucidated networks associated with outcome and mutation. Associations with prognosis were replicated for miR‐150‐5p, miR‐142‐3p and miR‐142‐5p. Co‐analysis of miRNA and mRNA uncovered a network associated with poor prognosis (PP) that paradoxically favoured expression of miRNAs opposing tumorigenesis. These miRNAs are likely part of an autoregulatory response to oncogenic drivers, rather than drivers themselves. Robust association of miR‐150‐5p and the miR‐142 duplex with good prognosis and earlier stage metastatic melanoma supports their potential as biomarkers. miRNAs overexpressed in association with PP in an autoregulatory fashion will not be suitable therapeutic targets. 相似文献
933.
Predicted avian responses to bioenergy development scenarios in an intensive agricultural landscape 下载免费PDF全文
Daniel R. Uden Craig R. Allen Rob B. Mitchell Tim D. McCoy Qingfeng Guan 《Global Change Biology Bioenergy》2015,7(4):717-726
Conversion of native prairie to agriculture has increased food and bioenergy production but decreased wildlife habitat. However, enrollment of highly erodible cropland in conservation programs has compensated for some grassland loss. In the future, climate change and production of second-generation perennial biofuel crops could further transform agricultural landscapes and increase or decrease grassland area. Switchgrass (Panicum virgatum) is an alternative biofuel feedstock that may be economically and environmentally superior to maize (Zea mays) grain for ethanol production on marginally productive lands. Switchgrass could benefit farmers economically and increase grassland area, but there is uncertainty as to how conversions between rowcrops, switchgrass monocultures and conservation grasslands might occur and affect wildlife. To explore potential impacts on grassland birds, we developed four agricultural land-use change scenarios for an intensively cultivated landscape, each driven by potential future climatic changes and ensuing irrigation limitations, ethanol demand, commodity prices, and continuation of a conservation program. For each scenario, we calculated changes in area for landcover classes and predicted changes in grassland bird abundances. Overall, birds responded positively to the replacement of rowcrops with switchgrass and negatively to the conversion of conservation grasslands to switchgrass or rowcrops. Landscape context and interactions between climate, crop water use, and irrigation availability could influence future land-use, and subsequently, avian habitat quality and quantity. Switchgrass is likely to provide higher quality avian habitat than rowcrops but lower quality habitat than conservation grasslands, and therefore, may most benefit birds in heavily cultivated, irrigation dependent landscapes under warmer and drier conditions, where economic profitability may also encourage conversions to drought tolerant bioenergy feedstocks. 相似文献
934.
Sean Lal Amy Li David Allen Paul D. Allen Paul Bannon Tim Cartmill Roger Cooke Alan Farnsworth Anne Keogh Cristobal dos Remedios 《Biophysical reviews》2015,7(4):399-406
This review provides a guide to researchers who wish to establish a biobank. It also gives practical advice to investigators seeking access to samples of healthy or diseased human hearts. We begin with a brief history of the Sydney Heart Bank (SHB) from when it began in 1989, including the pivotal role played by the late Victor Chang. We discuss our standard operating procedures for tissue collection which include cryopreservation and the quality assurance needed to maintain the long-term molecular and cellular integrity of the samples. The SHB now contains about 16,000 heart samples derived from over 450 patients who underwent isotopic heart transplant procedures and from over 100 healthy organ donors. These enable us to provide samples from a wide range of categories of heart failure. So far, we have delivered heart samples to more than 50 laboratories over two decades, and we answer their most frequently asked questions. Other SHB services include the development of tissue microarrays (TMA). These enable end users to perform preliminary examinations of the expression and localisation of target molecules in diseased or aging donor hearts, all in a single section of the TMA. Finally, the processes involved in managing tissue requests from external users and logistics considerations for the shipment of human tissue are discussed in detail.
Electronic supplementary material
The online version of this article (doi:10.1007/s12551-015-0182-6) contains supplementary material, which is available to authorized users. 相似文献935.
The clinicopathological and gene expression patterns associated with ulceration of primary melanoma 下载免费PDF全文
Rosalyn Jewell Faye Elliott Jonathan Laye Jérémie Nsengimana John Davies Christy Walker Caroline Conway Angana Mitra Mark Harland Martin G. Cook Andy Boon Sarah Storr Sabreena Safuan Stewart G. Martin Karin Jirström Håkan Olsson Christian Ingvar Martin Lauss Tim Bishop Göran Jönsson Julia Newton‐Bishop 《Pigment cell & melanoma research》2015,28(1):94-104
Ulceration of primary melanomas is associated with poor prognosis yet is reported to predict benefit from adjuvant interferon. To better understand the biological processes involved, clinicopathological factors associated with ulceration were determined in 1804 patients. From this cohort, 348 primary tumor blocks were sampled to generate gene expression data using a 502‐gene cancer panel and 195 blocks were used for immunohistochemistry to detect macrophage infiltration and vessel density. Gene expression results were validated using a whole genome array in two independent sample sets. Ulceration of primary melanomas was associated with more proliferative tumors, tumor vessel invasion, and increased microvessel density. Infiltration of tumors with greater number of macrophages and gene expression pathways associated with wound healing and up‐regulation of pro‐inflammatory cytokines suggests that ulceration is associated with tumor‐related inflammation. The relative benefit from interferon reported in patients with ulcerated tumors may reflect modification of signaling pathways involved in inflammation. 相似文献
936.
937.
Simon D. S. Fraser Grant Aitken Maarten W. Taal Jennifer S. Mindell Graham Moon Julie Day Donal O’Donoghue Paul J. Roderick 《PloS one》2015,10(2)
BackgroundChronic kidney disease (CKD) diagnosis relies on glomerular filtration rate (eGFR) estimation, traditionally using the creatinine-based Modification of Diet in Renal Disease (MDRD) equation. The Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) equation performs better in estimating eGFR and predicting mortality and CKD progression risk. Cystatin C is an alternative glomerular filtration marker less influenced by muscle mass. CKD risk stratification is improved by combining creatinine eGFR with cystatin C and urinary albumin to creatinine ratio (uACR). We aimed to identify the impact of introducing CKDEPI and cystatin C on the estimated prevalence and risk stratification of CKD in England and to describe prevalence and associations of cystatin C.LimitationsCross sectional study, single eGFR measure, no measured (‘true’) GFR.ConclusionsIntroducing the CKDEPI equation and targeted cystatin C measurement reduces estimated CKD prevalence and improves risk stratification. 相似文献
938.
Matías Alejandro Molina Ailén Magalí Díaz Christina Hesse Wiebke Ginter María Virginia Gentilini Guillermo Gabriel Nu?ez Andrea Mercedes Canellada Tim Sparwasser Luciana Berod Marisa Silvia Castro Marcela Alejandra Manghi 《PloS one》2015,10(5)
Probiotics can modulate the immune system, conferring beneficial effects on the host. Understanding how these microorganisms contribute to improve the health status is still a challenge. Previously, we have demonstrated that Enterococcus faecalis CECT7121 implants itself and persists in the murine gastrointestinal tract, and enhances and skews the profile of cytokines towards the Th1 phenotype in several biological models. Given the importance of dendritic cells (DCs) in the orchestration of immunity, the aim of this work was to elucidate the influence of E. faecalis CECT7121 on DCs and the outcome of the immune responses. In this work we show that E. faecalis CECT7121 induces a strong dose-dependent activation of DCs and secretion of high levels of IL-12, IL-6, TNFα, and IL-10. This stimulation is dependent on TLR signaling, and skews the activation of T cells towards the production of IFNγ. The influence of this activation in the establishment of Th responses in vivo shows the accumulation of specific IFNγ-producing cells. Our findings indicate that the activation exerted by E. faecalis CECT7121 on DCs and its consequence on the cellular adaptive immune response may have broad therapeutic implications in immunomodulation. 相似文献
939.
940.
Alexander Klistorner Nikitha Vootakuru Chenyu Wang Con Yiannikas Stuart L. Graham John Parratt Raymond Garrick Netta Levin Lynette Masters Jim Lagopoulos Michael H. Barnett 《PloS one》2015,10(3)