2,684 research outputs found

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    https://openspace.dmacc.edu/banner_news/1206/thumbnail.jp

    How to study basement membrane stiffness as a biophysical trigger in prostate cancer and other age-related pathologies or metabolic diseases

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    Here we describe a protocol that can be used to study the biophysical microenvironment related to increased thickness and stiffness of the basement membrane (BM) during age-related pathologies and metabolic disorders (e.g. cancer, diabetes, microvascular disease, retinopathy, nephropathy and neuropathy). The premise of the model is non-enzymatic crosslinking of reconstituted BM (rBM) matrix by treatment with glycolaldehyde (GLA) to promote advanced glycation endproduct (AGE) generation via the Maillard reaction. Examples of laboratory techniques that can be used to confirm AGE generation, non-enzymatic crosslinking and increased stiffness in GLA treated rBM are outlined. These include preparation of native rBM (treated with phosphate-buffered saline, PBS) and stiff rBM (treated with GLA) for determination of: its AGE content by photometric analysis and immunofluorescent microscopy, its non-enzymatic crosslinking by ((sodium dodecyl sulfate polyacrylamide gel electrophoresis)) (SDS PAGE) as well as confocal microscopy, and its increased stiffness using rheometry. The procedure described here can be used to increase the rigidity (elastic moduli, E) of rBM up to 3.2-fold, consistent with measurements made in healthy versus diseased human prostate tissue. To recreate the biophysical microenvironment associated with the aging and diseased prostate gland three prostate cell types were introduced on to native rBM and stiff rBM: RWPE-1, prostate epithelial cells (PECs) derived from a normal prostate gland; BPH-1, PECs derived from a prostate gland affected by benign prostatic hyperplasia (BPH); and PC3, metastatic cells derived from a secondary bone tumor originating from prostate cancer. Multiple parameters can be measured, including the size, shape and invasive characteristics of the 3D glandular acini formed by RWPE-1 and BPH-1 on native versus stiff rBM, and average cell length, migratory velocity and persistence of cell movement of 3D spheroids formed by PC3 cells under the same conditions. Cell signaling pathways and the subcellular localization of proteins can also be assessed

    Female adipose tissue-specific Bscl2 knockout mice develop only moderate metabolic dysfunction when housed at thermoneutrality and fed a high-fat diet

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    The authors would like to thank the staff at the University of Aberdeenā€™s Medical Research Facility. We are very grateful for the gift of the Adiponectin-Cre mice from Dr. Evan Rosen (Beth Israel Deaconess Medical Centre and Harvard Medical School, Boston, USA). Work was supported by the Medical Research Council (GDM/JJR; MR/L002620/1, MC/PC/15077), the Biotechnology and Biological Sciences Research Council (JJR; BB/K017772/1), the British Heart Foundation (MD; PG/14/43/30889) and The Agency for Science, Technology and Research, Singapore (A*STAR) (WH). The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.Peer reviewedPublisher PD

    Application of Structured Decision Making to Wildlife Management in Montana

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    Good decision-making is essential to conserving wildlife populations. Whereas there may be multiple ways to address a problem, perfect solutions rarely exist. Managers are therefore tasked with identifying optimal decisions that will best achieve desired outcomes. Structured decision making (SDM) is a method of decision analysis used to identify the most effective, efficient, and realistic optimal decisions while accounting for values and priorities of the decision maker. The stepwise process includes identifying the management problem, defining objectives for solving the problem, developing alternative approaches to achieve the objectives, and formally evaluating which alternative is most likely to accomplish the objectives. The SDM process can be more effective than informal decision-making because it provides a transparent way to quantitatively evaluate decisions for addressing multiple management objectives while incorporating science, uncertainty, and risk tolerance. We illustrate the application of this process to management needs, including an SDM-based decision tool developed to identify optimal decisions for proactively managing risk of pneumonia epizootics in bighorn sheep (Ovis canadensis). Pneumonia epizootics are a major challenge for managers, including in terms of knowing how or when to manage risk. The decision tool facilitates analysis of alternative decisions for how to manage herds based on predictions from a risk model, herd-specific objectives, and predicted costs and benefits of each alternative. Managers can be confident resulting decisions are most effective, efficient, and realistic because they explicitly account for important considerations managers implicitly weigh when making decisions, including competing management objectives, uncertainty in potential outcomes and risk tolerance

    Ablation of Bscl2/Seipin in hepatocytes does not cause metabolic dysfunction in congenital generalised lipodystrophy

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    Funding Work was supported by the Medical Research Council (GDM/JJR; MR/L002620/1, MC/PC/15077), the Biotechnology and Biological Sciences Research Council (JJR; BB/K017772/1), Diabetes UK (GDM/JJR; 18/0005884), the British Heart Foundation (MD;PG/14/43/30889) and the Wellcome Trust and the University of Aberdeen ISSF Fund (GDM; ISSF Fellowship Support Fund).Peer reviewedPublisher PD

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    Meniscal Repair in Pediatric Populations: A Systematic Review of Outcomes

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    Background: Loss of meniscal tissue in the pediatric population can have long-term consequences on joint health, highlighting the importance of meniscal preservation in this group. Purpose: To systematically review reported knee outcome measures and complication rates after repair of meniscal tears in children and adolescents. Study Design: Systematic review; Level of evidence, 4. Methods: A review of the literature regarding the existing evidence for pediatric meniscal tear outcomes was performed through use of the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed (1980-present), and MEDLINE (1980-present). Included were articles in English that reported the outcomes of meniscal tears in the pediatric population (\u3c18 years old) with a follow-up of more than 12 months. Clinical outcome scores were reviewed. Results: A total of 1003 total studies were initially retrieved, with 8 meeting the inclusion criteria. The review included 287 patients (165 male, 122 female), mean age 15.1 years (range, 4-18 years), with 301 meniscal tears (reported: 134 medial, 127 lateral, and 32 both medial and lateral, 8 location unspecified). Concomitant anterior cruciate ligament reconstruction was performed in 52% (158/ 301) of meniscal repairs. The average reported postoperative Lysholm scores ranged from 85.4 to 96.3, and the average reported postoperative Tegner activity scores ranged from 6.2 to 8. Conclusion: Arthroscopic repair of a meniscal tear in the pediatric and adolescent population is an effective treatment option that has a low failure rate, enhances postoperative clinical outcomes, and preserves meniscal tissues
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