3,048 research outputs found

    Altered sleep and EEG power in the P301S Tau transgenic mouse model

    Get PDF
    OBJECTIVE: Sleep disturbances are prevalent in human tauopathies yet despite the importance of sleep, little is known about its relationship with tau pathology. Here, we investigate this interaction by analyzing sleep and tau pathology throughout tauopathy disease progression in P301S human tau transgenic mice. METHODS: P301S and wild‐type mice were analyzed by electroencephalography (EEG)/electromyography at 3, 6, 9, and 11 months of age for sleep/wake time, EEG power, and homeostatic response. Cortical volume and tau pathology was also assessed by anti‐phospho‐tau AT8 staining. RESULTS: P301S tau mice had significantly decreased rapid eye movement (REM) sleep at 9 months of age and decreased REM and non‐REM (NREM) sleep as well as increased wakefulness at 11 months. Sleep loss was characterized by fewer wake, REM, and NREM bouts, increased wake bout duration, and decreased sleep bout duration. Decreased REM and NREM sleep was associated with increased brainstem tau pathology in the sublaterodorsal area and parafacial zone, respectively. P301S mice also showed increased EEG power at 6 and 9 months of age and decreased power at 11 months. Decreased EEG power was associated with decreased cortical volume. Despite sleep disturbances, P301S mice maintained homeostatic response to sleep deprivation. INTERPRETATION: Our results indicate that tau pathology is associated with sleep disturbances that worsen with age and these changes may be related to tau pathology in brainstem sleep regulating regions as well as neurodegeneration. Tau‐induced sleep changes could affect disease progression and be a marker for therapeutic efficacy in this and other tauopathy models

    Correlation of Patient Symptoms With Labral and Articular Cartilage Damage in Femoroacetabular Impingement.

    Get PDF
    BackgroundFemoroacetabular impingement (FAI) can lead to labral and articular cartilage injuries as well as early osteoarthritis of the hip. Currently, the association of patient symptoms with the progression of labral and articular cartilage injuries due to FAI is poorly understood.PurposeTo evaluate the correlation between patient-reported outcome (PRO) scores and cartilage compositional changes seen on quantitative magnetic resonance imaging (MRI) as well as cartilage and labral damage seen during arthroscopic surgery in patients with FAI.Study designCohort study; Level of evidence, 3.MethodsPatients were prospectively enrolled before hip arthroscopic surgery for symptomatic FAI. Patients were included if they had cam-type FAI without radiographic arthritis. All patients completed PRO scores, including the Hip disability and Osteoarthritis Outcome Score (HOOS) and a visual analog scale for pain. MRI with mapping sequences (T1ρ and T2) on both the acetabular and femoral regions was performed before surgery to quantitatively assess the cartilage composition. During arthroscopic surgery, cartilage and labral injury grades were recorded using the Beck classification. Pearson and Spearman correlation coefficients were then obtained to evaluate the association between chondrolabral changes and PRO scores.ResultsA total of 46 patients (46 hips) were included for analysis (mean age, 35.5 years; mean body mass index [BMI], 23.9 kg/m2; 59% male). Increasing BMI was correlated with a more severe acetabular cartilage grade (ρ = 0.37; 95% CI, 0.08-0.65). A greater alpha angle was correlated with an increased labral tear grade (ρ = 0.59; 95% CI, 0.37-0.82) and acetabular cartilage injuries (ρ = 0.61; 95% CI, 0.42-0.80). With respect to PRO scores, increasing femoral cartilage damage in the anterosuperior femoral head region, as measured on quantitative MRI using T1ρ and T2 mapping, correlated with lower (worse) scores on the HOOS Activities of Daily Living (r = 0.35; 95% CI, 0.06-0.64), Symptoms (r = 0.32; 95% CI, 0.06-0.57), and Pain (r = 0.31; 95% CI, 0.06-0.55) subscales. There was no correlation between PRO scores and acetabular cartilage damage or labral tearing found on quantitative MRI or during arthroscopic surgery.ConclusionFemoral cartilage damage, as measured on T1ρ and T2 mapping, appears to have a greater correlation with clinical symptoms than acetabular cartilage damage or labral tears in patients with symptomatic FAI

    Tissue specific induction of p62/sqstm1 by farnesoid X receptor

    Get PDF
    Background: Farnesoid X Receptor (FXR) is a member of the nuclear receptor superfamily and is a ligand-activated transcription factor essential for maintaining liver and intestinal homeostasis. FXR is protective against carcinogenesis and inflammation in liver and intestine as demonstrated by the development of inflammation and tumors in the liver and intestine of FXR knock-out mice. However, mechanisms for the protective effects of FXR are not completely understood. This study reports a novel role of FXR in regulating expression of Sqstm1, which encodes for p62 protein. p62 plays an important role in maintaining cellular homeostasis through selective autophagy and activating signal transduction pathways, such as NF-ÎșB to support cell survival and caspase-8 to initiate apoptosis. FXR regulation of Sqstm1 may serve as a protective mechanism. Methods and Results: This study showed that FXR bound to the Sqstm1 gene in both mouse livers and ileums as determined by chromatin immunoprecipitation. In addition, FXR activation enhanced transcriptional activation of Sqstm1 in vitro. However, wild-type mice treated with GW4064, a synthetic FXR ligand, showed that FXR activation induced mRNA and protein expression of Sqstm1/p62 in ileum, but not in liver. Interestingly, FXR-transgenic mice showed induced mRNA expression of Sqstm1 in both liver and ileum compared to wild-type mice. Conclusions: Our current study has identified a novel role of FXR in regulating the expression of p62, a key factor in protein degradation and cell signaling. Regulation of p62 by FXR indicates tissue-specific and gene-dosage effects. Furthermore, FXR-mediated induction of p62 may implicate a protective mechanism of FXR. © 2012 Williams et al

    Chemical recovery

    Get PDF
    "October 4, 1971.""The Institute of Paper Chemistry ... T. M. Grace ... N. L. Chang.

    Instrumentation study - black liquor solids content. Project 3025, report one : a summary report to members of Group Project 3025

    Get PDF
    "Members of Group Project 3025: American Can Company, Bowaters Southern Paper Corporation, Container Corporation of America, Continental Can Company, Inc., Crown Zellerbach Corporation, W. R. Grace and Co., Green Bay Packaging Inc., Hammermill Paper Company, Hoerner Waldorf Corporation, Inland Container Corporation, International Paper Company, Kimberly-Clark Corporation, Longview Fibre Company, MacMillan Bloedel Limited, The Mead Corporation, St. Regis Paper Company, Scott Paper Company, Weyerh"The Institute of Paper Chemistry, T.M. Grace ... Robert N. Larsen.""February 23, 1972.
    • 

    corecore