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

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

Shearing Interferometer for Quantifying the Coherence of Hard X-Ray Beams

We report a quantitative measurement of the full transverse coherence function of the 14.4 keV x-ray radiation produced by an undulator at the Swiss Light Source. An x-ray grating interferometer consisting of a beam splitter phase grating and an analyzer amplitude grating has been used to measure the degree of coherence as a function of the beam separation out to 30 m. Importantly, the technique provides a model-free and spatially resolved measurement of the complex coherence function and is not restricted to high resolution detectors and small fields of view. The spatial characterization of the wave front has important applications in discovering localized defects in beam line optics

A Website to help the International Students Experience (WISE)

Our VCU campus has been steadily expanding its international student population and has become an increasingly global university community. We have identified together with GEO, the need to build tangible resources that can support faculty and staff to more effectively educate our international student population. The creation of online content to be added to GEO’s current webpage seems to best fit the existing need. Our project outlines a blueprint for this online content by means of identifying data and resources that should be included as well as determining cost, sustainability and feasibility plans. Ultimately, the goal is to pave the way for centralized online content that can connect faculty and staff with important resources to optimize the academic experience and success of international students at VCU

Accelerated recovery of postischemic stunned myocardium after induced expression of myocardial heat-shock protein (HSP70)

AbstractIn vitro studies suggest that interventions targeted at myocardial gene regulation of endogenous cytoprotective elements, such as heat-shock protein, may attenuate myocardial ischemic injury. We tested the hypothesis that heat shock-induced expression of myocardial heat-shock protein before ischemia accelerates functional recovery of postischemic stunned myocardium in the intact circulation. Sixteen dogs underwent partial femoral arteriovenous bypass and core temperature was raised to 42° C for 15 minutes in eight dogs (heat-shocked) and maintained at 37° C in eight dogs (nonheat-shocked). After 24 hours dogs were studied to measure myocardial segment length in the circumflex artery region with ultrasonic dimension transducers, left ventricular pressure with a micromanometer, and circumflex coronary flow with an ultrasonic probe. Regional contractile function was quantified by the area beneath the linear preload recruitable stroke work relationship at baseline and at intervals during reperfusion after a 15-minute circumflex artery occlusion followed by 3 hours of reperfusion. Baseline and peak reperfusion hyperemic circumflex flows were 37 ± 9 ml/min and 154 ± 33 ml/min, respectively, in heat-shocked dogs (p < 0.001) and 46 ± 24 ml/min and 171 ± 57 ml/min, respectively, in nonheat-shocked dogs (p < 0.001), with no differences between groups (p = not significant) at any time during reperfusion. Heart rate and left ventricular peak pressure, end-diastolic pressure, and first derivative of left ventricular pressure were similar (all p = not significant) in heat-shocked and nonheat-shocked dogs during ischemia and reperfusion. Before ischemia, preload recruitable stroke work relationship did not differ (p = not significant) in heat-shocked and nonheat-shocked dogs. Ischemia reduced preload recruitable stroke work relationship to 32% ± 8% control (p < 0.001) in heat-shocked dogs and to 19% ± 15% control in nonheat-shocked dogs (p < 0.001) at 15 minutes of reperfusion, indicating a similar (p = not significant) initial degree of injury. During 3 hours of reperfusion, preload recruitable stroke work relationship returned to 80% ± 38% control in heat-shocked dogs but to only 33% ± 13% control in nonheat-shocked dogs (p < 0.0001). Myocardial expression of heat-shock protein, quantified by optical densitometry of Western blots using an antibody specific for HSP70, was greater in heat-shocked than in nonheat-shocked dogs (108 ± 27 versus 71 ± 14 densitometry units, p < 0.005). Exact causal mechanisms remain to be defined, but these data indicate (1) hyperthermic bypass triggers induction of myocardial heat-shock protein and (2) elevated myocardial heat-shock protein is associated with accelerated recovery of stunned myocardium. Promotion of endogenous molecular cytoprotective systems represents a novel and potentially useful strategy for myocardial protection. (J THORAC CARDIOVASC SURG 1995;109:753-64

The effects of peripheral and central high insulin on brain insulin signaling and amyloid-β in young and old APP/PS1 mice

Hyperinsulinemia is a risk factor for late-onset Alzheimer's disease (AD). In vitro experiments describe potential connections between insulin, insulin signaling, and amyloid-β (Aβ), but in vivo experiments are needed to validate these relationships under physiological conditions. First, we performed hyperinsulinemic-euglycemic clamps with concurrent hippocampal microdialysis in young, awake, behaving APP(swe)/PS1(dE9) transgenic mice. Both a postprandial and supraphysiological insulin clamp significantly increased interstitial fluid (ISF) and plasma Aβ compared with controls. We could detect no increase in brain, ISF, or CSF insulin or brain insulin signaling in response to peripheral hyperinsulinemia, despite detecting increased signaling in the muscle. Next, we delivered insulin directly into the hippocampus of young APP/PS1 mice via reverse microdialysis. Brain tissue insulin and insulin signaling was dose-dependently increased, but ISF Aβ was unchanged by central insulin administration. Finally, to determine whether peripheral and central high insulin has differential effects in the presence of significant amyloid pathology, we repeated these experiments in older APP/PS1 mice with significant amyloid plaque burden. Postprandial insulin clamps increased ISF and plasma Aβ, whereas direct delivery of insulin to the hippocampus significantly increased tissue insulin and insulin signaling, with no effect on Aβ in old mice. These results suggest that the brain is still responsive to insulin in the presence of amyloid pathology but increased insulin signaling does not acutely modulate Aβ in vivo before or after the onset of amyloid pathology. Peripheral hyperinsulinemia modestly increases ISF and plasma Aβ in young and old mice, independent of neuronal insulin signaling. SIGNIFICANCE STATEMENT The transportation of insulin from blood to brain is a saturable process relevant to understanding the link between hyperinsulinemia and AD. In vitro experiments have found direct connections between high insulin and extracellular Aβ, but these mechanisms presume that peripheral high insulin elevates brain insulin significantly. We found that physiological hyperinsulinemia in awake, behaving mice does not increase CNS insulin to an appreciable level yet modestly increases extracellular Aβ. We also found that the brain of aged APP/PS1 mice was not insulin resistant, contrary to the current state of the literature. These results further elucidate the relationship between insulin, the brain, and AD and its conflicting roles as both a risk factor and potential treatment

TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy

Significance Alzheimer’s disease (AD) is the most common cause of dementia and is a major public health problem for which there is currently no disease-modifying treatment. There is an urgent need for greater understanding of the molecular mechanisms underlying neurodegeneration in patients to create better therapeutic options. Recently, genetic studies uncovered novel AD risk variants in the microglial receptor, triggering receptor expressed on myeloid cells 2 (TREM2). Previous studies suggested that loss of TREM2 function worsens amyloid-β (Aβ) plaque-related toxicity. In contrast, we observe TREM2 deficiency mitigates neuroinflammation and protects against brain atrophy in the context of tau pathology. These findings indicate dual roles for TREM2 and microglia in the context of amyloid versus tau pathology, which are important to consider for potential treatments targeting TREM2.</jats:p

Downtown Providence Farmers Market Design

This market essentially combines a marketplace with an existing or new industrial building. The hybrid created results in space that has daily retail sales and hours, as well as other goods available at other times. The industrial aspect typically acts as the anchor, as the market’s activities help attract a different group of consumers at other business times. An example of this would be a seafood supply warehouse that also provides dining and entertainment as a nightlife destination

The Power of Principled Bayesian Methods in the Study of Stellar Evolution

It takes years of effort employing the best telescopes and in- struments to obtain high-quality stellar photometry, astrometry, and spectroscopy. Stellar evolution models contain the experience of life- times of theoretical calculations and testing. Yet most astronomers fit these valuable models to these precious datasets by eye. We show that a principled Bayesian approach to fitting models to stellar data yields substantially more information over a range of stellar astrophysics. We highlight advances in determining the ages of star clusters, mass ratios of binary stars, limitations in the accuracy of stellar models, post-main-sequence mass loss, and the ages of individual white dwarfs. We also outline a number of unsolved problems that would benefit from principled Bayesian analyses

The zebrafish xenograft platform-A novel tool for modeling KSHV-associated diseases

Kaposi\u27s sarcoma associated-herpesvirus (KSHV, also known as human herpesvirus-8) is a gammaherpesvirus that establishes life-long infection in human B lymphocytes. KSHV infection is typically asymptomatic, but immunosuppression can predispose KSHV-infected individuals to primary effusion lymphoma (PEL); a malignancy driven by aberrant proliferation of latently infected B lymphocytes, and supported by pro-inflammatory cytokines and angiogenic factors produced by cells that succumb to lytic viral replication. Here, we report the development of the firs