Regional association of pCASL-MRI with FDG-PET and PiB-PET in people at risk for autosomal dominant Alzheimer's disease.

Autosomal dominant Alzheimer's disease (ADAD) is a small subset of Alzheimer's disease that is genetically determined with 100% penetrance. It provides a valuable window into studying the course of pathologic processes that leads to dementia. Arterial spin labeling (ASL) MRI is a potential AD imaging marker that non-invasively measures cerebral perfusion. In this study, we investigated the relationship of cerebral blood flow measured by pseudo-continuous ASL (pCASL) MRI with measures of cerebral metabolism (FDG PET) and amyloid deposition (Pittsburgh Compound B (PiB) PET). Thirty-one participants at risk for ADAD (age 39 ± 13 years, 19 females) were recruited into this study, and 21 of them received both MRI and FDG and PiB PET scans. Considerable variability was observed in regional correlations between ASL-CBF and FDG across subjects. Both regional hypo-perfusion and hypo-metabolism were associated with amyloid deposition. Cross-sectional analyses of each biomarker as a function of the estimated years to expected dementia diagnosis indicated an inverse relationship of both perfusion and glucose metabolism with amyloid deposition during AD development. These findings indicate that neurovascular dysfunction is associated with amyloid pathology, and also indicate that ASL CBF may serve as a sensitive early biomarker for AD. The direct comparison among the three biomarkers provides complementary information for understanding the pathophysiological process of AD

The Characterization of Aerosol Particle Contamination as the Result of Carry-Over and Cross-Over in Enthalpy Wheels

This paper provides results from a study that characterized the particle distributions found from variable contaminated airstreams in energy recovery ventilators (ERV) during two different test scenarios. The first scenario involved the measurement of the particulate concentrations during an operational situation when the pressure differential forces cross-flow leakage between the exhaust and intake streams. The second scenario involved the characterization of aerosol particulate concentrations from the carry-over contamination when the wheel was not in operation. The findings from the study concluded that if a source of aerosol particulate matter is present in an environment utilizing an ERV system, then cross-over and carry-over contamination will occur proportionally to the amount of aerosol particulate matter released into the system

atToc159 is a selective transit peptide receptor for the import of nucleus-encoded chloroplast proteins

The members of the Toc159 family of GTPases act as the primary receptors for the import of nucleus-encoded preproteins into plastids. Toc159, the most abundant member of this family in chloroplasts, is required for chloroplast biogenesis (Bauer, J., K. Chen, A. Hiltbunner, E. Wehrli, M. Eugster, D. Schnell, and F. Kessler. 2000. Nature. 403:203–207) and has been shown to covalently cross-link to bound preproteins at the chloroplast surface (Ma, Y., A. Kouranov, S. LaSala, and D.J. Schnell. 1996. J. Cell Biol. 134:1–13; Perry, S.E., and K. Keegstra. 1994. Plant Cell. 6:93–105). These reports led to the hypothesis that Toc159 functions as a selective import receptor for preproteins that are required for chloroplast development. In this report, we provide evidence that Toc159 is required for the import of several highly expressed photosynthetic preproteins in vivo. Furthermore, we demonstrate that the cytoplasmic and recombinant forms of soluble Toc159 bind directly and selectively to the transit peptides of these representative photosynthetic preproteins, but not representative constitutively expressed plastid preproteins. These data support the function of Toc159 as a selective import receptor for the targeting of a set of preproteins required for chloroplast biogenesis

Imbalance of Functional Connectivity and Temporal Entropy in Resting-State Networks in Autism Spectrum Disorder: A Machine Learning Approach

Background: Two approaches to understanding the etiology of neurodevelopmental disorders such as Autism Spectrum Disorder (ASD) involve network level functional connectivity (FC) and the dynamics of neuronal signaling. The former approach has revealed both increased and decreased FC in individuals with ASD. The latter approach has found high frequency EEG oscillations and higher levels of epilepsy in children with ASD. Together, these findings have led to the hypothesis that atypical excitatory-inhibitory neural signaling may lead to imbalanced association pathways. However, simultaneously reconciling local temporal dynamics with network scale spatial connectivity remains a difficult task and thus empirical support for this hypothesis is lacking.Methods: We seek to fill this gap by combining two powerful resting-state functional MRI (rs-fMRI) methods—functional connectivity (FC) and wavelet-based regularity analysis. Wavelet-based regularity analysis is an entropy measure of the local rs-fMRI time series signal. We examined the relationship between the RSN entropy and integrity in individuals with ASD and controls from the Autism Brain Imaging Data Exchange (ABIDE) cohort using a putative set of 264 functional brain regions-of-interest (ROI).Results: We observed that an imbalance in intra- and inter-network FC across 11 RSNs in ASD individuals (p = 0.002) corresponds to a weakened relationship with RSN temporal entropy (p = 0.02). Further, we observed that an estimated RSN entropy model significantly distinguished ASD from controls (p = 0.01) and was associated with level of ASD symptom severity (p = 0.003).Conclusions: Imbalanced brain connectivity and dynamics at the network level coincides with their decoupling in ASD. The association with ASD symptom severity presents entropy as a potential biomarker

Water Exchange Rate across the Blood-Brain Barrier Is Associated with CSF Amyloid-β 42 in Healthy Older Adults

INTRODUCTION: We tested if water exchange across the blood-brain barrier (BBB), estimated with a noninvasive magnetic resonance imaging (MRI) technique, is associated with cerebrospinal fluid (CSF) biomarkers of Alzheimer\u27s disease (AD) and neuropsychological function. METHODS: Forty cognitively normal older adults (67–86 years old) were scanned with diffusion‐prepared, arterial spin labeling (DP‐ASL), which estimates water exchange rate across the BBB (kw). Participants also underwent CSF draw and neuropsychological testing. Multiple linear regression models were run with kw as a predictor of CSF concentrations and neuropsychological scores. RESULTS: In multiple brain regions, BBB kw was positively associated with CSF amyloid beta (Aβ)42 concentration levels. BBB kw was only moderately associated with neuropsychological performance. DISCUSSION: Our results suggest that low water exchange rate across the BBB is associated with low CSF Aβ42 concentration. These findings suggest that kw may be a promising noninvasive indicator of BBB Aβ clearance functions, a possibility which should be further tested in future research

Impaired cerebrovascular function in coronary artery disease patients and recovery following cardiac rehabilitation

© 2016 Anazodo, Shoemaker, Suskin, Ssali, Wang and St. Lawrence. Coronary artery disease (CAD) poses a risk to the cerebrovascular function of older adults and has been linked to impaired cognitive abilities. Using magnetic resonance perfusion imaging, we investigated changes in resting cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to hypercapnia in 34 CAD patients and 21 age-matched controls. Gray matter volume (GMV)s were acquired and used as a confounding variable to separate changes in structure from function. Compared to healthy controls, CAD patients demonstrated reduced CBF in the superior frontal, anterior cingulate (AC), insular, pre- and post-central gyri, middle temporal, and superior temporal regions. Subsequent analysis of these regions demonstrated decreased CVR in the AC, insula, post-central and superior frontal regions. Except in the superior frontal and precentral regions, regional reductions in CBF and CVR were identified in brain areas where no detectable reductions in GMV were observed, demonstrating that these vascular changes were independent of brain atrophy. Because aerobic fitness training can improve brain function, potential changes in regional CBF were investigated in the CAD patients after completion of a 6-months exercise-based cardiac rehabilitation program. Increased CBF was observed in the bilateral AC, as well as recovery of CBF in the dorsal aspect of the right AC, where the magnitude of increased CBF was roughly equal to the reduction in CBF at baseline compared to controls. These exercise-related improvements in CBF in the AC is intriguing given the role of this area in cognitive processing and regulation of cardiovascular autonomic control

Default Mode Network Complexity and Cognitive Decline in Mild Alzheimer’s Disease

The human resting-state is characterized by spatially coherent brain activity at a low temporal frequency. The default mode network (DMN), one of so-called resting-state networks, has been associated with cognitive processes that are directed toward the self, such as introspection and autobiographic memory. The DMN’s integrity appears to be crucial for mental health. For example, patients with Alzheimer’s disease or other psychiatric conditions show disruptions of functional connectivity within the brain regions of the DMN. However, in prodromal or early stages of Alzheimer’s disease, physiological alterations are sometimes elusive, despite manifested cognitive impairment. While functional connectivity assesses the signal correlation between brain areas, multi-scale entropy (MSE) measures the complexity of the blood-oxygen level dependent signal within an area and thus might show local changes before connectivity is affected. Hence, we investigated alterations of functional connectivity and MSE within the DMN in fifteen mild Alzheimer’s disease patients as compared to fourteen controls. Potential associations of MSE with functional connectivity and cognitive abilities [i.e., mini-mental state examination (MMSE)] were assessed. A moderate decrease of DMN functional connectivity between posterior cingulate cortex and right hippocampus in Alzheimer’s disease was found, whereas no differences were evident for whole-network functional connectivity. In contrast, the Alzheimer’s disease group yielded lower global DMN-MSE than the control group. The most pronounced regional effects were localized in left and right hippocampi, and this was true for most scales. Moreover, MSE significantly correlated with functional connectivity, and DMN-MSE correlated positively with the MMSE in Alzheimer’s disease. Most interestingly, the right hippocampal MSE was positively associated with semantic memory performance. Thus, our results suggested that cognitive decline in Alzheimer’s disease is reflected by decreased signal complexity in DMN nodes, which might further lead to disrupted DMN functional connectivity. Additionally, altered entropy in Alzheimer’s disease found in the majority of the scales indicated a disturbance of both local information processing and information transfer between distal areas. Conclusively, a loss of nodal signal complexity potentially impairs synchronization across nodes and thus preempts functional connectivity changes. MSE presents a putative functional marker for cognitive decline that might be more sensitive than functional connectivity alone

A simultaneous search for prompt radio emission associated with the short GRB 170112A using the all-sky imaging capability of the OVRO-LWA

We have conducted the most sensitive low frequency (below 100 MHz) search to date for prompt, low-frequency radio emission associated with short-duration gamma-ray bursts (GRBs), using the Owens Valley Radio Observatory Long Wavelength Array (OVRO-LWA). The OVRO-LWA's nearly full-hemisphere field-of-view ($\sim20$,$000$ square degrees) allows us to search for low-frequency (sub-$100$ MHz) counterparts for a large sample of the subset of GRB events for which prompt radio emission has been predicted. Following the detection of short GRB 170112A by Swift, we used all-sky OVRO-LWA images spanning one hour prior to and two hours following the GRB event to search for a transient source coincident with the position of GRB 170112A. We detect no transient source, with our most constraining $1\sigma$ flux density limit of $650~\text{mJy}$ for frequencies spanning $27~\text{MHz}-84~\text{MHz}$. We place constraints on a number of models predicting prompt, low-frequency radio emission accompanying short GRBs and their potential binary neutron star merger progenitors, and place an upper limit of $L_\text{radio}/L_\gamma \lesssim 7\times10^{-16}$ on the fraction of energy released in the prompt radio emission. These observations serve as a pilot effort for a program targeting a wider sample of both short and long GRBs with the OVRO-LWA, including bursts with confirmed redshift measurements which are critical to placing the most constraining limits on prompt radio emission models, as well as a program for the follow-up of gravitational wave compact binary coalescence events detected by advanced LIGO and Virgo.Comment: 14 pages, 5 figures, ApJ submitte

Conformal Field Theory Interpretation of Black Hole Quasi-normal Modes

We obtain exact expressions for the quasi-normal modes of various spin for the BTZ black hole. These modes determine the relaxation time of black hole perturbations. Exact agreement is found between the quasi-normal frequencies and the location of the poles of the retarded correlation function of the corresponding perturbations in the dual conformal field theory. This then provides a new quantitative test of the AdS/CFT correspondence.Comment: 4 pages, RevTeX, references adde