Neuroinflammation and J2 Prostaglandins: Linking Impairment of the Ubiquitin-Proteasome Pathway and Mitochondria to Neurodegeneration

The immune response of the CNS is a defense mechanism activated upon injury to initiate repair mechanisms while chronic over-activation of the CNS immune system (termed neuroinflammation) may exacerbate injury. The latter is implicated in a variety of neurological and neurodegenerative disorders such as Alzheimer and Parkinson diseases, amyotrophic lateral sclerosis, multiple sclerosis, traumatic brain injury, HIV dementia, and prion diseases. Cyclooxygenases (COX-1 and COX-2), which are key enzymes in the conversion of arachidonic acid into bioactive prostanoids, play a central role in the inflammatory cascade. J2 prostaglandins are endogenous toxic products of cyclooxygenases, and because their levels are significantly increased upon brain injury, they are actively involved in neuronal dysfunction induced by pro-inflammatory stimuli. In this review, we highlight the mechanisms by which J2 prostaglandins (1) exert their actions, (2) potentially contribute to the transition from acute to chronic inflammation and to the spreading of neuropathology, (3) disturb the ubiquitin-proteasome pathway and mitochondrial function, and (4) contribute to neurodegenerative disorders such as Alzheimer and Parkinson diseases, and amyotrophic lateral sclerosis, as well as stroke, traumatic brain injury (TBI), and demyelination in Krabbe disease. We conclude by discussing the therapeutic potential of targeting the J2 prostaglandin pathway to prevent/delay neurodegeneration associated with neuroinflammation. In this context, we suggest a shift from the traditional view that cyclooxygenases are the most appropriate targets to treat neuroinflammation, to the notion that J2 prostaglandin pathways and other neurotoxic prostaglandins downstream from cyclooxygenases, would offer significant benefits as more effective therapeutic targets to treat chronic neurodegenerative diseases, while minimizing adverse side effects

Mechanisms of tidal oscillatory salt transport in a partially stratified estuary

Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 45 (2015): 2773–2789, doi:10.1175/JPO-D-15-0031.1.Tidal oscillatory salt transport, induced by the correlation between tidal variations in salinity and velocity, is an important term for the subtidal salt balance under the commonly used Eulerian method of salt transport decomposition. In this paper, its mechanisms in a partially stratified estuary are investigated with a numerical model of the Hudson estuary. During neap tides, when the estuary is strongly stratified, the tidal oscillatory salt transport is mainly due to the hydraulic response of the halocline to the longitudinal variation of topography. This mechanism does not involve vertical mixing, so it should not be regarded as oscillatory shear dispersion, but instead it should be regarded as advective transport of salt, which results from the vertical distortion of exchange flow obtained in the Eulerian decomposition by vertical fluctuations of the halocline. During spring tides, the estuary is weakly stratified, and vertical mixing plays a significant role in the tidal variation of salinity. In the spring tide regime, the tidal oscillatory salt transport is mainly due to oscillatory shear dispersion. In addition, the transient lateral circulation near large channel curvature causes the transverse tilt of the halocline. This mechanism has little effect on the cross-sectionally integrated tidal oscillatory salt transport, but it results in an apparent left–right cross-channel asymmetry of tidal oscillatory salt transport. With the isohaline framework, tidal oscillatory salt transport can be regarded as a part of the net estuarine salt transport, and the Lagrangian advective mechanism and dispersive mechanism can be distinguished.Tao Wang was supported by the Open Research Fund of State Key Laboratory of Estuarine and Coastal Research (Grant SKLEC-KF201509) and Chinese Scholarship Council. Geyer was supported by by NSF Grant OCE 0926427. Wensheng Jiang was supported by NSFC-Shandong Joint Fund for Marine Science Research Centers (Grant U1406401).2016-05-0

Females exhibit higher GluA2 levels and outperform males in active place avoidance despite increased amyloid plaques in TgF344‑Alzheimer’s rats

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that is most prevalent in females. While estrogen provides neuroprotection in females, sex mediated differences in the development of AD pathology are not fully elucidated. Therefore, comparing events between sexes in early-stage AD pathology may reveal more effective therapeutic targets of intervention. To address sex differences, we analyzed early-stage 9-month male and female TgF344-AD (Tg-AD) rats, an AD model carrying the APPswe and Presenilin 1 (PS1ΔE9) mutations that develops progressive age-dependent AD pathology similar to humans. Tg-AD females significantly outperformed Tg-AD males in the active place avoidance (aPAT) test that assesses hippocampal-dependent spatial learning and memory. However, comparisons between Tg-AD male or female rats and their WT counterparts showed significant deficits for female but not male rats. Nevertheless, Tg-AD females experienced significantly less hippocampal neuronal loss with higher GluA2 subunit levels than Tg-AD males. Unexpectedly, Tg-AD females displayed higher levels of hippocampal amyloid plaques than Tg-AD males. Thus, we propose that GluA2 may provide a neuroprotective function for Tg-AD females in our rat model by mitigating cognitive impairment independently of amyloid plaques. Elucidating this protective mechanism in AD could lead to new targets for early intervention

The voice of deceit: Comparing acoustic and perceptual data.

This study examined the nature of deceptive vocal behavior in interactive situations. It compared those vocal features of deception that can be measured by acoustic equipment with those vocal features of deception that can be measured perceptually by human coders. As deception researchers traditionally measure vocal behavior with either acoustic or perceptual methods, it is uncertain what correspondence, if any, exists between these two methods. This study attempted to determine this correspondence. Deceptive interactions from an earlier study (Buller, Burgoon, Buslig & Roiger, 1993; Burgoon, Buller, Ebesu, White, and Rockwell, 1994) were used to conduct a detailed analysis of vocal features of deceptive speech. The vocal samples were analyzed perceptually and acoustically. Results indicated moderate correlations between some acoustic and perceptual variables, with neither measurement type proving conclusively superior to the other in discriminating between truth and deception. Of three categories examined (time, pitch, and intensity), the time variables of shorter message length, longer response latencies, slower tempo, and less fluency best discriminated between truthful and deceptive statements. Other variables that discriminated truth from deceit were increased intensity range, increased pitch level and variance, and less pleasant vocal quality. Analyses of deception type showed that fabricated deceptions were louder and lower pitched than equivocal deceptions. An analysis of deception planning, showed that planned deceptions exhibited more fluency, a lower pitch level, and less pitch variance than unplanned deceptions. An examination of correlations between deceiver/receiver evaluations of deceiver honesty and deceiver vocal behaviors showed moderate correlations occurred between these evaluations and length of response latencies, pitch level, pitch range, and pitch variance. In general, these findings provide further confirmation of Interpersonal Deception Theory

PROTEIN-BOUND FORM of THIOACETAMIDE in LIVER NUCLEOLI

CUNY CITY COLL,SOPHIE DAVIS SCH BIOMED EDUC,NEW YORK,NY 10031Web of Scienc

Potential Alzheimer’s early biomarkers in a transgenic rat model and benefits of diazoxide/dibenzoylmethane co-treatment on spatial memory and AD-pathology

Abstract Alzheimer’s disease (AD) is the major form of dementia prevalent in older adults and with a high incidence in females. Identification of early biomarkers is essential for preventive intervention to delay its progression. Furthermore, due to its multifactorial nature, a multi-target approach could be therapeutically beneficial. Our studies included 4- (pre-pathology) and 11-month (mild-pathology) TgF344-AD rats, a transgenic Alzheimer’s model that exhibits age-dependent AD progression. We identified two potential early biomarker genes for AD, early growth response 2 (EGR2) and histone 1H2AA (HIST1H2AA), in the hippocampus of 4-month females. Out of 17,168 genes analyzed by RNA sequencing, expression of these two genes was significantly altered in 4-month TgF344-AD rats compared to wild-type littermates. We also evaluated co-treatment with diazoxide (DZ), a potassium channel activator, and dibenzoylmethane (DIB), which inhibits eIF2α-P activity, on TgF344-AD and wild-type rats. DZ/DIB-treatment mitigated spatial memory deficits and buildup of hippocampal Aβ plaques and tau PHF in 11-month TgF344-AD rats but had no effect on wild-type littermates. To our knowledge, this preclinical study is the first to report EGR2 and HIST1H2AA as potential AD biomarkers in females, and the benefits of DZ/DIB-treatment in AD. Evaluations across multiple AD-related models is warranted to corroborate our findings