Apolipoprotein E-Mimetics Inhibit Neurodegeneration and Restore Cognitive Functions in a Transgenic Drosophila Model of Alzheimer's Disease

BACKGROUND: Mutations of the amyloid precursor protein gene (APP) are found in familial forms of Alzheimer's disease (AD) and some lead to the elevated production of amyloid-beta-protein (Abeta). While Abeta has been implicated in the causation of AD, the exact role played by Abeta and its APP precursor are still unclear. PRINCIPAL FINDINGS: In our study, Drosophila melanogaster transgenics were established as a model to analyze AD-like pathology caused by APP overexpression. We demonstrated that age related changes in the levels and pattern of synaptic proteins accompanied progressive neurodegeneration and impairment of cognitive functions in APP transgenic flies, but that these changes may be independent from the generation of Abeta. Using novel peptide mimetics of Apolipoprotein-E, COG112 or COG133 proved to be neuroprotective and significantly improved the learning and memory of APP transgenic flies. CONCLUSIONS: The development of neurodegeneration and cognitive deficits was corrected by injections of COG112 or COG133, novel mimetics of apolipoprotein-E (apoE) with neuroprotective activities

Statistics of Neutron Stars at the Stage of Supersonic Propeller

We analyze the statistical distribution of neutron stars at the stage of a supersonic propeller. An important point of our analysis is allowance for the evolution of the angle of inclination of the magnetic axis to the spin axis of the neutron star for the boundary of the transition to the supersonic propeller stage for two models: the model with hindered particle escape from the stellar surface and the model with free particle escape. As a result, we have shown that a consistent allowance for the evolution of the inclination angle in the region of extinct radio pulsars for the two models leads to an increase in the total number of neutron stars at the supersonic propeller stage. This increase stems from he fact that when allowing for the evolution of the inclination angle $\chi$ for neutron stars in the region of extinct radio pulsars and, hence, for the boundary of the transition to the propeller stage, this transition is possible at shorter spin periods (P~5-10 s) than assumed in the standard model.Comment: 15 pages, 6 figures; scale corrected for figures 3-

The effect of zebra mussel colonization on native snail species of Douglas Lake in northern Michigan.

General EcologyThe introduction of invasive species has caused extensive ecological and economic damage in freshwater ecosystems. In the Great Lakes region, zebra mussels (Dreissena polymorpha) have outcompeted native mollusks and driven many species towards extinction. They cause over $200 million of damage to the Great Lakes region annually. This study was performed to analyze the effect of zebra mussel colonization on native snail species of Douglas Lake in Northern Michigan. Four snail species: Campeloma decisum, Elimia livescens, Planorbella campanulata, and Stagnicola emarginata were collected with and without zebra mussels from South Fishtail Bay of Douglas Lake. The zebra mussel likelihood of colonization and horizontal movement as a measure of fitness were analyzed per species for differences between snails with zebra mussels and without. Our research showed that C. decisum and E. livescens were colonized most frequently. In addition, zebra mussel load was found to have a negative effect on horizontal movement of all snail species. Based on these results, our study concluded that zebra mussels have a significant negative effect on native snail species of Douglas Lake in Northern Michigan.http://deepblue.lib.umich.edu/bitstream/2027.42/95922/1/Fletcher_Hetherington_Schwarzman_Vaughan_2012.pd

An association between electronic nicotine delivery systems use and a history of stroke using the 2016 behavioral risk factor surveillance system

Electronic nicotine delivery systems (ENDS) are growing in use and many of the health implications with these devices remain unknown. This study aims to assess, using a survey representative of the USA general population, if an association exists between a history of ENDS use and a history of stroke. This cross-sectional study was a secondary data analysis using the 2016 behavioral risk factor surveillance system survey. The main exposure variable of the study was a self-reported history of ENDS use. The main outcome was a self-reported history of stroke. Covariates included sex, race, traditional cigarette use, smokeless tobacco use, chronic kidney disease, diabetes, myocardial infarction, and coronary artery disease. Unadjusted and adjusted logistic regression analyses were done. Adjusted odds ratios (AOR) and their corresponding 95% confidence intervals (CI) were calculated. Of the 486,303 total behavioral risk factor surveillance system survey participants, 465,594 met the inclusion criteria for this study of ENDS use and stroke. This study shows that current ENDS use was positively associated with a history of stroke. AOR of some daily ENDS use with stroke was 1.28 (95% CI: 1.02-1.61) and AOR of current daily ENDS use with stroke was 1.62 (95% CI: 1.18-2.31). The majority (55.9%) of current daily ENDS users reported former traditional cigarette smoking. Female sex, non-white ethnicity, elderly age, chronic kidney disease, coronary artery disease, diabetes, and traditional cigarette use characteristics were all also associated with increased odds of reporting a stroke. This study found a statistically significant and positive association between ENDS use and a history of stroke. Further research is warranted to investigate the reproducibility and temporality of this association. Nevertheless, this study contributes to the growing body of knowledge about the potential cardiovascular concerns related to ENDS use and the need for large cohort studies.Peer reviewe

Transthyretin Protects against A-Beta Peptide Toxicity by Proteolytic Cleavage of the Peptide: A Mechanism Sensitive to the Kunitz Protease Inhibitor

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of amyloid β-peptide (A-Beta) in the brain. Transthyretin (TTR) is a tetrameric protein of about 55 kDa mainly produced in the liver and choroid plexus of the brain. The known physiological functions of TTR are the transport of thyroid hormone T4 and retinol, through binding to the retinol binding protein. TTR has also been established as a cryptic protease able to cleave ApoA-I in vitro. It has been described that TTR is involved in preventing A-Beta fibrilization, both by inhibiting and disrupting A-Beta fibrils, with consequent abrogation of toxicity. We further characterized the nature of the TTR/A-Beta interaction and found that TTR, both recombinant or isolated from human sera, was able to proteolytically process A-Beta, cleaving the peptide after aminoacid residues 1, 2, 3, 10, 13, 14,16, 19 and 27, as determined by mass spectrometry, and reversed phase chromatography followed by N-terminal sequencing. A-Beta peptides (1–14) and (15–42) showed lower amyloidogenic potential than the full length counterpart, as assessed by thioflavin binding assay and ultrastructural analysis by transmission electron microscopy. A-Beta cleavage by TTR was inhibited in the presence of an αAPP peptide containing the Kunitz Protease Inhibitor (KPI) domain but not in the presence of the secreted αAPP derived from the APP isoform 695 without the KPI domain. TTR was also able to degrade aggregated forms of A-Beta peptide. Our results confirmed TTR as a protective molecule in AD, and prompted A-Beta proteolysis by TTR as a protective mechanism in this disease. TTR may prove to be a useful therapeutic agent for preventing or retarding the cerebral amyloid plaque formation implicated in AD pathology