Angiotensin II-inhibition:effect on Alzheimer's pathology in the aged triple transgenic mouse

Reducing excessive accumulation of amyloid-β (Aβ) in Alzheimer's disease (AD) is a key objective of most AD therapies, and inhibition of angiotensin-converting enzyme (ACE) may delay onset or progression of AD. The effects of an ACE-inhibitor (ACE-I) and an angiotensin II receptor blocker (ARB) on Aβ and tau pathology in a triple transgenic (3xTGAD) mouse model of AD were investigated. 9-10month 3xTGAD mice were treated with ARB, ACE-I or vehicle for 6 months. Mean arterial blood pressure (MABP) was measured periodically and mice were assessed behaviourally. Aβ, phospho-tau, amyloid precursor protein (APP) and ACE activity were analysed. MABP was significantly reduced at 2 weeks and 3 months in the ACE-I group and at 3 months in the ARB group, compared to vehicle. Neither drug altered performance of 3xTGAD mice in Morris Water Maze or T-maze, nor were Aβ, tau immunolabelling or APP levels altered. ACE-I significantly reduced ACE activity in kidney. Prolonged treatment with ACE-I or ARB does not affect Aβ or phospho-tau accumulation in brains of aged 3xTGAD mice

Nest Success and Duckling Survival of Greater Scaup, Aythya marila, at Grassy Island, New Brunswick

Nesting biology and duckling survival of Greater Scaup (Aythya marila) at Grassy Island on the Saint John River in southern New Brunswick were compared between 1995 and 1996. Grassy Island in New Brunswick is an area that is notably removed from other scaup breeding areas, being located farther south from main breeding areas in North America. The Mayfield estimates of nest success were 61% and 21% in 1995 and 1996, respectively. Mean daily survival rates were 0.99 in 1995 and 0.96 in 1996 and were significantly different (t = 4.86, P < 0.001). Duckling survival was estimated to range from 38 to 54% in 1995, and was 8% in 1996. The lower breeding success in 1996 may have been due to factors associated with decreased temperatures and increased precipitation, but the fact that the breeding location is atypical to other Greater Scaup breeding areas should not be overlooked

Small RNA modifications in Alzheimer's disease

BACKGROUND: While significant advances have been made in uncovering the aetiology of Alzheimer’s disease and related dementias at the genetic level, molecular events at the epigenetic level remain largely undefined. Emerging evidence indicates that small non-coding RNAs (sncRNAs) and their associated RNA modifications are important regulators of complex physiological and pathological processes, including aging, stress responses, and epigenetic inheritance. However, whether small RNAs and their modifications are altered in dementia is not known. METHODS: We performed LC-MS/MS–based, high-throughput assays of small RNA modifications in post-mortem samples of the prefrontal lobe cortices of Alzheimer’s disease (AD) and control individuals. We noted that some of the AD patients has co-occurring vascular cognitive impairment-related pathology (VaD). FINDINGS: We report altered small RNA modifications in AD samples compared with normal controls. The 15–25-nucleotide (nt) RNA fraction of these samples was enriched for microRNAs, whereas the 30–40-nt RNA fraction was enriched for tRNA-derived small RNAs (tsRNAs), rRNA-derived small RNAs (rsRNAs), and YRNA-derived small RNAs (ysRNAs). Interestingly, most of these altered RNA modifications were detected both in the AD and AD with co-occurring vascular dementia subjects. In addition, sequencing of small RNA in the 30–40-nt fraction from AD cortices revealed reductions in rsRNA-5S, tsRNA-Tyr, and tsRNA-Arg. INTERPRETATION: These data suggest that sncRNAs and their associated modifications are novel signals that may be linked to the pathogenesis and development of Alzheimer’s disease. FUNDING: NIH grants (R01HL122770, R01HL091905, 1P20GM130459, R01HD092431, P50HD098593, GM103440), AHA grant (17IRG33370128), Sigmund Gestetner Foundation Fellowship to P Kehoe

Blood type gene locus has no influence on ACE association with Alzheimer's disease

The ABO blood group locus was recently found to contribute independently as well as via interactions with ACE gene variation to plasma levels of angiotensin converting enzyme (ACE). Variation in ACE has also previously been implicated as conferring susceptibility for Alzheimer’s disease (AD), but has also been proposed to confer risk via interactions with other as yet unknown genes. More recently, larger studies have not supported ACE as a risk factor for AD, while the role of ACE pathway in AD has come under increased levels of scrutiny with respect to various aspects of AD pathology and possible therapies. We explored the potential combined involvement of ABO and ACE variation in the genetic susceptibility of 2067 AD cases compared to 1376 non-demented elderly. Including the effects of ABO haplotype did not provide any evidence for the genetic association of ACE with AD

Light color acclimation is a key process in the global ocean distribution of Synechococcus cyanobacteria

Understanding the functional diversity of specific microbial groups at the global scale is critical yet poorly developed. By combining the considerable knowledge accumulated through recent years on the molecular bases of photosynthetic pigment diversity in marine Synechococcus, a major phytoplanktonic organism, with the wealth of metagenomic data provided by the Tara Oceans expedition, we have been able to reliably quantify all known pigment types along its transect and provide a global distribution map. Unexpectedly, cells able to dynamically change their pigment content to match the ambient light color were ubiquitous and predominated in many environments. Altogether, our results unveiled the role of adaptation to light quality on niche partitioning in a key primary producer

Aβ degradation or cerebral perfusion? Divergent effects of multifunctional enzymes:Divergent effects of multifunctional enzymes

There is increasing evidence that deficient clearance of β-amyloid (Aβ) contributes to its accumulation in late-onset Alzheimer disease (AD). Several Aβ-degrading enzymes, including neprilysin (NEP), endothelin-converting enzyme (ECE), and angiotensin-converting enzyme (ACE) reduce Aβ levels and protect against cognitive impairment in mouse models of AD. In post-mortem human brain tissue we have found that the activity of these Aβ-degrading enzymes rise with age and increases still further in AD, perhaps as a physiological response that helps to minimize the build-up of Aβ. ECE-1/-2 and ACE are also rate-limiting enzymes in the production of endothelin-1 (ET-1) and angiotensin II (Ang II), two potent vasoconstrictors, increases in the levels of which are likely to contribute to reduced blood flow in AD. This review considers the possible interdependence between Aβ-degrading enzymes, ischemia and Aβ in AD: ischemia has been shown to increase Aβ production both in vitro and in vivo, whereas increased Aβ probably enhances ischemia by vasoconstriction, mediated at least in part by increased ECE and ACE activity. In contrast, NEP activity may help to maintain cerebral perfusion, by reducing the accumulation of Aβ in cerebral blood vessels and lessening its toxicity to vascular smooth muscle cells. In assessing the role of Aβ-degrading proteases in the pathogenesis of AD and, particularly, their potential as therapeutic agents, it is important to bear in mind the multifunctional nature of these enzymes and to consider their effects on other substrates and pathways