Mechanisms regulating material transfer from subducted slabs to arc magmas remain debated, centered on metasomatized mantle wedge interactions versus mélange mobilization at the slab-mantle interface. The South Sandiwch Islands arc offers a unique setting to distinguish between these models due to the significant barium isotope contrast between altered oceanic crust and sediments, the latter displaying unusually light barium isotope compositions compared to the global sediment range. Here we show substantial barium isotope variations coupled with invariant strontium isotope ratios in arc lavas, consistent with mélange mobilization beneath the arc.
View Article and Find Full Text PDFIntroduction: MicroRNAs (miRNAs) play important roles in gene expression regulation and Alzheimer's disease (AD) pathogenesis.
Methods: We investigated the association between baseline plasma miRNAs and central AD biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI; NÂ =Â 803): amyloid, tau, and neurodegeneration (A/T/N). Differentially expressed miRNAs and their targets were identified, followed by pathway enrichment analysis.
Anthropogenic activities have fundamentally changed the chemistry of the Baltic Sea. According to results reported in this study, not even the thallium (Tl) isotope cycle is immune to these activities. In the anoxic and sulfidic ("euxinic") East Gotland Basin today, Tl and its two stable isotopes are cycled between waters and sediments as predicted based on studies of other redox-stratified basins (e.
View Article and Find Full Text PDFAlzheimer's disease (AD) is characterized by cognitive and memory impairments and neuropathological abnormalities. AD has no cure, inadequate treatment options, and a limited understanding of possible prevention measures. Previous studies have demonstrated that AD model mice that received a diet high in the essential nutrient choline had reduced amyloidosis, cholinergic deficits, and gliosis, and increased neurogenesis.
View Article and Find Full Text PDFDietary choline is needed to maintain normal health, including normal liver function in adults. Fatty liver induced by a choline-deficient diet has been consistently observed in human and animal studies. The effect of insufficient choline intake on hepatic fat accumulation is specific and reversible when choline is added to the diet.
View Article and Find Full Text PDFThe observation that many lavas associated with mantle plumes have higher He/He ratios than the upper convecting mantle underpins geophysical, geodynamic and geochemical models of Earth's deep interior. High He/He ratios are thought to derive from the solar nebula or from solar-wind-irradiated material that became incorporated into Earth during early planetary accretion. Traditionally, this high-He/He component has been considered intrinsic to the mantle, having avoided outgassing caused by giant impacts and billions of years of mantle convection.
View Article and Find Full Text PDFBackground: Multiple studies have reported brain lipidomic abnormalities in Alzheimer's disease (AD) that affect glycerophospholipids, sphingolipids, and fatty acids. However, there is no consensus regarding the nature of these abnormalities, and it is unclear if they relate to disease progression.
Objective: Monogalactosyl diglycerides (MGDGs) are a class of lipids which have been recently detected in the human brain.
Background: The positive association of choline for cognition has been reported in both animal and human studies, yet the associations of choline with the risks of incident dementia or Alzheimer's disease (AD) in humans is unclear.
Objectives: Our objective was to test the hypothesis that lower or higher dietary choline intake is associated with increased or decreased, respectively, risks of incident dementia and AD.
Methods: Data from the Framingham Heart Study Offspring Cohort exam 5 to exam 9 were used.
Numerous studies have demonstrated defects in multiple metabolic pathways in Alzheimer's disease (AD), detected in autopsy brains and in the cerebrospinal fluid in vivo. However, until the advent of techniques capable of measuring thousands of metabolites in a single sample, it has not been possible to rank the relative magnitude of these abnormalities. A recent study provides evidence that the abnormal turnover of the brain's most abundant phospholipids: phosphatidylcholine and phosphatidylethanolamine, constitutes a major metabolic pathology in AD.
View Article and Find Full Text PDFFluids mediate the transport of subducted slab material and play a crucial role in the generation of arc magmas. However, the source of subduction-derived fluids remains debated. The Kamchatka arc is an ideal subduction zone to identify the source of fluids because the arc magmas are comparably mafic, their source appears to be essentially free of subducted sediment-derived components, and subducted Hawaii-Emperor Seamount Chain (HESC) is thought to contribute a substantial fluid flux to the Kamchatka magmas.
View Article and Find Full Text PDFIn chronic peripheral inflammation, endothelia in brain capillary beds could play a role for the apolipoprotein E4 (ApoE4)-mediated risk for Alzheimer's disease (AD) risk. Using human brain tissues, here we demonstrate that the interactions of endothelial CD31 with monomeric C-reactive protein (mCRP) versus ApoE were linked with shortened neurovasculature for AD pathology and cognition. Using ApoE knock-in mice, we discovered that intraperitoneal injection of mCRP, via binding to CD31 on endothelial surface and increased CD31 phosphorylation (pCD31), leading to cerebrovascular damage and the extravasation of T lymphocytes into the ApoE4 brain.
View Article and Find Full Text PDFThe neurological damage of Alzheimer's disease (AD) is thought to be irreversible upon onset of dementia-like symptoms, as it takes years to decades for occult pathologic changes to become symptomatic. It is thus necessary to identify individuals at risk for the development of the disease before symptoms manifest in order to provide early intervention. Surrogate markers are critical for early disease detection, stratification of patients in clinical trials, prediction of disease progression, evaluation of response to treatment, and also insight into pathomechanisms.
View Article and Find Full Text PDFCerebral amyloid angiopathy (CAA) in Alzheimer's disease (AD)-deposition of beta amyloid (Aβ) within the walls of cerebral blood vessels-typically accompanies Aβ buildup in brain parenchyma and causes abnormalities in vessel structure and function. We recently demonstrated that the immunoreactivity of activin receptor-like kinase 1 (ALK1), the type I receptor for circulating BMP9/BMP10 (bone morphogenetic protein) signaling proteins, is reduced in advanced, but not early stages of AD in CA3 pyramidal neurons. Here we characterize vascular expression of ALK1 in the context of progressive AD pathology accompanied by amyloid angiopathy in postmortem hippocampi using immunohistochemical methods.
View Article and Find Full Text PDFAn amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDFThe Nd isotope composition of seawater has been used to reconstruct past changes in the contribution of different water masses to the deep ocean. In the absence of contrary information, the Nd isotope compositions of endmember water masses are usually assumed constant during the Quaternary. Here we show that the Nd isotope composition of North Atlantic Deep Water (NADW), a major component of the global overturning ocean circulation, was significantly more radiogenic than modern during the Last Glacial Maximum (LGM), and shifted towards modern values during the deglaciation.
View Article and Find Full Text PDFCholine is an essential nutrient for proper liver, muscle, and brain functions as well as for lipid metabolism and cellular membrane composition and repair. Humans can produce small amounts of choline via the hepatic phosphatidylethanolamine -methyltransferase pathway; however, most individuals must consume this vitamin through the diet to prevent deficiency. An individual's dietary requirement for choline is dependent on common genetic variants in genes required for choline, folate, and one-carbon metabolism.
View Article and Find Full Text PDFCholine has been recognized as an essential nutrient by the Food and Nutrition Board of the National Academies of Medicine since 1998. Its metabolites have structural, metabolic, and regulatory roles within the body. Humans can endogenously produce small amounts of choline via the hepatic phosphatidylethanolamine -methyltransferase pathway.
View Article and Find Full Text PDFGenome-wide association studies identified a single nucleotide polymorphism (SNP) in the MSRB3 gene encoding Methionine Sulfoxide Reductase-B3 (MsrB3) to be associated with the risk for low hippocampal volume and late onset Alzheimer's disease (AD). Subsequently, we identified AD-associated abnormal patterns of neuronal and vascular MsrB3 expression in postmortem hippocampi. The present study investigated the relationship between the MSRB3 SNP rs61921502, G (minor/risk allele) and MRI measures of brain injury including total brain volume, hippocampal volume, and white matter hyperintensities using linear regression models; the presence of brain infarcts using logistic regression models; and the incidence of stroke, dementia, and AD using Cox proportional hazards models in 2,038 Framingham Heart Study Offspring participants with MRI administered close to examination cycle 7 (1998-2001).
View Article and Find Full Text PDFThe upper mantle, as sampled by mid-ocean ridge basalts (MORBs), exhibits significant chemical variability unrelated to mechanisms of melt extraction at ridges. We show that barium isotope variations in global MORBs vary systematically with radiogenic isotopes and trace element ratios, which reflects mixing between depleted and enriched MORB melts. In addition, modern sediments and enriched MORBs share similar Ba isotope signatures.
View Article and Find Full Text PDFThe pathophysiology of Alzheimer's disease (AD) includes signaling defects mediated by the transforming growth factor β-bone morphogenetic protein-growth and differentiation factor (TGFβ-BMP-GDF) family of proteins. In animal models of AD, administration of BMP9/GDF2 improves memory and reduces amyloidosis. The best characterized type I receptor of BMP9 is ALK1.
View Article and Find Full Text PDFInterest in brain-derived neurotrophic factor (BDNF) was greatly enhanced when it was recognized that its expression is reduced in neurodegenerative disorders, especially in Alzheimer's disease (AD). BDNF signaling through the TrkB receptor has a central role in promoting synaptic transmission, synaptogenesis, and facilitating synaptic plasticity making the BDNF-TrkB signaling pathway an attractive candidate for targeted therapies. Here we investigated the early effect of the small molecule TrkB agonist, 7,8 dihydroxyflavone (7,8-DHF), on AD-related pathology, dendritic arborization, synaptic density, and neurochemical changes in the 5xFAD mouse model of AD.
View Article and Find Full Text PDFStudies suggest that a single injection of pramlintide, an amylin analog, induces changes in Alzheimer's disease (AD) biomarkers in the blood of AD mouse models and AD patients. The aim of this study was to examine whether a pramlintide challenge combined with a phosphatidylcholine (PC) profile diagnoses of AD and mild cognitive impairment (MCI) better than PC alone. Non-diabetic subjects with cognitive status were administered a single subcutaneous injection of 60 mcg of pramlintide under fasting condition.
View Article and Find Full Text PDFGulf War Illness (GWI) is a chronic disease that affects the 1991 Gulf War (GW) veterans for which treatment is lacking. It has been hypothesized that drugs used to protect military personnel from chemical attacks and insects during the war: pyridostigmine bromide (PB),N, N-diethyl-m-toluamide (DEET), and permethrin (PER) together with stress may have contributed collectively and synergistically to generate GWI. There is a need to find markers of pathology to be used in pre-clinical trials.
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