Effect of polymer properties and adherend surfaces on adhesion

The surface properties associated with good adhesive joints were evaluated in terms of application of adhesive bonding in aerospace technology. The physical and chemical nature was determined of Ti and Al adherend surfaces after various surface treatments, and the effects on fracture surfaces of high temperature aging, and variations in amide, anhydride, and solvent during polymer synthesis. The effects were characterized of (1) high temperature during shear strength testing, (2) fiber-reinforced composites as adherends, (3) acid/base nature of adherends, (4) aluminum powder adhesive filler, and (5) bonding pressure

Regulator Of Cell Cycle (Rgcc) Expression During The Progression Of Alzheimer\u27s Disease

Unscheduled cell cycle reentry of postmitotic neurons has been described in cases of mild cognitive impairment (MCI) and Alzheimer\u27s disease (AD) and may form a basis for selective neuronal vulnerability during disease progression. In this regard, the multifunctional protein regulator of cell cycle (RGCC) has been implicated in driving G1/S and G2/M phase transitions through its interactions with cdc/cyclin-dependent kinase 1 (cdk1) and is induced by p53, which mediates apoptosis in neurons. We tested whether RGCC levels were dysregulated in frontal cortex samples obtained postmortem from subjects who died with a clinical diagnosis of no cognitive impairment (NCI), MCI, or AD. RGCC mRNA and protein levels were upregulated by ~50%–60% in MCI and AD compared to NCI, and RGCC protein levels were associated with poorer antemortem global cognitive performance in the subjects examined. To test whether RGCC might regulate neuronal cell cycle reentry and apoptosis, we differentiated neuronotypic PC12 cultures with nerve growth factor (NGF) followed by NGF withdrawal to induce abortive cell cycle activation and cell death. Experimental reduction of RGCC levels increased cell survival and reduced levels of the cdk1 target cyclin B1. RGCC may be a candidate cell cycle target for neuroprotection during the onset of AD

Intravenous immunoglobulin (IVIG) treatment exerts antioxidant and neuropreservatory effects in preclinical models of Alzheimer's disease

Intravenous immunoglobulin (IVIG) has shown limited promise so far in human clinical studies on Alzheimer's disease (AD), yet overwhelmingly positive preclinical work in animals and human brain cultures support the notion that the therapy remains potentially efficacious. Here, we elaborate on IVIG neuropreservation by demonstrating that IVIG protects human primary neurons against oxidative stress in vitro and that IVIG preserves antioxidant defense mechanisms in vivo. Based on these results, we propose the following translational impact: If the dosage and treatment conditions are adequately optimized, then IVIG treatment could play a significant role in preventing and/or delaying the progression of neurodegenerative diseases, such as AD. We suggest that IVIG warrants further investigation to fully exploit its potential as an anti-oxidant, neuroprotective and synapto-protecting agent

Pseudophosphorylation of tau at S422 enhances SDS-stable dimer formation and impairs both anterograde and retrograde fast axonal transport

AbstractIn Alzheimer's disease (AD), tau undergoes numerous modifications, including increased phosphorylation at serine-422 (pS422). In the human brain, pS422 tau protein is found in prodromal AD, correlates well with cognitive decline and neuropil thread pathology, and appears associated with increased oligomer formation and exposure of the N-terminal phosphatase-activating domain (PAD). However, whether S422 phosphorylation contributes to toxic mechanisms associated with disease-related forms of tau remains unknown. Here, we report that S422-pseudophosphorylated tau (S422E) lengthens the nucleation phase of aggregation without altering the extent of aggregation or the types of aggregates formed. When compared to unmodified tau aggregates, the S422E modification significantly increased the amount of SDS-stable tau dimers, despite similar levels of immunoreactivity with an oligomer-selective antibody (TOC1) and another antibody that reports PAD exposure (TNT1). Vesicle motility assays in isolated squid axoplasm further revealed that S422E tau monomers inhibited anterograde, kinesin-1 dependent fast axonal transport (FAT). Unexpectedly, and unlike unmodified tau aggregates, which selectively inhibit anterograde FAT, aggregates composed of S422E tau were found to inhibit both anterograde and retrograde FAT. Highlighting the relevance of these findings to human disease, pS422 tau was found to colocalize with tau oligomers and with a fraction of tau showing increased PAD exposure in the human AD brain. This study identifies novel effects of pS422 on tau biochemical properties, including prolonged nucleation and enhanced dimer formation, which correlate with a distinct inhibitory effect on FAT. Taken together, these findings identify a novel mechanistic basis by which pS422 confers upon tau a toxic effect that may directly contribute to axonal dysfunction in AD and other tauopathies

Nerve Growth Factor Pathobiology During The Progression Of Alzheimer\u27s Disease

The current review summarizes the pathobiology of nerve growth factor (NGF) and its cognate receptors during the progression of Alzheimer’s disease (AD). Both transcript and protein data indicate that cholinotrophic neuronal dysfunction is related to an imbalance between TrkA-mediated survival signaling and the NGF precursor (proNGF)/p75NTR-mediated pro-apoptotic signaling, which may be related to alteration in the metabolism of NGF. Data indicate a spatiotemporal pattern of degeneration related to the evolution of tau pathology within cholinotrophic neuronal subgroups located within the nucleus basalis of Meynert (nbM). Despite these degenerative events the cholinotrophic system is capable of cellular resilience and/or plasticity during the prodromal and later stages of the disease. In addition to neurotrophin dysfunction, studies indicate alterations in epigenetically regulated proteins occur within cholinotrophic nbM neurons during the progression of AD, suggesting a mechanism that may underlie changes in transcript expression. Findings that increased cerebrospinal fluid levels of proNGF mark the onset of MCI and the transition to AD suggests that this proneurotrophin is a potential disease biomarker. Novel therapeutics to treat NGF dysfunction include NGF gene therapy and the development of small molecule agonists for the cognate prosurvival NGF receptor TrkA and antagonists against the pan-neurotrophin p75NTR death receptor for the treatment of AD

Human MicroRNA (miR-20b-5p) Modulates Alzheimer’s Disease Pathways and Neuronal Function, and a Specific Polymorphism Close to the \u3cem\u3eMIR20B\u3c/em\u3e Gene Influences Alzheimer’s Biomarkers

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with loss of cognitive, executive, and other mental functions, and is the most common form of age-related dementia. Amyloid-β peptide (Aβ) contributes to the etiology and progression of the disease. Aβ is derived from the amyloid-β precursor protein (APP). Multiple microRNA (miRNA) species are also implicated in AD. We report that human hsa-miR20b-5p (miR-20b), produced from the MIR20B gene on Chromosome X, may play complex roles in AD pathogenesis, including Aβ regulation. Specifically, miR-20b-5p miRNA levels were altered in association with disease progression in three regions of the human brain: temporal neocortex, cerebellum, and posterior cingulate cortex. In cultured human neuronal cells, miR-20b-5p treatment interfered with calcium homeostasis, neurite outgrowth, and branchpoints. A single-nucleotide polymorphism (SNP) upstream of the MIR20B gene (rs13897515) associated with differences in levels of cerebrospinal fluid (CSF) Aβ1-42 and thickness of the entorhinal cortex. We located a miR-20b-5p binding site in the APP mRNA 3′-untranslated region (UTR), and treatment with miR-20b-5p reduced APP mRNA and protein levels. Network analysis of protein-protein interactions and gene coexpression revealed other important potential miR-20b-5p targets among AD-related proteins/genes. MiR-20b-5p, a miRNA that downregulated APP, was paradoxically associated with an increased risk for AD. However, miR-20b-5p also reduced, and the blockade of APP by siRNA likewise reduced calcium influx. As APP plays vital roles in neuronal health and does not exist solely to be the source of “pathogenic” Aβ, the molecular etiology of AD is likely to not just be a disease of “excess” but a disruption of delicate homeostasi

The Mississippian Section at Paddys Bluff, Crittenden County, Kentucky

Paddys Bluff (Figs. 1-3) is located on the south side of the Illinois Basin on the Cumberland River, 1.7 miles downstream from Dycusburg in Crittenden County, Ky., in Carter coordinate section 23-I-16 and ecoregion 71f of the Western Highland Rim of Kentucky (Woods and others, 2002). This bluff is on a right-descending bend 18 liver miles above its junction with the Ohio River at Smithland, Livingston County. The bluff (Figs. 4A, B) is locally famous as the location for a scene from the classic 1962 film, How the West Was Won,\u27 a winner of three Academy Awards, starling James Stewart, John Wayne, and others. We observed Paddys Bluff from the starboard Texas deck of the steamboat Della Queen one rainy morning in October 2005; the thick, persistent white bed midway in the bluff especially attracted our attention (Fig. 4). Paddys Bluff is the best natural exposure of Mississippian limestone between Barkley Dam and the Ohio River, a distance of 31 river miles. The bluff, some 1,700 feet long (Fig. 4), rises 160 feet above the Cumberland River and deflects it about 16° into a long westward reach, the river removing all talus at the base of the bluff. The bluff lies in a graben between two inferred faults st liking N40 to 45°E (Amos and Hayes, 1974). Readily seen in the limestones along the river at the base of the bluff is a prominent joint set parallel to these faults. This bluff is mapped on the Dycusburg geologic quadrangle map (Table 1) as the combined Salem and St. Louis Limestones (Amos and Hayes, 1974) and is capped by at least 15 feet of poorly exposed gravel of the Cretaceous Tuscaloosa Formation (Olive, 1980). Across the river less than 2 miles distant are scattered continental deposits of reddish brown Lafayette-type, sandy cobble-gravel (Olive, 1980), below which are outliers of the Cretaceous Tuscaloosa Formation; both cap hilltops of the same underlying Mississippian limestones. Why is Paddys Bluff of interest? There are at least six reasons to study it. First, can the Salem and St. Louis Limestones be individually identified at the bluff? If, in fact, they can be separated, the upper boundary of sequence S4 recognized in the Lake Cumberland area of south-central Kentucky by Khetani and Read (2002, Fig. 12) extends much farther west. Still another challenge is the enigmatic, massive, fine-grained, whitish-weathering carbonate mudstone bed, unit C of our section, high in the bluff. What does it represent? How widespread is it? Why do beds below rt have a strong petroliferous odor and not those above it? Why are some of the coral heads (Fig. 5) at Paddys Bluff overturned and others not? The last challenge is the bluff itself: Why is it there and how long has it been there

AGING PERFORMANCE OF VITON GLT O-RINGS IN RADIOACTIVE MATERIAL PACKAGES

Radioactive material packages used for transportation of plutonium-bearing materials often contain multiple O-ring seals for containment. Packages such as the Model 9975 are also being used for interim storage of Pu-bearing materials at the Savannah River Site (SRS). One of the seal materials used in such packages is Viton{reg_sign} GLT fluoroelastomer. The aging behavior of containment vessel O-rings based on Viton{reg_sign} GLT at long-term containment term storage conditions is being characterized to assess its performance in such applications. This paper summarizes the program and test results to date

Beyond the culture effect on credibility perception on microblogs

We investigated the credibility perception of tweet readers from the USA and by readers from eight Arabic countries; our aim was to understand if credibility was affected by country and/or by culture. Results from a crowd-sourcing experiment, showed a wide variety of factors affected credibility perception, including a tweet author's gender, profile image, username style, location, and social network overlap with the reader. We found that culture determines readers' credibility perception, but country has no effect. We discuss the implications of our findings for user interface design and social media systems

Amelioration of bleomycin-induced lung fibrosis in hamsters by dietary supplementation with taurine and niacin: biochemical mechanisms.

Interstitial pulmonary fibrosis induced by intratracheal instillation of bleomycin (BL) involves an excess production of reactive oxygen species, unavailability of adequate levels of NAD and ATP to repair the injured pulmonary epithelium, and an overexuberant lung collagen reactivity followed by deposition of highly cross-linked mature collagen fibrils resistant to enzymatic degradation. In the present study, we have demonstrated that dietary supplementation with taurine and niacin offered almost complete protection against the lung fibrosis in a multidose BL hamster model. The mechanisms for the protective effect of taurine and niacin are multifaceted. These include the ability of taurine to scavenge HOCl and stabilize the biomembrane; niacin's ability to replenish the BL-induced depletion of NAD and ATP; and the combined effect of taurine and niacin to suppress all aspects of BL-induced increases in the lung collagen reactivity, a hallmark of interstitial pulmonary fibrosis. It was concluded from the data presented at this Conference that the combined treatment with taurine and niacin, which offers a multipronged approach, will have great therapeutic potential in the intervention of the development of chemically induced interstitial lung fibrosis in animals and humans