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21.
Annalisa Cavallini Suzanne Brewerton Amanda Bell Samantha Sargent Sarah Glover Clare Hardy Roger Moore John Calley Devaki Ramachandran Michael Poidinger Eric Karran Peter Davies Michael Hutton Philip Szekeres Suchira Bose 《The Journal of biological chemistry》2013,288(32):23331-23347
Neurofibrillary tangles, one of the hallmarks of Alzheimer disease (AD), are composed of paired helical filaments of abnormally hyperphosphorylated tau. The accumulation of these proteinaceous aggregates in AD correlates with synaptic loss and severity of dementia. Identifying the kinases involved in the pathological phosphorylation of tau may identify novel targets for AD. We used an unbiased approach to study the effect of 352 human kinases on their ability to phosphorylate tau at epitopes associated with AD. The kinases were overexpressed together with the longest form of human tau in human neuroblastoma cells. Levels of total and phosphorylated tau (epitopes Ser(P)-202, Thr(P)-231, Ser(P)-235, and Ser(P)-396/404) were measured in cell lysates using AlphaScreen assays. GSK3α, GSK3β, and MAPK13 were found to be the most active tau kinases, phosphorylating tau at all four epitopes. We further dissected the effects of GSK3α and GSK3β using pharmacological and genetic tools in hTau primary cortical neurons. Pathway analysis of the kinases identified in the screen suggested mechanisms for regulation of total tau levels and tau phosphorylation; for example, kinases that affect total tau levels do so by inhibition or activation of translation. A network fishing approach with the kinase hits identified other key molecules putatively involved in tau phosphorylation pathways, including the G-protein signaling through the Ras family of GTPases (MAPK family) pathway. The findings identify novel tau kinases and novel pathways that may be relevant for AD and other tauopathies. 相似文献
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Sara Kleindienst Sharon Grim Mitchell Sogin Annalisa Bracco Melitza Crespo-Medina Samantha B Joye 《The ISME journal》2016,10(2):400-415
The Deepwater Horizon (DWH) oil well blowout generated an enormous plume of dispersed hydrocarbons that substantially altered the Gulf of Mexico''s deep-sea microbial community. A significant enrichment of distinct microbial populations was observed, yet, little is known about the abundance and richness of specific microbial ecotypes involved in gas, oil and dispersant biodegradation in the wake of oil spills. Here, we document a previously unrecognized diversity of closely related taxa affiliating with Cycloclasticus, Colwellia and Oceanospirillaceae and describe their spatio-temporal distribution in the Gulf''s deepwater, in close proximity to the discharge site and at increasing distance from it, before, during and after the discharge. A highly sensitive, computational method (oligotyping) applied to a data set generated from 454-tag pyrosequencing of bacterial 16S ribosomal RNA gene V4–V6 regions, enabled the detection of population dynamics at the sub-operational taxonomic unit level (0.2% sequence similarity). The biogeochemical signature of the deep-sea samples was assessed via total cell counts, concentrations of short-chain alkanes (C1–C5), nutrients, (colored) dissolved organic and inorganic carbon, as well as methane oxidation rates. Statistical analysis elucidated environmental factors that shaped ecologically relevant dynamics of oligotypes, which likely represent distinct ecotypes. Major hydrocarbon degraders, adapted to the slow-diffusive natural hydrocarbon seepage in the Gulf of Mexico, appeared unable to cope with the conditions encountered during the DWH spill or were outcompeted. In contrast, diverse, rare taxa increased rapidly in abundance, underscoring the importance of specialized sub-populations and potential ecotypes during massive deep-sea oil discharges and perhaps other large-scale perturbations. 相似文献
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Marcello Locatelli Roberta Cifelli Giuseppe Carlucci Annalisa Romagnoli 《Journal of enzyme inhibition and medicinal chemistry》2016,31(1):106-111
A new and specific HPLC–DAD method for the direct determination of Prulifloxacin and its active metabolite, Ulifloxacin, in human plasma has been developed. Plasma samples were analysed after a simple solid phase extraction (SPE) clean-up using a new HILIC stationary phase based high-performance liquid chromatography (HPLC) column and an ammonium acetate buffer (5?mM, pH 5.8)/acetonitrile (both with 1% Et3N, v/v) mobile phase in isocratic elution mode, with Danofloxacin as the internal standard. Detection was performed using DAD from 200 to 500?nm and quantitative analyses were carried out at 278?nm. The LOQ of the method was 1?μg/mL of the cited analytes and the calibration curve showed a good linearity up to 25?μg/mL. For both analytes the precision (RSD%) and the trueness (bias%) of the method fulfil with International Guidelines. The method was applied for stability studies, at three QC concentration levels, in human plasma samples stored at different temperature of?+?25,?+?4 and ?20?°C in order to evaluate plasma stability profiles. 相似文献
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Annalisa?Barera Silvio?Buscemi Roberto?Monastero Calogero?Caruso Rosalia?Caldarella Marcello?CiaccioEmail author 《Immunity & ageing : I & A》2016,13(1):14
Background
It is well known that Mediterranean Diet can positively influence the health of each individual, in particular it is know that fibers have an important role. However, in Mediterranean cities most people do not have a close adherence to Mediterranean diet. Thus, in our study, we considered fibers like β-glucans that have been added to pasta with a percentage of 6 %. Our study aimed to evaluate the capacity of β-glucans intake on oxidative stress and inflammation in a cohort of middle aged slightly overweight subjects.Methods
We used a longitudinal study design. The study lasted 30 days during which time, each participant acted with no food restriction. Participants underwent morning fasting blood venous sample for blood chemistry and other biological parameters at the beginning of the study and after 30 days of pasta supplemented with 6 % of β-glucan intake 4 times a week. We performed anthropometric, biochemical, oxidative stress and cytokine analysis at the beginning and the end of study.Results
After the 30 days of pasta intake we obtained a significant decrease of LDL-cholesterol, IL-6 and AGEs levels.Conclusion
The results confirmed a capacity of β-glucans intake to lower oxidative stress. Additional longitudinal observation on community-based cohorts are needed to confirm these data and investigate the biological mechanisms through which effects are induced, and to fully explore the therapeutic potential of β-glucans.27.
Canovetti Annalisa Rossi Francesca Rossi Michele Menabuoni Luca Malandrini Alex Pini Roberto Ferrara Paolo 《Biomechanics and modeling in mechanobiology》2019,18(2):319-325
Biomechanics and Modeling in Mechanobiology - The aim of this study was to qualitatively evaluate the biomechanical load resistance of different surgical wound configurations (mushroom, zig-zag,... 相似文献
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Among the diseases caused by protein misfolding is the family associated with the prion protein (PrP). This is a small extracellular membrane-anchored molecule of yet unknown function. Understanding how PrP folds both into its cellular and pathological forms is thought to be crucial for explaining protein misfolding in general and the specific role of PrP in disease. Since the first structure determination, an increasing number of structural studies of PrP have become available, showing that the protein is formed by a flexible N-terminal region and a highly conserved globular C-terminal domain. We review here the current knowledge on PrP structure. We focus on vertebrate PrPs and analyse in detail the similarities and the differences among the coordinates of the C-terminal domain of PrP from different species, in search for understanding the mechanism of disease-causing mutations and the molecular bases of species barrier.Key Words: amyloid, NMR, prion, scrapie, structure, X-ray 相似文献