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https://www.readbyqxmd.com/read/28324600/light-sheet-fluorescence-microscopy-chemical-clearing-and-labeling-protocols-for-ultramicroscopy
#1
Nina Jährling, Klaus Becker, Saiedeh Saghafi, Hans-Ulrich Dodt
Light-sheet microscopy is an effective technique in neuroscience, developmental biology, and cancer research for visualizing and analyzing cellular networks and whole organs in three dimensions. Because this technique requires specimens to be translucent they commonly have to be cleared before microscopy inspection. Here, we provide 3DISCO based protocols for preparing cleared samples of immuno-stained neural networks, lectin-labeled vascular networks, and Methoxy-X04 labeled beta-amyloid plaques in mice. 3DISCO utilizes the lipophilic solvents tetrahydrofuran (THF) and dibenzylether (DBE) for dehydration and successive clearing...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28324341/beta-amyloid-deposition-in-patients-with-major-depressive-disorder-with-differing-levels-of-treatment-resistance-a-pilot-study
#2
Peng Li, Ing-Tsung Hsiao, Chia-Yih Liu, Chia-Hsiang Chen, She-Yao Huang, Tzu-Chen Yen, Kuan-Yi Wu, Kun-Ju Lin
BACKGROUND: Lack of treatment response in patients with late-life depression is common. The role of brain beta-amyloid (Aβ) deposition in treatment outcome in subjects with late-life depression remains unclear. The present study aimed to investigate brain Aβ deposition in patients with major depressive disorder (MDD) with differing treatment outcomes in vivo using (18)F-florbetapir imaging. This study included 62 MDD patients and 18 healthy control subjects (HCs).We first employed the Maudsley staging method (MSM) to categorize MDD patients into two groups according to treatment response: mild treatment resistance (n = 29) and moderate-to-severe treatment resistance (n = 33)...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28324113/microrna-expression-patterns-involved-in-amyloid-beta-induced-retinal-degeneration
#3
Peirong Huang, Junran Sun, Fenghua Wang, Xueting Luo, Jingyang Feng, Qing Gu, Te Liu, Xiaodong Sun
Purpose: Dry age-related macular degeneration (AMD) is characterized by the accumulation of drusen under Bruch's membrane, and amyloid beta (Aβ) is speculated to be one of the key pathologic factors. While the detrimental effects of Aβ on retinas have been widely explored, Aβ-induced epigenetic regulatory changes have yet to be fully investigated. We therefore aimed to identify the microRNA (miRNA) expression profiles in an Aβ-induced mouse model of retinal degeneration. Methods: C57BL/6 mice were intravitreally injected with Aβ1-40 or PBS and the eye tissues were collected for hematoxylin and eosin (H&E) staining, apoptosis immunofluorescence staining, and miRNA profiling...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28324109/sex-specific-life-course-changes-in-the-neuro-metabolic-phenotype-of-glut3-null-heterozygous-mice-ketogenic-diet-ameliorates-electroencephalographic-seizures-and-improves-sociability
#4
Yun Dai, Yuanzi Zhao, Masatoshi Tomi, Bo-Chul Shin, Shanthie Thamotharan, Andrey Mazarati, Raman Sankar, Elizabeth A Wang, Carlos Cepeda, Michael S Levine, Jingjing Zhang, Andrew Frew, Jeffry R Alger, Peter Clark, Monica Sondhi, Sudatip Kositamongkol, Leah Leibovitch, Sherin U Devaskar
We tested the hypothesis that exposure of glut3+/- mice to a ketogenic diet ameliorates autism-like features which includes aberrant behavior and electrographic seizures. We first investigated the life course sex-specific changes in basal plasma-CSF-brain metabolic profile, brain glucose transport/uptake, glucose and monocarboxylate transporter proteins, and ATP in the presence or absence of systemic insulin administration. Glut3+/- male but not female mice (5m of age) displayed reduced CSF glucose/lactate concentrations with no change in brain Glut1, Mct2, glucose uptake or ATP...
January 24, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323849/bis-sulfosuccinimidyl-suberate-bs3-crosslinking-analysis-of-the-behavior-of-amyloid-%C3%AE-peptide-in-solution-and-in-phospholipid-membranes
#5
Jing-Ming Shi, Jie Pei, En-Qi Liu, Lin Zhang
The structure and state of amyloid-β peptide (Aβ) oligomers often need to be checked by reliable experimental methods. Electrophoresis is a commonly applied measurement method. However, due to the presence of detergents, oligomers are easily broken during electrophoresis, which makes it very hard to accurately assess Aβ aggregate states. In the current study, bis(sulfosuccinimidyl) suberate (BS3) was used to cross-link Aβ1-42 oligomers prior to electrophoresis. When compared to a previously reported Aβ cross-linking agent, glutaraldehyde, it was quite apparent that BS3 is more suitable for detecting intra-membrane Aβ oligomers and extra-membrane Aβ oligomers states...
2017: PloS One
https://www.readbyqxmd.com/read/28323844/nuclear-localization-of-amyloid-%C3%AE-precursor-protein-binding-protein-fe65-is-dependent-on-regulated-intramembrane-proteolysis
#6
Niina A Koistinen, Anna K Edlund, Preeti K Menon, Elena V Ivanova, Smaranda Bacanu, Kerstin Iverfeldt
Fe65 is an adaptor protein involved in both processing and signaling of the Alzheimer-associated amyloid-β precursor protein, APP. Here, the subcellular localization was further investigated using TAP-tagged Fe65 constructs expressed in human neuroblastoma cells. Our results indicate that PTB2 rather than the WW domain is important for the nuclear localization of Fe65. Electrophoretic mobility shift of Fe65 caused by phosphorylation was not detected in the nuclear fraction, suggesting that phosphorylation could restrict nuclear localization of Fe65...
2017: PloS One
https://www.readbyqxmd.com/read/28323618/contact-dependent-killing-by-caulobacter-crescentus-via-cell-surface-associated-glycine-zipper-proteins
#7
Leonor Garcia-Bayona, Monica S Guo, Michael T Laub
Most bacteria are in fierce competition with other species for limited nutrients. Some bacteria can kill nearby cells by secreting bacteriocins, a diverse group of proteinaceous antimicrobials. However, bacteriocins are typically freely diffusible, and so of little value to planktonic cells in aqueous environments. Here, we identify an atypical two-protein bacteriocin in the α-proteobacterium Caulobacter crescentus that is retained on the surface of producer cells where it mediates cell contact-dependent killing...
March 21, 2017: ELife
https://www.readbyqxmd.com/read/28320141/functional-magnetic-resonance-imaging-responses-in-cadasil
#8
Ikreet Cheema, Aaron R Switzer, Cheryl R McCreary, Michael D Hill, Richard Frayne, Bradley G Goodyear, Eric E Smith
OBJECTIVES: The magnitude of the blood oxygen dependent level (BOLD) functional MRI (fMRI) response to visual stimulation is reduced in the small vessel disease cerebral amyloid angiopathy (CAA), reflecting impaired vascular reactivity. We determined whether BOLD responses were reduced in another small vessel disease, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: BOLD fMRI data were collected using a visual stimulus (contrast-reversing checkerboard) and motor task (finger-tapping)...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28319241/alzheimer-disease-signature-neurodegeneration-and-apoe-genotype-in-mild-cognitive-impairment-with-suspected-non-alzheimer-disease-pathophysiology
#9
Stefanie Schreiber, Frank Schreiber, Samuel N Lockhart, Andy Horng, Alexandre Bejanin, Susan M Landau, William J Jagust
Importance: There are conflicting results claiming that Alzheimer disease signature neurodegeneration may be more, less, or similarly advanced in individuals with β-amyloid peptide (Aβ)-negative (Aβ-) suspected non-Alzheimer disease pathophysiology (SNAP) than in Aβ-positive (Aβ+) counterparts. Objective: To examine patterns of neurodegeneration in individuals with SNAP compared with their Aβ+ counterparts. Design, Setting, and Participants: A longitudinal cohort study was conducted among individuals with mild cognitive impairment (MCI) and cognitively normal individuals receiving care at Alzheimer's Disease Neuroimaging Initiative sites in the United States and Canada for a mean follow-up period of 30...
March 20, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28319116/quenched-hydrogen-deuterium-exchange-nmr-of-a-disease-relevant-a%C3%AE-1-42-amyloid-polymorph
#10
Marielle Aulikki Wälti, Julien Orts, Roland Riek
Alzheimer's disease is associated with the aggregation into amyloid fibrils of Aβ(1-42) and Aβ(1-40) peptides. Interestingly, these fibrils often do not obtain one single structure but rather show different morphologies, so-called polymorphs. Here, we compare quenched hydrogen-deuterium (H/D) exchange of a disease-relevant Aβ(1-42) fibril for which the 3D structure has been determined by solid-state NMR with H/D exchange previously determined on another structural polymorph. This comparison reveals secondary structural differences between the two polymorphs suggesting that the two polymorphisms can be classified as segmental polymorphs...
2017: PloS One
https://www.readbyqxmd.com/read/28319103/microglia-activation-due-to-obesity-programs-metabolic-failure-leading-to-type-two-diabetes
#11
REVIEW
R Maldonado-Ruiz, L Montalvo-Martínez, L Fuentes-Mera, A Camacho
Obesity is an energy metabolism disorder that increases susceptibility to the development of metabolic diseases. Recently, it has been described that obese subjects have a phenotype of chronic inflammation in organs that are metabolically relevant for glucose homeostasis and energy. Altered expression of immune system molecules such as interleukins IL-1, IL-6, IL-18, tumor necrosis factor alpha (TNF-α), serum amyloid A (SAA), and plasminogen activator inhibitor-1 (PAI-1), among others, has been associated with the development of chronic inflammation in obesity...
March 20, 2017: Nutrition & Diabetes
https://www.readbyqxmd.com/read/28318905/thermodynamic-properties-of-amyloid-fibrils-in-equilibrium
#12
Tomaz Urbic, Sara Najem, Cristiano L Dias
In this manuscript we use a two-dimensional coarse-grained model to study how amyloid fibrils grow towards an equilibrium state where they coexist with proteins dissolved in a solution. Free-energies to dissociate proteins from fibrils are estimated from the residual concentration of dissolved proteins. Consistent with experiments, the concentration of proteins in solution affects the growth rate of fibrils but not their equilibrium state. Also, studies of the temperature dependence of the equilibrium state can be used to estimate thermodynamic quantities, e...
March 7, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28318364/defective-retrograde-transport-impairs-autophagic-clearance-in-alzheimer-disease-neurons
#13
Prasad Tammineni, Qian Cai
Macroautophagy/autophagy plays a key role in cellular quality control by eliminating protein aggregates and damaged organelles, which is essential for the maintenance of neuronal homeostasis. Defective autophagy has been implicated in the pathogenesis of Alzheimer disease (AD). In AD brains, autophagic vacuoles (AVs) accumulate massively within dystrophic neurites. This raises a fundamental question as to whether impaired autophagic clearance contributes to AD-associated autophagic stress. We recently revealed that AD neurons display defective retrograde transport and accumulation of amphisomes predominantly in axons and presynaptic terminals...
February 28, 2017: Autophagy
https://www.readbyqxmd.com/read/28318355/dementia-incidence-and-predictors-in-cerebral-amyloid-angiopathy-patients-without-intracerebral-hemorrhage
#14
Li Xiong, Gregoire Boulouis, Andreas Charidimou, Duangnapa Roongpiboonsopit, Michael J Jessel, Marco Pasi, Yael D Reijmer, Panagiotis Fotiadis, Alison Ayres, Emily Merrill, Kristin Schwab, Deborah Blacker, M Edip Gurol, Steven M Greenberg, Anand Viswanathan
Cerebral amyloid angiopathy (CAA) is a common cause of cognitive impairment in older individuals. This study aimed to investigate predictors of dementia in CAA patients without intracerebral hemorrhage (ICH). A total of 158 non-demented patients from the Stroke Service or the Memory Clinic who met the modified Boston Criteria for probable CAA were included. At baseline, neuroimaging markers, including lobar microbleeds (cerebral microbleeds (CMBs)), white matter hyperintensities (WMH), cortical superficial siderosis (cSS), magnetic resonance imaging (MRI)-visible centrum semiovale perivascular spaces (CSO-PVS), lacunes, and medial temporal atrophy (MTA) were assessed...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28318262/fluorescent-copper-probe-inhibiting-a%C3%AE-1-16-copper-ii-catalyzed-intracellular-reactive-oxygen-species-production
#15
Gulshan R Walke, Dnyanesh S Ranade, Shefali N Ramteke, Srikanth Rapole, Cristina Satriano, Enrico Rizzarelli, Gaetano A Tomaselli, Giuseppe Trusso Sfrazzetto, Prasad P Kulkarni
A variety of fluorescent probes are proposed to monitor the intracellular copper content. So far, none of the probes have been evaluated for their potential to inhibit copper-associated intracellular oxidative stress. Herein, we studied the ability of a fluorescent copper probe, OBEP-CS1, to inhibit intracellular oxidative stress associated with an amyloid β (Aβ) peptide-copper complex. The data showed that OBEP-CS1 completely inhibits the copper-catalyzed oxidation as well as decarboxylation/deamination of Aβ1-16...
March 20, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28318232/histology-compatible-maldi-mass-spectrometry-based-imaging-of-neuronal-lipids-for-subsequent-immunofluorescent-staining
#16
Ibrahim Kaya, Wojciech Michno, Dimitri Brinet, Yasmine Iacone, Giulia Zanni, Kaj Blennow, Henrik Zetterberg, Jörg Hanrieder
Matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) enables acquisition of spatial distribution maps for molecular species in situ. This can provide comprehensive insights on the pathophysiology of different diseases. However, current sample preparation and MALDI-IMS acquisition methods have limitations in preserving molecular and histological tissue morphology, resulting in interfered correspondence of MALDI-IMS data with subsequently acquired immunofluorescent staining results...
March 20, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28318059/low-normal-csf-a%C3%AE-42-levels-predict-clinical-progression-in-non-demented-subjects
#17
Betty M Tijms, Daniela Bertens, Rosalinde E Slot, Alida A Gouw, Charlotte E Teunissen, Philip Scheltens, Wiesje M van der Flier, Pieter Jelle Visser
We studied whether continuous lower normal cerebrospinal fluid (CSF) amyloid β 1-42 (≥640 pg/ml) levels related with rate of clinical progression in a sample of 393 non-demented memory clinic patients. Lower normal levels were associated with faster clinical progression and this depended on baseline cognitive status (subjective cognitive decline: HR = 0.59, p <.05; mild cognitive impairment: HR=0.12, p <.001), indicating that normal CSF amyloid levels do not exclude incident Alzheimer's disease. These findings suggest that research on preclinical markers for Alzheimer's disease should take the continuum of CSF amyloid β 1-42 levels within the normal range into account...
March 20, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28317984/stabilizing-the-monomeric-amyloid-%C3%AE-peptide-by-tyrocidine-a-prevents-and-reverses-amyloidogenesis-without-the-accumulation-of-oligomers
#18
Gesi Wen, Wenjing Qin, Daoyuan Chen, Youqiao Wang, Xin Yue, Ziyi Liu, Yingnan Cao, Jun Du, Binhua Zhou, Xianzhang Bu
Amyloid-β (Aβ) oligomers are causative agents triggering AD pathogenesis, but their elimination remains challenging. We herein reported a natural cyclopeptide tyrocidine A prevents and reverses amyloidogenesis without Aβ oligomer accumulation by stabilizing the monomeric, but not the oligomeric state of Aβ peptides.
March 20, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28317650/clinical-validity-of-increased-cortical-uptake-of-amyloid-ligands-on-pet-as-a-biomarker-for-alzheimer-s-disease-in-the-context-of-a-structured-5-phase-development-framework
#19
REVIEW
Konstantinos Chiotis, Laure Saint-Aubert, Marina Boccardi, Anton Gietl, Agnese Picco, Andrea Varrone, Valentina Garibotto, Karl Herholz, Flavio Nobili, Agneta Nordberg
The use of biomarkers has been proposed for diagnosing Alzheimer's disease in recent criteria, but some biomarkers have not been sufficiently investigated to justify their routine clinical use. Here, we evaluate in a literature review the clinical validity of amyloid positron emission tomography (PET) imaging using a structured framework developed for the assessment of oncological biomarkers. Homogenous criteria have been addressed in reviews of other Alzheimer's disease biomarkers. There is adequate evidence that the main aims of phases 1 (rationale for use) and 2 (discriminative ability) have been achieved...
April 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28317487/impact-of-cytokines-and-chemokines-on-alzheimer-s-disease-neuropathological-hallmarks
#20
Catarina Domingues, Odete A B da Cruz E Silva, Ana Gabriela Henriques
Alzheimer's disease (AD) is the most common neurodegenerative disorder, neuropathologically characterized by aggregates of β-amyloid peptides, which deposit as senile plaques, and of TAU protein, which forms neurofibrillary tangles. It is now widely accepted that neuroinflammation is implicated in AD pathogenesis. Indeed, inflammatory mediators, such as cytokines and chemokines (chemotactic cytokines) can impact on the Alzheimer´s amyloid precursor protein by affecting its expression levels and amyloidogenic processing and/or β-amyloid aggregation...
March 17, 2017: Current Alzheimer Research
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