scholarly journals Mapping protein abundance patterns in the brain using voxelation combined with liquid chromatography and mass spectrometry

Methods ◽  
2010 ◽  
Vol 50 (2) ◽  
pp. 77-84 ◽  
Author(s):  
Vladislav A. Petyuk ◽  
Wei-Jun Qian ◽  
Richard D. Smith ◽  
Desmond J. Smith
2021 ◽  
Vol 69 (7) ◽  
pp. 2279-2286
Author(s):  
Christopher J. Silva ◽  
Bruce C. Onisko ◽  
Irina C. Dynin ◽  
Melissa Erickson-Beltran ◽  
Jesús R. Requena

2011 ◽  
Vol 57 (7) ◽  
pp. 1005-1012 ◽  
Author(s):  
Haoyue Zhang ◽  
Sarah P Young ◽  
Christiane Auray-Blais ◽  
Paul J Orchard ◽  
Jakub Tolar ◽  
...  

BACKGROUND New therapies for the treatment of mucopolysaccharidoses that target the brain, including intrathecal enzyme replacement, are being explored. Quantitative analysis of the glycosaminoglycans (GAGs) that accumulate in these disorders is required to assess the disease burden and monitor the effect of therapy in affected patients. Because current methods lack the required limit of quantification and specificity to analyze GAGs in small volumes of cerebrospinal fluid (CSF), we developed a method based on ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). METHODS Samples of CSF (25 μL) were evaporated to dryness and subjected to methanolysis. The GAGs were degraded to uronic acid-N-acetylhexosamine dimers and mixed with internal standards derived from deuteriomethanolysis of GAG standards. Specific dimers derived from heparan, dermatan and chondroitin sulfates (HS, DS and CS) were separated by UPLC and analyzed by electrospray ionization MS/MS using selected reaction monitoring for each targeted GAG product and its corresponding internal standard. RESULTS CSF from control pediatric subjects (n = 22) contained <0.38 mg/L HS, 0.26 mg/L DS, and 2.8 mg/L CS, whereas CSF from patients with Hurler syndrome (n = 7) contained concentrations of DS and HS that were at least 6-fold greater than the upper control limits. These concentrations were reduced by 17.5% to 82.5% after allogeneic transplantation and treatment with intrathecal and intravenous enzyme replacement therapy. CONCLUSIONS The method described here has potential value in monitoring patients with mucopolysaccharidoses receiving treatment targeted to the brain.


Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5163
Author(s):  
Ting Hu ◽  
Quanfei Zhu ◽  
Yuning Hu ◽  
Ghulam Mustafa Kamal ◽  
Yuqi Feng ◽  
...  

Free fatty acids serve as important bioactive molecules in the brain. They are involved in message transfer in the brain. There are many reports available in the literature regarding the role of cerebral fatty acids in message transfer; however, most of the studies are mainly focused on limited fatty acid species or only a few specific brain regions. To understand the relationship between cerebral functions and free fatty acids, it is necessary to investigate the distribution of the free fatty acids among different regions in the whole brain. In this study, free fatty acids were extracted from different brain regions and analyzed qualitatively and quantitatively using the stable isotopic labeling liquid chromatography–mass spectrometry approach. In total, 1008 potential free fatty acids were detected in the whole brain out of which 38 were found to be commonly present in all brain regions. Among different brain regions, the highest and the smallest amounts of potential free fatty acids were detected in the olfactory bulb and cerebellum, respectively. From a statistical point of view, 4-methyl-2-oxovaleric acid, cis-11, 14-eicosadienoic acid, tridecanoic acid, myristic acid, nonadecanoic acid, and arachidic acid were found to significantly vary among the four different brain regions (olfactory bulb, occipital lobe, hippocampus, and cerebellum). The variation in the composition of free fatty acids among different brain regions may be very important for investigating the relationship between free fatty acids and functions of cerebral regions.


2021 ◽  
Vol 8 ◽  
Author(s):  
Megan Grobman ◽  
Hansjörg Rindt ◽  
Carol R. Reinero

Reflux and aspiration in people cause and exacerbate respiratory diseases in the absence of gastrointestinal signs. Protein biomarkers in humans detect extraesophageal reflux (EER) from oropharyngeal (OP) and bronchoalveloar lavage samples. Reflux likely contributes to respiratory disease in dogs. The objectives of this study were to analyze the canine gastric fluid (GF) proteome and compare this to the OP proteome in normal, vomiting/regurgitating, and coughing dogs to identify biomarkers for EER/aspiration. Twenty-three client-owned dogs were enrolled. Canine GF samples (n = 5) and OP swabs in normal (n = 6), vomiting/regurgitating (n = 7), and coughing (n = 5) dogs were within 2 weeks of sample collection. Protein digests were analyzed by liquid chromatography–mass spectrometry. Differential abundance (DA) of proteins between groups was evaluated by Fisher's exact test with p < 0.0004 significance level after correction for multiple comparisons. DA was found between all groups (p < 0.0001): GF vs. normal (n = 130 proteins), coughing vs. normal (n = 22 proteins), and vomiting/regurgitating vs. normal (n = 20 proteins). Protein abundance was highly variable between dogs. Gastrointestinal-specific proteins were found in OP swabs from vomiting/regurgitating and coughing dogs but not from healthy dogs. In conclusion, the proteomic composition of the OP varies between health and disease. The presence of gastrointestinal-specific proteins in OP of coughing dogs may suggest reflux and/or aspiration as contributing factors. The variable protein abundance warrants investigation into biomarker panels.


2007 ◽  
Vol 177 (4S) ◽  
pp. 295-295
Author(s):  
Michael Mullerad ◽  
Haleem J. Issaq ◽  
Alexander Kravtsov ◽  
Timothy Waybright ◽  
Brian Luke ◽  
...  

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