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Shen, Jianqiao, Vishwajeeth R. Pagala, Alex M. Breuer, Junmin Peng, Bin Ma, and Xusheng Wang. "Spectral Library Search Improves Assignment of TMT Labeled MS/MS Spectra." Journal of Proteome Research 17, no. 9 (August 10, 2018): 3325–31. http://dx.doi.org/10.1021/acs.jproteome.8b00594.
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Khan, Omar Farooq, Ellen R. Cusano, Soundouss Raissouni, Mica Pabia, Johanna Haeseker, Nicholas Bosma, Jenny J. Ko, Aalok Kumar, Michael M. Vickers, and Patricia A. Tang. "Immediate-term chemotherapy-related cognitive impairment (CRCI) following administration of intravenous (IV) chemotherapy." Journal of Clinical Oncology 35, no. 5_suppl (February 10, 2017): 146. http://dx.doi.org/10.1200/jco.2017.35.5_suppl.146.
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146 Background: The acute impact of chemotherapy on cognition is unknown. This study utilized performance on the psychomotor vigilance task (PVT) and trail-making test B (TMT) to assess CRCI immediately following chemotherapy administration. Methods: Patients aged 18-80 years receiving first-line IV chemotherapy for any stage of breast or colorectal cancer were eligible. Patients with brain metastases, neurologic disorders or allergic reactions to chemotherapy were excluded. Patient symptoms, peripheral neuropathy and Stanford Sleepiness Scale were assessed. A five-minute PVT and TMT were completed on a tablet computer pre-chemotherapy and immediately post-chemotherapy. Paired Wilcoxon Rank Sum tests were used to assess changes in median PVT reaction time, TMT completion time, TMT errors and PVT lapses. A priori, increases of 20 ms or over in median PVT reaction times (approximating reaction time changes with blood alcohol concentrations of 0.04 to 0.05 g%) were considered clinically relevant. Results: 144 patients (74 breast, 70 colorectal, median age 55.5 years) were tested. Post-chemotherapy, median PVT reaction time slowed by an average of 12.4 ms (p = 0.01). Post-chemotherapy median PVT times slowed by over 20 ms in 59 patients (40.9%). TMT completion post-chemotherapy was faster by an average of 6.1 seconds (p < 0.001). No differences were seen in TMT errors (p = 0.417) or PVT lapses (p = 0.845). Change in median PVT reaction time was not associated with age, gender, number of prior chemotherapy cycles, use of paclitaxel (which contains alcohol), peripheral neuropathy grade, or self-reported anxiety, fatigue or depression. Conclusions: Median PVT reaction time was significantly slower immediately after chemotherapy compared to a pre-chemotherapy baseline, and impairment correlating to effects of alcohol was seen in 41% of patients. This effect appears independent of age, self-reported symptoms or prior chemotherapy cycles. Further studies assessing the functional implications of immediate-term CRCI are warranted.
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Baetge, Sharon Jean, Michael Dietrich, Melanie Filser, Alina Renner, Nathalie Stute, Marcia Gasis, Margit Weise, et al. "Association of Retinal Layer Thickness With Cognition in Patients With Multiple Sclerosis." Neurology - Neuroimmunology Neuroinflammation 8, no. 4 (May 27, 2021): e1018. http://dx.doi.org/10.1212/nxi.0000000000001018.
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ObjectiveRetinal layer thickness (RLT) measured by optical coherence tomography (OCT) is considered a noninvasive, cost-efficient marker of neurodegeneration in multiple sclerosis (MS). We aimed to investigate associations of RLT with cognitive performance and its potential as indicator of cognitive status in patients with MS by performing generalized estimating equation (GEE) analyses.MethodsIn this cross-sectional study, patients with at least mild signs of cognitive impairment were examined by OCT as well as by the Brief International Cognitive Assessment for MS and tests assessing attention and executive functions (Trail Making Test [TMT] A and B). Associations of these factors were investigated using GEE models controlling for demographic and disease-related factors and correcting for multiple testing.ResultsA total of 64 patients entered the study. In the final sample (n = 50 [n = 14 excluded due to missing data or drop-outs]; n = 44 relapsing-remitting MS and n = 6 secondary progressive MS, mean Expanded Disability Status Scale score = 2.59 [SD = 1.17], disease duration [median] = 7.34 [interquartile range = 12.1]), 36.0% were cognitively impaired. RLT of the macular retinal nerve fiber layer was associated with performance in TMT-B (β = −0.259). Analyses focusing on the upper and lower tertile of RLT additionally revealed associations between macular ganglion cell-inner plexiform layer and TMT-B and verbal short-term memory and learning, respectively.ConclusionIn patients with MS, at less advanced disease stages, RLT was especially associated with cognitive flexibility promoting OCT as a potential marker advocating further extensive neuropsychological examination.
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Khan, Omar Farooq, Ellen R. Cusano, Soundouss Raissouni, Mica Pabia, Johanna Haeseker, Nicholas Adam Bosma, Jenny J. Ko, et al. "Immediate-term chemotherapy-related cognitive impairment (CRCI) following administration of intravenous (IV) chemotherapy." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 10084. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.10084.
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10084 Background: The acute impact of chemotherapy on cognition is unknown. This study utilized performance on the psychomotor vigilance task (PVT) and trail-making test B (TMT) to assess CRCI immediately following chemotherapy administration. Methods: Patients aged 18-80 years receiving first-line IV chemotherapy for any stage of breast or colorectal cancer were eligible. Patients with brain metastases, neurologic disorders or allergic reactions to chemotherapy were excluded. Patient symptoms, peripheral neuropathy and Stanford Sleepiness Scale were assessed. A five-minute PVT and TMT were completed on a tablet computer pre-chemotherapy and immediately post-chemotherapy. Paired Wilcoxon Rank Sum tests were used to assess change in median PVT reaction time, TMT completion time, TMT errors and PVT lapses. A priori, an increase in median PVT reaction times by over 20 ms (approximating reaction time changes with blood alcohol concentrations of 0.04 to 0.05 g%) was considered a clinically relevant change. Results: 144 patients (74 breast, 70 colorectal, median age 55.5 years) were tested. Post-chemotherapy, median PVT reaction time slowed by an average of 12.4 ms ( p = 0.01). Post-chemotherapy median PVT times slowed by over 20 ms in 59 patients (40.9%). TMT completion post-chemotherapy was faster by an average of 6.1 seconds ( p < 0.001). No differences were seen in TMT errors ( p = 0.417) or PVT lapses ( p = 0.845). Change in median PVT reaction time was not associated with age, gender, number of prior chemotherapy cycles, peripheral neuropathy grade, self-reported symptoms (anxiety, fatigue or depression). Change in median PVT reaction time was also not significantly associated with use of any specific chemotherapeutic drug or class, including paclitaxel (which includes ethanol as an excipient). Conclusions: Median PVT reaction time was significantly slower immediately after chemotherapy compared to a pre-chemotherapy baseline, and impairment correlating to effects of alcohol was seen in 41% of patients. This effect appears independent of age, self-reported symptoms or prior chemotherapy cycles. Further studies assessing functional impact of immediate-term CRCI are warranted.
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Sinclair, John, and John F. Timms. "Quantitative profiling of serum samples using TMT protein labelling, fractionation and LC–MS/MS." Methods 54, no. 4 (August 2011): 361–69. http://dx.doi.org/10.1016/j.ymeth.2011.03.004.
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Huang, Ting, Meena Choi, Manuel Tzouros, Sabrina Golling, Nikhil Janak Pandya, Balazs Banfai, Tom Dunkley, and Olga Vitek. "MSstatsTMT: Statistical Detection of Differentially Abundant Proteins in Experiments with Isobaric Labeling and Multiple Mixtures." Molecular & Cellular Proteomics 19, no. 10 (July 17, 2020): 1706–23. http://dx.doi.org/10.1074/mcp.ra120.002105.
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Tandem mass tag (TMT) is a multiplexing technology widely-used in proteomic research. It enables relative quantification of proteins from multiple biological samples in a single MS run with high efficiency and high throughput. However, experiments often require more biological replicates or conditions than can be accommodated by a single run, and involve multiple TMT mixtures and multiple runs. Such larger-scale experiments combine sources of biological and technical variation in patterns that are complex, unique to TMT-based workflows, and challenging for the downstream statistical analysis. These patterns cannot be adequately characterized by statistical methods designed for other technologies, such as label-free proteomics or transcriptomics. This manuscript proposes a general statistical approach for relative protein quantification in MS- based experiments with TMT labeling. It is applicable to experiments with multiple conditions, multiple biological replicate runs and multiple technical replicate runs, and unbalanced designs. It is based on a flexible family of linear mixed-effects models that handle complex patterns of technical artifacts and missing values. The approach is implemented in MSstatsTMT, a freely available open-source R/Bioconductor package compatible with data processing tools such as Proteome Discoverer, MaxQuant, OpenMS, and SpectroMine. Evaluation on a controlled mixture, simulated datasets, and three biological investigations with diverse designs demonstrated that MSstatsTMT balanced the sensitivity and the specificity of detecting differentially abundant proteins, in large-scale experiments with multiple biological mixtures.
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Niesta, Daniela, Immo Fritsche, and Eva Jonas. "Mortality Salience and Its Effects on Peace Processes." Social Psychology 39, no. 1 (January 2008): 48–58. http://dx.doi.org/10.1027/1864-9335.39.1.48.
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Abstract. The present paper offers a review of the relationship between existential individual threats and peace-hampering as well as peace-facilitating factors. An overwhelming bulk of literature on terror management theory (TMT) demonstrates negative effects of mortality salience such as derogation of outgroup members, prejudice, stereotyping, aggression, and racism. These negative reactions may be detrimental in peace-processes and critical in explaining intergroup conflicts, severe hostilities, and war. Complementary empirical insights derived from TMT, however, demonstrate positive effects of mortality salience (MS) that lead to prosocial reactions. The findings that are reviewed throughout this paper aim at reconciling the seemingly contradictory findings of antisocial and prosocial reactions to reminders of death. In concluding, a variety of conceivable interventions are discussed that may override genuinely detrimental consequences of MS and help to foster peace processes.
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Gich, Jordi, Jordi Freixanet, Rafael García, Joan Carles Vilanova, David Genís, Yolanda Silva, Xavier Montalban, and Lluís Ramió-Torrentà. "A randomized, controlled, single-blind, 6-month pilot study to evaluate the efficacy of MS-Line!: a cognitive rehabilitation programme for patients with multiple sclerosis." Multiple Sclerosis Journal 21, no. 10 (February 25, 2015): 1332–43. http://dx.doi.org/10.1177/1352458515572405.
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Background: MS-Line! was created to provide an effective treatment for cognitive impairment in multiple sclerosis (MS) patients. Objective: To assess the efficacy of MS-Line!. Methods: A randomized, controlled, single-blind, 6-month pilot study. Patients were randomly assigned to an experimental group (cognitive rehabilitation with the programme) or to a control group (no cognitive rehabilitation). Randomization was stratified by cognitive impairment level. Cognitive assessment included: selective reminding test, 10/36 spatial recall test (10/36 SPART), symbol digit modalities test, paced auditory serial addition test, word list generation (WLG), FAS test, subtests of WAIS-III, Boston naming test (BNT), and trail making test (TMT). Results: Forty-three patients (22 in the experimental group, 21 in the control group) were analyzed. Covariance analysis showed significant differences in 10/36 SPART ( P=0.0002), 10/36 SPART delayed recall ( P=0.0021), WLG ( P=0.0123), LNS ( P=0.0413), BNT ( P=0.0007) and TMT-A ( P=0.010) scores between groups. Conclusions: The study showed a significant improvement related to learning and visual memory, executive functions, attention and information processing speed, and naming ability in those patients who received cognitive rehabilitation. The results suggest that MS-Line! is effective in improving cognitive impairment in MS patients.
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Nazeer, Khurram, Michael G. Janech, Jim J. C. Lin, Kevin J. Ryan, John M. Arthur, and Milos N. Budisavljevic. "Changes in protein profiles during course of experimental glomerulonephritis." American Journal of Physiology-Renal Physiology 296, no. 1 (January 2009): F186—F193. http://dx.doi.org/10.1152/ajprenal.90222.2008.
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Better characterization of the molecular mechanisms underlying glomerular cell proliferation may improve our understanding of the pathogenesis of glomerulonephritis and yield disease-specific markers. We used two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS) to generate expression profiles of glomerular proteins in the course of anti-Thy-1 nephritis. Glomeruli were isolated from Wistar rats by sieving, and proteins were separated by 2DE. In preliminary studies using normal rats, we identified known glomerular proteins from microfilaments [tropomyosin (Tm)] and intermediate filaments (vimentin and lamin A), proteins involved in assembly (α-actinin-4, F-actin capping protein) and membrane cytoskeletal linking (ezrin), as well as several enzymes (protein disulfide isomerase, ATP synthase, and aldehyde dehydrogenase). Comparison of glomerular protein abundance between normal rats and rats in the early phase of anti-Thy-1 nephritis yielded 28 differentially expressed protein spots. MS analysis identified 16 differentially expressed proteins including Tm. Altered Tm abundance in the course of anti-Thy-1 nephritis was confirmed, and specific isoforms were characterized by Western blotting. We demonstrated a complex change in Tm isoform abundance in the course of anti-Thy-1 nephritis. The early mesangiolytic phase of the disease was characterized by decreased abundance of low-molecular-weight isoforms Tm5a/5b and increased abundance of high-molecular-weight isoforms Tm6, Tm1, Tm2, and Tm3. The late proliferative phase of the disease was associated with increased abundance of isoforms Tm5a/5b, Tm6, and Tm1 and decreased abundance of Tm3. Isoforms Tm4 and Tm5 remained unchanged in the course of this model of experimental glomerulonephritis. Characterization of Tm isoform abundance in the course of clinical glomerulonephritis may identify disease-specific markers.
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Fenstermacher, Erika A., Jessica Birg, Vincent Barbieri, and Nathaniel Herr. "THE IMPACT OF MORTALITY SALIENCE ON COLLEGE STUDENTS’ INTENT TO HELP OLDER ADULTS." Innovation in Aging 3, Supplement_1 (November 2019): S80. http://dx.doi.org/10.1093/geroni/igz038.311.
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Abstract Terror Management Theory (TMT) states that the awareness of one’s own death causes humans to experience intense anxiety, which must be continuously managed. Much of the research on TMT has focused on negative outcomes, rather than prosocial behavior, begging the question: “Can priming individuals with the thought of their own death trigger them to behave in ways that benefit others?”. Jonas et al. (2002), found that when mortality salience was primed prosocial behavior increased. In line with TMT, they hypothesized that people may behave in a more prosocial manner as it fits in with their personal values. The present study recruited 108 students who were randomly assigned to a mortality salience (MS) or control condition. Participants also completed baseline self-reports, which included measures of ageism, social desirability, personality, and empathy. After the study seemed to end, participants were given a disguised measure of helping behavior, which they believed to be an interest survey for a student volunteer group. Preliminary analyses indicate that those in the MS condition were more willing to be contacted to volunteer with kids than being contacted to volunteer with older adults. We also found that those in the MS condition were more likely to be contacted to volunteer with kids than those in the control condition. Our findings are consistent with previous work showing that individuals favor their ingroup when primed with their death. This reflects the importance of focused efforts on encouraging young people to identify with older adults and on promoting prosocial behavior.
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Gallant, Cynthia, Sarah Appel, Philip Graceffa, Paul Leavis, Jim Jung-Ching Lin, Peter W. Gunning, Galina Schevzov, et al. "Tropomyosin variants describe distinct functional subcellular domains in differentiated vascular smooth muscle cells." American Journal of Physiology-Cell Physiology 300, no. 6 (June 2011): C1356—C1365. http://dx.doi.org/10.1152/ajpcell.00450.2010.
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Tropomyosin (Tm) is known to be an important gatekeeper of actin function. Tm isoforms are encoded by four genes, and each gene produces several variants by alternative splicing, which have been proposed to play roles in motility, proliferation, and apoptosis. Smooth muscle studies have focused on gizzard smooth muscle, where a heterodimer of Tm from the α-gene (Tmsm-α) and from the β-gene (Tmsm-β) is associated with contractile filaments. In this study we examined Tm in differentiated mammalian vascular smooth muscle (dVSM). Liquid chromatography-tandem mass spectrometry (LC MS/MS) analysis and Western blot screening with variant-specific antibodies revealed that at least five different Tm proteins are expressed in this tissue: Tm6 (Tmsm-α) and Tm2 from the α-gene, Tm1 (Tmsm-β) from the β-gene, Tm5NM1 from the γ-gene, and Tm4 from the δ-gene. Tm6 is by far most abundant in dVSM followed by Tm1, Tm2, Tm5NM1, and Tm4. Coimmunoprecipitation and coimmunofluorescence studies demonstrate that Tm1 and Tm6 coassociate with different actin isoforms and display different intracellular localizations. Using an antibody specific for cytoplasmic γ-actin, we report here the presence of a γ-actin cortical cytoskeleton in dVSM cells. Tm1 colocalizes with cortical cytoplasmic γ-actin and coprecipitates with γ-actin. Tm6, on the other hand, is located on contractile bundles. These data indicate that Tm1 and Tm6 do not form a classical heterodimer in dVSM but rather describe different functional cellular compartments.
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Li, Lihui, Qiangmin Huang, Marco Barbero, Lin Liu, Thitham Nguyen, Anle Xu, and Lijuan Ji. "Proteins and Signaling Pathways Response to Dry Needling Combined with Static Stretching Treatment for Chronic Myofascial Pain in a RAT Model: An Explorative Proteomic Study." International Journal of Molecular Sciences 20, no. 3 (January 29, 2019): 564. http://dx.doi.org/10.3390/ijms20030564.
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A quantitative proteomic analysis of the response to dry needling combined with static stretching treatment was performed in a rat model of active myofascial trigger points (MTrPs). 36 rats were divided into a model group (MG), a stretching group (SG) and a dry needling combined with stretching group (SDG). We performed three biological replicates to compare large-scale differential protein expression between groups by tandem mass tag (TMT) labeling technology based on nanoscale liquid chromatography mass spectrometry analysis (LC–MS/MS). Hierarchical clustering, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and protein-protein interaction network analyses were performed for the general characterization of overall enriched proteins. For validation of the results of TMT, the candidate proteins were verified by parallel reaction monitoring (PRM) analysis. 285 differentially expressed proteins between groups were identified and quantified. Tight junction pathway played a dominant role in dry needling combined with static stretching treatment for the rat model of active MTrPs. Three candidate proteins, namely actinin alpha 3, calsequestrin-1 and parvalbumin alpha, were further validated, consistent with the results of LC–MS/MS. This is the first proteomics-based study to report the therapeutic mechanism underlying dry needling and static stretching treatment for MTrPs. Further functional verification of the potential signaling pathways and the enriched proteins is warranted.
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Kang, Jin Yong, Du Sang Lee, Seon Kyeong Park, Jeong Su Ha, Jong Min Kim, Gi Jeong Ha, Weon Taek Seo, and Ho Jin Heo. "Cognitive Function of Artemisia argyi H. Fermented by Monascus purpureus under TMT-Induced Learning and Memory Deficits in ICR Mice." Evidence-Based Complementary and Alternative Medicine 2017 (2017): 1–16. http://dx.doi.org/10.1155/2017/5809370.
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The cognitive effect of Artemisia argyi H. under liquid-state fermentation by Monascus purpureus (AAFM), which has cellular antioxidant activity and neuronal cell viability, on trimethyltin- (TMT-) induced learning and memory impairment in Institute of Cancer Research (ICR) mice was confirmed. Tests were conducted to determine the neuroprotective effects against H2O2-induced oxidative stress, and the results showed that AAFM has protective effects through the repression of mitochondrial injury and cellular membrane damage against H2O2-induced neurotoxicity. In animal experiments, such as the Y-maze, passive avoidance, and Morris water maze tests, AAFM also showed excellent ameliorating effects on TMT-induced cognitive dysfunction. After behavioral tests, brain tissues were extracted to assess damage to brain tissue. According to the experimental results, AAFM improved the cholinergic system by upregulating acetylcholine (ACh) contents and inhibiting acetylcholinesterase (AChE) activity. AAFM effectively improved the decline of the superoxide dismutase (SOD) level and the increase of the oxidized glutathione (GSH) ratio and lipid peroxidation (malondialdehyde (MDA) production) caused by TMT-induced oxidative stress. The occurrence of mitochondrial dysfunction and apoptosis was also decreased compared with the TMT group. Finally, quinic acid derivatives were identified as the major phenolic compounds in AAFM using ultra-performance liquid chromatography quadrupole-time-of-flight (UPLC-Q-TOF) MS analysis.
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Azevedo, R. A., L. M. A. Rufino, A. C. R. Santos, C. S. Ribeiro Júnior, N. M. Rodriguez, and L. C. Geraseev. "Comportamento ingestivo de cordeiros alimentados com torta de macaúba." Arquivo Brasileiro de Medicina Veterinária e Zootecnia 65, no. 2 (April 2013): 490–96. http://dx.doi.org/10.1590/s0102-09352013000200027.
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Avaliaram-se os efeitos de diferentes porcentagens (0, 10, 20 e 30%) de inclusão da torta de macaúba (TM) no comportamento ingestivo de 24 cordeiros Santa Inês, com média de cinco meses de idade e peso vivo de 23,9kg, distribuídos em delineamento em blocos ao acaso, com quatro tratamentos e seis repetições, durante 60 dias de confinamento. Foram avaliados os tempos médios despendidos com alimentação, ruminação (TR), ócio (TO), tempo de mastigação total (TMT), eficiência de alimentação (EA MS e EA FDN) e eficiência de ruminação, além do número de bolos ruminados (NBR) e número diário de mastigações merícicas (MMnd). A adição de TM à dieta aumentou linearmente o TR, TMT, NBR, MMnd e EA FDN e reduziu de forma linear o TO, em consequência do maior teor de fibra em detergente neutro das dietas com o coproduto. Mesmo com o aumento no TMT, não foi verificada diferença no consumo e na eficiência de ruminação e alimentação da matéria seca, possivelmente em razão da baixa efetividade de fibra da TM, demonstrando o potencial de utilização desse coproduto na dieta de ovinos em crescimento.
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Gong, Qian, Xiuming Zhang, Aifeng Liang, Sinian Huang, Guangang Tian, Mengjiao Yuan, Qing Ke, et al. "Proteomic screening of potential N-glycoprotein biomarkers for colorectal cancer by TMT labeling combined with LC-MS/MS." Clinica Chimica Acta 521 (October 2021): 122–30. http://dx.doi.org/10.1016/j.cca.2021.07.001.
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Reilly, Sean, and Sinéad M. Hynes. "A Cognitive Occupation-Based Programme for People with Multiple Sclerosis: A Study to Test Feasibility and Clinical Outcomes." Occupational Therapy International 2018 (2018): 1–9. http://dx.doi.org/10.1155/2018/1614901.
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Cognitive impairments are common in MS and affect personal, social, and occupational functioning. There is a developing body of evidence highlighting the role of cognitive rehabilitation, but there is still no evidence for a validated holistic approach. The aim of this study was to assess the effectiveness of Cognitive Occupation-Based Programme for People with Multiple Sclerosis (COB-MS) for improving daily life and cognitive impairment. This study used an experimental pretest/posttest design with eight-week follow-up. Participants were recruited from MS networks using convenience sampling. The primary outcome measure was the GAS. Secondary outcomes included the OSA-DLS, CVLT-II, BVMT-R, SDMT, TMT, BRIEF-A, and EMQ-R. Twelve participants were recruited, aged 39–73 years (mean: 55.08; SD: 9.61). There were statistically significant improvements in the GAS (p<.002), CVLT-II: total free recall (p<.000), short delay free recall (p<.018), long delay free recall (p<.008), BVMT-R total recall (p<.000), TMT part B (p<.044), and EMQ-R (p<.006). Except for the BRIEF-A, clinically significant improvements were observed in secondary outcome measures at posttest and follow-up. Limitations include selection bias and subtle practice effects in cognitive measures. Results suggest that a larger scale study is justified considering improvements seen in daily life and cognitive measures.
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Xiao, Xijuan, Caihong Xin, Yuqin Zhang, Jie Yan, Zhao Chen, Huiyong Xu, Min Liang, Buling Wu, Fuchun Fang, and Wei Qiu. "Characterization of Odontogenic Differentiation from Human Dental Pulp Stem Cells Using TMT-Based Proteomic Analysis." BioMed Research International 2020 (December 10, 2020): 1–14. http://dx.doi.org/10.1155/2020/3871496.
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Background. The repair of dental pulp injury relies on the odontogenic differentiation of dental pulp stem cells (DPSCs). To better understand the odontogenic differentiation of DPSCs and identify proteins involved in this process, tandem mass tags (TMTs) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were applied to compare the proteomic profiles of induced and control DPSCs. Methods. The proteins expressed during osteogenic differentiation of human DPSCs were profiled using the TMT method combined with LC-MS/MS analysis. The identified proteins were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Then, a protein-protein interaction (PPI) network was constructed. Two selected proteins were confirmed by western blotting (WB) analysis. Results. A total of 223 proteins that were differentially expressed were identified. Among them, 152 proteins were significantly upregulated and 71 were downregulated in the odontogenic differentiation group compared with the control group. On the basis of biological processes in GO, the identified proteins were mainly involved in cellular processes, metabolic processes, and biological regulation, which are connected with the signaling pathways highlighted by KEGG pathway analysis. PPI networks showed that most of the differentially expressed proteins were implicated in physical or functional interaction. The protein expression levels of FBN1 and TGF-β2 validated by WB were consistent with the proteomic analysis. Conclusions. This is the first proteomic analysis of human DPSC odontogenesis using a TMT method. We identified many new differentially expressed proteins that are potential targets for pulp-dentin complex regeneration and repair.
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Park, J., J. Daeun, C. Youn Wook, C. Jae Hee, and R. Ji-Hwan. "P058 Proteomic analysis-based discovery of a novel biomarker that differentiates intestinal Behçet’s disease from Crohn’s disease." Journal of Crohn's and Colitis 15, Supplement_1 (May 1, 2021): S164—S165. http://dx.doi.org/10.1093/ecco-jcc/jjab076.187.
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Abstract Background Intestinal Behçet’s disease (BD) and Crohn’s disease (CD) present similar manifestations, but there are no specific pathognomonic clinical, laboratory, or histological diagnostic tests to differentiate intestinal BD from CD. We used a proteomic approach to discover a novel diagnostic biomarker specific to intestinal BD. Methods The colon mucosa tissue samples were obtained using colonoscopy-guided biopsy of the affected bowel from patients with intestinal BD or CD at the Inflammatory Bowel Disease Clinic of Severance Hospital, Seoul, Korea. Peptides from seven intestinal BD and seven CD patients were extracted and labeled using tandem mass tag (TMT) reagents. The labeled peptides were identified and quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The differentially expressed proteins were further validated using immunohistochemical (IHC) analysis with tissue samples and an ELISA test with serum samples from 20 intestinal BD and 20 CD patients. Results A total of 3,266 proteins were identified using TMT/LC-MS/MS-based proteomic quantification, including 39 candidate proteins differentially expressed between intestinal BD and CD. Beta-2 glycoprotein 1 (APOH) and maltase-glucoamylase (MGAM) showed significantly higher intensity in the IHC staining of the intestinal BD tissues than that of CD tissues. Furthermore, the serum MGAM level was significantly higher in patients with intestinal BD than in patients with CD. Conclusion Our proteomic analysis revealed that some proteins were differentially expressed in intestinal BD patients compared to CD patients. Differential MGAM expression in intestinal BD suggests its role as a potential novel diagnostic biomarker in the differentiation of intestinal BD from CD.
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Kneer, Julia, Inna Hemme, and Gary Bente. "Vicarious Belongingness." Journal of Media Psychology 23, no. 3 (January 2011): 133–40. http://dx.doi.org/10.1027/1864-1105/a000045.
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There is empirical evidence that mortality salience (MS) influences effects of advertisements. For instance, mere exposure to high-value goods can enhance cultural worldview and self-esteem and thus act as a buffer against existential anguish. Besides cultural worldview and self-esteem, close relationships can help to reduce existential anguish. Drawing upon terror management theory (TMT), the current study addressed the question of whether MS combined with emotional commercials influences perception of the ads as well as further behavior. We compared the effects of socioemotional versus informational ads after MS induction, measuring perceived emotionality of the ads, evaluation of ads and products, recall, and buying intention. Significant effects were found in all outcome variables, except for recall, supporting the hypothesis that under MS induction, commercials with a socioemotional content can enhance advertisement impact.
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Gabriels, Ralf, Lennart Martens, and Sven Degroeve. "Updated MS²PIP web server delivers fast and accurate MS² peak intensity prediction for multiple fragmentation methods, instruments and labeling techniques." Nucleic Acids Research 47, W1 (April 27, 2019): W295—W299. http://dx.doi.org/10.1093/nar/gkz299.
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AbstractMS²PIP is a data-driven tool that accurately predicts peak intensities for a given peptide's fragmentation mass spectrum. Since the release of the MS²PIP web server in 2015, we have brought significant updates to both the tool and the web server. In addition to the original models for CID and HCD fragmentation, we have added specialized models for the TripleTOF 5600+ mass spectrometer, for TMT-labeled peptides, for iTRAQ-labeled peptides, and for iTRAQ-labeled phosphopeptides. Because the fragmentation pattern is heavily altered in each of these cases, these additional models greatly improve the prediction accuracy for their corresponding data types. We have also substantially reduced the computational resources required to run MS²PIP, and have completely rebuilt the web server, which now allows predictions of up to 100 000 peptide sequences in a single request. The MS²PIP web server is freely available at https://iomics.ugent.be/ms2pip/.
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C. Onah, Paschal, and Daniel I. Omatalu. "EFFECT OF MORTALITY SALIENCE ON HEALTH COMPROMISING BEHAVIOR." International Journal of Advanced Research 9, no. 5 (May 31, 2021): 384–89. http://dx.doi.org/10.21474/ijar01/12849.
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Over the decades, researchers have leaned on the TMT to explain numerous phenomena, including consumer choice, exercise motivation, risky driving behavior, and other behavioral domains. The present study aimed to investigate the effect of mortality salience on RSB as a health-compromising behavior. Sixty-two participants took part in the study. A quasi-experimental design was adopted. The result showed that MS increased resentment to RSB in the experimental condition (M = 44.82, SD= 9.28) compare to the control condition (M = 21.27, SD = 5.19). An independent t-test was used to test the studys hypothesis, and the result established a statistically significant differential effect of MS on RSB resentment between the conditions. We conclude that MS is effective in mitigating the incidence of RSB.
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Gao, Xin, Peiyun Li, Jun Mei, and Jing Xie. "TMT-Based Quantitative Proteomics Analysis of the Fish-Borne Spoiler Shewanella putrefaciens Subjected to Cold Stress Using LC-MS/MS." Journal of Chemistry 2021 (January 8, 2021): 1–16. http://dx.doi.org/10.1155/2021/8876986.
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Shewanella putrefaciens is a specific spoilage bacterium for fish during cold storage. To better understand the molecular mechanisms of cold stress adaptation of S. putrefaciens, tandem mass tag- (TMT-) based quantitative proteomic analysis was performed to detect the effects of cold stress on protein expression profiles in S. putrefaciens which had been cultivated at 4°C and 30°C, respectively. A total of 266670 peptide spectrum matching numbers were quantified proteins after data analysis. Of the 2292 proteins quantitatively analyzed, a total of 274 were found to be differentially expressed (DE) under cold stress compared with the nonstress control. By integrating the results of Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, 9 common KEGG terms were found notable for the cold-responsive proteins. Generally, the DE proteins involved in carbohydrate, amino acid, and fatty acid biosynthesis and metabolism were significantly upregulated, leading to a specific energy conservation survival mode. The DE proteins related to DNA repair, transcription, and translation were upregulated, implicating change of gene expression and more protein biosynthesis needed in response to cold stress.
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Gao, Xin, Peiyun Li, Jun Mei, and Jing Xie. "TMT-Based Quantitative Proteomics Analysis of the Fish-Borne Spoiler Shewanella putrefaciens Subjected to Cold Stress Using LC-MS/MS." Journal of Chemistry 2021 (January 8, 2021): 1–16. http://dx.doi.org/10.1155/2021/8876986.
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Shewanella putrefaciens is a specific spoilage bacterium for fish during cold storage. To better understand the molecular mechanisms of cold stress adaptation of S. putrefaciens, tandem mass tag- (TMT-) based quantitative proteomic analysis was performed to detect the effects of cold stress on protein expression profiles in S. putrefaciens which had been cultivated at 4°C and 30°C, respectively. A total of 266670 peptide spectrum matching numbers were quantified proteins after data analysis. Of the 2292 proteins quantitatively analyzed, a total of 274 were found to be differentially expressed (DE) under cold stress compared with the nonstress control. By integrating the results of Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, 9 common KEGG terms were found notable for the cold-responsive proteins. Generally, the DE proteins involved in carbohydrate, amino acid, and fatty acid biosynthesis and metabolism were significantly upregulated, leading to a specific energy conservation survival mode. The DE proteins related to DNA repair, transcription, and translation were upregulated, implicating change of gene expression and more protein biosynthesis needed in response to cold stress.
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Zein, Leila E., Hussein Akil, and Said Hussein. "Behavioral Effects of Mortality Salience: An Experimental Study." Journal of Management and Sustainability 8, no. 4 (November 25, 2018): 65. http://dx.doi.org/10.5539/jms.v8n4p65.
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The study is intended to explain the effect of Mortality Salience (MS) on consumer behaviors. In a first part, we present a state of the art of Terror Management Theory (TMT) and its contributions in management sciences by focusing on the impact of MS on consumption. In a second part, we illustrate the results of an experiment testing the effect of death reminders on consumption choices. The results of the experiment show that the reminders of death generate, for the most part of participants, pro-materialistic consumption choices. Based on these results, we highlight the effect the death reminders can generate on Lebanese consumers.
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Liu, Guang-Xue, Feng Xu, Ming-Ying Shang, Xuan Wang, and Shao-Qing Cai. "The Relative Content and Distribution of Absorbed Volatile Organic Compounds in Rats Administered Asari Radix et Rhizoma Are Different between Powder- and Decoction-Treated Groups." Molecules 25, no. 19 (September 27, 2020): 4441. http://dx.doi.org/10.3390/molecules25194441.
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Asari Radix et Rhizoma (ARR) is an important traditional Chinese medicine. Volatile organic compounds (VOCs) are the main active constituents of ARR. Research on the metabolite profile of VOCs and the difference of absorbed constituents in vivo after an administration of ARR decoction and powder will be helpful to understand the pharmacological activity and safety of ARR. In this study, headspace solid-phase microextraction gas chromatography mass spectrometry (HS–SPME–GC–MS) was applied to profile the VOCs from ARR in rats in vivo. A total of 153 VOCs were tentatively identified; 101 were original constituents of ARR (98 in the powder-treated group and 43 in the decoction-treated group) and 15 were metabolites, and their metabolic reactions were mainly oxidation and reduction, with only two cases of methylation and esterification, and 37 unclassified compounds were identified only in the ARR-treated group. Of the 153 VOCs identified, 131 were reported in rats after oral administration of ARR for the first time, containing 79 original constituents, 15 metabolites, and 37 unclassified compounds. In the powder-treated group, methyleugenol, safrole, 3,5-dimethoxytoluene (3,5-DMT), 2,3,5-trimethoxytoluene (2,3,5-TMT), and 3,4,5-trimethoxytoluene (3,4,5-TMT) were the main absorbed constituents, the relative contents of which were significantly higher compared to the decoction-treated group, especially methyleugenol, safrole, and 3,5-DMT. In the decoction-treated group, 3,4,5-TMT, 2,3,5-TMT, kakuol, and eugenol were the main constituents with a higher content and wider distribution. The results of this study provide a reference for evaluating the efficacy and safety of ARR.
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Dan, Kisoon, Ji Eun Lee, Dohyun Han, Sun Min Kim, Subeen Hong, Hyeon Ji Kim, and Kyo Hoon Park. "Proteomic identification of biomarkers in maternal plasma that predict the outcome of rescue cerclage for cervical insufficiency." PLOS ONE 16, no. 4 (April 15, 2021): e0250031. http://dx.doi.org/10.1371/journal.pone.0250031.
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Objective We sought to identify plasma protein biomarkers that are predictive of the outcome of rescue cerclage in patients with cervical insufficiency. Methods This retrospective cohort study included 39 singleton pregnant women undergoing rescue cerclage for cervical insufficiency (17–25 weeks) who gave plasma samples. Three sets of pooled plasma samples from controls (cerclage success, n = 10) and cases (cerclage failure, n = 10, defined as spontaneous preterm delivery at <33 weeks) were labeled with 6-plex tandem mass tag (TMT) reagents and analyzed by liquid chromatography-tandem mass spectrometry. Differentially expressed proteins between the two groups were selected from the TMT-based quantitative analysis. Multiple reaction monitoring-mass spectrometry (MRM-MS) analysis was further used to verify the candidate proteins of interest in patients with cervical insufficiency in the final cohort (n = 39). Results From MRM-MS analysis of the 40 proteins showing statistically significant changes (P < 0.05) from the TMT-based quantitative analysis, plasma IGFBP-2, PSG4, and PGLYRP2 levels were found to be significantly increased, whereas plasma MET and LXN levels were significantly decreased in women with cerclage failure. Of these, IGFBP-2, PSG4, and LXN levels in plasma were independent of cervical dilatation. A multiple-biomarker panel was developed for the prediction of cerclage failure, using a stepwise regression procedure, which included the plasma IGFBP-2, PSG4, and LXN (area under the curve [AUC] = 0.916). The AUC for this multiple-biomarker panel was significantly greater than the AUC for any single biomarker included in the multi-biomarker model. Conclusions Proteomic analysis identified useful and independent plasma biomarkers (IGFBP-2, PSG4, and LXN; verified by MRM) that predict poor pregnancy outcome following rescue cerclage. Their combined analysis in a multi-biomarker panel significantly improved predictability.
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Hosseini, Banafsheh, David B. Flora, Brenda L. Banwell, and Christine Till. "Age of Onset as a Moderator of Cognitive Decline in Pediatric-Onset Multiple Sclerosis." Journal of the International Neuropsychological Society 20, no. 8 (July 17, 2014): 796–804. http://dx.doi.org/10.1017/s1355617714000642.
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AbstractCognitive impairment is often reported in pediatric-onset multiple sclerosis (MS). Using serial cognitive data from 35 individuals with pediatric-onset MS, this study examined how age at disease-onset and proxies of cognitive reserve may impact cognitive maturation over the course of childhood and adolescence. Neuropsychological evaluations were conducted at baseline and up to four more assessments. Of the 35 participants, 7 completed only one assessment, 5 completed two assessments, 13 completed three assessments, 10 completed four or more assessments. Growth curve modeling was used to assess longitudinal trajectories on the Trail Making Test-Part B (TMT-B) and the Symbol Digit Modalities (SDMT; oral version) and to examine how age at disease onset, baseline Full Scale IQ, and social status may moderate rate of change on these measures. Mean number of evaluations completed per patient was 2.8. Younger age at disease onset was associated with a greater likelihood of cognitive decline on both the TMT-B (p=.001) and SDMT (p=.005). Baseline IQ and parental social status did not moderate any of the cognitive trajectories. Findings suggest that younger age at disease-onset increases the vulnerability for disrupted performance on measures of information processing, visual scanning, perceptual/motor speed, and working memory. Proxies of cognitive reserve did not protect against the progression of decline on these measures. Young patients with MS should be advised to seek follow-up cognitive evaluation to assess cognitive maturation and to screen for the potential late emergence of cognitive deficits. (JINS, 2014, 20, 1–9)
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Gebauer, Fabian, Marius H. Raab, and Claus-Christian Carbon. "Imagine All the Forces." Journal of Media Psychology 29, no. 2 (April 2017): 1–7. http://dx.doi.org/10.1027/1864-1105/a000180.
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Abstract. A world divided into East versus West: The so-called Ukraine crisis has once more summoned outdated patterns of political thinking. Simultaneously, media discourses have flared up debating diplomatic and military solutions as possible policy responses. A majority of Germans, however, have remained hesitant to advocate any escalation of military conflict. We were interested in how far reputable journalism concerning the Ukraine crisis might activate a disposition toward military engagement. To evaluate the supposed impact of actual news coverage, we used explicit existential threats (mortality salience; MS) as a comparative measure. Typical effects of MS were derived from terror management theory (TMT), which predicts that the awareness of existential threats amplifies the efforts to defend one’s own culture, even by military means. We used a 2 × 2 factorial design (N = 112) with the factors article (original bellicose vs. neutral, nonmilitant depiction) and salience condition (MS vs. control). Results revealed a strong impact of the original, bellicose article, with increased willingness to deploy German forces at the Russian border, independently of the salience condition. Additional existential threats did not add further effects, as values for willingness were already very high. Classic effects regarding TMT were observed when people had read the Non-Militant article. Here, the willingness to deploy forces only increased after a confrontation with existential threats. We conclude that threatening news coverage on the Ukraine crisis has the ability to alter willingness for first-step military action at the Russian border by inducing effects that are – at least in their outcome – comparable to explicit existential threats.
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Bazenet, Chantal, Nicholas Ashton, Steven Kiddle, Lennart Thurfjell, John Graf, Malcolm Ward, Alison Baird, et al. "P3-113: NOVEL CANDIDATE BLOOD PROTEOME MARKERS OF ALZHEIMER'S DISEASE BRAIN AMYLOID BURDEN: A MULTIPLEX TMT-LC/MS-MS DISCOVERY APPROACH." Alzheimer's & Dementia 10 (July 2014): P669—P670. http://dx.doi.org/10.1016/j.jalz.2014.05.1202.
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Wang, Li, Chen Liu, Yujie Liu, and Ming Luo. "Fumonisin B1-Induced Changes in Cotton Fiber Elongation Revealed by Sphingolipidomics and Proteomics." Biomolecules 10, no. 9 (August 31, 2020): 1258. http://dx.doi.org/10.3390/biom10091258.
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Sphingolipids are essential biomolecules and membrane components, but their regulatory role in cotton fiber development is poorly understood. Here, we found that fumonisin B1 (FB1)—a sphingolipid synthesis inhibitor—could block fiber elongation severely. Using liquid chromatography tandem mass spectrometry (LC-MS/MS), we detected 95 sphingolipids that were altered by FB1 treatment; of these, 29 (mainly simple sphingolipids) were significantly increased, while 33 (mostly complex sphingolipids) were significantly decreased. A quantitative analysis of the global proteome, using an integrated quantitative approach with tandem mass tag (TMT) labeling and LC-MS/MS, indicated the upregulation of 633 and the downregulation of 672 proteins after FB1 treatment. Most differentially expressed proteins (DEPs) were involved in processes related to phenylpropanoid and flavonoid biosynthesis. In addition, up to 20 peroxidases (POD) were found to be upregulated, and POD activity was also increased by the inhibitor. To our knowledge, this is the first report on the effects of FB1 treatment on cotton fiber and ovule sphingolipidomics and proteomics. Our findings provide target metabolites and biological pathways for cotton fiber improvement.
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Yang, Dongjun, Xin Fu, Shiyi He, Xueping Ning, and Min Ling. "Analysis of Differentially Expressed Proteins in Mycobacterium avium-Infected Macrophages Comparing with Mycobacterium tuberculosis-Infected Macrophages." BioMed Research International 2017 (2017): 1–9. http://dx.doi.org/10.1155/2017/5103803.
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Mycobacterium avium (MA) belongs to the intracellular parasitic bacteria. To better understand how MA survives within macrophages and the different pathogenic mechanisms of MA and Mycobacterium tuberculosis (MTB), tandem mass tag (TMT) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis have been used to determine the proteins which are differentially expressed in MA-infected and MTB-infected macrophages. 369 proteins were found to be differentially expressed in MA-infected cells but not in MTB-infected cells. By using certain bioinformatics methods, we found the 369 proteins were involved in molecular function, biological process, and cellular component including binding, catalytic activity, metabolic process, cellular process, and cell part. In addition, some identified proteins were involved in multiple signaling pathways. These results suggest that MA probably survive within macrophages by affecting the expression of some crucial proteins.
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Liu, Bin, Xuewei Yin, Huixia Wei, Zhe Wang, Hongying Tang, Yan Qiu, Yixian Hao, Xiuyan Zhang, Hongsheng Bi, and Dadong Guo. "Quantitative proteomic analysis of rat retina with experimental autoimmune uveitis based on tandem mass tag (TMT) peptide labeling coupled with LC-MS/MS." Journal of Chromatography B 1153 (September 2020): 122293. http://dx.doi.org/10.1016/j.jchromb.2020.122293.
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Schiltenwolf, Marcus, Michael Akbar, Eva Neubauer, Simone Gantz, Herta Flor, Andreas Hug, and Haili Wang. "The cognitive impact of chronic low back pain: Positive effect of multidisciplinary pain therapy." Scandinavian Journal of Pain 17, no. 1 (October 1, 2017): 273–78. http://dx.doi.org/10.1016/j.sjpain.2017.07.019.
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AbstractObjectivesLittle is known about the affected cognitive problems in chronic low back pain patients. For this patient cohort research mostly focused on memory of pain, rather than cognitive difficulties related to pain. Chronic pain may be associated with specific (yet undefined) cognitive deficits that affect everyday behaviour. We set out to compare the cognitive function of patients with chronic low back pain (cLBP) in the course of multidisciplinary pain treatments before and after therapy.MethodsThirty-three patients with cLBP and 25 healthy controls between 20 and 70 years were recruited into the study. The inclusion criteria for patients were: (1) a history of at least 12 weeks of chronic myofascial low back pain without radicular pain sensation before enrolment; (2) grade II and higher chronicity according to von Korff; (3) no opioid medication. The patients recruited had a mean pain duration of 7.13 ± 7.16 years and reported a mean pain intensity of 6.62 ± 2.04 (visual analogue score, VAS). Their mean back function according to the Funktionsfragebogen Hannover (FFbH, a questionnaire comparable with the Health Assessment Questionnaire) was 52.39 ± 20.23%.At three time points (before therapy, 3 weeks and 6 months after therapy) the study subjects were assessed prospectively with a battery of visual memory tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). These included choice reaction time (CRT), pattern recognition memory (PRM) and spatial span (SSP). In parallel, the Trail-Making Test (TMT-A, TMT-B) and the Wechsler Adult Intelligence Scale (WAIS-III) were used to evaluate intelligence and cognitive flexibility.ResultsAt the beginning of MDPT (T1), it took patients with cLBP significantly longer than HC to complete TMT-A (38.29 ± 19.99 s vs 30.25 ± 14.19 s, p = 0.047) and TMT-B (72.10 ± 26.98 s vs 55.99 ± 22.14 s, p = 0.034). There were no significant differences between patients and HC in CRT, PRM and SSP. Three weeks (T2) and 6 months (T3) after MDPT, TMT-A reaction time of patients significantly improved by 6.5 s and 8.1 ms (38.3 ±19.9 s vs 31.8 ±12.3 s, p = 0.02 and 31.8 ± 12.3 s vs 30.2 ± 8.9 s, p = 0.021, respectively). The patients’ working memory was also better 6 months after MDPT (48.8 ± 11.1% at T1, 51.2 ±11.9% at T2, 57.1 ±10.9% at T3, p = 0.008). Significant correlations among pain, depression/anxiety, medication and neuropsychological tests were found.ConclusionsThese findings show that patients with cLBP have slowed speeds of information processing and working memory, but no alteration in attention and recognition memory. There are clearly interactions of cognitive function with pain, depression, anxiety, and medication. MDPT may improve the impaired cognitive function of patients with cLBP.ImplicationHealth professionals should contemplate the results from this study when planning therapy strategies especially when prescribing pain medications such opioids to patients with chronic low back pain.
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Huang, Shiyun, Hongfei Du, and Chen Qu. "Emotional responses to mortality salience: Behavioral and ERPs evidence." PLOS ONE 16, no. 3 (March 17, 2021): e0248699. http://dx.doi.org/10.1371/journal.pone.0248699.
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Terror Management Theory (TMT) suggests that death-related thoughts activate proximal defense which allows people to suppress or rationalize death awareness. So far there is no direct evidence to support the emotional response in the proximal defense process. The current research aimed to address this issue by examining behavioral (e.g., accuracy and reaction time) and neural responses (e.g., P1 and N400 amplitude) related to emotional arousal following death-related thoughts during proximal defense. Before engaged in emotional words (e.g., anxiety, fear and neutral) judgment task, participants answered questions that referred to emotional and physical changes about death to induce mortality salience (MS). In the control condition, participants received similar instructions concerning the experience of watching TV. Behavioral results showed that longer reaction time of words was seen in control group than MS group. The ERPs results showed that after reminders of death-related thoughts, in condition of MS, fear words elicited larger P1 ERP amplitudes, while the control group did not have this effect, which might reflect that emotional words caused different early attention patterns between MS group and control group. Moreover, compared with control group, larger N400 ERP amplitudes were elicited in condition of MS, suggesting larger cognitive inhibition of words processing caused by emotional reaction. The above results indicate that the early stages after mortality salience will induce fear and anxiety, but soon these negative emotions are suppressed and are at a lower level of accessibility. This result provides electrophysiological evidence for the proximal defense hypothesis of terror management theory.
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Trakarnsanga, Kongtana, Marieangela C. Wilson, Rebecca E. Griffiths, Ashley M. Toye, Lee Carpenter, Kate J. Heesom, Steve F. Parsons, David J. Anstee, and Jan Frayne. "Qualitative and Quantitative Comparison of the Proteome of Erythroid Cells Differentiated from Human iPSCs and Adult Erythroid Cells by Multiplex TMT Labelling and NanoLC-MS/MS." PLoS ONE 9, no. 7 (July 14, 2014): e100874. http://dx.doi.org/10.1371/journal.pone.0100874.
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Mai, Liping, Guodong He, Jing Chen, Jiening Zhu, Shaoxian Chen, Xinghua Hou, Hui Yang, et al. "Proteomic Analysis of Hypoxia-Induced Senescence of Human Bone Marrow Mesenchymal Stem Cells." Stem Cells International 2021 (August 27, 2021): 1–20. http://dx.doi.org/10.1155/2021/5555590.
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Background and Aim. The senescence of human bone marrow mesenchymal stem cells (hBMSCs) can be induced by oxidative stress, but the mechanism by which it occurs is not yet clear. Here, we performed an investigation on the pathogenesis of hypoxia-induced senescence through proteomic analyses and aimed to explore the mechanisms of stem cell senescence. Methods. Hypoxia in hBMSCs was induced for 0, 4, and 12 hours, and cellular senescence was evaluated by senescence-associated β-galactosidase (SA-β-gal) staining. Tandem mass tag (TMT) labeling was combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for differential proteomic analysis of hypoxia in hBMSCs. Parallel reaction monitoring (PRM) analysis was used to validate the candidate proteins. Verifications of signaling pathways were evaluated by western blotting. Cell apoptosis was evaluated using Annexin V/7-AAD staining by flow cytometry. The production of reactive oxygen species (ROS) was detected by the fluorescent probe 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA). Results. Cell senescence detected by SA-β-gal activity was higher in the 12-hour hypoxia-induced group. TMT analysis of 12-hour hypoxia-induced cells identified over 6000 proteins, including 686 differentially expressed proteins. Based on biological pathway analysis, we found that the senescence-associated proteins were predominantly enriched in the cancer pathways, PI3K-Akt pathway, and cellular senescence signaling pathways. CDK1, CDK2, and CCND1 were important nodes in PPI analyses. Moreover, the CCND1, UQCRH, and COX7C expressions were verified by PRM. Hypoxia induction for 12 hours in hBMSCs reduced CCND1 expression but promoted ROS production and cell apoptosis. Such effects were markedly reduced by the PI3K agonist, 740 Y-P, and attenuated by LY294002. Conclusions. Hypoxia of hBMSCs inhibited CCND1 expression but promoted ROS production and cell apoptosis through activating the PI3K-dependent signaling pathway. These findings provided a detailed characterization of the proteomic profiles related to hypoxia-induced senescence of hBMSCs and facilitated our understanding of the molecular mechanisms leading to stem cell senescence.
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Rampin, Olivier, Nathalie Jerôme, Audrey Saint-Albin, Christian Ouali, Frank Boué, Nicolas Meunier, and Birte L. Nielsen. "Where is the TMT? GC-MS analyses of fox feces and behavioral responses of rats to fear-inducing odors." Chemical Senses 43, no. 2 (December 8, 2017): 105–15. http://dx.doi.org/10.1093/chemse/bjx075.
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Gao, Xue, Yuming Zhou, Hongliu Sun, Desheng Liu, Jing Zhang, Junru Zhang, Weizhong Liu, and Xiaohong Pan. "Analysis of Comparative Proteomic and Potent Targets of Peniciketal A in Human Acute Monocytic Leukemia." Anti-Cancer Agents in Medicinal Chemistry 19, no. 4 (June 25, 2019): 515–27. http://dx.doi.org/10.2174/1871520619666190212124339.
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Background: Peniciketal A (Pe-A), a spiroketal compound, shows potent anticancer activities in human acute monocytic leukemia. However, the detailed mechanisms and potent targets of Pe-A remain largely unexplored. Here, we investigated the differentially expressed proteins between the Pe-A-treated group and the control group on human acute monocytic leukemia cell line THP-1. Methods: The DEPs were analyzed by the liquid chromatography-tandem mass spectrometry (LC-MS/MS) with TMT label. The function and feature of the identified proteins were analyzed by the bioinformatic analysis. Western blotting was used to evaluate protein expression. Results: The DEPs were primarily sub located in the cytoplasm and the nucleus by regulating 21 pathways enriched through the Kyoto Encyclopedia of Genes and Genomes (KEGG). Moreover, we preliminarily demonstrated that glucose-6-phosphate 1-dehydrogenase (G6PD), prolow-density lipoprotein receptor-related protein 1 (LRP1) and Calreticulin (CALR) might be the potent targets of Pe-A on death induction of THP-1 cells. Conclusion: Collectively, this study not only provides a global proteomic profile as the supplementary data of our previous studies but also provides interesting information that Pe-A may exert more bio-activities.
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Nguyen, Nam H. K., Huiyun Wu, Haiyan Tan, Junmin Peng, Jeffrey E. Rubnitz, Xueyuan Cao, Stanley Pounds, and Jatinder K. Lamba. "Global Proteomic Profiling of Pediatric AML: A Pilot Study." Cancers 13, no. 13 (June 24, 2021): 3161. http://dx.doi.org/10.3390/cancers13133161.
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Acute Myeloid Leukemia (AML) is a heterogeneous disease with several recurrent cytogenetic abnormalities. Despite genomics and transcriptomics profiling efforts to understand AML’s heterogeneity, studies focused on the proteomic profiles associated with pediatric AML cytogenetic features remain limited. Furthermore, the majority of biological functions within cells are operated by proteins (i.e., enzymes) and most drugs target the proteome rather than the genome or transcriptome, thus, highlighting the significance of studying proteomics. Here, we present our results from a pilot study investigating global proteomic profiles of leukemic cells obtained at diagnosis from 16 pediatric AML patients using a robust TMT-LC/LC-MS/MS platform. The proteome profiles were compared among patients with or without core binding factor (CBF) translocation indicated by a t(8;21) or inv(16) cytogenetic abnormality, minimal residual disease status at the end of the first cycle of chemotherapy (MRD1), and in vitro chemosensitivity of leukemic cells to cytarabine (Ara-C LC50). Our results established proteomic differences between CBF and non-CBF AML subtypes, providing insights to AML subtypes physiology, and identified potential druggable proteome targets such as THY1 (CD90), NEBL, CTSF, COL2A1, CAT, MGLL (MAGL), MACROH2A2, CLIP2 (isoform 1 and 2), ANPEP (CD13), MMP14, and AK5.
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Hulatt, Chris J., Irina Smolina, Adam Dowle, Martina Kopp, Ghana K. Vasanth, Galice G. Hoarau, René H. Wijffels, and Viswanath Kiron. "Proteomic and Transcriptomic Patterns during Lipid Remodeling in Nannochloropsis gaditana." International Journal of Molecular Sciences 21, no. 18 (September 22, 2020): 6946. http://dx.doi.org/10.3390/ijms21186946.
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Nutrient limited conditions are common in natural phytoplankton communities and are often used to increase the yield of lipids from industrial microalgae cultivations. Here we studied the effects of bioavailable nitrogen (N) and phosphorus (P) deprivation on the proteome and transcriptome of the oleaginous marine microalga Nannochloropsis gaditana. Turbidostat cultures were used to selectively apply either N or P deprivation, controlling for variables including the light intensity. Global (cell-wide) changes in the proteome were measured using Tandem Mass Tag (TMT) and LC-MS/MS, whilst gene transcript expression of the same samples was quantified by Illumina RNA-sequencing. We detected 3423 proteins, where 1543 and 113 proteins showed significant changes in abundance in N and P treatments, respectively. The analysis includes the global correlation between proteomic and transcriptomic data, the regulation of subcellular proteomes in different compartments, gene/protein functional groups, and metabolic pathways. The results show that triacylglycerol (TAG) accumulation under nitrogen deprivation was associated with substantial downregulation of protein synthesis and photosynthetic activity. Oil accumulation was also accompanied by a diverse set of responses including the upregulation of diacylglycerol acyltransferase (DGAT), lipase, and lipid body associated proteins. Deprivation of phosphorus had comparatively fewer, weaker effects, some of which were linked to the remodeling of respiratory metabolism.
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Schwill, Martin, Rastislav Tamaskovic, Aaron S. Gajadhar, Florian Kast, Forest M. White, and Andreas Plückthun. "Systemic analysis of tyrosine kinase signaling reveals a common adaptive response program in a HER2-positive breast cancer." Science Signaling 12, no. 565 (January 22, 2019): eaau2875. http://dx.doi.org/10.1126/scisignal.aau2875.
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Drug-induced compensatory signaling and subsequent rewiring of the signaling pathways that support cell proliferation and survival promote the development of acquired drug resistance in tumors. Here, we sought to analyze the adaptive kinase response in cancer cells after distinct treatment with agents targeting human epidermal growth factor receptor 2 (HER2), specifically those that induce either only temporary cell cycle arrest or, alternatively, apoptosis in HER2-overexpressing cancers. We compared trastuzumab, ARRY380, the combination thereof, and a biparatopic, HER2-targeted designed ankyrin repeat protein (DARPin; specifically, 6L1G) and quantified the phosphoproteome by isobaric tagging using tandem mass tag liquid chromatography/tandem mass spectrometry (TMT LC-MS/MS). We found a specific signature of persistently phosphorylated tyrosine peptides after the nonapoptotic treatments, which we used to distinguish between different treatment-induced cancer cell fates. Next, we analyzed the activation of serine/threonine and tyrosine kinases after treatment using a bait peptide chip array and predicted the corresponding active kinases. Through a combined system-wide analysis, we identified a common adaptive kinase response program that involved the activation of focal adhesion kinase 1 (FAK1), protein kinase C-δ (PRKCD), and Ephrin (EPH) family receptors. These findings reveal potential targets to prevent adaptive resistance to HER2-targeted therapies.
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Baysal Kıraç, Leyla, Özgül Ekmekçi, Nur Yüceyar, and Ayşe Sağduyu Kocaman. "Assessment of Early Cognitive Impairment in Patients with Clinically Isolated Syndromes and Multiple Sclerosis." Behavioural Neurology 2014 (2014): 1–5. http://dx.doi.org/10.1155/2014/637694.
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Objective. The aim of our study was to investigate the frequency and pattern of cognitive impairment in patients with clinically isolated syndromes and definite diagnosis of multiple sclerosis within the last 2 years.Methods. We assessed the cognitive status of 46 patients aged 18–49 years with clinically isolated syndromes or definite diagnosis of multiple sclerosis who have onset of their symptoms within the last 2 years. Patients were matched with 40 healthy participants for age, sex, and educational level. Neuropsychological assessment was performed by stroop test, paced auditory serial addition test (PASAT), controlled oral word association test (COWAT), clock drawing test, trail making test (TMT), faces symbol test (FST). Hamilton Depression Scale and Modified Fatigue Impact Scale were used to quantify the severity of any depression and fatigue the subjects might suffer.Results. 19.6% of early MS/CIS group failed at 4 and more tests and had significant cognitive impairment focused on attention, executive functions, memory, and learning. No significant relationship was found between cognitive impairment and disability and fatigue scores.Discussion. Cognitive impairment can be present from the earliest stage of multiple sclerosis. It should be considered among the main manifestations of MS even in the earliest stages of the disease.
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Končarević, Saša, Christopher Lößner, Karsten Kuhn, Thorsten Prinz, Ian Pike, and Hans-Dieter Zucht. "In-Depth Profiling of the Peripheral Blood Mononuclear Cells Proteome for Clinical Blood Proteomics." International Journal of Proteomics 2014 (March 3, 2014): 1–9. http://dx.doi.org/10.1155/2014/129259.
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Peripheral blood mononuclear cells (PBMCs) are an easy accessible cellular part of the blood organ and, along with platelets, represent the only site of active gene expression in blood. These cells undergo immunophenotypic changes in various diseases and represent a peripheral source of monitoring gene expression and posttranslational modifications relevant to many diseases. Little is known about the source of many blood proteins and we hypothesise that release from PBMCs through active and passive mechanisms may account for a substantial part of the plasma proteome. The use of state-of-the-art proteomic profiling methods in PBMCs will enable minimally invasive monitoring of disease progression or response to treatment and discovery of biomarkers. To achieve this goal, detailed mapping of the PBMC proteome using a sensitive, robust, and quantitative methodological setup is required. We have applied an indepth gel-free proteomics approach using tandem mass tags (TMT), unfractionated and SCX fractionated PBMC samples, and LC-MS/MS with various modulations. This study represents a benchmark in deciphering the PBMC proteome as we provide a deep insight by identifying 4129 proteins and 25503 peptides. The identified proteome defines the scope that enables PBMCs to be characterised as cellular major biomarker pool within the blood organ.
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Russo, Rosita, Nunzia Matrone, Valentina Belli, Davide Ciardiello, Mariangela Valletta, Sabrina Esposito, Paolo Vincenzo Pedone, Fortunato Ciardiello, Teresa Troiani, and Angela Chambery. "Macrophage Migration Inhibitory Factor Is a Molecular Determinant of the Anti-EGFR Monoclonal Antibody Cetuximab Resistance in Human Colorectal Cancer Cells." Cancers 11, no. 10 (September 25, 2019): 1430. http://dx.doi.org/10.3390/cancers11101430.
Full textAbstract:
Background: The clinical impact of the monoclonal antibody cetuximab targeting the EGFR in colorectal cancer (CRC) is widely recognized. Nevertheless, the onset of cetuximab resistance is a serious issue that limits the effectiveness of this drug in targeted therapies. Unraveling the molecular players involved in cancer resistance is the first step towards the identification of alternative signaling pathways that can be targeted to circumvent resistance mechanisms restoring the efficacy of therapeutic treatments in a tailored manner. Methods: By applying a nanoLC-MS/MS TMT isobaric labeling-based approach, we have delineated a molecular hallmark of cetuximab-resistance in CRC. Results: We identified macrophage migration inhibitory factor (MIF) as a molecular determinant capable of triggering cancer resistance in sensitive human CRC cells. Blocking the MIF axis in resistant cells by a selective MIF inhibitor restores cell sensitivity to cetuximab. The combined treatment with cetuximab and the MIF inhibitor further enhanced cell growth inhibition in CRC resistant cell lines with a synergistic effect depending on inhibition of key downstream effectors of the MAPK and AKT signaling pathways. Conclusions: Collectively, our results suggest the association of MIF signaling and its dysregulation to cetuximab drug resistance, paving the way to the development of personalized combination therapies targeting the MIF axis.
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Purdy, Graeme M., Marina A. James, Paige K. Wakefield, Rachel J. Skow, Sean Van Diepen, Linda E. May, Margie H. Davenport, and Craig D. Steinback. "Maternal cardioautonomic responses during and following exercise throughout pregnancy." Applied Physiology, Nutrition, and Metabolism 44, no. 3 (March 2019): 263–70. http://dx.doi.org/10.1139/apnm-2018-0397.
Full textAbstract:
Blood pressure regulation during pregnancy is poorly understood. Cardiovagal baroreflex gain (BRG) is an important contributor to blood pressure regulation through its influence on heart rate. Heart rate fluctuations occur in response to various physiological stimuli and can be measured using heart rate variability (HRV). It is unclear how these mechanisms operate during pregnancy, particularly with regard to exercise. We examined BRG and HRV prior to, during, and following prenatal exercise. Forty-three pregnant (n = 10 first trimester (TM1), n = 17 second trimester (TM2), n = 16 third trimester (TM3)) and 20 nonpregnant (NP) women underwent an incremental peak exercise test. Beat-by-beat blood pressure (photoplethysmography) and heart rate (lead II electrocardiogram) were measured throughout. BRG (the slope of the relationship between fluctuations in systolic blood pressure and the R–R interval) and HRV (root mean square of the successive differences; RMSSD) were assessed at rest, during steady-state exercise (EX), and during active recovery. BRG decreased with gestation and was lower in the TM3 group than in the NP group (17.9 ± 6.9 ms/mm Hg vs 24.8 ± 7.4 ms/mm Hg, p = 0.017). BRG was reduced during EX in all groups. Resting HRV (RMSSD) also decreased with gestation and was lower in the TM3 group than in the NP group (29 ± 17 ms vs 48 ± 20 ms, p < 0.001). RMSSD was blunted during EX in all groups compared with rest. During active recovery, RMSSD was further blunted compared with EX in the NP group but not during pregnancy (TM1, TM2, and TM3). Compared with the nonpregnant controls, the pregnant women had lower BRG and HRV at rest, but comparable cardioautonomic control during both exercise and active recovery following peak exercise.
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Bini, Luca, Domitille Schvartz, Chiara Carnemolla, Roberta Besio, Nadia Garibaldi, Jean-Charles Sanchez, Antonella Forlino, and Laura Bianchi. "Intracellular and Extracellular Markers of Lethality in Osteogenesis Imperfecta: A Quantitative Proteomic Approach." International Journal of Molecular Sciences 22, no. 1 (January 4, 2021): 429. http://dx.doi.org/10.3390/ijms22010429.
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Osteogenesis imperfecta (OI) is a heritable disorder that mainly affects the skeleton. The inheritance is mostly autosomal dominant and associated to mutations in one of the two genes, COL1A1 and COL1A2, encoding for the type I collagen α chains. According to more than 1500 described mutation sites and to outcome spanning from very mild cases to perinatal-lethality, OI is characterized by a wide genotype/phenotype heterogeneity. In order to identify common affected molecular-pathways and disease biomarkers in OI probands with different mutations and lethal or surviving phenotypes, primary fibroblasts from dominant OI patients, carrying COL1A1 or COL1A2 defects, were investigated by applying a Tandem Mass Tag labeling-Liquid Chromatography-Tandem Mass Spectrometry (TMT LC-MS/MS) proteomics approach and bioinformatic tools for comparative protein-abundance profiling. While no difference in α1 or α2 abundance was detected among lethal (type II) and not-lethal (type III) OI patients, 17 proteins, with key effects on matrix structure and organization, cell signaling, and cell and tissue development and differentiation, were significantly different between type II and type III OI patients. Among them, some non–collagenous extracellular matrix (ECM) proteins (e.g., decorin and fibrillin-1) and proteins modulating cytoskeleton (e.g., nestin and palladin) directly correlate to the severity of the disease. Their defective presence may define proband-failure in balancing aberrances related to mutant collagen.
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Polak, Iwona, Elżbieta Łopieńska-Biernat, Robert Stryiński, Jesús Mateos, and Mónica Carrera. "Comparative Proteomics Analysis of Anisakis simplex s.s.—Evaluation of the Response of Invasive Larvae to Ivermectin." Genes 11, no. 6 (June 26, 2020): 710. http://dx.doi.org/10.3390/genes11060710.
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Ivermectin (IVM), an antiparasitic drug, has a positive effect against Anisakis simplex s.s. infection and has been used for the treatment and prevention of anisakiasis in humans. However, the molecular mechanism of action of IVM on A. simplex s.s. remains unknown. Herein, tandem mass tag (TMT) labeling and extensive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis were used to identify the effect of IVM on the proteome of A. simplex s.s. in vitro. During the study, 3433 proteins, of which 1247 had at least two protein unique peptides, were identified. Comparative proteomics analysis revealed that 59 proteins were differentially regulated (DRPs) in IVM-treated larvae, of which 14 proteins were upregulated and 38 were downregulated after 12 h of culture, but after 24 h, 12 proteins were upregulated and 22 were downregulated. The transcription level of five randomly selected DRPs was determined by real-time PCR as a supplement to the proteomic data. The functional enrichment analysis showed that most of the DRPs were involved in oxidoreductase activity, immunogenicity, protein degradation, and other biological processes. This study has, for the first time, provided comprehensive proteomics data on A. simplex s.s. response to IVM and might deliver new insight into the molecular mechanism by which IVM acts on invasive larvae of A. simplex s.s.
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Thabit, Sara, Heba Handoussa, Mariana Roxo, Bruna Cestari de Azevedo, Nesrine S.E. El Sayed, and Michael Wink. "Styphnolobium japonicum (L.) Schott Fruits Increase Stress Resistance and Exert Antioxidant Properties in Caenorhabditis elegans and Mouse Models." Molecules 24, no. 14 (July 19, 2019): 2633. http://dx.doi.org/10.3390/molecules24142633.
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Styphnolobium japonicum (L.) Schott is a popular Asian tree widely used in traditional medicine. The current study explored the potential stress resistance and antioxidant activities of its fruits. Phytochemical profiling of the hydroalcoholic fruit extract was done via high performance liquid chromatography-photodiode array-electrospray ionization-mass/mass (HPLC-PDA-ESI-MS/MS). Twenty four phenolic constituents were tentatively identified in the extract. The Caenorhabditis elegans (C. elegans) nematode model in addition to trimethyltin (TMT)-induced neurotoxicity mouse model were used for in vivo evaluation of its antioxidant properties. The ability of the extract to enhance stress resistance was manifested through increasing survival rate by 44.7% and decreasing basal reactive oxygen species (ROS) levels by 72.3% in C. elegans. In addition, the extract increased the levels of the stress response enzyme superoxide dismutase-3 (Sod-3) by 55.5% and decreased the expression of heat shock protein-16.2 (Hsp-16.2) in nematodes, which had been challenged by juglone, by 21%. Using a mouse model, the extract significantly decreased the expression of the oxidative stress marker malondialdehyde (MDA). Furthermore, an elevation in the levels of the antioxidant marker glutathione (GSH), SOD and heme oxygenase-1 (HO-1) enzymes were observed. Our findings imply that Styphnolobium japonicum has the potential to be used in future studies focusing on diseases associated with oxidative stress.
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Yuan, Lingyun, Jie Wang, Shilei Xie, Mengru Zhao, Libing Nie, Yushan Zheng, Shidong Zhu, Jinfeng Hou, Guohu Chen, and Chenggang Wang. "Comparative Proteomics Indicates That Redox Homeostasis Is Involved in High- and Low-Temperature Stress Tolerance in a Novel Wucai (Brassica campestris L.) Genotype." International Journal of Molecular Sciences 20, no. 15 (August 1, 2019): 3760. http://dx.doi.org/10.3390/ijms20153760.
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The genotype WS-1, previously identified from novel wucai germplasm, is tolerant to both low-temperature (LT) and high-temperature (HT) stress. However, it is unclear which signal transduction pathway or acclimation mechanisms are involved in the temperature-stress response. In this study, we used the proteomic method of tandem mass tag (TMT) coupled with liquid chromatography-mass spectrometry (LC-MS/MS) to identify 1022 differentially expressed proteins (DEPs) common to WS-1, treated with either LT or HT. Among these 1022 DEPs, 172 were upregulated in response to both LT and HT, 324 were downregulated in response to both LT and HT, and 526 were upregulated in response to one temperature stress and downregulated in response to the other. To illustrate the common regulatory pathway in WS-1, 172 upregulated DEPs were further analyzed. The redox homeostasis, photosynthesis, carbohydrate metabolism, heat-shockprotein, and chaperones and signal transduction pathways were identified to be associated with temperature stress tolerance in wucai. In addition, 35S:BcccrGLU1 overexpressed in Arabidopsis, exhibited higher reduced glutathione (GSH) content and reduced glutathione/oxidized glutathione (GSH/GSSG) ratio and less oxidative damage under temperature stress. This result is consistent with the dynamic regulation of the relevant proteins involved in redox homeostasis. These data demonstrate that maintaining redox homeostasis is an important common regulatory pathway for tolerance to temperature stress in novel wucai germplasm.
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Griesser, Eva, Hannah Wyatt, Sara Ten Have, Birgit Stierstorfer, Martin Lenter, and Angus I. Lamond. "Quantitative Profiling of the Human Substantia Nigra Proteome from Laser-capture Microdissected FFPE Tissue." Molecular & Cellular Proteomics 19, no. 5 (March 4, 2020): 839–51. http://dx.doi.org/10.1074/mcp.ra119.001889.
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Laser-capture microdissection (LCM) allows the visualization and isolation of morphologically distinct subpopulations of cells from heterogeneous tissue specimens. In combination with formalin-fixed and paraffin-embedded (FFPE) tissue it provides a powerful tool for retrospective and clinically relevant studies of tissue proteins in a healthy and diseased context. We first optimized the protocol for efficient LCM analysis of FFPE tissue specimens. The use of SDS containing extraction buffer in combination with the single-pot solid-phase-enhanced sample preparation (SP3) digest method gave the best results regarding protein yield and protein/peptide identifications. Microdissected FFPE human substantia nigra tissue samples (∼3,000 cells) were then analyzed, using tandem mass tag (TMT) labeling and LC-MS/MS, resulting in the quantification of >5,600 protein groups. Nigral proteins were classified and analyzed by abundance, showing an enrichment of extracellular exosome and neuron-specific gene ontology (GO) terms among the higher abundance proteins. Comparison of microdissected samples with intact tissue sections, using a label-free shotgun approach, revealed an enrichment of neuronal cell type markers, such as tyrosine hydroxylase and alpha-synuclein, as well as proteins annotated with neuron-specific GO terms. Overall, this study provides a detailed protocol for laser-capture proteomics using FFPE tissue and demonstrates the efficiency of LCM analysis of distinct cell subpopulations for proteomic analysis using low sample amounts.