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Biochemical Contributors to Exercise Fatigue
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
Arthur J. Cheng, Maja Schlittler, Håkan Westerblad
The rate of cross-bridge cycling, and hence the speed of contraction, is determined by the MyHC isoform and in human muscle type 1 is the slowest, type 2A intermediate, and type 2X the fastest; type 2B, which is not expressed in human muscle, is faster than type 2X. The expression pattern of numerous other protein isoforms also differs between muscle fibres. For some protein isoforms there is a pattern of gene co-expression where, for instance, the slow MyHC type 1 is co-expressed with “slow” isoforms of other proteins. However, this is not always the case, and gene expression of different protein isoforms is controlled by multiple interacting mechanisms (80).
Recent advances in the management of CSF rhinorrhea
Published in Jyotirmay S. Hegde, Hemanth Vamanshankar, CSF Rhinorrhea, 2020
Hemanth Vamanshankar, Jyotirmay S Hegde
Tau proteins are a group of highly soluble intraneural protein isoforms that play a primary role in maintaining the stability of microtubules in axons. They were first identified in 1975, and their increased concentration in CSF is a diagnostic biomarker for Alzheimer’s disease.1 Their concentration in serum is much lower, with a CSF:serum ratio of 10:1, hence they are almost undetectable in other body fluids.2 Oudart et al. assessed 26 patients with a history of CSF rhinorrhea. Tau protein concentration in the collected samples were assessed by a sandwich ELISA, and were found to have a mean value of 711 ng/L in the CSF rhinorrhea group, as compared to a mean value of 87 ng/L in the non-CSF leakage group (viral or allergic rhinitis). The main advantage of tau protein markers is in the fact that their value is not affected by blood contamination, as compared to other markers like β2-transferrin and β-trace protein. This may be of advantage in cases of CSF rhinorrhea that occur following head trauma.3
Precision medicine in coronary artery disease
Published in Debmalya Barh, Precision Medicine in Cancers and Non-Communicable Diseases, 2018
Melvin George, Luxitaa Goenka, Sandhiya Selvarajan
A study was conducted to evaluate the modifications in the plasma protein map during unstable angina (UA) and AMI using proteomics. The protein plasma levels were quantified among patients with AMI (n = 11) and UA (n = 9). The control group was comprised of age-matched volunteers. The proteins that were analyzed included alpha-1-antitrypsin (AAT), apolipoprotein A-I, fibrinogen gamma chain, immunoglobulin gamma heavy chain, and albumin. The main finding of this study was that different AAT isoforms change in plasma during an acute coronary syndrome (ACS). Seven different AAT isoforms were seen in the plasma of control samples. However, the AAT isoform 1 was absent in the ACS samples. In the study, there was also a significant reduction of isoforms 5, 6, and 7 in the AMI samples when compared with UA samples. The fibrinogen gamma chain 1 and 2 were increased in AMI patients compared to UA patients. Five apolipoprotein A-I isoforms were also identified, but these were reduced in plasma from AMI patients with respect to UA patients. The γ-immunoglobulin heavy chains were identified and were found to be increased in the plasma among ACS patients. Thus, the proteomic analysis will help in the mapping of the protein isoforms that are expressed in plasma during an ACS (Mateos-Cáceres et al., 2004).
Targeted therapy in acute myeloid leukemia: current status and new insights from a proteomic perspective
Published in Expert Review of Proteomics, 2020
Anneke D. van Dijk, Eveline S. J. M. de Bont, Steven M. Kornblau
based proteomics is a well-established technique and commonly used for identification and quantitative assessment of proteins within complex samples. MS is based on the measurement of charged ions from a protein analyte. To increase the sensitivity of the measurement, different compounds in very complex samples can be separated by gel electrophoresis, liquid chromatography (LC-MS), gas chromatography (GC-MS), or another mass spectrometer (MS-MS) prior to analysis. Historically, there are two ways to detect proteins by MS including using a ‘top-down’ or ‘bottom-up’ approach [43,44]. After protein extraction, the top-down approach separates and quantitates purified intact proteins (ions) using 2D gel electrophoresis or MS-MS and enables the characterization of unique proteoforms including degradation products, protein isoforms, post-translational modifications (PTMs), as well as low-mass proteins. The usage of the top-down approach is however often limited to low-throughput individual protein studies. In contrast, the bottom-up approach is more broadly used for analyzing more complex protein mixtures. Bottom-up proteomics using LC-MS is also known as ‘shotgun proteomics’ [45]. With this technique, the proteins are digested into peptides by enzymes (e.g. trypsin) before analysis by MS. Since only one fraction of all produced peptides (ions) is restored into a protein, PTMs and alternative isoform information will not be recovered in bottom-up proteomics. Both approaches are thus associated with advantages and disadvantages and choice of technique depends on the research aim of the study.
Proteomics for cancer drug design
Published in Expert Review of Proteomics, 2019
Amanda Haymond, Justin B. Davis, Virginia Espina
A mindset transformation needs to occur in drug discovery for drug developers, scientists, investors, and clinicians. We need to discard the concepts of ‘one hit wonder drugs’ and ‘one drug/one target’. These concepts are naïve assumptions and fail to account for biological variability between individuals as well as similarities between protein motifs and ligand binding domains. Alternative splicing of mRNA creates various protein isoforms, which are not routinely profiled in clinical specimens. The biological redundancy in protein motifs and ligand binding domains potentially creates specificity issues for drugs and small peptides. Characterizing functional phenotypes of individual cancer specimens, utilizing the full spectrum of proteomics technologies, will eventually permit true designer drug for individualized cancer treatments.
Modulation of Inflammation-Related Genes in the Cornea of a Mouse Model of Dry Eye upon Treatment with Cyclosporine Eye Drops
Published in Current Eye Research, 2019
Philippe Daull, Stefano Barabino, Laurence Feraille, Karima Kessal, Mylene Docquier, Stephane Melik Parsadaniantz, Christophe Baudouin, Jean-Sébastien Garrigue
TGFB3 and IL1RAP also had ρ-values higher than 0.4, suggesting a link between CFS and their modulation. The TGFB3 gene correlated quite well with CFS (ρ = 0.406), while surprisingly TGFB1 did not, even though it was significantly modulated by the different treatments. TGF-β1, -β2, and -β3 are the three protein isoforms that have been identified in mammals. All three protein isoforms display overlapping and distinct spatial and temporal patterns of expression, and each isoform plays a distinct role. The TGF-β1protein was described as an anti-inflammatory factor,26,53 and TGFB1 gene overexpression upon anti-inflammatory treatments might explain the improvement in DED mice’s CFS condition. However, the TGF-β1 protein has also been implicated in T-helper cell differentiation54 and the production of pro-inflammatory IL17 interleukin, complicating the identification of its role in the CFS reduction observed. The TGF-β3 protein was described to play a pro-inflammatory role,55 but, like the TGF-β1 protein, the TGFB3 gene product was also identified as a bi-functional modulator of the immune system. Thus, the concomitant reduction in TGFB3 and increase in TGFB1 gene expression might support the improvement seen in CFS scores upon treatment. However, these two factors also need to be evaluated at the protein level, as the mRNA levels do not necessarily correlate with the protein distribution.