Cross-Platform Comparison of Untargeted and Targeted Lipidomics Approaches on Aging Mouse Plasma.

Lipidomics - the global assessment of lipids - can be performed using a variety of mass spectrometry (MS)-based approaches. However, choosing the optimal approach in terms of lipid coverage, robustness and throughput can be a challenging task. Here, we compare a novel targeted quantitative lipidomics platform known as the Lipidyzer to a conventional untargeted liquid chromatography (LC)-MS approach. We find that both platforms are efficient in profiling more than 300 lipids across 11 lipid classes in mouse plasma with precision and accuracy below 20% for most lipids. While the untargeted and targeted platforms detect similar numbers of lipids, the former identifies a broader range of lipid classes and can unambiguously identify all three fatty acids in triacylglycerols (TAG). Quantitative measurements from both approaches exhibit a median correlation coefficient (r) of 0.99 using a dilution series of deuterated internal standards and 0.71 using endogenous plasma lipids in the context of aging. Application of both platforms to plasma from aging mouse reveals similar changes in total lipid levels across all major lipid classes and in specific lipid species. Interestingly, TAG is the lipid class that exhibits the most changes with age, suggesting that TAG metabolism is particularly sensitive to the aging process in mice. Collectively, our data show that the Lipidyzer platform provides comprehensive profiling of the most prevalent lipids in plasma in a simple and automated manner

The Lid Domain of Caenorhabditis elegans Hsc70 Influences ATP Turnover, Cofactor Binding and Protein Folding Activity

Hsc70 is a conserved ATP-dependent molecular chaperone, which utilizes the energy of ATP hydrolysis to alter the folding state of its client proteins. In contrast to the Hsc70 systems of bacteria, yeast and humans, the Hsc70 system of C. elegans (CeHsc70) has not been studied to date

Discriminant and Concurrent Validity of Two Commonly Used Measures of Test Anxiety

For each of two groups of 34 and 71 undergraduate college students respectively categorized as clinically test anxious (CTA sample) and as non-test anxious (NTA sample), evidence was sought regarding the discriminant validity and the concurrent validity of each of two measures—the 20-item self-report Test Anxiety Inventory (TAI) and the 8-item behavior analogue measure of test-taking performance entitled Anagram Solution Task. Normative information was also obtained for each measure to provide a basis for classifying students as being test anxious or as being non-test anxious. The statistical outcomes led to the conclusion that both the TAI and AST exhibit substantial discriminant validity, but relatively little concurrent validity. The creation of 90% confidence scoring intervals for each of the two measures shows considerable promise as a means for identifying students with differential levels of test anxiety. These instruments appear to afford a basis for both counseling and research purposes. Future directions in the assessment of test anxiety are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67405/2/10.1177_001316448204200428.pd

Cross-Platform Comparison of Untargeted and Targeted Lipidomics Approaches on Aging Mouse Plasma.

Lipidomics - the global assessment of lipids - can be performed using a variety of mass spectrometry (MS)-based approaches. However, choosing the optimal approach in terms of lipid coverage, robustness and throughput can be a challenging task. Here, we compare a novel targeted quantitative lipidomics platform known as the Lipidyzer to a conventional untargeted liquid chromatography (LC)-MS approach. We find that both platforms are efficient in profiling more than 300 lipids across 11 lipid classes in mouse plasma with precision and accuracy below 20% for most lipids. While the untargeted and targeted platforms detect similar numbers of lipids, the former identifies a broader range of lipid classes and can unambiguously identify all three fatty acids in triacylglycerols (TAG). Quantitative measurements from both approaches exhibit a median correlation coefficient (r) of 0.99 using a dilution series of deuterated internal standards and 0.71 using endogenous plasma lipids in the context of aging. Application of both platforms to plasma from aging mouse reveals similar changes in total lipid levels across all major lipid classes and in specific lipid species. Interestingly, TAG is the lipid class that exhibits the most changes with age, suggesting that TAG metabolism is particularly sensitive to the aging process in mice. Collectively, our data show that the Lipidyzer platform provides comprehensive profiling of the most prevalent lipids in plasma in a simple and automated manner

Signal transduction in CHO-cells stably transfected with domain-selective forms of murine ACE

Membrane-bound human angiotensin-converting enzyme (ACE) has been reported to initiate an intracellular signaling after interaction with substrates or inhibitors. Somatic ACE is known to contain two distinct, extracellular catalytic centers. We analyzed the signal transduction mechanisms in cells transfected with different forms of murine ACE (mACE) and investigated whether the two domains are similarly involved in these processes. For this purpose, CHO-cells were stably transfected with mACE or with its domain-selective mutants. Besides these modified cellular models human umbilical vein endothelial cells were used in this study. Signal transduction molecules like JNK and c-Jun were analyzed after activation of cells with several ACE-substrates and -inhibitors. ACE-targeting compounds like substrates, inhibitors, or even the ACE product angiotensin-II induce in mACE-expressing cells a signal transduction response. These processes are also evoked by partially inactivated forms of mACE and result finally in an enhanced cyclooxygenase-2 transcription. Surprisingly, also the membrane-bound ACE activity is influenced by ACE-targeted interventions. Our data suggest that the two catalytic domains of mACE do not function independently; but the signal transduction is influenced by a negative co-operativity of the two catalytic domains. This work underlines that ACE has indeed receptor-like properties which occur in a species-specific manner

Cognitive-Behavioural Treatment of Musical Performance Anxiety

This pilot study evaluated the effectiveness of a treatment approach for musical performance anxiety that combined progressive muscle relaxation, cognitive therapy, and temperature biofeedback training. Twelve competent pianists who complained of debilitating performance anxiety were randomly assigned to a treatment group; and eight subjects were placed on a wait-list control group. Following a six-week programme of group therapy, signifi- cant differences between pre- and post-measurements were observed for the treatment group in performance anxiety, and trait anxiety. The results suggest that it is possible to lower debilitating stage fright in performance- anxious musicians through a cognitive-behavioural treatment approach.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69063/2/10.1177_0305735689171002.pd