Lipid changes within the epidermis of living skin equivalents observed across a time-course by MALDI-MS imaging and profiling

© 2015 Mitchell et al. Abstract Background: Mass spectrometry imaging (MSI) is a powerful tool for the study of intact tissue sections. Here, its application to the study of the distribution of lipids in sections of reconstructed living skin equivalents during their development and maturation is described. Methods: Living skin equivalent (LSE) samples were obtained at 14 days development, re-suspended in maintenance medium and incubated for 24 h after delivery. The medium was then changed, the LSE re-incubated and samples taken at 4, 6 and 24 h time points. Mass spectra and mass spectral images were recorded from 12 μm sections of the LSE taken at each time point for comparison using matrix assisted laser desorption ionisation mass spectrometry. Results: A large number of lipid species were identified in the LSE via accurate mass-measurement MS and MSMS experiments carried out directly on the tissue sections. MS images acquired at a spatial resolution of 50 μm × 50 μm showed the distribution of identified lipids within the developing LSE and changes in their distribution with time. In particular development of an epidermal layer was observable as a compaction of the distribution of phosphatidylcholine species. Conclusions: MSI can be used to study changes in lipid composition in LSE. Determination of the changes in lipid distribution during the maturation of the LSE will assist in the identification of treatment responses in future investigations

Descriptions of a new species of Physa from the Pleistocene of Florida

http://deepblue.lib.umich.edu/bitstream/2027.42/56603/1/OP164.pd

PSYCHO/PHYSIOLOGICAL EFFECTS OF VESTIBULAR AND AUDIO STIMULATION: The Trinity Table

The purpose of this research was to investigate the effects of vestibular and audio stimulation through the use of music and the Trinity Table TM, a horizontal motion machine, on psychophysiological changes and perception of altered states of consciousness in average adults

Mass spectrometry imaging of 3D tissue models

A 3D cell culture is an artificially created environment in which cells are permitted to grow/interact with their surroundings in all three dimensions. Derived from 3D cell culture, organoids are generally small‐scale constructs of cells that are fabricated in the laboratory to serve as 3D representations of in vivo tissues and organs. Due to regulatory, economic and societal issues concerning the use of animals in scientific research it seems clear that the use of 3D cell culture and organoids in for example early stage studies of drug efficacy and toxicity will increase. The combination of such 3D tissue models with mass spectrometry imaging provides a label free methodology for the study of drug absorption/penetration, drug efficacy/toxicity and drug biotransformation. In this article, some of the successes achieved to date and challenges to be overcome before this methodology is more widely adopted are discussed

Howard Gardner's multiple intelligences theory, outcomes-based education and curriculum implementation in South Africa : a critique of music education in the general education and training phase

This study examines the current curriculum for primary schools in South Africa – Curriculum 2005 (C2005) and the subsequent Revised National Curriculum Statement (RNCS), with Outcomes-Based Education (OBE) as its fundamental educational approach - with specific reference to the place of music education in it. While the underlying principles and scope of this curriculum has many positive attributes, numerous studies have shown that there are still major stumbling blocks in the way of its successful implementation. Since the emphasis of the Arts and Culture Learning Area is on the nurturing of generic values and attitudes towards culture, it does not provide for sufficient development of subject-specific musical skills and knowledge. Instead this vital form of musical learning continues to be provided in the form of extra-curricular music programmes by those few schools who have the staff expertise and the funding to do so. Music therefore remains accessible only to the privileged few. .Although C2005 encourages and requires significant levels of integration in Learning Outcomes and Assessment Standards within and across Learning Areas, this is currently one of the least successful aspects of its implementation. This lack of success, it is argued, is in part the result of severe limitations in the training of teachers and the availability of necessary resources in schools, and in part the result of the curriculum’s own limited interpretation of integration. Psychologist Dr Howard Gardner’s Theory of Multiple Intelligences is a holistic approach to education that stresses, amongst other things, that Musical Intelligence is one of eight vital forms of intelligence that should be accessible to all children. It is argued that educational approaches based on Gardner’s Multiple Intelligences Theory provide some insights into the integration of Musical Intelligence with other forms of learning that may usefully be applied in C2005

Matrix-assisted ionisation in vacuum mass spectrometry and imaging on a modified quadrupole-quadrupole-time-of-flight mass spectrometer

Matrix-Assisted Ionisation in Vacuum (MAIV) is a new ionisation technique which ionises non-volatile compounds producing electrospray ionisation-like spectra. Its simple, matrix-assisted laser desorption/ionisation-like sample preparation allows for rapid analysis, with no requirement for external energy in the form of a laser or high voltage to produce ions. Ionisation occurs when the matrix (often 3-nitrobenzonitrile) is exposed to sub-ambient pressure. Here, the first use of this revolutionary new ionisation technique to image biological samples is reported. A commercial quadrupole-quadrupole-time-of-flight mass spectrometer was modified to incorporate control of the ion source pressure and a reduced sampling cone orifice diameter. In initial experiments, optimisation of source pressure and matrix composition was carried out to increase the longevity of ion formation. It was noted during these experiments that ion production was only observed when the sample was directly under the sampling cone. Optimisation of sample extraction into the MAIV matrix by the addition of 5 % chloroform enabled MAIV mass spectrometry imaging of lipids in rat brain sections to be carried out in raster imaging mode. Modification of the size and position of the sampling cone improved the selectivity obtainable in these images. Although the quality of these initial images is relatively poor, work is underway to improve the spatial resolution by further modification of the ion source and progress is reported

The investigation of unexpected arsenic compounds observed in routine biological monitoring urinary speciation analysis

This study investigates the identity of two unexpected arsenic species found separately in a number of urine samples sent to the Health and Safety Executive's Health and Safety Laboratory for arsenic speciation (arsenobetaine, AB; arsenite, As3+; arsenate, As5+; monomethylarsonic acid, MMA5+; and dimethylarsinic acid, DMA5+). Micro liquid chromatography coupled to inductively coupled plasma mass spectrometry (μLC-ICP-MS) and electrospray time of flight tandem mass spectrometry (ESI-QqTOF-MS/MS) were used to identify the two arsenic peaks by comparison to several characterized arsenicals: arsenocholine, AC; trimethyl arsine oxide, TMAO; dimethylarsenoacetate, DMAA; dimethylarsenoethanol, DMAE; thio-dimethylarsinate, thio-DMA; thio-dimethylarsenoacetate, thio-DMAA and thio-dimethylarsenoethanol, thio-DMAE. The results from both the ICP-MS and ESI-QqTOF-MS/MS investigations indicate that the unexpected arsenic species termed peak 1 was thio-DMA. While the unexpected arsenic species termed peak 2 has yet to be identified, this investigation shows that it was not AC, TMAO, DMAA, DMAE, thio-DMA, thio-DMAA or thio-DMAE. This study demonstrates the incidence of unexpected arsenic species in both routine and non-routine urine samples from both workers and hospital patients

Coping strategies among adolescents with chronic headache and mental health problems: a cross-sectional population-based study

To examine prevalence of mental health problems among adolescents with chronic headache and compare internal and external coping strategies in young people with chronic headaches with and without mental health problems. This study is based on a cross-sectional survey undertaken in Akershus County in Norway. A total of 19,985 adolescents were included in the study, covering lower secondary and upper secondary students, aged 13–19 years. Chronic headache was measured with a single item question based on headache frequency. Mental health was assessed by using the strengths and difficulties questionnaire (SDQ). Internal and external coping strategies were assessed through seven options for answering the question: What do you do/what happens when you are burdened by painful thoughts and feelings? Adolescents with chronic headaches showed more frequent mental health problems overall (23 %) compared to those without chronic headache (6 %). Logistic regression analyses showed that those adolescents having both chronic headaches and comorbid mental health problems more frequently used internal coping strategies, such as keeping feelings inside (OR 2.05), using abusive substances (OR 1.79) and talking oneself out of problems (OR 1.55), compared to those without mental health problems. Groups with mental health problems, especially with chronic headache, less frequently used the external strategy of talking to others about their problem than controls (OR 0.7–0.8). Factor analyses revealed significant differences in profiles of coping strategies between groups. We suggest that attention should be paid towards the high risk group that has both chronic headaches and mental health problems and their tendency to use destructive internal coping strategies

Precision pharmacology: Mass spectrometry imaging and pharmacokinetic drug resistance

Failure of systemic cancer treatment can be, at least in part, due to the drug not being delivered to the tumour at sufficiently high concentration and/or sufficiently homogeneous distribution; this is termed as “pharmacokinetic drug resistance”. To understand whether a drug is being adequately delivered to the tumour, “precision pharmacology” techniques are needed. Mass spectrometry imaging (MSI) is a relatively new and complex technique that allows imaging of drug distribution within tissues. In this review we address the applicability of MSI to the study of cancer drug distribution from the bench to the bedside. We address: (i) the role of MSI in pre-clinical studies to characterize anti-cancer drug distribution within the body and the tumour, (ii) the application of MSI in pre-clinical studies to define optimal drug dose or schedule, combinations or new drug delivery systems, and finally (iii) the emerging role of MSI in clinical research