Ultraviolet Photodissociation of the N-Methylpyridinium Ion: Action Spectroscopy and Product Characterization

The ultraviolet photodissociation of gas-phase N-methylpyridinium ions is studied at room temperature using laser photodissociation mass spectrometry and structurally diagnostic ion-molecule reaction kinetics. The C5H5N-CH3+ (m/z 94), C5H5N-CD3+ (m/z 97), and C5D5N-CH3+(m/z 99) isotopologues are investigated, and it is shown that the N-methylpyridinium ion photodissociates by the loss of methane in the 36 000 - 43 000 cm(-1) (280 - 230 nm) region. The dissociation likely occurs on the ground state surface following internal conversion from the SI state. For each isotopologue, by monitoring the photofragmentation yield as a function of photon wavenumber, a broad vibronically featured band is recorded with origin (0-0) transitions assigned at 38 130, 38 140 and 38 320 cm(-1) for C5H5N-CH3+ C5H5N-CD3+ and C5D5N-CH3+, respectively. With the aid of quantum chemical calculations (CASSCF(6,6)/aug-cc-pVDZ), most of the observed vibronic detail is assigned to two in-plane ring deformation modes. Finally, using ion-molecule reactions, the methane coproduct at m/z 78 is confirmed as a 2-pyridinylium ion.

Ultraviolet action spectroscopy of iodine labeled peptides and proteins in the gas phase

Structural investigations of large biomolecules in the gas phase are challenging. Herein, it is reported that action spectroscopy taking advantage of facile carbon-iodine bond dissociation can be used to examine the structures of large molecules, including whole proteins. Iodotyrosine serves as the active chromophore, which yields distinctive spectra depending on the solvation of the side chain by the remainder of the molecule. Isolation of the chromophore yields a double featured peak at ∼290 nm, which becomes a single peak with increasing solvation. Deprotonation of the side chain also leads to reduced apparent intensity and broadening of the action spectrum. The method can be successfully applied to both negatively and positively charged ions in various charge states, although electron detachment becomes a competitive channel for multiply charged anions. In all other cases, loss of iodine is by far the dominant channel which leads to high sensitivity and simple data analysis. The action spectra for iodotyrosine, the iodinated peptides KGYDAKA, DAYLDAG, and the small protein ubiquitin are reported in various charge states. © 2012 American Chemical Society.

TNF and TNF receptor expression and insulin sensitivity in human omental and subcutaneous adipose tissue--influence of BMI and adipose distribution

Tumour necrosis factor (TNF)alpha is implicated in the relationship between obesity and insulin resistance/ type 2 diabetes. In an effort to understand this association better we (i) profiled gene expression patterns of TNF, TNFR1 and TNFR2 and (ii) investigated the effects of TNF on glucose uptake in isolated adipocytes and adipose tissue explants from omental and subcutaneous depots from lean, overweight and obese individuals. TNF expression correlated with expression of TNFR2, but not TNFR1, and TNF and TNFR2 expression increased in obesity. TNFR1 expression was higher in omental than in subcutaneous adipocytes. Expression levels of TNF or either receptor did not differ between adipocytes from individuals with central and peripheral obesity. TNF only suppressed glucose uptake in insulin-stimulated subcutaneous tissue and this suppression was only observed in tissue from lean subjects. These data support a relationship between the TNF system and body mass index (BMI), but not fat distribution, and suggest depot specificity of the TNF effect on glucose uptake. Furthermore, adipose tissue from obese subjects already appears insulin 'resistant' and this may be a result of the increased TNF levels.

Editorial : Action research, action learning and community services

This edition of ALARj has a focus on the contribution of action learning and action research to the development of community services, particularly nonprofits. The landscape of community services has been changing rapidly in recent decades, and can be typified by the notion of complexity. Complexity in the nature of issues that services seek to respond to, complexity in the policy environment and systems of support that have tended to silo and compartmentalise problems and people, and complexity in the institutional location non-profit services occupy in ‘helping’ those who are seen as ‘in need’ or marginalised. In addition to being typified by complexity the environment in which community services are located is dynamic, undergoing profound and ongoing change as neo-liberal approaches to understanding and responding to human need, which emphasise the individualisation of risk, and market principles such as choice, competition and innovation, drive social policy. How can long held values of empowerment, care, inclusivity and benefit to individuals and communities have expression in community services as they grapple with the challenges of being viable and relevant in such a dynamically changing environment? This edition brings together a range of contributions which speak to these challenges. The thematic through these is that processes are needed which engage services and communities in ongoing processes of inquiry about how they can best proceed in contexts typified by complexity and change. Action learning and action research can provide processes of this character.

Ghrelin and the brain-gut axis as a pharmacological target for appetite control

Appetite regulation is highly complex and involves a large number of orexigenic and anorexigenic peptide hormones. These are small, processed, secreted peptides derived from larger prepropeptide precursors. These peptides are important targets for the development of therapeutics for obesity, a global health epidemic. As a case study, we consider the ghrelin axis. The ghrelin axis is likely to be a particularly useful drug target, as it also plays a role in energy homeostasis, adipogenesis, insulin regulation and reward associated with food intake. Ghrelin is the only known circulating gut orexigenic peptide hormone. As it appears to play a role in diet-induced obesity, blocking the action of ghrelin is likely to be effective for treating and preventing obesity. The ghrelin peptide has been targeted using a number of approaches, with ghrelin mirror-image oligonucleotides (Spiegelmers) and immunotherapy showing some promise. The ghrelin receptor, the growth hormone secretagogue receptor, may also provide a useful target and a number of antagonists and inverse agonists have been developed. A particularly promising new target is the enzyme which octanoylates ghrelin, ghrelin O-acyltransferase (GOAT), and drugs that inhibit GOAT are likely to circumvent pharmacological issues associated with approaches that directly target ghrelin or its receptor.

Teacher understandings of orientation and transition programs from action research in five schools

Discontinuity between prior-to-school and school sectors in Australia reflects an historical, philosophical and pedagogical schism. This is most evident as children transition from one sector to the other. However, contemporary international research, alongside an intensive focus on policy and practice in early years education has challenged many of the taken-for-granted assumptions that perpetuate this rift. Drawing on data collected in a recent action research project, we present evidence of how a group of primary school kindergarten teachers define differences between orientation and transition programs, understand the importance of transition and how they position themselves in this process. The absence of Australian policy mandating and guiding the work of teachers across sectors is a significant factor perpetuating discontinuity in transition practices between prior–to-school and school sectors.

Teaching fractions to adult learners enrolled in a civil construction course : knowledge, action and materials action in tandem

This paper investigates the teaching and learning of fractions to Indigenous adult learners in a Civil Construction Certificate Course. More specifically it explores why the use of materials is critical to building knowledge and understanding. This focus is important for two reasons. First, it allows for considerations of a trainer’s approach for teaching fractions and, second it provides insights into how adult learners can be supported with representing their practical experiences of fractions to make generalisation thus building on their knowledge and learning experiences. The paper draws on teaching episodes from an Australian Research Council funded Linkage project that investigates how mathematics is taught and learned in Certificate Courses, here, Certificate 11 in Civil Construction. Action research and decolonising methods (Smith, 1999) were used to conduct the research. Video excerpts which feature one trainer and three students are analysed and described. Findings from the data indicate that adult learners need to be supported with materials to assist with building their capacity to know and apply understandings of fractions in a range of contexts, besides construction. Without materials and where fractions are taught via pen and paper tasks, students are less likely to retain and apply fraction ideas to their Certificate Course. Further they are less likely to understand decimals because of limited understanding of fractions.

Engaging creativity through an action learning and action research process to develop an Indigenous art exhibition

In most art exhibitions, the creative part of the exhibition is assumed to be the artworks on display. But for the Capricornia Arts Mob’s first collective art exhibition in Rockhampton during NAIDOC Week in 2012, the process of developing the exhibition became the focus of creative action learning and action research. In working together to produce a multi-media exhibition, we learned about the collaborative processes and time required to develop a combined exhibition. We applied Indigenous ways of working – including yarning, cultural respect, cultural protocols, mentoring young people, providing a culturally safe working environment and sharing both time and food – to develop our first collective art exhibition. We developed a process that allowed us to ask deep questions, engage in a joint journey of learning, and develop our collective story. This paper explores the processes that the Capricornia Arts Mob used to develop the exhibition for NAIDOC 2012.

Indexes of insulin resistance and secretion in obese children and adolescents : a validation study

OBJECTIVE To assess the concurrent validity of fasting indexes of insulin sensitivity and secretion in - obese prepubertal (Tanner stage 1) children and pubertal (Tanner stages 2-5) glucose tolerance test (FSIVGTT) as a criterion measure. RESEARCH DESIGN AND METHODS Eighteen obese children and adolescents (11 girls and 7 boys, mean age 12.2 +/- 2.4 years, mean BMI 35.4 +/- 6.2 kg/m(2), mean BMI-SDS 3.5 +/- 0.5, 7 prepubertal and I I pubertal) participated in the study. All participants underwent an insulin-modified FSIVGTT on two occasions, and 15 repeated this test a third time (mean 12.9 and 12.0 weeks apart). S-i measured by the FSIVGTT was compared with homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI), fasting glucose-to-insulin ratio (FGIR), and fasting insulin (estimates of insulin sensitivity derived from fasting samples). The acute insulin response (AIR) measured by the FSIVGTT was compared with HOMA of percent beta-cell function (HOMA-beta%), FGIR, and fasting insulin (estimates of insulin secretion derived from fasting samples). RESULTS There was a significant negative correlation between HOMA-IR and S-i (r = -0.89, r = -0.90, and r = -0.81, P < 0.01) and a significant positive correlation between QUICKI and S-i (r = 0.89, r = 0.90, and r = 0.81, P < 0.01) at each time point. There was a significant positive correlation between FGIR and S-i (r = 0.91, r = 0.91, and r = 0.82, P < 0.01) and a significant negative correlation between fasting insulin and S-i (r = -90, r = -0.90, and r = -0.88, P < 0.01). HOMA-beta% was not as strongly correlated with AIR (r = 0.60, r = 0.54, and r = 0.61, P < 0.05). CONCLUSIONS HOMA-IR, QUICKI, FGIR, and fasting insulin correlate strongly with S-i assessed by the FSIVGTT in obese children and adolescents. Correlations between HOMA-β% FGIR and fasting insulin, and AIR were not as strong. Indexes derived from fasting samples are a valid tool for assessing insulin sensitivity in prepubertal and pubertal obese children.

Planes, trains, automobiles and the action per quod servitium amisit

The action per quod servitium amisit compensates an employer for the loss of an employee’s services, where such loss is caused due to the commission of a tort by a third party which injures the employee. Although not commonly pleaded, such actions often arise when employees are harmed due to transportation accidents. For example, where allowed, physical injury caused by the negligent driving of automobiles, and the psychiatric injury suffered by an engine driver upon averting a collision with a motorcyclist crossing before an oncoming train...

Bimolecular interaction of Insulin-Like Growth Factor (IGF) binding protein-2 with αvβ3 negatively modulates IGF-I-Mediated migration and tumor growth

Both the integrin and insulin-like growth factor binding protein (IGFBP) families independently play important roles in modulating tumor cell growth and progression. We present evidence for a specific cell surface localization and a bimolecular interaction between the αvβ3 integrin and IGFBP-2. The interaction, which could be specifically perturbed using vitronectin and αvβ3 blocking antibodies, was shown to modulate IGF-mediated cellular migration responses. Moreover, this interaction was observed in vivo and correlated with reduced tumor size of the human breast cancer cells, MCF-7β3, which overexpressed the αvβ3 integrin. Collectively, these results indicate that αvβ3 and IGFBP-2 act cooperatively in a negative regulatory manner to reduce tumor growth and the migratory potential of breast cancer cells.

Mechanistic insights into RAD51-associated protein 1 (RAD51AP1) action in homologous DNA repair

Homologous recombination catalyzed by the RAD51 recombinase is essential for maintaining genome integrity upon the induction of DNA double strand breaks and other DNA lesions. By enhancing the recombinase activity of RAD51, RAD51AP1 (RAD51-associated protein 1) serves a key role in homologous recombination-mediated chromosome damage repair. We show here that RAD51AP1 harbors two distinct DNA binding domains that are both needed for maximal protein activity under physiological conditions. We have finely mapped the two DNA binding domains in RAD51AP1 and generated mutant variants that are impaired in either or both of the DNA binding domains. Examination of these mutants reveals that both domains are indispensable for RAD51AP1 function in cells. These and other results illuminate the mechanistic basis of RAD51AP1 action in homologous DNA repair.

Self-action of high-frequency surface waves in a magnetoactive planar plasma waveguide

The self-modulation process of a high-frequency surface wave (SW) in a wave-guiding structure - a semibounded magnetoactive plasma and perfectly conducting metal wall - is considered for the weak nonlinearity approximation. Estimates are given for the contributions to the nonlinear frequency shift of the SW from the two principal self-action channels: via the generation of a signal of the doubled frequency and of static surface perturbations, arising as the result of the action of a ponderomotive force. Solutions for the field envelope of the nonlinear wave are examined with regard to their stability with respect to longitudinal and transverse perturbations.

Reconceptualizing digital service quality : a call-to-action and research approach

The nature of services and service delivery has been changing rapidly since the 1980’s when many seminal papers in services research were published. Services are increasingly digital, or have a digital component. Further, a large and heterogeneous literature, with competing and overlapping definitions, many of which are dated and inappropriate to contemporary digital services offerings is impeding progress in digital services research. In this conceptual paper, we offer a critical review of some existing conceptualizations of services and digital services. We argue that an inductive approach to understanding cognition about digital services is required to develop a taxonomy of digital services and a new vocabulary. We argue that this is a pre-requisite to theorizing about digital services, including understanding quality drivers, value propositions, and quality determinants for different digital service types. We propose a research approach for reconceptualising digital services and service quality, and outline methodological approaches and outcomes.