Differentiation of isomeric N-glycan structures by normal-phase liquid chromatography-MALDI-TOF/TOF tandem mass spectrometry

The detailed characterization of protein N-glycosylation is very demanding given the many different glycoforms and structural isomers that can exist on glycoproteins. Here we report a fast and sensitive method for the extensive structure elucidation of reducing-end labeled N-glycan mixtures using a combination of capillary normal-phase HPLC coupled off-line to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and TOF/TOF-MS/MS. Using this method, isobaric N-glycans released from honey bee phospholipase A2 and Arabidopsis thaliana glycoproteins were separated by normal-phase chromatography and subsequently identified by key fragment ions in the MALDI-TOF/TOF tandem mass spectra. In addition, linkage and branching information were provided by abundant cross-ring and "elimination" fragment ions in the MALDI-CID spectra that gave extensive structural information. Furthermore, the fragmentation characteristics of N-glycans reductively aminated with 2-aminobenzoic acid and 2-aminobenzamide were compared. The identification of N-glycans containing 3-linked core fucose was facilitated by distinctive ions present only in the MALDI-CID spectra of 2-aminobenzoic acid-labeled oligosaccharides. To our knowledge, this is the first MS/MS-based technique that allows confident identification of N-glycans containing 3-linked core fucose, which is a major allergenic determinant on insect and plant glycoproteins.

Cardiac safety concerns for ondansetron, an antiemetic commonly used for nausea linked to cancer treatment and following anaesthesia

Introduction: Ondansetron is a 5-HT3 receptor antagonist commonly used as an anti-emetic to prevent the nausea and vomiting associated with anti-cancer drugs, cancer radiotherapy, or postoperatively. Recently, the US Food and Drug Administration (FDA) issued a warning for ondansetron due to a potential for prolongation of the QT interval of the electrocardiogram (ECG), a phenomenon that is associated with an increased risk of the potentially fatal arrhythmia torsade de pointes. Areas covered: We undertook a review of the cardiac safety of ondansetron. Our primary sources of information were PubMed (with downloading of full articles), and the internet. Expert opinion: The dose of ondansetron that the FDA has concerns about is 32 mg iv (or several doses that are equivalent to this), which is only used in preventing nausea and vomiting associated with cancer chemotherapy. This suggests that ondansetron may be safe in the lower doses used to prevent the nausea and vomiting in radiation treatment or postoperatively. However, as there is a report that a lower dose of ondansetron prolonged the QT interval in healthy volunteers, this needs to be clarified by the FDA. More research needs to be undertaken of the relationship between QT prolongation and torsades in order that the FDA can produce clear-cut evidence of pro-arrhythmic risk when introducing warnings for this.

Taking cues from outer space : the E&P sector can learn much about asset maintenance from the space and satellite industry

The E&P sector can learn much about asset maintenance from the space and satellite industry. Practitioners from both the upstream oil and gas industry and the space and satellite sector have repeatedly noted several striking similarities between the two industries over the years, which have in turn resulted in many direct comparisons in the media and industry press. The similarities between the two industries have even resulted in a modest amount of cross-pollinating between the respective supply chains. Because the operating conditions of both industries are so extreme, some oil and gas equipment vendors have occasionally sourced motors and other parts from aerospace contractors. Also, satellites are now being used to assess oil fires, detect subsidence in oil fields, measure oil spills, collect and transmit operational data from oil and gas fields, and monitor the movement of icebergs that might potentially collide with offshore oil and gas installations.

The acute effects of eccentrically-biased versus conventional weight training in older adults : a randomised controlled cross-over study

Background Whilst resistance training has been proven to convey considerable benefits to older people; immediately post-exercise there may be elevated transient risks for cardiac events and falls. Objectives and Measurements We assessed the acute effects of eccentrically-biased (EB) and conventional (CONV) resistance exercise on: platelet number, activation and granule exocytsosis; and mean velocity of centre of pressure displacement (Vm). Design, Setting, Participants and Intervention Ten older adults (7 males, 3 females; 69 ± 4 years) participated in this randomised controlled cross-over study in which they performed EB and CONV training sessions that were matched for total work and a control condition. Results Immediately post-exercise there was a statistically significant difference in platelet count between the control condition, in which it fell (pre 224 ± 35 109/L; post 211 ± 30 109/L: P < 0.05) and CONV in which it increased (pre 236 ± 55 109/L; post 242 ± 51 109/L: P > 0.05). There was no change in platelet activation and granule exocytsosis or Vm following EB and CONV. Conclusions Overall, while minor differences between regimens were observed, no major adverse effect on parameters of platelet function or centre of pressure displacement were observed acutely following either regimen. Eccentrically-biased and conventional resistance exercise training regimens do not appear to present an elevated acute risk in the context of changes to platelet function contributing to a cardiac event or postural stability increasing falls risk for apparently healthy older adults.

Cross-cultural learning experiences in architectural education

This qualitative study looks at the joint output of 20 architecture students from 2 different countries during their short respective Study Tours to each other’s country to discern the effect of cross-cultural experiences on their learning. This paper uses the students’ joint design efforts and reflective writings to investigate the outcome of this cross-cultural educational exchange. Their joint design efforts resulted in the making of small built structures, drawings and collaborative design proposals for an urban setting. In addition, a short questionnaire and personal interviews were also used as methods to gain insight into their experience and to use as a comparative study. The question is also raised in this paper of whether spontaneous friendship among students is integral to long term learning in a cross-cultural context in comparison to pre-designed learning objectives on the part of the educators. This paper also initiates the dialogue of the extent of cultural influences and universal ideas on collaborative architectural design. With increasing joint design ventures between architectural firms in different countries, there is interest in how collaborative design can be understood in a cross-cultural context. This paper examines short term cross cultural experiences and its contribution to architectural education.

Physical activity and health-related quality of life among physiotherapists : a cross sectional survey in an Australian hospital and health service

Background Physiotherapists are a professional group with a high rate of attrition and at high risk of musculoskeletal disorders. The purpose of this investigation was to examine the physical activity levels and health-related quality of life of physiotherapists working in metropolitan clinical settings in an Australian hospital and health service. It was hypothesized that practicing physiotherapists would report excellent health-related quality of life and would already be physically active. Such a finding would add weight to a claim that general physical activity conditioning strategies may not be useful for preventing musculoskeletal disorders among active healthy physiotherapists, but rather, future investigations should focus on the development and evaluation of role specific conditioning strategies. Methods A questionnaire was completed by 44 physiotherapists from three inpatient units and three ambulatory clinics (63.7% response rate). Physical activity levels were reported using the Active Australia Survey. Health-related quality of life was examined using the EQ-5D instrument. Physical activity and EQ-5D data were examined using conventional descriptive statistics; with domain responses for the EQ-5D presented in a frequency histogram. Results The majority of physiotherapists in this sample were younger than 30 years of age (n = 25, 56.8%) consistent with the presence of a high attrition rate. Almost all respondents exceeded minimum recommended physical activity guidelines (n = 40, 90.9%). Overall the respondents engaged in more vigorous physical activity (median = 180 minutes) and walking (median = 135 minutes) than moderate exercise (median = 35 minutes) each week. Thirty-seven (84.1%) participants reported no pain or discomfort impacting their health-related quality of life, with most (n = 35,79.5%) being in full health. Conclusions Physical-conditioning based interventions for the prevention of musculoskeletal disorders among practicing physiotherapists may be better targeted to role or task specific conditioning rather than general physical conditioning among this physically active population. It is plausible that an inherent attrition of physiotherapists may occur among those not as active or healthy as therapists who cope with the physical demands of clinical practice. Extrapolation of findings from this study may be limited due to the sample characteristics. However, this investigation addressed the study objectives and has provided a foundation for larger scale longitudinal investigations in this field.

Innovations in dietary interventions : Use of a photographic food diary method and telephone linked computerized care in chronic disease

Access to dietetic care is important in chronic disease management and innovative technologies assists in this purpose. Photographic dietary records (PhDR) using mobile phones or cameras are valid and convenient for patients. Innovations in providing dietary interventions via telephone and computer can also inform dietetic practice. Three studies are presented. A mobile phone method was validated by comparing energy intake (EI) to a weighed food record and a measure of energy expenditure (EE) obtained using the doubly labelled water technique in 10 adults with T2 diabetes. The level of agreement between mean (±sd) energy intake mobile phone (8.2±1.7 MJ) and weighed record (8.5±1.6 MJ) was high (p=0.392), however EI/EE for both methods gave similar levels of under-reporting (0.69 and 0.72). All subjects preferred using the mobile phone vs. weighed record. Nineteen individuals with Parkinsons disease kept 3-day PhDRs on three occasions using point-and-shoot digital cameras over a 12 week period. The camera was rated as easy to use by 89%, keeping a PhDR was considered acceptable by 94% and none would rather use a “pen and paper” method. Eighty-three percent felt confident to use the camera again to record intake. An interactive, automated telephone system designed to coach people with T2 diabetes to adopt and maintain diabetes self-care behaviours, including nutrition, showed trends for improvements in total fat, saturated fat and vegetable intake of the intervention group compared to control participants over 6 months. Innovative technologies are acceptable to patients with chronic conditions and can be incorporated into dietetic care.

Selective regulation of p38β protein and signaling by integrin-linked kinase mediates bladder cancer cell migration

Integrin-linked kinase (ILK) and p38MAPK are protein kinases that transduce extracellular signals regulating cell migration and actin cytoskeletal organization. ILK-dependent regulation of p38MAPK is critical for mammalian kidney development and in smooth muscle cell migration, however, specific p38 isoforms has not been previously examined in ILK-regulated responses. Signaling by ILK and p38MAPK is often dysregulated in bladder cancer, and here we report a strong positive correlation between protein levels of ILK and p38β, which is the predominant isoform found in bladder cancer cells, as well as in patient-matched normal bladder and tumor samples. Knockdown by RNA interference of either p38β or ILK disrupts serum-induced, Rac1-dependent migration and actin cytoskeletal organization in bladder cancer cells. Surprisingly, ILK knockdown causes the selective reduction in p38β cellular protein level, without inhibiting p38β messenger RNA (mRNA) expression. The loss of p38β protein in ILK-depleted cells is partially rescued by the 26S proteasomal inhibitor MG132. Using co-precipitation and bimolecular fluorescent complementation assays, we find that ILK selectively forms cytoplasmic complexes with p38β. In situ proximity ligation assays further demonstrate that serum-stimulated assembly of endogenous ILK–p38β complexes is sensitive to QLT-0267, a small molecule ILK kinase inhibitor. Finally, inhibition of ILK reduces the amplitude and period of serum-induced activation of heat shock protein 27 (Hsp27), a target of p38β implicated in actin cytoskeletal reorganization. Our work identifies Hsp27 as a novel target of ILK–p38β signaling complexes, playing a key role in bladder cancer cell migration.

Cross-cultural web user interface design for Indigenous internet users

This project investigated 1) Australian web designers’ cultural perceptions towards Australian Indigenous users and 2) Australian Indigenous cultural features in terms of user interface design. In doing so, it reviews the literature of cross-cultural user interface design by focusing on feasible models and arguments to articulate and integrate Australian Indigenous Internet users’ cultural needs of web user interface. The online survey results collected from 101 Indigenous users and 126 Web designers showed a distinctive difference between them on the integration of Indigenous users' cultural in Web sites. The interview data collected from 14 Indigenous users and 14 web designers suggested practical approaches to the design implications of Indigenous culture.

Cross-layer design for traffic management in wireless networked control systems

Wireless networked control systems (WNCSs) have been increasingly deployed in industrial applications. As they require timely data packet transmissions, it is difficult to make efficient use of the limited channel resources, particularly in contention based wireless networks in the layered network architecture. Aiming to maintain the WNCSs under critical real-time traffic condition at which the WNCSs marginally meet the real-time requirements, a cross-layer design (CLD) approach is presented in this paper to adaptively adjust the control period to achieve improved channel utilization while still maintaining effective and timely packet transmissions. The effectiveness of the proposed approach is demonstrated through simulation studies.

Exploration of novel routes to azo-linked oligoporphyrins

This research explored new ways of chemically combining porphyrins, which are vital biomolecules, to produce new pigments known as azoporphyrins, for applications in advanced technologies. Although the final targets have not yet been realized, numerous novel compounds and known compounds lacking experimental data in the literature were fully characterised by a range of techniques. The data will facilitate subsequent studies of other novel routes to azoporphyrins and related molecules.

Integrin αvβ3 upregulates integrin-linked kinase expression in human ovarian cancer cells via enhancement of ILK gene transcription

We previously showed that integrin alphavbeta3 overexpression and engagement by its ligand vitronectin increased adhesion, motility, and proliferation of human ovarian cancer cells. In search of differentially regulated genes involved in these tumor biological events, we previously identified the integrin-linked kinase (ILK) to be under control of alphavbeta3. In the present investigation we demonstrated significantly upregulated ILK protein as a function of alphavbeta3 in two ovarian cancer cell lines, OV-MZ-6 and OVCAR-3, and proved co-localization at the surface of alphavbeta3-overexpressing cells adherent to vitronectin. Increase of ILK protein was reflected by enhanced ILK promoter activity, an effect, which we further characterized with regard to transcriptional response elements involved. Abrogation of NF-kappaB/c-rel or p53 binding augmented ILK promoter activity and preserved induction by alphavbeta3. The AP1-mutant exhibited decreased promoter activity but was also still inducible by alphavbeta3. Disruption of the two DNA consensus motifs for Ets proteins led to divergent observations: mutation of the Ets motif at promoter position -462 bp did not significantly alter promoter activity but still allowed response to alphavbeta3. In contrast, disruption of the second Ets motif at position -85 bp did not only lead to slightly diminished promoter activity but also, in that case, abrogated ILK promoter induction by alphavbeta3. Subsequent co-transfection studies with ets-1 in the presence of the second Ets motif led to additional induction of ILK promoter activity. Taken together, these data suggest that ets-1 binding to the second Ets DNA motif strongly contributes to alphavbeta3-mediated ILK upregulation. By increasing ILK as an important integrin-proximal kinase, alphavbeta3 may promote its intracellular signaling and tumor biological processes arising thereof in favor of ovarian cancer metastasis.

Modeling perceived influences on journalism : evidence from a cross-national survey of journalists

Surveying 1,700 journalists from seventeen countries, this study investigates perceived influences on news work. Analysis reveals a dimensional structure of six distinct domains—political, economic, organizational, professional, and procedural influences, as well as reference groups. Across countries, these six dimensions build up a hierarchical structure where organizational, professional, and procedural influences are perceived as more powerful limits to journalists' work than political and economic influences.

Does gender determine journalists' professional views? A reassessment based on cross-national evidence

Research into journalism and gender to date has found somewhat contradictory evidence as to the ways in which women and men practice journalism. While some scholars claim that women have inherently different concepts and practices of journalism and that this has led to a feminization of journalism, others have found little evidence to suggest that men and women differ significantly in terms of their role conceptions. While numerous studies have been conducted into this issue around the world, few have taken a truly comparative approach. This paper presents results from a large-scale comparative survey into gender differences in journalists’ professional views in 18 diverse countries around the world. Results suggest that women and men do not differ in any meaningful ways in their role conceptions on neither the individual level, in newsrooms dominated by women, nor in socio-cultural contexts where women have achieved a certain level of empowerment.

Diporphyrins linked by two-atom bridges synthestic, structural and theoretical studies

The syntheses, properties and electronic structures of a series of porphyrin dimers connected by two-atom bridges were compared. The study found that an azo linker results in the most efficient electronic communication between the two porphyrin rings, and is the superior connector for dimers, trimers and oligomers in the design of nonlinear optical materials. This has implications for the design of molecular probes and sensors, photodynamic therapy, microfabrication, and three-dimensional optical data storage. The research led to the synthesis of a number of new porphyrin monomers and dimers, which were characterised using structural, spectroscopic and spectrometric techniques.