Phosphorylation of β-catenin at Serine552 correlates with invasion and recurrence of non-functioning pituitary neuroendocrine tumours.

Non-functioning pituitary tumours (NF-PitNETs) are common intracranial benign neoplasms that can exhibit aggressive behaviour by invading neighbouring structures and, in some cases, have multiple recurrences. Despite resulting in severe co-morbidities, no predictive biomarkers of recurrence have been identified for NF-PitNETs. In this study we have used high-throughput mass spectrometry-based analysis to examine the phosphorylation pattern of different subsets of NF-PitNETs. Based on histopathological, radiological, surgical and clinical features, we have grouped NF-PitNETs into non-invasive, invasive, and recurrent disease groups. Tumour recurrence was determined based on regular clinical and radiological data of patients for a mean follow-up of 10 years (SD ± 5.4 years). Phosphoproteomic analyses identified a unique phosphopeptide enrichment pattern which correlates with disease recurrence. Candidate phosphorylated proteins were validated in a large cohort of NF-PitNET patients by western blot and immunohistochemistry. We identified a cluster of 22 phosphopeptides upregulated in recurrent NF-PitNETs compared to non-invasive and invasive subgroups. We reveal significant phosphorylation of the β-catenin at Ser552 in recurrent and invasive NF-PitNETs, compared to non-invasive/non-recurrent NF-PitNET subgroup. Moreover, β-catenin pSer552 correlates with the recurrence free survival among 200 patients with NF-PitNET. Together, our results suggest that the phosphorylation status of β-catenin at Ser552 could act as potential biomarker of tumour recurrence in NF-PitNETs

A grounded theory study of the narrative behind Indian physiotherapists global migration

It is estimated that an additional 6.4 million allied health professionals are required to address India's health challenges. Physiotherapy is amongst the largest of these professions. Over the last decade, thousands of Indian physiotherapists have sought to study and work overseas. In this study, 19 physiotherapists from across India were interviewed. Data were collected and analysed using construct+ivist grounded theory methods. The findings indicate that the Indian physiotherapy profession faces many political and clinical hierarchical challenges within the Indian healthcare infrastructure. The profession's education provision has developed, and the private clinical sector has grown, but there are significant disparities in quality and standards across the sector. The profession in India has variable autonomy, is not nationally regulated, is poorly paid, and the leadership has been divided. The political, educational, and clinical context in Indian physiotherapy impacts upon physiotherapists' ability to practise effectively to their professional satisfaction. Individual physiotherapists are frustrated by their workplace and travel overseas where they hear that the physiotherapy profession and practice is different. Whilst the disjunctures influencing these factors continue, and overseas physiotherapy practice is perceived as different and superior, Indian physiotherapists will continue to seek to migrate overseas, and facilitating their return will be challenging

Development of Photonic Crystal Fiber Based Gas/ Chemical Sensors

The development of highly-sensitive and miniaturized sensors that capable of real-time analytes detection is highly desirable. Nowadays, toxic or colorless gas detection, air pollution monitoring, harmful chemical, pressure, strain, humidity, and temperature sensors based on photonic crystal fiber (PCF) are increasing rapidly due to its compact structure, fast response and efficient light controlling capabilities. The propagating light through the PCF can be controlled by varying the structural parameters and core-cladding materials, as a result, evanescent field can be enhanced significantly which is the main component of the PCF based gas/chemical sensors. The aim of this chapter is to (1) describe the principle operation of PCF based gas/ chemical sensors, (2) discuss the important PCF properties for optical sensors, (3) extensively discuss the different types of microstructured optical fiber based gas/ chemical sensors, (4) study the effects of different core-cladding shapes, and fiber background materials on sensing performance, and (5) highlight the main challenges of PCF based gas/ chemical sensors and possible solutions

Trust Perceptions of Online Travel Information by Different Content Creators: Some Social and Legal Implications

Consumers are increasingly turning to the online environment to provide information to assist them in making purchase decisions related to travel products. They often rely on travel recommendations from different sources, such as sellers, independent experts and, increasingly, other consumers. A new type of online content, usergenerated content (UGC), provides a number of legal and social challenges to providers and users of that content, especially in relation to areas such as defamation, misrepresentation and social embarrassment. This paper reports research that examined the level of trustworthiness of online travel information from these different sources. The study used a survey of Australian travel consumers (n= 12,000) and results support the notion that there are differences in the level of trust for online travel information from different sources. Respondents ‘tended to agree’ that they trusted information provided by travel agents, information from commercial operators and comments made by travellers on third party websites. However, the highest level of trust was afforded to information provided on State government tourism websites. These results suggest that greater trust is placed in online travel comments when they are on a specific travel website than when they are on a more generic social networking website. However, respondents were ‘not sure’ that they trusted comments made by travellers on weblogs and on social networking sites. Some 88% of respondents that had not visited UGC websites (or were unsure if they had) indicated that they thought that UGC would be useful in the future – suggesting that they feel that any concerns they may have in relation to legal and social problems resulting from its use will be resolved

The Structural Features of Trask That Mediate Its Anti-Adhesive Functions

Trask/CDCP1 is a transmembrane protein with a large extracellular and small intracellular domains. The intracellular domain (ICD) undergoes tyrosine phosphorylation by Src kinases during anchorage loss and, when phosphorylated, Trask functions to inhibit cell adhesion. The extracellular domain (ECD) undergoes proteolytic cleavage by serine proteases, although the functional significance of this remains unknown. There is conflicting evidence regarding whether it functions to signal the phosphorylation of the ICD. To better define the structural determinants that mediate the anti-adhesive functions of Trask, we generated a series of deletion mutants of Trask and expressed them in tet-inducible cell models to define the structural elements involved in cell adhesion signaling. We find that the ECD is dispensable for the phosphorylation of the ICD or for the inhibition of cell adhesion. The anti-adhesive functions of Trask are entirely embodied within its ICD and are specifically due to tyrosine phosphorylation of the ICD as this function is completely lost in a phosphorylation-defective tyrosine-phenylalanine mutant. Both full length and cleaved ECDs are fully capable of phosphorylation and undergo phosphorylation during anchorage loss and cleavage is not an upstream signal for ICD phosphorylation. These data establish that the anti-adhesive functions of Trask are mediated entirely through its tyrosine phosphorylation. It remains to be defined what role, if any, the Trask ECD plays in its adhesion functions

Diverging Mechanisms of Activation of Chemokine Receptors Revealed by Novel Chemokine Agonists

CXCL8/interleukin-8 is a pro-inflammatory chemokine that triggers pleiotropic responses, including inflammation, angiogenesis, wound healing and tumorigenesis. We engineered the first selective CXCR1 agonists on the basis of residue substitutions in the conserved ELR triad and CXC motif of CXCL8. Our data reveal that the molecular mechanisms of activation of CXCR1 and CXCR2 are distinct: the N-loop of CXCL8 is the major determinant for CXCR1 activation, whereas the N-terminus of CXCL8 (ELR and CXC) is essential for CXCR2 activation. We also found that activation of CXCR1 cross-desensitized CXCR2 responses in human neutrophils co-expressing both receptors, indicating that these novel CXCR1 agonists represent a new class of anti-inflammatory agents. Further, these selective CXCR1 agonists will aid at elucidating the functional significance of CXCR1 in vivo under pathophysiological conditions

A Genetic Basis of Susceptibility to Acute Pyelonephritis

For unknown reasons, urinary tract infections (UTIs) are clustered in certain individuals. Here we propose a novel, genetically determined cause of susceptibility to acute pyelonephritis, which is the most severe form of UTI. The IL-8 receptor, CXCR1, was identified as a candidate gene when mIL-8Rh mutant mice developed acute pyelonephritis (APN) with severe tissue damage.We have obtained CXCR1 sequences from two, highly selected APN prone patient groups, and detected three unique mutations and two known polymorphisms with a genotype frequency of 23% and 25% compared to 7% in controls (p<0.001 and p<0.0001, respectively). When reflux was excluded, 54% of the patients had CXCR1 sequence variants. The UTI prone children expressed less CXCR1 protein than the pediatric controls (p<0.0001) and two sequence variants were shown to impair transcription.The results identify a genetic innate immune deficiency, with a strong link to APN and renal scarring

Production of 3,4-dihydroxy L-phenylalanine by a newly isolated Aspergillus niger and parameter significance analysis by Plackett-Burman design

<p>Abstract</p> <p>Background</p> <p>The amino acid derivative 3,4-dihydroxy L-phenylalanine (L-dopa) is gaining interest as a drug of choice for Parkinson's disease. <it>Aspergillus oryzae </it>is commonly used for L-dopa production; however, a slower growth rate and relatively lower tyrosinase activity of mycelia have led to an increasing interest in exploiting alternative fungal cultures. In the present investigation, we report on the microbiological transformation of L-tyrosine to L-dopa accomplished by a newly isolated filamentous fungus <it>Aspergillus niger</it>.</p> <p>Results</p> <p>The culture <it>A. niger </it>(isolate GCBT-8) was propagated in 500 ml Erlenmeyer flasks and the pre-grown mycelia (48 h old) were used in the reaction mixture as a source of enzyme tyrosinase. Grinded mycelia gave 1.26 fold higher L-dopa production compared to the intact at 6% glucose (pH 5.5). The rate of L-tyrosine consumption was improved from 0.198 to 0.281 mg/ml. Among the various nitrogen sources, 1.5% peptone, 1% yeast extract and 0.2% ammonium chloride were optimized. The maximal L-dopa was produced (0.365 mg/ml) at 0.3% potassium dihydrogen phosphate with L-tyrosine consumption of 0.403 mg/ml.</p> <p>Conclusion</p> <p>Over ~73% yield was achieved (degree of freedom 3) when the process parameters were identified using 2k-Plackett-Burman experimental design. The results are highly significant (p ≤ 0.05) and mark the commercial utility (LSD 0.016) of the mould culture which is perhaps the first ever report on L-dopa production from <it>A. niger</it>.</p