Interleukin-23 mediates the intestinal response to microbial β-1,3-glucan and the development of spondyloarthritis pathology in SKG mice

Objective Spondyloarthritides (SpA) occur in 1% of the population and include ankylosing spondylitis (AS) and arthropathy of inflammatory bowel disease (IBD), with characteristic spondylitis, arthritis, enthesitis, and IBD. Genetic studies implicate interleukin-23 (IL-23) receptor signaling in the development of SpA and IBD, and IL-23 overexpression in mice is sufficient for enthesitis, driven by entheseal-resident T cells. However, in genetically prone individuals, it is not clear where IL-23 is produced and how it drives the SpA syndrome, including IBD or subclinical gut inflammation of AS. Moreover, it is unclear why specific tissue involvement varies between patients with SpA. We undertook this study to determine the location of IL-23 production and its role in SpA pathogenesis in BALB/c ZAP-70W163C-mutant (SKG) mice injected intraperitoneally with β-1,3-glucan (curdlan). Methods Eight weeks after curdlan injection in wild-type or IL-17A-/- SKG or BALB/c mice, pathology was scored in tissue sections. Mice were treated with anti-IL-23 or anti-IL-22. Cytokine production and endoplasmic reticulum (ER) stress were determined in affected organs. Results In curdlan-treated SKG mice, arthritis, enthesitis, and ileitis were IL-23 dependent. Enthesitis was specifically dependent on IL-17A and IL-22. IL-23 was induced in the ileum, where it amplified ER stress, goblet cell dysfunction, and proinflammatory cytokine production. IL-17A was pathogenic, while IL-22 was protective against ileitis. IL-22+CD3- innate-like cells were increased in lamina propria mononuclear cells of ileitis-resistant BALB/c mice, which developed ileitis after curdlan injection and anti-IL-22. Conclusion In response to systemic β-1,3-glucan, intestinal IL-23 provokes local mucosal dysregulation and cytokines driving the SpA syndrome, including IL-17/IL-22-dependent enthesitis. Innate IL-22 production promotes ileal tolerance.

Crystal structure of ammonium (3,5-dichlorophenoxy)acetate hemihydrate

In the structure of the title hydrated salt, NH4+·C8H5Cl2O3-·0.5H2O, where the anion derives from (3,5-di­chloro­phen­oxy)acetic acid, the ammonium cation is involved in extensive N-H...O hydrogen bonding with both carboxyl­ate and ether O-atom acceptors giving sheet structures lying parallel to (100). The water mol­ecule of solvation lies on a crystallographic twofold rotation axis and is involved in intra-sheet O-H...Ocarboxyl­ate hydrogen-bonding inter­actions. In the anion, the oxoacetate side chain assumes an antiperiplanar conformation with the defining C-O-C-C torsion angle = -171.33 (15)°.

Crystal structures of the potassium and rubidium salts of (3,5-dichlorophenoxy)acetic acid: Two isotypic coordination polymers

The two-dimensional coordination polymeric structures of the hydrated potassium and rubidium salts of (3,5-dichlorophenoxy)acetic acid, (3,5-D) namely, poly[mu-aqua-bis[mu3-2-(3,5-dichlorophenoxy)acetato]potassium, [K2(C8H5Cl2O3)2 (H2O)]n (I) and poly[mu-aqua-bis[mu3-2-(3,5-dichlorophenoxy)acetato]dirubidium] [Rb2(C8H5Cl2O3)2 (H2O)]n (II), respectively have been determined and are described. The two compounds are isotypic and the polymer is based on centrosymmetric dinuclear bridged complex units. The irregular six-coordination about the metal centres comprises a bridging water molecule lying on a twofold rotation axis, the phenoxy O-atom donor and and a triple bridging carboxylate O-atom of the oxoacetate side chain of the 3,5-D ligand in a bidentate chelate mode, the second carboxy O-donor, also bridging. The K-O and Rb-O bond-length ranges are 2.7238(15)--2.9459(14) and 2.832(2)--3.050(2) \%A respectively and the K...K and Rb...Rb separations in the dinuclear unit are 4.0214(7) and 4.1289(6) \%A, respectively. Within the two-dimensional layers which lie parallel to (100), the coordinated water molecule forms an O---H...O hydrogen bond to the single bridging carboxylate O atom.

Genetic studies of chondrocalcinosis

Purpose of review Our understanding of the causation of the chondrocalcinosis and other disorders characterized by ectopic mineralization is rapidly increasing, and genetic studies have contributed substantially to recent major advances in the field. This review will discuss what is known about the genetics of chondrocalcinosis and what we have learned from genetic studies to date. Recent findings: Chondrocalcinosis is one of a family of conditions associated with ectopic mineralization. This family also includes disorders of mineralization of bone and spinal and other ligaments, and vascular calcification. There has been increasing evidence of the key role of transport and metabolism of inorganic pyrophosphate (PPi) in control of mineralization, and as the likely explanation for the association of a variety of genetic variants with chondrocalcinosis and ectopic mineralization elsewhere. This may be an overly simplistic view of this family of conditions, with recent evidence suggesting that, for example, ANKH variants may not all predispose to chondrocalcinosis by effects on PPi transport, but may also influence chondrocyte maturation. Summary: Understanding the control of the process of mineralization and its tissue specificity are important steps in the search for rational therapies for these conditions.

Pharmacology in one semester [Version 3, Semester 1, 2014]

- For use in Introductory Units/Courses to Biomedical/Science Students - For use with Allied Health Students who are taking pharmacology as a Unit/Course or a part Unit/Course

Synthesis and luminescent properties of star-burst D-Pi-A compounds based on 1,3,5-triazine core and carbazole end-capped phenylene ethynylene arms

Two new star-burst compounds based on 1,3,5-triazine core and carbazole end-capped phenylene ethynylene arms (1a and 1b) were synthesized and characterized. Their photophysical properties were investigated systematically via spectroscopic and theoretical methods. Both compounds exhibit strong 1π–π⁎ transitions in the UV region and intense 1π–π⁎/intramolecular charge transfer (1ICT) absorption bands in the UV–vis region. Introducing the carbazole end-capped phenylene ethynylene arm on the 1,3,5-triazine core causes a slight bathochromic shift and enhanced molar extinction coefficient of the 1π–π⁎/1ICT transition band. Both compounds are emissive in solution at room temperature and 77 K, which exhibit pronounced positive solvatochromic effect. The emitting state could be ascribed to 1ICT state in more polar solvent, and 1π–π⁎ state in low-polarity solvent. The high emission quantum yields (Φem=0.90~1.0) of 1a and 1b (in hexane and toluene) make them potential candidates as efficient light-emitting materials. The spectroscopic studies and theoretical calculations indicate that the photophysical properties of these compounds can be tuned by the carbazole end-capped phenylene ethynylene arm, which would also be useful for rational design of photofunctional materials.

Increased risk of emergency hospital admissions for children with renal diseases during heatwaves in Brisbane, Australia

Background Heatwaves have a significant impact on population health including both morbidity and mortality. In this study we examined the association between heatwaves and emergency hospital admissions (EHAs) for renal diseases in children (aged 0–14 years) in Brisbane, Australia. Methods Daily data on EHAs for renal diseases in children and exposure to temperature and air pollution were obtained for Brisbane city from January 1, 1996 to December 31, 2005. A time-stratified case-crossover design was used to compare the risks for renal diseases between heatwave and non-heatwave periods. Results There were 1565 EHAs for renal diseases in children during the study period. Heatwaves exhibited a significant impact on EHAs for renal diseases in children after adjusting for confounding factors (odds ratio: 3.6; 95% confidence interval: 1.4–9.5). The risk estimates differed with lags and the use of different heatwave definitions. Conclusions There was a significant increase in EHAs for renal diseases in children during heatwaves in Brisbane, a subtropical city where people are well accustomed to warm weather. This finding may have significant implications for pediatric renal care, particularly in subtropical and tropical regions.

Editorial for Journal of Learning Design, 6(3) - "Special issue: Legal education and curriculum renewal"

Welcome to this special edition of the Journal of Learning Design which focuses on legal education and curriculum renewal in law. At the outset ,we would like to thank the editors of the Journal, Margaret Lloyd and Nan Bahr for agreeing to host this special edition. The special edition is timely as legal education in Australia is enjoying a lively period of renewal.

'Sink or swim': An evaluation of the clinical characteristics of individuals with high bone mass

Summary High bone mineral density on routine dual energy X-ray absorptiometry (DXA) may indicate an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained high bone mass (HBM), 236 relatives (41% with HBM) and 58 spouses were studied. Cases could not float, had mandible enlargement, extra bone, broad frames, larger shoe sizes and increased body mass index (BMI). HBM cases may harbour an underlying genetic disorder. Introduction High bone mineral density is a sporadic incidental finding on routine DXA scanning of apparently asymptomatic individuals. Such individuals may have an underlying skeletal dysplasia, as seen in LRP5 mutations. We aimed to characterize unexplained HBM and determine the potential for an underlying skeletal dysplasia. Methods Two hundred fifty-eight individuals with unexplained HBM (defined as L1 Z-score ≥ +3.2 plus total hip Z-score ≥ +1.2, or total hip Z-score ≥ +3.2) were recruited from 15 UK centres, by screening 335,115 DXA scans. Unexplained HBM affected 0.181% of DXA scans. Next 236 relatives were recruited of whom 94 (41%) had HBM (defined as L1 Z-score + total hip Z-score ≥ +3.2). Fifty-eight spouses were also recruited together with the unaffected relatives as controls. Phenotypes of cases and controls, obtained from clinical assessment, were compared using random-effects linear and logistic regression models, clustered by family, adjusted for confounders, including age and sex. Results Individuals with unexplained HBM had an excess of sinking when swimming (7.11 [3.65, 13.84], p < 0.001; adjusted odds ratio with 95% confidence interval shown), mandible enlargement (4.16 [2.34, 7.39], p < 0.001), extra bone at tendon/ligament insertions (2.07 [1.13, 3.78], p = 0.018) and broad frame (3.55 [2.12, 5.95], p < 0.001). HBM cases also had a larger shoe size (mean difference 0.4 [0.1, 0.7] UK sizes, p = 0.009) and increased BMI (mean difference 2.2 [1.3, 3.1] kg/m 2, p < 0.001). Conclusion Individuals with unexplained HBM have an excess of clinical characteristics associated with skeletal dysplasia and their relatives are commonly affected, suggesting many may harbour an underlying genetic disorder affecting bone mass.

Editorial of "Communication Research and Practice, 1(3)"

For the third issue of Communication Research and Practice, we bring together a mix of submitted content and papers presented at events that were hosted under the auspices of the International Communication Association. Dal Yong Jin captures the dynamic and contradictory elements of both convergence and transmedia storytelling, and the ‘Korean Wave’, in his paper on webtoons. Exploring this distinctive online form of transmedia storytelling, Jin considers its evolution from the perspectives of digital content, political economy, convergent media and digital labour, and the tensions that surround its potential expansion into global cultural markets.

Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls

Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with diseaseIRGM for Crohns disease, HLA for Crohns disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetesalthough in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases. © 2010 Macmillan Publishers Limited. All rights reserved.

Partial epilepsy syndrome in a Gypsy family linked to 5q31.3-q32

PURPOSE The restricted genetic diversity and homogeneous molecular basis of Mendelian disorders in isolated founder populations have rarely been explored in epilepsy research. Our long-term goal is to explore the genetic basis of epilepsies in one such population, the Gypsies. The aim of this report is the clinical and genetic characterization of a Gypsy family with a partial epilepsy syndrome. METHODS Clinical information was collected using semistructured interviews with affected subjects and informants. At least one interictal electroencephalography (EEG) recording was performed for each patient and previous data obtained from records. Neuroimaging included structural magnetic resonance imaging (MRI). Linkage and haplotype analysis was performed using the Illumina IVb Linkage Panel, supplemented with highly informative microsatellites in linked regions and Affymetrix SNP 5.0 array data. RESULTS We observed an early-onset partial epilepsy syndrome with seizure semiology strongly suggestive of temporal lobe epilepsy (TLE), with mild intellectual deficit co-occurring in a large proportion of the patients. Psychiatric morbidity was common in the extended pedigree but did not cosegregate with epilepsy. Linkage analysis definitively excluded previously reported loci, and identified a novel locus on 5q31.3-q32 with an logarithm of the odds (LOD) score of 3 corresponding to the expected maximum in this family. DISCUSSION The syndrome can be classified as familial temporal lobe epilepsy (FTLE) or possibly a new syndrome with mild intellectual deficit. The linked 5q region does not contain any ion channel-encoding genes and is thus likely to contribute new knowledge about epilepsy pathogenesis. Identification of the mutation in this family and in additional patients will define the full phenotypic spectrum.

The effects of gas and air flow distributions on the performance of the Farleigh No. 3 boiler

As more raw sugar factories become involved in the manufacture of by-products and cogeneration, bagasse is becoming an increasingly valuable commodity. However, in most factories, most of the bagasse produced is used to generate steam in relatively old and inefficient boilers. Efficient bagasse fired boilers are a high capital cost item and the cost of supplying the steam required to run a sugar factory by other means is prohibitive. For many factories a more realistic way to reduce bagasse consumption is to increase the efficiency of existing boilers. The Farleigh No. 3 boiler is a relatively old low efficiency boiler. Like many in the industry, the performance of this boiler has been adversely affected by uneven gas and air flow distributions and air heater leaks. The combustion performance and efficiency of this boiler have been significantly improved by making the gas and air flow distributions through the boiler more uniform and repairing the air heater. The estimated bagasse savings easily justify the cost of the boiler improvements.

Destinations: 3 Large Cast Plays for Young People

This book is a collection of three large-cast plays written in response to a very specific problem. My work as a teacher of drama often required me to locate a script that would somehow miraculously work for a cast of unknown number and gender, and most likely uneven skills and enthusiasm, who I hadn’t even met yet. It’s a familiar dilemma for teachers and students of drama in education contexts, at whatever level you’re teaching. I’d first addressed this creative problem with scripts such as Gate 38 (2010). I had tried using scripts that already existed, but found they required such extensive editing to suit the parameters of cast and performance duration that I may as well have been writing them myself. Even in the setting of a closed studio, in altering these plays I felt I was bending the vision of the playwright, and certainly their narrative structure, out of shape. Everyone who’s attempted to stage a performance with a large cast of students in an educational setting knows it takes time to truly connect with a play, its social contexts, themes and characters. It also takes a lot of time to get on top of the practicalities of learning, rehearsing, directing and running a performance with young people. Often the curtain goes up on something unfinished and unstable. I was looking for ways to reduce the complexity of staging a script, while maintaining the potential of this process as a site of rich, enjoyable learning. Two of the plays (Duty Free and Please Be Seated) are comprised of multiple monologues, combined with music-driven ensemble sequences. The monologues enable individuals to develop and polish their own performances, work in small groups, and cut down on the laborious detail of directing naturalistic scenes based in character interaction. The third (Australian Drama) involves a lot of duologues, meaning that its rehearsal process can happily employ that mainstay of the drama classroom: small group work. There’s plenty of room to move in terms of gender-blind casting as well. Please be Seated is mainly young women. The scripts also contain ensemble-based interludes which are non-verbal, music driven, with a choreographic element. They have also springboarded further explorations in form. The ethical and aesthetic complexities of verbatim works; the interaction between music and theatre; and meta-concerns related to the performing of performance: ‘how can the act of acting ‘acted’. The narratives of all three of these plays are deliberately open, enabling the flexible casting and on-the hop editing that large-group, time-poor processes sometimes necessitate. Duty Free is about the overseas ‘adventures’ of young people. Please Be Seated is based in verbatim text about young people falling in and out of love. Australian Drama is about young people in a drama classroom trying to connect with each other and put their own shine on dull fragments of the theatrical canon. The plays were published as a collection in hardcopy and digital editions by Playlab Press in 2015. Please be Seated is a co-write with a large group. These co-author’s names are listed in the publication, and below in ‘additional information’.

A 3-hour quantitative comparison of glucose-based versus rice-based oral rehydration solution intake by children with diarrhoea in Port Moresby General Hospital

Measurements were made of the intake of a WHO/UNICEF glucose-based and a rice cereal-based oral rehydration solution (ORS) by children with diarrhoea. Twenty children who presented to the Children's Outpatient Department at Port Moresby General Hospital with acute diarrhoea and mild dehydration were randomly assigned to an ORS and measurements were taken over the following 3 hours. For data analysis, the patients were paired by weight. Testing the means of the paired samples by t test showed that there was no significant difference between the amount of rice ORS and the amount of glucose ORS taken over 3 hours. The discovery of oral rehydration solution (ORS) for the treatment of diarrheal disease has been heralded as the most important medical discovery of the century. Cereal-based ORS is able to decrease stool output and the duration of diarrheal illness more than the standard glucose-based ORS, through the increased absorption provided by oligosaccharides without the imposition of a greater osmotic penalty. Moreover, the peptides in cereals enhance amino acid and water absorption, while providing nutritional benefits. UNICEF's glucose-based ORS is becoming more widely used in Papua New Guinea (PNG). 20 children aged 6-37 months (mean age, 15 months) who presented to the Children's Outpatient Department at Port Moresby General Hospital during September-October 1993 with acute diarrhea and mild dehydration were randomly assigned to receive either a rice-based ORS or standard glucose ORS, and measurements were taken over the following 3 hours. The patients were paired by weight for analysis. No statistically significant difference was found between the amount of rice ORS and the amount of glucose ORS taken over 3 hours.