Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development

Objective To investigate the role of matrix metalloproteinase 13 (MMP-13; collagenase 3) in osteoarthritis (OA). Methods OA was surgically induced in the knees of MMP-13-knockout mice and wild-type mice, and mice were compared. Histologic scoring of femoral and tibial cartilage aggrecan loss (0-3 scale), erosion (0-7 scale), and chondrocyte hypertrophy (0-1 scale), as well as osteophyte size (0-3 scale) and maturity (0-3 scale) was performed. Serial sections were stained for type X collagen and the MMP-generated aggrecan neoepitope DIPEN. Results Following surgery, aggrecan loss and cartilage erosion were more severe in the tibia than femur (P < 0.01) and tibial cartilage erosion increased with time (P < 0.05) in wild-type mice. Cartilaginous osteophytes were present at 4 weeks and underwent ossification, with size and maturity increasing by 8 weeks (P < 0.01). There was no difference between genotypes in aggrecan loss or cartilage erosion at 4 weeks. There was less tibial cartilage erosion in knockout mice than in wild-type mice at 8 weeks (P < 0.02). Cartilaginous osteophytes were larger in knockout mice at 4 weeks (P < 0.01), but by 8 weeks osteophyte maturity and size were no different from those in wild-type mice. Articular chondrocyte hypertrophy with positive type X collagen and DIPEN staining occurred in both wild-type and knockout mouse joints. Conclusion Our findings indicate that structural cartilage damage in a mouse model of OA is dependent on MMP-13 activity. Chondrocyte hypertrophy is not regulated by MMP-13 activity in this model and does not in itself lead to cartilage erosion. MMP-13 deficiency can inhibit cartilage erosion in the presence of aggrecan depletion, supporting the potential for therapeutic intervention in established OA with MMP-13 inhibitors.

Why are early maturing girls less active? Links between pubertal development, psychological well-being, and physical activity among girls at ages 11 and 13

Previous research has shown that early maturing girls at age I I have lower subsequent physical activity at age 13 in comparison to later maturing girls. Possible reasons for this association have not been assessed. This study examines girls' psychological response to puberty and their enjoyment of physical activity as intermediary factors linking pubertal maturation and physical activity. Participants included 178 girls who were assessed at age 11, of whom 168 were reassessed at age 13. All participants were non-Hispanic white and resided in the US. Three measures of pubertal development were obtained at age I I including Tanner breast stage, estradiol levels, and mothers' reports of girls' development on the Pubertal Development Scale (PDS). Measures of psychological well-being at ages I I and 13 included depression, global self-worth, perceived athletic competence, maturation fears, and body esteem. At age 13, girls' enjoyment of physical activity was assessed using the Physical Activity Enjoyment Scale and their daily minutes of moderate-to-vigorous physical activity (MVPA) were assessed using objective monitoring. Structural Equation Modeling was used to assess direct and indirect pathways between pubertal development at age I I and MVPA at age 13. In addition to a direct effect of pubertal development on MVPA, indirect effects were found for depression, global self-worth and maturity fears controlling for covariates. In each instance, more advanced pubertal development at age I I was associated with lower psychological wellbeing at age 13, which predicted lower enjoyment of physical activity at age 13 and in turn lower MVPA. Results from this study suggest that programs designed to increase physical activity among adolescent girls should address the self-consciousness and discontent that girls' experience with their bodies during puberty, particularly if they mature earlier than their peers, and identify activities or settings that make differences in body shape less conspicuous.

Upregulation of matrix metalloproteinases (MMPs) in breast cancer xenografts : a major induction of stromal MMP-13

In human breast cancer (HBC), as with many carcinoma systems, most matrix metalloproteinases (MMPs) are largely expressed by the stromal cells, whereas the tumour cells are relatively silent in MMP expression. To determine the tissue source of the most relevant MMPs, we xenografted HBC cell lines and HBC tissues into the mammary fat pad (MFP) or bone of immunocompromised mice and measured the expression of human and mouse MMP-2, -9, -11, -13, membrane-type-1 MMP (MT1-MMP), MT2-MMP and MT3-MMP by species-specific real-time quantitative RT-PCR. Our data confirm a stromal origin for most tumour-associated MMPs and indicate marked and consistent upregulation of stromal (mouse) MMP-13 and MT1-MMP in all xenografts studied, irrespective of implantation in the MFP or bone environments. In addition, we show increased expression of both human MMP-13 and human MT1-MMP by the MDA-MB-231 tumour cells grown in the MFP compared to in vitro production. MMP protein and activity data confirm the upregulation of MMP mRNA production and indicate an increase in the activated MMP-2 species as a result of tumour implantation. These data directly demonstrate tumour induction of MMP production by stromal cells in both the MFP and bone environments. These xenografts are a valuable means for examining in vivo production of MMPs and suggest that MMP-13 and MT1-MMP will be relevant targets for inhibiting breast cancer progression.

Alcohol-related emergency department injury presentations in Queensland adolescents and young adults over a 13-year period

Introduction and Aims. The rate of alcohol-related emergency department (ED) presentations in young people has increased dramatically in recent decades. Injuries are the most common type of youth alcohol-related ED presentation, yet little is known about these injuries in young people. This paper describes the characteristics of alcohol-related ED injury presentations in young people over a 13-year period and determines if they differ by gender and/or age group (adolescents: 12–17 years; young adults: 18–24 years). Design and Method. The Queensland Injury Surveillance Unit (QISU) database collects injury surveillance data at triage in participating EDs throughout Queensland, Australia. A total of 4667 cases of alcohol-related injuries in young people (aged 12–24 years) were identified in the QISU database between January 1999 and December 2011, using an injury surveillance code and nursing triage text-based search strategy. Results. Overall, young people accounted for 38% of all QISU alcohol-related ED injury presentations in patients aged 12 years or over. The majority of young adults presented with injuries due to violence and falls, whereas adolescents presented due to self-harm or intoxication without other injury. Males presented with injuries due to violence, whereas females presented with alcohol-related self-harm and intoxication. Discussion and Conclusions. There is a need for more effective ways of identifying the degree of alcohol involvement in injuries among young people presenting to EDs.

Information Security and Privacy : Proceedings of the 9th Australasian Conference, ACISP 2004, Sydney, Australia, July 13-15, 2004.

Preface The 9th Australasian Conference on Information Security and Privacy (ACISP 2004) was held in Sydney, 13–15 July, 2004. The conference was sponsored by the Centre for Advanced Computing – Algorithms and Cryptography (ACAC), Information and Networked Security Systems Research (INSS), Macquarie University and the Australian Computer Society. The aims of the conference are to bring together researchers and practitioners working in areas of information security and privacy from universities, industry and government sectors. The conference program covered a range of aspects including cryptography, cryptanalysis, systems and network security. The program committee accepted 41 papers from 195 submissions. The reviewing process took six weeks and each paper was carefully evaluated by at least three members of the program committee. We appreciate the hard work of the members of the program committee and external referees who gave many hours of their valuable time. Of the accepted papers, there were nine from Korea, six from Australia, five each from Japan and the USA, three each from China and Singapore, two each from Canada and Switzerland, and one each from Belgium, France, Germany, Taiwan, The Netherlands and the UK. All the authors, whether or not their papers were accepted, made valued contributions to the conference. In addition to the contributed papers, Dr Arjen Lenstra gave an invited talk, entitled Likely and Unlikely Progress in Factoring. This year the program committee introduced the Best Student Paper Award. The winner of the prize for the Best Student Paper was Yan-Cheng Chang from Harvard University for his paper Single Database Private Information Retrieval with Logarithmic Communication. We would like to thank all the people involved in organizing this conference. In particular we would like to thank members of the organizing committee for their time and efforts, Andrina Brennan, Vijayakrishnan Pasupathinathan, Hartono Kurnio, Cecily Lenton, and members from ACAC and INSS.

The dominant 55kDa allergen of the subtropical Bahia grass (Paspalum notatum) pollen is a group 13 pollen allergen, Pas n 13

Bahia grass, Paspalum notatum, is an important pollen allergen source with a long season of pollination and wide distribution in subtropical and temperate regions. We aimed to characterize the 55. kDa allergen of Bahia grass pollen (BaGP) and ascertain its clinical importance. BaGP extract was separated by 2D-PAGE and immunoblotted with serum IgE of a grass pollen-allergic patient. The amino-terminal protein sequence of the predominant allergen isoform at 55. kDa had similarity with the group 13 allergens of Timothy grass and maize pollen, Phl p 13 and Zea m 13. Four sequences obtained by rapid amplification of the allergen cDNA ends represented multiple isoforms of Pas n 13. The predicted full length cDNA for Pas n 13 encoded a 423 amino acid glycoprotein including a signal peptide of 28 residues and with a predicted pI of 7.0. Tandem mass spectrometry of tryptic peptides of 2D gel spots identified peptides specific to the deduced amino acid sequence for each of the four Pas n 13 cDNA, representing 47% of the predicted mature protein sequence of Pas n 13. There was 80.6% and 72.6% amino acid identity with Zea m 13 and Phl p 13, respectively. Reactivity with a Phl p 13-specific monoclonal antibody AF6 supported designation of this allergen as Pas n 13. The allergen was purified from BaGP extract by ammonium sulphate precipitation, hydrophobic interaction and size exclusion chromatography. Purified Pas n 13 reacted with serum IgE of 34 of 71 (48%) grass pollen-allergic patients and specifically inhibited IgE reactivity with the 55. kDa band of BaGP for two grass pollen-allergic donors. Four isoforms of Pas n 13 from pI 6.3-7.8 had IgE-reactivity with grass pollen allergic sera. The allergenic activity of purified Pas n 13 was demonstrated by activation of basophils from whole blood of three grass pollen-allergic donors tested but not control donors. Pas n 13 is thus a clinically relevant pollen allergen of the subtropical Bahia grass likely to be important in eliciting seasonal allergic rhinitis and asthma in grass pollen-allergic patients.

Suggestive linkage of 2p22-25 and 11q12-13 with low bone mineral density at the lumbar spine in the Irish population

Osteoporosis is a disease characterized by low bone mineral density (BMD) and poor bone quality. Peak bone density is achieved by the third decade of life, after which bone is maintained by a balanced cycle of bone resorption and synthesis. Age-related bone loss occurs as the bone resorption phase outweighs the bone synthesis phase of bone metabolism. Heritability accounts for up to 90% of the variability in BMD. Chromosomal loci including 1p36, 2p22-25, 11q12-13, parathyroid hormone receptor type 1 (PTHR1), interleukin-6 (IL-6), interleukin 1 alpha (IL-1α) and type II collagen A1/vitamin D receptor (COL11A1/VDR) have been linked or shown suggestive linkage with BMD in other populations. To determine whether these loci predispose to low BMD in the Irish population, we investigated 24 microsatellite markers at 7 chromosomal loci by linkage studies in 175 Irish families of probands with primary low BMD (T-score ≤ -1.5). Nonparametric analysis was performed using the maximum likelihood variance estimation and traditional Haseman-Elston tests on the Mapmaker/Sibs program. Suggestive evidence of linkage was observed with lumbar spine BMD at 2p22-25 (maximum LOD score 2.76) and 11q12-13 (MLS 2.55). One region, 1p36, approached suggestive linkage with femoral neck BMD (MLS 2.17). In addition, seven markers achieved LOD scores > 1.0, D2S149, D11S1313, D11S987, D11S1314 including those encompassing the PTHR1 (D3S3559, D3S1289) for lumbar spine BMD and D2S149 for femoral neck BMD. Our data suggest that genes within a these chromosomal regions are contributing to a predisposition to low BMD in the Irish population.

Catalyst engineering for lithium ion batteries: The catalytic role of Ge in enhancing the electrochemical performance of SnO2(GeO2)0.13/G anodes

The catalytic role of germanium (Ge) was investigated to improve the electrochemical performance of tin dioxide grown on graphene (SnO(2)/G) nanocomposites as an anode material of lithium ion batteries (LIBs). Germanium dioxide (GeO(20) and SnO(2) nanoparticles (<10 nm) were uniformly anchored on the graphene sheets via a simple single-step hydrothermal method. The synthesized SnO(2)(GeO(2))0.13/G nanocomposites can deliver a capacity of 1200 mA h g(-1) at a current density of 100 mA g(-1), which is much higher than the traditional theoretical specific capacity of such nanocomposites (∼ 702 mA h g(-1)). More importantly, the SnO(2)(GeO(2))0.13/G nanocomposites exhibited an improved rate, large current capability (885 mA h g(-1) at a discharge current of 2000 mA g(-1)) and excellent long cycling stability (almost 100% retention after 600 cycles). The enhanced electrochemical performance was attributed to the catalytic effect of Ge, which enabled the reversible reaction of metals (Sn and Ge) to metals oxide (SnO(2) and GeO(2)) during the charge/discharge processes. Our demonstrated approach towards nanocomposite catalyst engineering opens new avenues for next-generation high-performance rechargeable Li-ion batteries anode materials.

Genome-wide association analysis identifies 13 new risk loci for schizophrenia

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-Analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

Molecular-Conformation of 1,3-Pyridylphenylureas by H-1 and C-13 NMR-study

1H and 13C NMR spectra are reported for several 1,3-pyridylphenyl ureas. Analysis of the spectra yielded the chemical shifts. The variations in the chemical shifts have been discussed in terms of the molecular conformations.

Microbiological status of piggery effluent from 13 piggeries in the south east Queensland region of Australia

Aims: To assist in the development of safe piggery effluent re-use guidelines by determining the level of selected pathogens and indicator organisms in the effluent ponds of 13 south-east Queensland piggeries. Methods and Results: The numbers of thermotolerant coliforms, Campylobacter jejuni/coli, Erysipelothrix rhusiopathiae, Escherichia coli, Salmonella and rotavirus were determined in 29 samples derived from the 13 piggeries. The study demonstrated that the 13 final effluent ponds contained an average of 1Æ2 · 105 colony-forming units (CFU) 100 ml)1 of thermotolerant coliforms and 1Æ03 · 105 CFU 100 ml)1 of E. coli. The Campylobacter level varied from none detectable (two of 13 piggeries) to a maximum of 930 most probable number (MPN) 100 ml)1 (two of 13 piggeries). Salmonella was detected in the final ponds of only four of the 13 piggeries and then only at a low level (highest level being 51 MPN 100 ml)1). No rotavirus and no Erysip. rhusiopathiae were detected. The average log10 reductions across the ponding systems to the final irrigation pond were 1Æ77 for thermotolerant coliforms, 1Æ71 for E. coli and 1Æ04 for Campylobacter. Conclusions: This study has provided a baseline knowledge on the levels of indicator organisms and selected pathogens in piggery effluent. Significance and Impact of the Study: The knowledge gained in this study will assist in the development of guidelines to ensure the safe and sustainable re-use of piggery effluent.

Studies of Phosphazenes. Part 13.' Thermal Rearrangement Reactions of Some Met hoxycyclo phosp hazenes

The methoxycyclophosphazenes [NP(OMe),], (n = 3-6) rearrange on heating to give oxocyclophosphazanes, [N(Me)PO(OMe)],. Isomeric products are formed when n = 4-6. The lH, ,lP, and 13C n.m.r. data for the starting materials and the products are presented. The ethoxy- and n-propoxy-derivatives N,P,( OR)* do not undergo the above rearrangement. The geminal derivatives N,P,R,(OMe), (R = Ph or NHBut) on heating yield both fully and partially rearranged products, namely dioxophosphaz-1 -enes and oxophosphazadienes, as shown by 270- MHz lH n.m.r. spectroscopy. The non-geminal derivative N,P,( NMe,),(OMe), gives only the fully rearranged product N,Me,P,(NMe,),O,(OMe), whose structure has been established from its lH and 31P n.m.r. spectra.

Litteraturundervisning och ämnessyn i modersmål och litteratur: En kvalitativ undersökning bland 13 modersmålslärare inom den grundläggande utbildningen (åk 7–9)

I denna avhandling undersöker jag hur modersmålslärare inom den grundläggande utbildningen (åk 7–9) undervisar i litteratur. De frågor jag ställer mig är: Hur förverkligar lärarna sin litteraturundervisning i praktiken, hur förhåller de sig till den nya läroplanen i ämnet, Grunderna för läroplanen för den grundläggande utbildningen 2004, samt med vilken ämnes-, litteratur- och kunskapssyn utgår de från i sin undervisning? Undersökningsresultatet analyseras utifrån läroplan och utifrån en läsarorienterad, sociokulturell och funktionell litteratursyn och litteraturpedagogik. Undersökningen är kvalitativ och riktar sig i form av ett frågeformulär till alla modersmålslärare i högstadierna i huvudstadsregionen. Tretton lärare deltar slutligen och åtta av dessa svar uppföljs genom en tematisk intervju. Undersökningen sker våren 2005. Forskningsresultatet visar på att flera av lärarna till stor del bygger upp sin undervisning utifrån färdiga uppgifter och koncept och att undervisningen styrs av metoden, av frågan hur. Dessa lärares undervisning sker således inte utgående från en enhetlig ämnes-, litteratur- och kunskapssyn, utan ämnessynen varierar beroende på uppgift. Recensionen är den arbetsuppgift som är vanligast bland lärarna, även om flera lärare ställer sig tveksamma till den. Övriga uppgifter som förekommer bland flera lärare är uppgiftskoncept kring klassiker och litterära samtal inför klass. Tematisk litteraturundervisning används även av flera lärare, liksom Netlibris, som innebär att två klasser från olika skolor över nätet diskuterar en skönlitterär text. Både Netlibris och tematisk litteraturundervisning är metoder som lärarna förhåller sig positiva till och ser pedagogiska fördelar med. Den tematiska undervisningen sker emellertid ofta i form av koncept som återkommer i samma form år efter år. Två lärare strävar dock efter att arbeta utifrån en enhetlig ämnessyn – den erfarenhetspedagogiska. Dessa lärare använder sig av färre koncept i sin undervisning. De bygger snarare upp sin undervisning utifrån frågan varför än hur, vilket innebär att de i högre grad har möjlighet att beakta elevernas intressen och behov i utformandet av undervisningen. Detta syns bland annat i valet av böcker och teman. En av dessa lärare använder sig även av portfölj- och loggboksmetodik och låter, i enlighet med läroplanen, eleverna själva vara med och utvärdera undervisningen och den egna utvecklingen. Lärarna verkar överlag förhålla sig mera positiva till de uppgifter som bygger på dialog och som tar fasta på läsaren i läsprocessen. Trots att lärarna betonar dialogens betydelse i litteraturundervisningen, bygger undervisningen ändå ofta, och i flera fall helt och hållet, på uppgifter som saknar dialog. En av orsakerna till detta kan vara att gamla koncept, trots nya uppgifter, lever kvar i undervisningen. Att lärarna framhåller de uppgifter som utgår från läsning av gemensamma texter och som tar fasta på en läsarorienterad och sociokulturell litteratursyn, visar dock på att de nya uppgifterna håller på att omkullkasta de gamla; lärarnas litteraturundervisning befinner sig således i förändring. Samtliga lärare förhåller sig positiva till litteraturundervisning och framhåller att litteraturen sedan deras egen skoltid fått en mera framträdande roll i undervisningen. De påpekar också att modersmålsundervisningen idag är mindre färdighetsinriktad och går mot en ökad dialog.