Rheumatoid arthritis sera react with a phage-displayed peptide selected by a monoclonal antibody to type II collagen that has homology to EBNA-1

Antibodies to type II collagen, and to Epstein Barr virus nuclear antigen-1 (EBNA-1) have been associated with rheumatoid arthritis (RA). In studies involving probing of phage-displayed random peptide libraries with an antibody to type II collagen, CII-C1, we observed that among 17 phagotopes selected 5 expressed peptides with homology with the sequence of EBNA-1. The residues in common were RLPFG. Hence we tested sera from 50 patients with RA, of whom 26 had antibodies to native type II collagen, and 43 healthy controls, for reactivity by ELISA with a phagotope selected 4 times, which expressed the peptide RRLPFGSQM. Eight RA sera (16%) but no normal sera reacted with the phagotope (p = 0.025). This reactivity could not be correlated with reactivity of RA sera with EBNA-1 by semi-quantitative western blot, with which reactivity occurred in 78% of RA patients and 81% of controls. Evidence for molecular mimicry was not found insofar as the phagotope did not inhibit reactivity of RA sera with EBNA-1 and CII-C1 was not reactive with EBNA-1. We conclude that the reactivity of the RA sera with the phagotope is most likely due to the phagotope being a mimic of an epitope of type II collagen for a proportion of RA sera.

Mimotopes identified by phage display for the monoclonal antibody CII- C1 to type II collagen

The characterization of B cell epitopes has been advanced by the use of random peptide libraries displayed within the coat protein of bacteriophage. This technique was applied to the monoclonal antibody (mAb) C1 to type II collagen (CII-C1). CII-C1 is known to react with a conformational epitope on type II collagen that includes residues 359-363. Three rounds of selection were used to screen two random nonameric phage libraries and 18 phagotopes were isolated. CII-C1 reacted by ELISA with 17 of the 18 phagotopes: one phagotope contained a stop codon. Of the eight most reactive phage, seven inhibited the reactivity by ELISA of CII-C1 with type II collagen. Of the 18 phage isolated, 11 encoded the motif F-G-x-Q with the sequence F-G-S-Q in 6, 2 encoded F-G-Q, and one the reverse motif Q-x-y-F. Most phagotopes that inhibited the reactivity of CII-C1 encoded two particular motifs consisting of two basic amino acid residues and a hydrophobic residue in the first part of the insert and the F-G-x-Q or F-G-Q motif ill the second part; phagotopes which contained only one basic residue in the first part of the sequence were less reactive. These motifs are not represented in the linear sequence of type II collagen and thus represent mimotopes of the epitope for CII-C1 on type II collagen. There were five phagotopes with peptide inserts containing the sequence RLPFG occurring in the Epstein-Barr virus nuclear antigen, EBNA- 1. This is of interest because EBV has been implicated in the initiation of rheumatoid arthritis (RA) by reason of increased reactivity to EBNA-1 in RA sera. In conclusion, the phage display technique disclosed mimotopes for a conformational epitope of type II collagen, and revealed an interesting homology with a sequence of the EBNA-1 antigen from Epstein Barr virus.

Associated schools of construction of southern Africa infrastructure design and delivery workshop - Report. CIB task group 91 infrastructure

This workshop comprised a diverse group of African construction experts, ranging far wider than RSA. Each of the attendees had attended the annual ASOCSA conference and was additionally provided with a short workshop pre-brief. The aim was to develop a view of their 15-20 year vision of construction improvement in RSA and the steps necessary to get there. These included sociological, structural, technical and process changes. Whilst some suggestions are significantly challenging, none are impossible, given sufficient collaboration between government, industry, academia and NGOs. The highest priority projects (more properly, programmes) were identified and further explored. These are: 1. Information Hub (‘Open Africa’). Aim – to utilise emerging trends in Open Data to provide a force for African unity. 2. Workforce Development. Aim – to rebuild a competent, skilled construction industry for RSA projects and for export. 3. Modular DIY Building. Aim – to accelerate the development of sustainable, cost-efficient and desirable housing for African economic immigrants and others living in makeshift and slum dwellings. Open Data is a maturing theme in different cities and governments around the world and the workshop attendees were very keen to seize such a possibility to assist in developing an environment where Africans can share information and foster collaboration. It is likely that NGOs might be keen to follow up such an initiative. There are significant developments taking place around the world in the construction sector currently, with comparatively large savings being made for taxpayers (20% plus in the UK). Not all of these changes would be easy to transplant to RSA (even more so to much of the rest of Africa). Workforce development was a keen plea amongst the attendees, who seemed concerned that expertise has leaked away and is not being replaced with sufficient intensity. It is possible today to develop modular buildings in such a way that even unskilled residents can assist in their construction, and even their appropriate design. These buildings can be sited nearly autonomously from infrastructures, thus relieving the tensions on cities and townships, whilst providing humane accommodation for the economically disadvantaged. Development of suitable solutions could either be conducted with other similarly stressed countries or developed in-country and the expertise exported. Finally, it should be pointed out that this was very much a first step. Any opportunity to collaborate from an Australian, QUT or CIB perspective would be welcomed, whilst acknowledging that the leading roles belong to RSA, CSIR, NRF, ASOCSA and the University of KwaZulu-Natal.

The subordinated processes controlled by a family of subordinators and corresponding Fokker-Planck type equations

In this work, we consider subordinated processes controlled by a family of subordinators which consist of a power function of a time variable and a negative power function of an α-stable random variable. The effect of parameters in the subordinators on the subordinated process is discussed. By suitable variable substitutions and the Laplace transform technique, the corresponding fractional Fokker–Planck-type equations are derived. We also compute their mean square displacements in a free force field. By choosing suitable ranges of parameters, the resulting subordinated processes may be subdiffusive, normal diffusive or superdiffusive

Effects of different instructional constraints on task performance and emergence of coordination in children

The objectives of this study were to determine the impact of different instructional constraints on standing board jump (sbj) performance in children and understand the underlying changes in emergent movement patterns. Two groups of novice participants were provided with either externally or internally focused attentional instructions during an intervention phase. Pre- and post-test sessions were undertaken to determine changes to performance and movement patterns. Thirty-six primary fourth-grade male students were recruited for this study and randomly assigned to either an external, internal focus or control group. Different instructional constraints with either an external focus (image of the achievement) or an internal focus (image of the act) were provided to the participants. Performance scores (jump distances), and data from key kinematic (joint range of motion, ROM) and kinetic variables (jump impulses) were collected. Instructional constraints with an emphasis on an external focus of attention were generally more effective in assisting learners to improve jump distances. Intra-individual analyses highlighted how enhanced jump distances for successful participants may be concomitant with specific changes to kinematic and kinetic variables. Larger joint ROM and adjustment to a comparatively larger horizontal impulse to a vertical impulse were observed for more successful participants at post-test performance. From a constraints-led perspective, the inclusion of instructional constraints encouraging self-adjustments in the control of movements (i.e., image of achievement) had a beneficial effect on individuals performing the standing broad jump task. However, the advantage of using an external focus of attentional instructions could be task- and individual-specific.

High threshold of β1 integrin inhibition required to block collagen I-induced membrane type-1 matrix metalloproteinase (MT1-MMP) activation of matrix metalloproteinase 2 (MMP-2)

Background Matrix metalloproteinase-2 (MMP-2) is an endopeptidase that facilitates extracellular matrix remodeling and molecular regulation, and is implicated in tumor metastasis. Type I collagen (Col I) regulates the activation of MMP-2 through both transcriptional and post-transcriptional means; however gaps remain in our understanding of the involvement of collagen-binding ?1 integrins in collagen-stimulated MMP-2 activation. Methods Three ?1 integrin siRNAs were used to elucidate the involvement of ?1 integrins in the Col I-induced MMP-2 activation mechanism. ?1 integrin knockdown was analyzed by quantitative RT-PCR, Western Blot and FACS analysis. Adhesion assay and collagen gel contraction were used to test the biological effects of ?1 integrin abrogation. MMP-2 activation levels were monitored by gelatin zymography. Results All three ?1 integrin siRNAs were efficient at ?1 integrin knockdown and FACS analysis revealed commensurate reductions of integrins ?2 and ?3, which are heterodimeric partners of ?1, but not ?V, which is not. All three ?1 integrin siRNAs inhibited adhesion and collagen gel contraction, however only the siRNA showing the greatest magnitude of ?1 knockdown inhibited Col I-induced MMP-2 activation and reduced the accompanying upregulation of MT1-MMP, suggesting a dose response threshold effect. Re-transfection with codon-swapped ?1 integrin overcame the reduction in MMP-2 activation induced by Col-1, confirming the ?1 integrin target specificity. MMP-2 activation induced by TPA or Concanavalin A (Con A) was not inhibited by ?1 integrin siRNA knockdown. Conclusion Together, the data reveals that strong abrogation of ?1 integrin is required to block MMP-2 activation induced by Col I, which may have implications for the therapeutic targeting of ?1 integrin.

An anticipative reactive control strategy to deal with unforeseen obstacles during a multi-sensor-based navigation task

We address the problem of the rangefinder-based avoidance of unforeseen static obstacles during a visual navigation task. We extend previous strategies which are efficient in most cases but remain still hampered by some drawbacks (e.g., risks of collisions or of local minima in some particular cases, etc.). The key idea is to complete the control strategy by adding a controller providing the robot some anticipative skills to guarantee non collision and by defining more general transition conditions to deal with local minima. Simulation results show the proposed strategy efficiency.

Differences in L1 linguistic attention control between monolinguals and bilinguals

Relational elements of language (e.g. spatial prepositions) act to direct attention to aspects of an incoming message. The listener or reader must be able to use these elements to focus and refocus attention on the mental representation being constructed. Research has shown that this type of attention control is specific to language and can be distinguished from attention control for non-relational (semantic or content) elements. Twenty-two monolinguals (18–30 years) and nineteen bilinguals (18–30 years) completed two conditions of an alternating-runs task-switching paradigm in their first language. The relational condition involved processing spatial prepositions, and the non-relational condition involved processing concrete nouns and adjectives. Overall, monolinguals had significantly larger shift costs (i.e. greater attention control burden) in the relational condition than the non-relational condition, whereas bilinguals performed similarly in both conditions. This suggests that proficiency in a second language has a positive impact on linguistic attention control in one's native language.

Missing in space: An evaluation of imputation methods for missing data in spatial analysis of risk factors for type II diabetes

Background Spatial analysis is increasingly important for identifying modifiable geographic risk factors for disease. However, spatial health data from surveys are often incomplete, ranging from missing data for only a few variables, to missing data for many variables. For spatial analyses of health outcomes, selection of an appropriate imputation method is critical in order to produce the most accurate inferences. Methods We present a cross-validation approach to select between three imputation methods for health survey data with correlated lifestyle covariates, using as a case study, type II diabetes mellitus (DM II) risk across 71 Queensland Local Government Areas (LGAs). We compare the accuracy of mean imputation to imputation using multivariate normal and conditional autoregressive prior distributions. Results Choice of imputation method depends upon the application and is not necessarily the most complex method. Mean imputation was selected as the most accurate method in this application. Conclusions Selecting an appropriate imputation method for health survey data, after accounting for spatial correlation and correlation between covariates, allows more complete analysis of geographic risk factors for disease with more confidence in the results to inform public policy decision-making.

Threat of resource loss: The role of self-regulation in adaptive task performance

Changes at work are often accompanied with the threat of, or actual, resource loss. Through an experiment, we investigated the detrimental effect of the threat of resource loss on adaptive task performance. Self-regulation (i.e., task focus and emotion control) was hypothesized to buffer the negative relationship between the threat of resource loss and adaptive task performance. Adaptation was conceptualized as relearning after a change in task execution rules. Threat of resource loss was manipulated for 100 participants undertaking an air traffic control task. Using discontinuous growth curve modeling, 2 kinds of adaptation—transition adaptation and reacquisition adaptation—were differentiated. The results showed that individuals who experienced the threat of resource loss had a stronger drop in performance (less transition adaptation) and a subsequent slower recovery (less reacquisition adaptation) compared with the control group who experienced no threat. Emotion control (but not task focus) moderated the relationship between the threat of resource loss and transition adaptation. In this respect, individuals who felt threatened but regulated their emotions performed better immediately after the task change (but not later on) compared with those individuals who felt threatened and did not regulate their emotions as well. However, later on, relearning (reacquisition adaptation) under the threat of resource loss was facilitated when individuals concentrated on the task at hand.

The thrill of victory: Women and sport shopping

This study explores a new shopper type, ‘Sport Shoppers’, who are unique in their actions, attitudes and behaviors. We present evidence that these shoppers exhibit behavior similar to that of competitive athletes in that they view bargain shopping as an achievement domain. Data were collected through open-ended surveys, in-depth interviews and closet inventories. Thematic analysis of transcripts was undertaken based on three achievement goal categories; task-oriented, ego-oriented and social approval-oriented. Achievement goal theory is employed to offer an explanation of the Sport Shoppers’ behaviors and motivations. We argue the Sport Shopper is an economically viable and important shopper for fashion retailers to target.

Serum vitamin D levels are lower in Australian children and adolescents with type 1 diabetes than in children without diabetes

Vitamin D is synthesised in the skin through the action of UVB radiation (sunlight), and 25-hydroxy vitamin D (25OHD) measured in serum as a marker of vitamin D status. Several studies, mostly conducted in high latitudes, have shown an association between type 1 diabetes mellitus (T1DM) and low serum 25OHD. We conducted a case-control study to determine whether, in a sub-tropical environment with abundant sunlight (latitude 27.5°S), children with T1DM have lower serum vitamin D than children without diabetes. Fifty-six children with T1DM (14 newly diagnosed) and 46 unrelated control children participated in the study. Serum 25OHD, 1,25-dihydroxy vitamin D (1,25(OH)2D) and selected biochemical indices were measured. Vitamin D receptor (VDR) polymorphisms Taq1, Fok1, and Apa1 were genotyped. Fitzpatrick skin classification, self-reported daily hours of outdoor exposure, and mean UV index over the 35d prior to blood collection were recorded. Serum 25OHD was lower in children with T1DM (n=56) than in controls (n=46) [mean (95%CI)=78.7 (71.8-85.6) nmol/L vs. 91.4 (83.5-98.7) nmol/L, p=0.02]. T1DM children had lower self-reported outdoor exposure and mean UV exposure, but no significant difference in distribution of VDR polymorphisms. 25OHD remained lower in children with T1DM after covariate adjustment. Children newly diagnosed with T1DM had lower 1,25(OH)2D [median (IQR)=89 (68-122) pmol/L] than controls [121 (108-159) pmol/L, p=0.03], or children with established diabetes [137 (113-153) pmol/L, p=0.01]. Children with T1DM have lower 25OHD than controls, even in an environment of abundant sunlight. Whether low vitamin D is a risk factor or consequence of T1DM is unknown. © 2012 John Wiley & Sons A/S.

Risedronate in adults with osteogenesis imperfecta type I: Increased bone mineral density and decreased bone turnover, but high fracture rate persists

Summary Bisphosphonates can increase bone mineral density (BMD) in children with osteogenesis imperfecta (OI). In this study of adults with OI type I, risedronate increased BMD at lumbar spine (but not total hip) and decreased bone turnover. However, the fracture rate in these patients remained high. Introduction Intravenous bisphosphonates given to children with OI can increase BMD and reduce fracture incidence. Oral and/or intravenous bisphosphonates may have similar effects in adults with OI. We completed an observational study of the effect of risedronate in adults with OI type I. Methods Thirty-two adults (mean age, 39 years) with OI type I were treated with risedronate (total dose, 35 mg weekly) for 24 months. Primary outcome measures were BMD changes at lumbar spine (LS) and total hip (TH). Secondary outcome measures were fracture incidence, bone pain, and change in bone turnover markers (serum procollagen type I aminopropeptide (P1NP) and bone ALP). A meta-analysis of published studies of oral bisphosphonates in adults and children with OI was performed. Results Twenty-seven participants (ten males and seventeen females) completed the study. BMD increased at LS by 3.9% (0.815 vs. 0.846 g/cm 2, p=0.007; mean Z-score, -1.93 vs. -1.58, p=0.002), with no significant change at TH. P1NP fell by 37% (p=0.00041), with no significant change in bone ALP (p=0.15). Bone pain did not change significantly (p=0.6). Fracture incidence remained high, with 25 clinical fractures and 10 major fractures in fourteen participants (0.18 major fractures per person per year), with historical data of 0.12 fractures per person per year. The meta-analysis did not demonstrate a significant difference in fracture incidence in patients with OI treated with oral bisphosphonates. Conclusions Risedronate in adults with OI type I results in modest but significant increases in BMD at LS, and decreased bone turnover. However, this may be insufficient to make a clinically significant difference to fracture incidence.

Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes

Metformin is the most commonly used pharmacological therapy for type 2 diabetes. We report a genome-wide association study for glycemic response to metformin in 1,024 Scottish individuals with type 2 diabetes with replication in two cohorts including 1,783 Scottish individuals and 1,113 individuals from the UK Prospective Diabetes Study. In a combined meta-analysis, we identified a SNP, rs11212617, associated with treatment success (n = 3,920, P = 2.9 P×-9, odds ratio = 1.35, 95% CI 1.22-1.49) at a locus containing ATM, the ataxia telangiectasia mutated gene. In a rat hepatoma cell line, inhibition of ATM with KU-55933 attenuated the phosphorylation and activation of AMP-activated protein kinase in response to metformin. We conclude that ATM, a gene known to be involved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of AMP-activated protein kinase, and variation in this gene alters glycemic response to metformin. © 2011 Nature America, Inc. All rights reserved.