Osteocytes and mechanical loading: The Wnt connection

Bone adapts to the mechanical forces that it experiences. Orthodontic tooth movement harnesses the cell‐ and tissue‐level properties of mechanotransduction to achieve alignment and reorganization of the dentition. However, the mechanisms of action that permit bone resorption and formation in response to loads placed on the teeth are incompletely elucidated, though several mechanisms have been identified. Wnt/Lrp5 signalling in osteocytes is a key pathway that modulates bone tissue's response to load. Numerous mouse models that harbour knock‐in, knockout and transgenic/overexpression alleles targeting genes related to Wnt signalling point to the necessity of Wnt/Lrp5, and its localization to osteocytes, for proper mechanotransduction in bone. Alveolar bone is rich in osteocytes and is a highly mechanoresponsive tissue in which components of the canonical Wnt signalling cascade have been identified. As Wnt‐based agents become clinically available in the next several years, the major challenge that lies ahead will be to gain a more complete understanding of Wnt biology in alveolar bone so that improved/expedited tooth movement becomes a possibility

Activated Ion Electron Capture Dissociation (AI ECD) of proteins: synchronization of infrared and electron irradiation with ion magnetron motion.

Here, we show that to perform activated ion electron capture dissociation (AI-ECD) in a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer equipped with a CO(2) laser, it is necessary to synchronize both infrared irradiation and electron capture dissociation with ion magnetron motion. This requirement is essential for instruments in which the infrared laser is angled off-axis, such as the Thermo Finnigan LTQ FT. Generally, the electron irradiation time required for proteins is much shorter (ms) than that required for peptides (tens of ms), and the modulation of ECD, AI ECD, and infrared multiphoton dissociation (IRMPD) with ion magnetron motion is more pronounced. We have optimized AI ECD for ubiquitin, cytochrome c, and myoglobin; however the results can be extended to other proteins. We demonstrate that pre-ECD and post-ECD activation are physically different and display different kinetics. We also demonstrate how, by use of appropriate AI ECD time sequences and normalization, the kinetics of protein gas-phase refolding can be deconvoluted from the diffusion of the ion cloud and measured on the time scale longer than the period of ion magnetron motion

Periodicity Manifestations in the Turbulent Regime of Globally Coupled Map Lattice

We revisit the globally coupled map lattice (GCML). We show that in the so called turbulent regime various periodic cluster attractor states are formed even though the coupling between the maps are very small relative to the non-linearity in the element maps. Most outstanding is a maximally symmetric three cluster attractor in period three motion (MSCA) due to the foliation of the period three window of the element logistic maps. An analytic approach is proposed which explains successfully the systematics of various periodicity manifestations in the turbulent regime. The linear stability of the period three cluster attractors is investigated.Comment: 34 pages, 8 Postscript figures, all in GCML-MSCA.Zi

Flows and cohesion: balancing capabilities across an expanded union

The dynamics of physical relocation of intellectual capital is seen in the flow of skilled workers across international boundaries and the internal movements within the increasingly integrated economy of the European Union. This article describes a research framework developed within the context of a globalised economy and its potential application to issues within the boundaries of the European Unio

Independent components of human brain morphology

Quantification of brain morphology has become an important cornerstone in understanding brain structure. Measures of cortical morphology such as thickness and surface area are frequently used to compare groups of subjects or characterise longitudinal changes. However, such measures are often treated as independent from each other. A recently described scaling law, derived from a statistical physics model of cortical folding, demonstrates that there is a tight covariance between three commonly used cortical morphology measures: cortical thickness, total surface area, and exposed surface area. We show that assuming the independence of cortical morphology measures can hide features and potentially lead to misinterpretations. Using the scaling law, we account for the covariance between cortical morphology measures and derive novel independent measures of cortical morphology. By applying these new measures, we show that new information can be gained; in our example we show that distinct morphological alterations underlie healthy ageing compared to temporal lobe epilepsy, even on the coarse level of a whole hemisphere. We thus provide a conceptual framework for characterising cortical morphology in a statistically valid and interpretable manner, based on theoretical reasoning about the shape of the cortex

Co-constructing the assessment criteria for EFL writing by instructors and students: A participative approach to constructively aligning the CEFR, curricula, teaching and learning

The current assessment in language classrooms prevailingly utilizes the criteria provided by instructors, regarding learners as passive recipients of assessment. The current study drew upon sustainable assessment and the community of practice to highlight the importance of involving learners in co-constructing the assessment criteria and argued that using the criteria provided by instructors could lead to discrepancy between assessment, teaching, and learning. It adopted a participatory approach and investigated how to involve learners in co-constructing the assessment criteria with instructors in tertiary English writing instruction in China, based on the European Language Profile (ELP), an evolved version of the Common European Framework of Reference for Languages (CEFR). Two writing instructors and 146 tertiary students played different, yet interactive roles in adapting the assessment criteria in the local context. Instructors drafted the criteria in line with curricula, teaching, learning and learners. Learners utilized the draft criteria in a training session and suggested possible modifications to the criteria in a survey. Suggestions were used to revise the descriptors alongside teachers’ reflections via reflective logs. A follow-up survey explored students’ perceptions of the feasibility and usefulness of the modified descriptors to investigate the effectiveness of co-constructing the assessment criteria for learning and reveal further improvement if necessary. Vigilant decision-making processes were thickly described regarding how assessment descriptors were selected, arranged, and modified to constructively align them with curricula, teaching, and learning. Statistical and thematic analyses were conducted to examine the accessibility, feasibility, and usefulness of the assessment descriptors prior to and after the modifications. Results substantiated the effectiveness and thus the importance of co-constructing assessment criteria for enhancing the quality of assessment criteria and developing learners’ cognitive and metacognitive knowledge of writing and assessment. Implications for language tutors regarding co-constructing assessment criteria in local contexts were deliberated on at the end of the article

Can HRCT be used as a marker of airway remodelling in children with difficult asthma?

BACKGROUND: Whole airway wall thickening on high resolution computed tomography (HRCT) is reported to parallel thickening of the bronchial epithelial reticular basement membrane (RBM) in adult asthmatics. A similar relationship in children with difficult asthma (DA), in whom RBM thickening is a known feature, may allow the use of HRCT as a non-invasive marker of airway remodelling. We evaluated this relationship in children with DA. METHODS: 27 children (median age 10.5 [range 4.1-16.7] years) with DA, underwent endobronchial biopsy from the right lower lobe and HRCT less than 4 months apart. HRCTs were assessed for bronchial wall thickening (BWT) of the right lower lobe using semi-quantitative and quantitative scoring techniques. The semi-quantitative score (grade 0-4) was an overall assessment of BWT of all clearly identifiable airways in HRCT scans. The quantitative score (BWT %; defined as [airway outer diameter - airway lumen diameter]/airway outer diameter x100) was the average score of all airways visible and calculated using electronic endpoint callipers. RBM thickness in endobronchial biopsies was measured using image analysis. 23/27 subjects performed spirometry and the relationships between RBM thickness and BWT with airflow obstruction evaluated. RESULTS: Median RBM thickness in endobronchial biopsies was 6.7(range 4.6-10.0) microm. Median qualitative score for BWT of the right lower lobe was 1(range 0-1.5) and quantitative score was 54.3 (range 48.2-65.6)%. There was no relationship between RBM thickness and BWT in the right lower lobe using either scoring technique. No relationship was found between FEV1 and BWT or RBM thickness. CONCLUSION: Although a relationship between RBM thickness and BWT on HRCT has been found in adults with asthma, this relationship does not appear to hold true in children with D

Structural and biochemical characterization of the exopolysaccharide deacetylase Agd3 required for Aspergillus fumigatus biofilm formation

The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Deletion of a gene encoding a putative deacetylase, Agd3, leads to defects in GAG deacetylation, biofilm formation, and virulence. Here, we show that Agd3 deacetylates GAG in a metal-dependent manner, and is the founding member of carbohydrate esterase family CE18. The active site is formed by four catalytic motifs that are essential for activity. The structure of Agd3 includes an elongated substrate-binding cleft formed by a carbohydrate binding module (CBM) that is the founding member of CBM family 87. Agd3 homologues are encoded in previously unidentified putative bacterial exopolysaccharide biosynthetic operons and in other fungal genomes. The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Here, the authors study an A. fumigatus enzyme that deacetylates GAG in a metal-dependent manner and constitutes a founding member of a new carbohydrate esterase family.Bio-organic Synthesi