20 research outputs found
Loss of MMP-2 disrupts skeletal and craniofacial development and results in decreased bone mineralization, joint erosion and defects in osteoblast and osteoclast growth
No full textThe 'vanishing bone' or inherited osteolysis/arthritis syndromes represent a heterogeneous group of skeletal disorders characterized by mineralization defects of affected bones and joints. Differing in anatomical distribution, severity and associated syndromic features, gene identification in each 'vanishing bone' disorder should provide unique insights into genetic/molecular pathways contributing to the overall control of skeletal growth and development. We previously described and then demonstrated that the novel autosomal recessive osteolysis/arthritis syndrome, multicentric osteolysis with arthritis (MOA) (MIM #605156), was caused by inactivating mutations in the MMP2 gene [Al Aqeel, A., Al Sewairi, W., Edress, B., Gorlin, R.J., Desnick, R.J. and Martignetti, J.A. (2000) Inherited multicentric osteolysis with arthritis: A variant resembling Torg syndrome in a Saudi family. Am. J. Med. Genet., 93, 11-18.]. These in vivo results were counterintuitive and unexpected since previous in vitro studies suggested that MMP-2 overexpression and increased activity, not deficiency, would result in the bone and joint features of MOA. The apparent lack of a murine model [Itoh, T., Ikeda, T., Gomi, H., Nakao, S., Suzuki, T. and Itohara, S. (1997) Unaltered secretion of beta-amyloid precursor protein in gelatinase A (matrix metalloproteinase 2)-deficient mice. J. Biol. Chem., 272, 22389-22392.] has hindered studies on disease pathogenesis and, more fundamentally, in addressing the paradox of how functional loss of a single proteolytic enzyme results in an apparent increase in bone loss. Here, we report that Mmp2-/- mice display attenuated features of human MOA including progressive loss of bone mineral density, articular cartilage destruction and abnormal long bone and craniofacial development. Moreover, these changes are associated with markedly and developmentally restricted decreases in osteoblast and osteoclast numbers in vivo. Mmp2-/- mice have ∼50% fewer osteoblasts and osteoclasts than control littermates at 4 days of life but these differences have nearly resolved by 4 weeks of age. In addition, despite normal cell numbers in vivo at 8 weeks of life, Mmp2-/- bone marrow cells are unable to effectively support osteoblast and osteoclast growth and differentiation in culture. Targeted inhibition of MMP-2 using siRNA in human SaOS2 and murine MC3T3 osteoblast cell lines resulted in decreased cell proliferation rates. Taken together, our findings suggest that MMP-2 plays a direct role in early skeletal development and bone cell growth and proliferation. Thus, Mmp2-/- mice provide a valuable biological resource for studying the pathophysiological mechanisms underlying the human disease and defining the in vivo physiological role of MMP-2. © The Author 2007. Published by Oxford University Press. All rights reserved
Population Movement in Japan: A Hierarchical Bayesian Approach
No full textAs Japan\u27s population ages, the shifting age distribution threatens to destabilize economic and social conditions. Exacerbating this issue is increasing urbanization that leaves vulnerable demographics isolated in more rural regions. To make meaningful statements about the future of Japan\u27s demographic distribution, it is necessary to analyze population movement within the country. To this end, we perform a descriptive analysis examining the net immigration rates into each prefecture of Japan from other prefectures over the course of 2004 to 2013. In particular, we propose a Bayesian regression model of net immigration rates which incorporates eects of census variables, latent differences between prefectures, and anomalous shocks in wake of the 2011 Tohoku earthquake and subsequent nuclear meltdown. We use two-component spike-and-slab priors on regression coefficients that allow for selective shrinkage of parameters. We further propose a framework for predicting from the model and demonstrate that it provides accurate predictions even for years for which covariate values are not known. Our model is seen to give robust predictions of immigration rates, while also yielding valuable insights about the potential factors influencing migration between regions of Japan
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Intercultural communication and the United States-Japan wood products trade
No full textThis paper seeks to answer whether problems in intercultural communication
contribute to difficulties in wood products trade between the United States and Japan. It
summarizes the more commonly heard complaints about the current state of this trade
flow, including trade barriers and product specifications. It then offers a list of rules to
follow in intercultural business situations, as distilled from various publications on the
subject. The author surveyed American companies that export wood products to Japan
and the Japanese companies that import the products to assess these companies’ performance
in relation to these rules. The quantitative survey identified several key areas of concern
to these businesses, and these concerns served as the basis to a series of qualitative
interviews with the individuals who filled out the survey. The paper reports the comments
of these interviewees and discusses the results. The paper finds that the interviewees do
find intercultural communication to be problematic, reveals that the two sides interpret
some aspects of their communication differently, and relates several pieces of advice
offered by the participants concerning U.S.-Japan wood products trade. The paper concludes
that the long distribution channels characteristic of the trade flow hinder the flow of
information and thus prevent better communication
Measuring the Metabolic Response Curves of Rufus and Melanistic Fox Squirrels (Sciurus niger)
No full textMelanism, the presence of black fur, skin, or feathers, is a trait commonly found in vertebrates. Eastern fox squirrels (Sciurus niger) are usually a reddish orange (rufus) color, but some individuals express a melanistic trait making them completely black. The proportion of these individuals is increasing and moving westward in the Omaha area. Melanism has been associated with crypsis from predators on dark substrate, but the selective advantage in Omaha is currently unknown. Previous research investigated melanism and skin temperature, but metabolic activity (heat production) was unknown. I assessed the metabolic rates of the two color morphs at eight temperatures in order to examine any differences in metabolic production. I measured the metabolic rates of 23 (13 rufus and 10 melanistic) wild-caught fox squirrels in the Omaha area. No significant difference was detected between the metabolic response curves of the two color morphs. The lower critical temperature for the combined melanistic and rufus fox squirrels was 28.63 ºC. In order to fully understand thermal advantages of S. niger in Omaha, further studies need to be carried out involving the assessment of hair morphology, genetics, and insulation (fat)
Distinctive functions of membrane type 1 matrix-metalloprotease (MT1-MMP or MMP-14) in lung and submandibular gland development are independent of its role in pro-MMP-2 activation
No full textMembrane type 1-matrix metalloprotease (MT1-MMP or MMP-14) is a major activator of pro-MMP-2 and is essential for skeletal development. We show here that it is required for branching morphogenesis of the submandibular gland but not the lung. Instead, in the lung, it is essential for postnatal development of alveolar septae. Lung development in Mmp14-/- mice is arrested at the prealveolar stage with compensatory hyperinflation of immature saccules. Mmp2-/- mice lacked comparable defects in the lung and submandibular gland, suggesting that MT1-MMP acts via mechanisms independent of pro-MMP-2 activation. Since the developmental defects in the lung are first manifest around the time of initial vascularization (E16.5), we investigated the behavior of pulmonary endothelial cells from Mmp14+/+ and Mmp14-/- mice. Endothelial cells from lungs of 1-week-old Mmp14-/- mice show reduced migration and formation of three-dimensional structures on Matrigel. Since pulmonary septal development requires capillary growth, the underlying mechanism of pulmonary hypoplasia in Mmp14-/- mice may be defective angiogenesis, supporting a model in which angiogenesis is a critical rate-limiting step for acquisition of pulmonary parenchymal mass. © 2004 Elsevier Inc. All rights reserved.link_to_subscribed_fulltex
Variants within the MMP3 gene are associated with achilles tendinopathy: possible interaction with the COL5A1 gene
No full textObjectives: Sequence variation within the COL5A1 and TNC genes are known to associate with Achilles tendinopathy. The primary aim of this case-control genetic association study was to investigate whether variants within the matrix metalloproteinase 3 (MMP3) gene also contributed to both Achilles tendinopathy and Achilles tendon rupture in a Caucasian population. A secondary aim was to establish whether variants within the MMP3 gene interacted with the COL5A1 rs12722 variant to raise risk of these pathologies.
Methods: 114 subjects with symptoms of Achilles tendon pathology and 98 healthy controls were genotyped for MMP3 variants rs679620, rs591058 and rs650108.
Results: As single markers, significant associations were found between the GG genotype of rs679620 (OR = 2.5, 95% CI 1.2 to 4.90, p = 0.010), the CC genotype of rs591058 (OR = 2.3, 95% CI 1.1 to 4.50, p = 0.023) and the AA genotype of rs650108 (OR = 4.9, 95% CI 1.0 to 24.1, p = 0.043) and risk of Achilles tendinopathy. The ATG haplotype (rs679620, rs591058, and rs650108) was under-represented in the tendinopathy group when compared to the control group (41% vs 53%, p = 0.038). Finally, the G allele of rs679620 and the T allele of COL5A1 rs12722 significantly interacted to raise risk of AT (p = 0.006). No associations were found between any of the MMP3 markers and Achilles tendon rupture.
Conclusion: Variants within the MMP3 gene are associated with Achilles tendinopathy. Furthermore, the MMP3 gene variant rs679620 and the COL5A1 marker rs12722 interact to modify the risk of tendinopathy. These data further support a genetic contribution to a common sports related injur
Complications related to cochlear implants: experience in Tehran
No full textObjective: Cochlear implantation (CI) is an effective treatment for profound deaf patients. To study the cochlear
implant complications in patients at Amir Aalam Hospital.
Methods: The study population involved 177 profoundly deaf patients, implanted within the same cochlear
implant center.
Results: Twenty-four (13.6%) patients experienced complications. Early complications accrued in 9 (37.7%)
patients within the first 24 hours. Eight (4.5%) patients had major complications including facial nerve paralysis,
suture rupture and prosthesis rejection. Prosthesis rejection 6 (30%) was the most frequent major complication.
Minor complications were found in 16 (9%) cases which were managed medically. Older age with CI was
correlated with higher major complications.
Conclusion: In contrast to minor complications, the frequency of major complications in this cohort was higher
than that published by other group
Students with dyslexia: research projects at Northumbria University
No full textNorthumbria University has about 700 registered disabled students, the majority of whom (around 58 per cent) are registered as having dyslexia and account for approximately two per cent of the total student population. Therefore dyslexic students represent the largest single group of disabled students and are those with whom most staff are likely to come into contact. The research authors were keen to ascertain whether there was a difference in academic performance between dyslexic and non-dyslexic students in respect of degree classification and assignment marks and to investigate whether dyslexic students generally felt supported in their academic studies. Research involved both qualitative and quantitative strands and the areas explored include pre expectations; general support throughout study; methods, flexibility and clarity of learning tasks, in particular assessment and levels of performance throughout and at the end of their study. This research is ongoing, however, findings have proved invaluable as a basis in the construction of good practice guidelines in dealing with the pedagogic needs of this diverse student grou
Membrane Type 1-Matrix Metalloproteinase Is Regulated by Chemokines Monocyte-Chemoattractant Protein-1/CCL2 and Interleukin-8/CXCL8 in Endothelial Cells during Angiogenesis
No full textA tale of two libraries: space, place and reading in Porto’s public libraries
No full textUntil 2001, people in Porto, Portugal could only visit or borrow books from one library − São Lázaro − located where the historical centre and the eastern end of the city meet. Then, a new building, the Almeida Garrett Library, was designed and placed in an almost equidistant position between the historical centre and the western zone. Both buildings and their reading atmospheres are quite different. Readers and professionals tend to compare them. And so the question arises: how do two different architectural spaces shape reading practices, even though they are inserted in the same city and serving potentially similar readers? The question sought to explore the interaction between people and space, in other words, how a space provided for reading may be appropriated, how it shapes reading practices, and, what social relations are performed in such reading spaces. Buildings tend to reflect both public reading and local cultural policies, even though the use of the space may alter and circumvent the programmed institutional aims. This analysis of space usage takes into account such policies and actual reading practices, along with their meanings and emotions. Social issues such as class, gender, ethnicity, age and power relationships provided a context for this analysis. As the public services and public buildings were analyzed, a research approach was designed to place reading in the context of urban public space, urban conviviality and the importance of democratic places for encounter and discovery
