201 research outputs found

    Tissue eosinophilia and eosinophil degranulation in Riedel's invasive fibrous thyroiditis.

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    The etiology of Riedel's invasive fibrous thyroiditis (IFT) has remained obscure. This rare disorder has been confused in the past with the more common fibrous variant of Hashimoto's disease. The typical histological features of IFT, in particular the presence of an invasive fibrosclerotic process in conjunction with a prominent chronic inflammatory infiltrate, suggest that the release of fibrogenic cytokines and other factors from these cellular infiltrates may play an important role in the pathogenesis of this condition. Our observations in routinely processed tissue sections obtained from patients with documented IFT of striking tissue eosinophilia led us to hypothesize that eosinophils and their products may play a role in the evolution of this disease. Immunofluorescence staining with affinity-purified polyclonal rabbit antibody directed against human eosinophil granule major basic protein revealed marked tissue eosinophilia and abundant extracellular deposition of major basic protein in all specimens from 16 patients with IFT. By contrast, only occasional eosinophils and no extracellular major basic protein were detected in control thyroid tissues obtained from patients with multinodular goiter, Graves' disease, Hashimoto's disease, and normal thyroid tissue. The presence of marked eosinophil infiltration and extracellular major basic protein deposition in IFT and other associated fibrosclerotic conditions suggests a role for eosinophils and their products in propagating the fibrogenesis seen in IFT

    Effects of experience and body size on refuge choice in the crayfish Orconectes immunis

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    We investigated whether refuge size or experience with a refuge affected the refuge use of male Orconectes immunis crayfish. Individuals were given choices among seven refuges for 10 consecutive days. Refuges were formed from equal length but different diameter PVC pipe and placed in an array in a random sequence. Three treatments were used. In the Novel Refuge treatment, individuals were placed in a new test arena with a new arrangement of cleaned refuges every day. In the Nonremoval treatment, individuals were left in the same arena with the same set of refuges each day. In the Removal treatment, individuals were removed from the refuges each day but placed back in the same arena with the same set of refuges after the refuges had been cleaned. We found that refuge occupation was correlated with an individual\u27s size; smaller crayfish tended to use smaller refuges than larger crayfish, even though all crayfish could fit in all of the different sized refuges. When first tested, individuals initially chose larger refuges than they would subsequently settle in, suggesting that under duress, they were not as particular about refuge characteristics. Individuals in the Nonremoval and Removal treatments were significantly more consistent in their refuge use than those in the Novel Refuge treatment, suggesting that experience with a particular refuge increased use of that refuge. Individuals from the Novel Refuge treatment that were housed for a month with a single refuge did not increase their use of that sized refuge more than those that were housed without a refuge, indicating that simply occupying a refuge of a given size did not affect refuge preference

    Determining how internal and external process connectivity affect supply chain agility: a life-cycle theory perspective

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    This paper examines how organizations connect internal and external processes to enable an agile response to continuous change. Drawing on life cycle theory, a hypothetical model is developed regarding the independent and combinative effects of internal and external process connectivity on supply chain agility and the moderating effect of product and supply complexity. The model is tested using hierarchical regression analysis based on survey data from 143 managers at German manufacturing firms. Our findings suggest that internal and external process connectivity have a positive effect on supply chain agility independently and collectively, with complexity having a moderating effect in particular instances. The findings build on prior research regarding the process-related enablers of supply chain agility; research that has yet to clearly differentiate between internal and external processes or uses the terms interchangeably. The theoretical contribution of the paper rests on its extension of life cycle theory to the supply chain

    The Ubiquitin-Proteasome Reporter GFPu Does Not Accumulate in Neurons of the R6/2 Transgenic Mouse Model of Huntington's Disease

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    Impairment of the ubiquitin-proteasome system (UPS) has long been considered an attractive hypothesis to explain the selective dysfunction and death of neurons in polyglutamine disorders such as Huntington's disease (HD). The fact that inclusion bodies in HD mouse models and patient brains are rich in ubiquitin and proteasome components suggests that the UPS may be hindered directly or indirectly by inclusion bodies or their misfolded monomeric or oligomeric precursors. However, studies into UPS function in various polyglutamine disease models have yielded conflicting results, suggesting mutant polyglutamine tracts may exert different effects on the UPS depending on protein context, expression level, subcellular localisation and cell-type. To investigate UPS function in a well-characterised mouse model of HD, we have crossed R6/2 HD mice with transgenic UPS reporter mice expressing the GFPu construct. The GFPu construct comprises GFP fused to a constitutive degradation signal (CL-1) that promotes its rapid degradation under conditions of a healthy UPS. Using a combination of immunoblot analysis, fluorescence and immunofluorescence microscopy studies, we found that steady-state GFPu levels were not detectably different between R6/2 and non-R6/2 brain. We observed no correlation between inclusion body formation and GFPu accumulation, suggesting no direct relationship between protein aggregation and global UPS inhibition in R6/2 mice. These findings suggest that while certain branches of the UPS can be impaired by mutant polyglutamine proteins, such proteins do not necessarily cause total blockade of UPS-dependent degradation. It is therefore likely that the relationship between mutant polyglutamine proteins and the UPS is more complex than originally anticipated

    Integration between Women’s and Men’s Football Clubs: A Comparison between Brazil, China and Italy

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    Despite an increasing interest from media and fans, one of the challenges women’s football currently faces is the lack of resources to sustain its growth at both grassroots and elite levels. To cope with this issue, National Associations (NAs) of various countries have recently formulated a policy demanding men’s football clubs to integrate a women’s team within their structure. Using the Multiple Streams Framework (Kingdon, 1984), this article examines the context, timing and conditions leading to the implementation of the policy of integration in three different countries: Brazil, China and Italy. The authors collected and analysed policy documents and media reports to identify factors influencing the policy formulation. Results indicate declining performances of senior women’s national team, low participation rates, external pressures from supranational football institutions and increased societal need to reduce gender disparities contribute to influence NAs’ engagement with policies for the development of women’s football. While potentially helping women’s football enhance its visibility and commercialisation, the policy of integration risks the women’s game continuing to be seen as subaltern to its men’s counterpart. Implications of the policy of integration for the long-term development of women’s football and its possible future scenarios are discussed

    A Bovine Model of Respiratory Chlamydia psittaci Infection: Challenge Dose Titration

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    This study aimed to establish and evaluate a bovine respiratory model of experimentally induced acute C. psittaci infection. Calves are natural hosts and pathogenesis may resemble the situation in humans. Intrabronchial inoculation of C. psittaci strain DC15 was performed in calves aged 2–3 months via bronchoscope at four different challenge doses from 106 to 109 inclusion-forming units (ifu) per animal. Control groups received either UV-inactivated C. psittaci or cell culture medium. While 106 ifu/calf resulted in a mild respiratory infection only, the doses of 107 and 108 induced fever, tachypnea, dry cough, and tachycardia that became apparent 2–3 days post inoculation (dpi) and lasted for about one week. In calves exposed to 109 ifu C. psittaci, the respiratory disease was accompanied by severe systemic illness (apathy, tremor, markedly reduced appetite). At the time point of most pronounced clinical signs (3 dpi) the extent of lung lesions was below 10% of pulmonary tissue in calves inoculated with 106 and 107 ifu, about 15% in calves inoculated with 108 and more than 30% in calves inoculated with 109 ifu C. psittaci. Beside clinical signs and pathologic lesions, the bacterial load of lung tissue and markers of pulmonary inflammation (i.e., cell counts, concentration of proteins and eicosanoids in broncho-alveolar lavage fluid) were positively associated with ifu of viable C. psittaci. While any effect of endotoxin has been ruled out, all effects could be attributed to infection by the replicating bacteria. In conclusion, the calf represents a suitable model of respiratory chlamydial infection. Dose titration revealed that both clinically latent and clinically manifest infection can be reproduced experimentally by either 106 or 108 ifu/calf of C. psittaci DC15 while doses above 108 ifu C. psittaci cannot be recommended for further studies for ethical reasons. This defined model of different clinical expressions of chlamydial infection allows studying host-pathogen interactions

    An Open, Large-Scale, Collaborative Effort to Estimate the Reproducibility of Psychological Science

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    Reproducibility is a defining feature of science. However, because of strong incentives for innovation and weak incentives for confirmation, direct replication is rarely practiced or published. The Reproducibility Project is an open, large-scale, collaborative effort to systematically examine the rate and predictors of reproducibility in psychological science. So far, 72 volunteer researchers from 41 institutions have organized to openly and transparently replicate studies published in three prominent psychological journals in 2008. Multiple methods will be used to evaluate the findings, calculate an empirical rate of replication, and investigate factors that predict reproducibility. Whatever the result, a better understanding of reproducibility will ultimately improve confidence in scientific methodology and findings

    Control of Bone Mass and Remodeling by PTH Receptor Signaling in Osteocytes

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    Osteocytes, former osteoblasts buried within bone, are thought to orchestrate skeletal adaptation to mechanical stimuli. However, it remains unknown whether hormones control skeletal homeostasis through actions on osteocytes. Parathyroid hormone (PTH) stimulates bone remodeling and may cause bone loss or bone gain depending on the balance between bone resorption and formation. Herein, we demonstrate that transgenic mice expressing a constitutively active PTH receptor exclusively in osteocytes exhibit increased bone mass and bone remodeling, as well as reduced expression of the osteocyte-derived Wnt antagonist sclerostin, increased Wnt signaling, increased osteoclast and osteoblast number, and decreased osteoblast apoptosis. Deletion of the Wnt co-receptor LDL related receptor 5 (LRP5) attenuates the high bone mass phenotype but not the increase in bone remodeling induced by the transgene. These findings demonstrate that PTH receptor signaling in osteocytes increases bone mass and the rate of bone remodeling through LRP5-dependent and -independent mechanisms, respectively
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