Transcriptional down-regulation of suppressor of cytokine signaling (SOCS)-3 in chronic obstructive pulmonary disease

Background: Tobacco is a leading environmental factor in the initiation of respiratory diseases and causes chronic obstructive pulmonary disease (COPD). Suppressor of cytokine signaling (SOCS) family members are involved in the pathogenesis of many inflammatory diseases and SOCS-3 has been shown to play an important role in the regulation, onset and maintenance of airway allergic inflammation indicating that SOCS-3 displays a potential therapeutic target for anti-inflammatory respiratory drugs development. Since chronic obstructive pulmonary disease (COPD) is also characterized by inflammatory changes and airflow limitation, the present study assessed the transcriptional expression of SOCS-3 in COPD. Methods: Real-time PCR was performed to assess quantitative changes in bronchial biopsies of COPD patients in comparison to unaffected controls. Results: SOCS-3 was significantly down-regulated in COPD at the transcriptional level while SOCS-4 and SOCS-5 displayed no change. Conclusions: It can be concluded that the presently observed inhibition of SOCS-3 mRNA expression may be related to the dysbalance of cytokine signaling observed in COPD

Optical Properties of Pentacene and Perfluoropentacene Thin Films

The optical properties of pentacene (PEN) and perfluoropentacene(PFP) thin films on various SiO2 substrates were studied using variable angle spectroscopic ellipsometry. Structural characterization was performed using X-ray reflectivity and atomic force microscopy. A uniaxial model with the optic axis normal to the sample surface was used to analyze the ellipsometry data. A Strong optical anisotropy was observed and enabled the direction of the transition dipole of the absorption bands to be determined. Furthermore, comparison of the optical constants of PEN and PFP thin films with the absorption spectra of the monomers in solution shows significant changes due to the crystalline environment. Relative to the monomer spectrum the HOMO-LUMO transition observed in PEN (PFP) thin film is reduced by 210 meV (280 meV). Surprisingly, a second absorption band in the PFP thin film shows a slight blueshift (40 meV) compared to the spectrum of the monomer with its transition dipole perpendicular to that of the first absorption band.Comment: 6 pages, 6 figures, submitted to J. Chem. Phy

Mutations of the ret protooncogene in German multiple endocrine neoplasia families: Relation between genotype and phenotype.

It has been suggested that not only the position but also the nature of the mutations of the ret protooncogene strongly correlate with the clinical manifestation of the multiple endocrine neoplasm type 2 (MEN 2) syndrome. In particular, individuals with a Cys634-Arg substitution should have a greater risk of developing parathyroid disease. We, therefore, analyzed 94 unrelated families from Germany with inherited medullary thyroid carcinoma (MTC) for mutation of the ret protooncogene. In all but 1 of 59 families with MEN 2A, germline mutations in the extracellular domain of the ret protein were found. Some 81% of the MEN 2A mutations affected codon 634. Phenotype-genotype correlations suggested that the prevalence of pheochromocytoma and hyperparathyroidism is significantly higher in families with codon 634 mutations, but there was no correlation with the nature of the mutation. In all but 1 of 27 familial MTC (FMTC) families, mutations were detected in 1 of 4 cysteines in the extracellular domain of the ret protooncogene. Half of the FMTC mutations affected codon 634. Mutations outside of codon 634 occurred more often in FMTC families than in MEN 2A families. In all but 1 of 8 MEN 2B patients, de novo mutations in codon 918 were found. These data confirm the preferential localization of MEN 2-associated mutations and the correlation between disease phenotype and the position of the ret mutation, but there was no correlation between the occurrence of hyperparathyroidism or pheochromocytoma and the nature of the mutation

Academic careers and the valuation of academics. A discursive perspective on status categories and academic salaries in France as compared to the U.S., Germany and Great Britain

Academic careers are social processes which involve many members of large populations over long periods of time. This paper outlines a discursive perspective which looks into how academics are categorized in academic systems. From a discursive view, academic careers are organized by categories which can define who academics are (subjectivation) and what they are worth (valuation). The question of this paper is what institutional categorizations such as status and salaries can tell us about academic subject positions and their valuation. By comparing formal status systems and salary scales in France with those in the U.S., Great Britain and Germany, this paper reveals the constraints of institutional categorization systems on academic careers. Special attention is given to the French system of status categories which is relatively homogeneous and restricts the competitive valuation of academics between institutions. The comparison shows that academic systems such as the U.S. which are characterized by a high level of heterogeneity typically present more negotiation opportunities for the valuation of academics. From a discursive perspective, institutional categories, therefore, can reflect the ways in which academics are valuated in the inter-institutional job market, by national bureaucracies or in professional oligarchies

Launching of Conical Winds and Axial Jets from the Disk-Magnetosphere Boundary: Axisymmetric and 3D Simulations

We investigate the launching of outflows from the disk-magnetosphere boundary of slowly and rapidly rotating magnetized stars using axisymmetric and exploratory 3D magnetohydrodynamic (MHD) simulations. We find long-lasting outflows in both cases. (1) In the case of slowly rotating stars, a new type of outflow, a conical wind, is found and studied in simulations. The conical winds appear in cases where the magnetic flux of the star is bunched up by the disk into an X-type configuration. The winds have the shape of a thin conical shell with a half-opening angle 30-40 degrees. The conical winds may be responsible for episodic as well as long-lasting outflows in different types of stars. (2) In the case of rapidly rotating stars (the "propeller regime"), a two-component outflow is observed. One component is similar to the conical winds. A significant fraction of the disk matter may be ejected into the winds. A second component is a high-velocity, low-density magnetically dominated axial jet where matter flows along the opened polar field lines of the star. The jet has a mass flux about 10% that of the conical wind, but its energy flux (dominantly magnetic) can be larger than the energy flux of the conical wind. The jet's angular momentum flux (also dominantly magnetic) causes the star to spin-down rapidly. Propeller-driven outflows may be responsible for the jets in protostars and for their rapid spin-down. The jet is collimated by the magnetic force while the conical winds are only weakly collimated in the simulation region.Comment: 29 pages and 29 figures. This version has a major expansion after comments by a referee. The 1-st version is correct but mainly describes the conical wind. This version describes in greater detail both the conical winds and the propeller regime. Accepted to the MNRA

How phyllosilicate mineral structure affects fault strength in Mg-rich fault systems

The clay mineralogy of fault gouges has important implications for the frictional properties of faults, often identified as a major factor contributing to profound fault weakness. This work compares the frictional strength of a group of Mg‐rich minerals common in the Mg‐Al‐Si‐O compositional space (talc, saponite, sepiolite, and palygorskite) by conducting triaxial frictional tests with water or argon as pore fluid. The studied minerals are chemically similar but differ in their crystallographic structure. Results show that fibrous Mg‐rich phyllosilicates are stronger than their planar equivalents. Frictional strength in this group of minerals is highly influenced by strength of the atomic bonds, continuity of water layers within the crystals, and interactions of mineral surfaces with water molecules, all of which are dictated by crystal structure. The formation and stability of the minerals studied are mainly controlled by small changes in pore fluid chemistry, which can lead to significant differences in fault strength

Neuronal hypoxia in vitro: Investigation of therapeutic principles of HUCB-MNC and CD133+ stem cells

Background The therapeutic capacity of human umbilical cord blood mononuclear cells (HUCB-MNC) and stem cells derived thereof is documented in animal models of focal cerebral ischemia, while mechanisms behind the reduction of lesion size and the observed improvement of behavioral skills still remain poorly understood. Methods A human in vitro model of neuronal hypoxia was used to address the impact of total HUCB-MNC (tMNC), a stem cell enriched fraction (CD133+, 97.38% CD133-positive cells) and a stem cell depleted fraction (CD133-, 0.06% CD133-positive cells) of HUCB-MNC by either direct or indirect co-cultivation with post-hypoxic neuronal cells (differentiated SH-SY5Y). Over three days, development of apoptosis and necrosis of neuronal cells, chemotaxis of MNC and production of chemokines (CCL2, CCL3, CCL5, CXCL8, CXCL9) and growth factors (G-CSF, GM-CSF, VEGF, bFGF) were analyzed using fluorescence microscopy, FACS and cytometric bead array. Results tMNC, CD133+ and surprisingly CD133- reduced neuronal apoptosis in direct co-cultivations significantly to levels in the range of normoxic controls (7% ± 3%). Untreated post-hypoxic control cultures showed apoptosis rates of 85% ± 11%. tMNC actively migrated towards injured neuronal cells. Both co-cultivation types using tMNC or CD133- reduced apoptosis comparably. CD133- produced high concentrations of CCL3 and neuroprotective G-CSF within indirect co-cultures. Soluble factors produced by CD133+ cells were not detectable in direct co-cultures. Conclusion Our data show that heterogeneous tMNC and even CD133-depleted fractions have the capability not only to reduce apoptosis in neuronal cells but also to trigger the retaining of neuronal phenotypes

Bacterial community development in experimental gingivitis.

Current knowledge of the microbial composition of dental plaque in early gingivitis is based largely on microscopy and cultural methods, which do not provide a comprehensive description of oral microbial communities. This study used 454-pyrosequencing of the V1-V3 region of 16S rRNA genes (approximately 500 bp), and bacterial culture, to characterize the composition of plaque during the transition from periodontal health to gingivitis. A total of 20 healthy volunteers abstained from oral hygiene for two weeks, allowing plaque to accumulate and gingivitis to develop. Plaque samples were analyzed at baseline, and after one and two weeks. In addition, plaque samples from 20 chronic periodontitis patients were analyzed for cross-sectional comparison to the experimental gingivitis cohort. All of the healthy volunteers developed gingivitis after two weeks. Pyrosequencing yielded a final total of 344,267 sequences after filtering, with a mean length of 354 bases, that were clustered into an average of 299 species-level Operational Taxonomic Units (OTUs) per sample. Principal coordinates analysis (PCoA) plots revealed significant shifts in the bacterial community structure of plaque as gingivitis was induced, and community diversity increased significantly after two weeks. Changes in the relative abundance of OTUs during the transition from health to gingivitis were correlated to bleeding on probing (BoP) scores and resulted in the identification of new health- and gingivitis-associated taxa. Comparison of the healthy volunteers to the periodontitis patients also confirmed the association of a number of putative periodontal pathogens with chronic periodontitis. Taxa associated with gingivitis included Fusobacterium nucleatum subsp. polymorphum, Lachnospiraceae [G-2] sp. HOT100, Lautropia sp. HOTA94, and Prevotella oulorum, whilst Rothia dentocariosa was associated with periodontal health. Further study of these taxa is warranted and may lead to new therapeutic approaches to prevent periodontal disease.BBSRC Industrial Case Studentship ref no. BB/G01714X/1 in collaboration with GlaxoSmithKline