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1.
Cancer progression towards metastasis follows a defined sequence of events described as the metastatic cascade. For extravasation and transendothelial migration metastatic cells interact first with endothelial cells. Yet the role of endothelial cells during the process of metastasis formation and extravasation is still unclear, and the interaction between metastatic and endothelial cells during transendothelial migration is poorly understood. Since tumor cells are well known to express TGF-β, and the compact endothelial layer undergoes a series of changes during metastatic extravasation (cell contact disruption, cytoskeletal reorganization, enhanced contractility), we hypothesized that an EndMT may be necessary for metastatic extravasation. We demonstrate that primary cultured rat brain endothelial cells (BEC) undergo EndMT upon TGF-β1 treatment, characterized by the loss of tight and adherens junction proteins, expression of fibronectin, β1-integrin, calponin and α-smooth muscle actin (SMA). B16/F10 cell line conditioned and activated medium (ACM) had similar effects: claudin-5 down-regulation, fibronectin and SMA expression. Inhibition of TGF-β signaling during B16/F10 ACM stimulation using SB-431542 maintained claudin-5 levels and mitigated fibronectin and SMA expression. B16/F10 ACM stimulation of BECs led to phosphorylation of Smad2 and Smad3. SB-431542 prevented SMA up-regulation upon stimulation of BECs with A2058, MCF-7 and MDA-MB231 ACM as well. Moreover, B16/F10 ACM caused a reduction in transendothelial electrical resistance, enhanced the number of melanoma cells adhering to and transmigrating through the endothelial layer, in a TGF-β-dependent manner. These effects were not confined to BECs: HUVECs showed TGF-β-dependent SMA expression when stimulated with breast cancer cell line ACM. Our results indicate that an EndMT may be necessary for metastatic transendothelial migration, and this transition may be one of the potential mechanisms occurring during the complex phenomenon known as metastatic extravasation.  相似文献   
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Eastern European grasslands are still inhabited by a rich arthropod fauna, but the drivers and mechanisms influencing their communities have to be understood to ensure their future survival. Heteroptera communities were studied in 20 plot-pairs in Pannonic salt steppe–salt marsh mosaics in Hungary. The effects of vegetation characteristics, landscape diversity and the proportion of surrounding grasslands on the composition, species richness and abundance of different feeding groups of true bugs (carnivores, specialist and generalist herbivores) were examined using ordinations and mixed-effect models. We found distinct herbivorous assemblages corresponding to microtopography-driven differences in water regime and vegetation between steppe and marsh plots, but this pattern was less pronounced in carnivorous assemblages. A higher species richness of true bugs was found in the more diverse steppe vegetation than in the salt marsh vegetation, while the abundance pattern of true bugs was opposite. Landscape diversity had a positive effect on the species richness and abundance of generalist herbivores and carnivores. Our results suggested that generalist herbivores and carnivores appear to drive diversity patterns in the local landscape due to their high dispersal abilities and the broader range of resources they can utilize. Specialist herbivores strongly influence the local insect biomass in relation to the distribution and density of their host plants. The present study highlights the importance of both habitat and landscape diversity for local insect diversity in Pannonic salt grasslands and suggests that the main threats for arthropod diversity are those processes and activities that homogenize these areas.  相似文献   
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alpha 1-Antitrypsin (alpha 1-AT) is the best-characterized member of the serpin superfamily of plasma proteins. Protease inhibitor members of this family undergo a characteristic reactive-center cleavage during expression of their inhibitory activity. The physical basis of this transition in alpha 1-AT from the stressed native conformation to the more stable reactive center cleaved (split) form was studied by Fourier transform infrared (FT-IR) spectroscopy and neutron scattering. The FT-IR spectra show that, while split alpha 1-AT has three intense well-resolved components associated with the presence of antiparallel beta-sheet and alpha-helix conformations, the amide I band of native alpha 1-AT has only one intense component, associated with the presence of beta-sheet structure. 1H-2H exchange within the polypeptide backbone, studied by FT-IR and NMR spectroscopy, shows that the native form undergoes greater exchange than the split form. Under the same conditions, neutron scattering shows no differences in the radius of gyration RG of the native and the split forms. In contrast, in high concentrations of phosphate approaching those used for crystallization, the native form (unlike the split form) undergoes dimerization. These data indicate that the conformational transition largely involves localized secondary and tertiary structure rearrangements. We propose that the energetically stressed native alpha 1-AT structure is the consequence of a significantly reduced number of hydrogen bonds in secondary structure components and that reactive-site cleavage between Met358 and Ser359 is the key for the development of the fully hydrogen bonded more stable serpin structure.  相似文献   
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Introduction

Suitable biomarkers are essential for therapeutic strategies in personalized medicine in terms of diagnosis as well as of prognosis. With highly specific biomarkers, it is possible, for example, to identify patients with poor prognosis, which enables early intervention and intensive treatment. The aim of this study was to identify and validate biomarkers and possible combinations for a prospective use in immunoscintigraphy, which may improve diagnosis of rheumatoid arthritis (RA) patients with consideration of inflammatory activity in the affected joints. Therefore, we tested several monoclonal antibodies (mAbs) directed against cellular-surface molecules on cells likely to be involved in the pathogenesis of RA.

Methods

Synovial tissue from patients with long-standing RA (accompanied by synovitis with varying states of current activity) and patients with acute non-RA arthritis were stained for surface molecules on different cell types by using fluorochrome-labeled antibodies. Tissue analysis was done by laser scanning cytometry (LSC), and statistical evaluation, by discriminant analysis and ROC analysis.

Results

CD11b, HLA-DR, CD90, and CD64 revealed significant differences between tissues from patients with RA and acute non-RA arthritis. Especially with the expression of CD64, both patient cohorts could be discriminated with high sensitivity and specificity. RA classification was improved by simultaneously investigating the expression of two or three different surface proteins, such as HLA-DR, CD90, and CD29 in the tissue. The simultaneous analysis of CD64 together with CD304 or the combination of CD11b and CD38 was suitable for the identification of RA patients with high current activity in synovitis.

Conclusions

In this study, we showed that LSC is a novel reliable method in biomarker prevalidation in RA. Hence, identified mAbs in situ may allow their potential use in in vivo approaches. Moreover, we proved that biomarker-combination analysis resulted in better discrimination than did single-marker analysis. Combinations of these markers make a novel and reliable panel for the discrimination between RA and acute non-RA arthritis. In addition, further expedient combinations may be novel promising biomarker panels to identify current activity in synovitis in RA.  相似文献   
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Objective: Aminoterminal pro‐brain natriuretic peptide (NT‐proBNP), like brain natriuretic peptide, might have diagnostic utility in detecting left ventricular hypertrophy and/or left ventricular dysfunction. The aim of the study was to investigate the relationship between morbid obesity and NT‐proBNP and the effect of weight reduction on this parameter. Research Methods and Procedures: A total of 34 morbidly obese patients underwent laparoscopic adjustable gastric banding (LAGB). NT‐proBNP levels were measured before and 12 months after the surgery. Results: Metabolic features and systolic and diastolic blood pressure were significantly decreased (p < 0.00001 for both) after a cumulative weight loss of 19.55 kg 1 year after LAGB. NT‐proBNP concentration was significantly higher in morbidly obese patients before LAGB than in normal‐weight control subjects (341.15 ± 127.78 fmol/mL vs. 161.68 ± 75.78 fmol/mL; p < 0.00001). After bariatric surgery, NT‐proBNP concentration decreased significantly from 341.15 ± 127.78 fmol/mL to 204.87 ± 59.84 fmol/mL (p < 0.00, 001) and remained statistically significantly elevated (204.88 ± 59.84 fmol/mL vs. 161.68 ± 75.78 fmol/mL; p = 0.04) compared with normal‐weight subjects. Discussion: This investigation demonstrates higher levels of NT‐proBNP in morbidly obese subjects and a significant decrease during weight loss after laparoscopic adjustable gastric banding. In obesity, NT‐proBNP might be useful as a routine screening method for identifying left ventricular hypertrophy and/or left ventricular dysfunction.  相似文献   
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Prondvai E  Stein K  Osi A  Sander MP 《PloS one》2012,7(2):e31392

Background

Rhamphorhynchus from the Solnhofen Limestones is the most prevalent long tailed pterosaur with a debated life history. Whereas morphological studies suggested a slow crocodile-like growth strategy and superprecocial volant hatchlings, the only histological study hitherto conducted on Rhamphorhynchus concluded a relatively high growth rate for the genus. These controversial conclusions can be tested by a bone histological survey of an ontogenetic series of Rhamphorhynchus.

Methodology/Principal Findings

Our results suggest that Bennett''s second size category does not reflect real ontogenetic stage. Significant body size differences of histologically as well as morphologically adult specimens suggest developmental plasticity. Contrasting the ‘superprecocial hatchling’ hypothesis, the dominance of fibrolamellar bone in early juveniles implies that hatchlings sustained high growth rate, however only up to the attainment of 30–50% and 7–20% of adult wingspan and body mass, respectively. The early fast growth phase was followed by a prolonged, slow-growth phase indicated by parallel-fibred bone deposition and lines of arrested growth in the cortex, a transition which has also been observed in Pterodaustro. An external fundamental system is absent in all investigated specimens, but due to the restricted sample size, neither determinate nor indeterminate growth could be confirmed in Rhamphorhynchus.

Conclusions/Significance

The initial rapid growth phase early in Rhamphorhynchus ontogeny supports the non-volant nature of its hatchlings, and refutes the widely accepted ‘superprecocial hatchling’ hypothesis. We suggest the onset of powered flight, and not of reproduction as the cause of the transition from the fast growth phase to a prolonged slower growth phase. Rapidly growing early juveniles may have been attended by their parents, or could have been independent precocial, but non-volant arboreal creatures until attaining a certain somatic maturity to get airborne. This study adds to the understanding on the diversity of pterosaurian growth strategies.  相似文献   
10.
A minute new species of Kyllinga, i.e. K. carinalaevis Lye & Mesterházy, from Benin in west tropical Africa is described. It is one of three or four annual species of the genus, and the characters separating it from two other annual species are given. The species is ephemeral and occurs in a vegetation type which belongs to a Nanocyperion association. The species is probably critically endangered as it was found in a single locality out of the numerous sites that have been investigated in Benin in recent years.  相似文献   
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