399 research outputs found
Important amino acid residues of hexachlorocyclohexane dehydrochlorinases (LinA) for enantioselective transformation of hexachlorocyclohexane isomers
The effect of functional splinting on mild dysplastic hips after walking onset
BACKGROUND: For treatment of Graf class IIb dysplastic hips at walking onset a treatment concept with abduction splints allowing patterns as walking and crawling under constant abduction control was investigated. However, as the splint still incapacitates child movements the research question remains whether the physiologically progressing maturation of hips can be significantly altered using such abduction splints for walking children. METHODS: Of 106 children showing late hip dysplasia, 68 children treated with the Hoffman-Daimler (HD-splint) abduction splint were compared with 38 children with neglect of the abduction treatment in this retrospective study. Radiographic analyses were performed measuring the development of the age dependent acetabular angle. RESULTS: The regression analysis for splint treatment showed a significant linear regression for both splint treatment and no splint treatment group (r(2 )= 0,31 respectively r(2 )= 0,33). No statistical difference between both treatment groups was apparent. CONCLUSION: Considering the characteristics of this study, there seems to be no strong rationale supporting the use of an abduction device in growing children. As no significant difference between treatment groups is apparent, a future controlled prospective study on splinting effects can be considered ethically allowed
Red blood cell-derived semaphorin 7A promotes thrombo-inflammation in myocardial ischemia-reperfusion injury through platelet GPIb.
Myocardial ischemia is one of the leading health problems worldwide. Therapy consists of the restitution of coronary perfusion which is followed by myocardial inflammation. Platelet-neutrophil interaction is a crucial process during inflammation, yet its consequences are not fully understood. Here, we show that platelet-neutrophil complexes (PNCs) are increased in patients with acute myocardial infarction and that this is associated with increased levels of neuronal guidance protein semaphorin 7A (SEMA7A). To investigate this further, we injected WT animals with Sema7a and found increased infarct size with increased numbers of PNCs. Experiments in genetically modified animals identify Sema7a on red blood cells to be crucial for this condition. Further studies revealed that Sema7a interacts with the platelet receptor glycoprotein Ib (GPIb). Treatment with anti-Sema7a antibody protected from myocardial tissue injury. In summary, we show that Sema7a binds to platelet GPIb and enhances platelet thrombo-inflammatory activity, aggravating post-ischemic myocardial tissue injury
Expression of VjbR under Nutrient Limitation Conditions Is Regulated at the Post-Transcriptional Level by Specific Acidic pH Values and Urocanic Acid
VjbR is a LuxR homolog that regulates transcription of many genes including important virulence determinants of the facultative intracellular pathogen Brucella abortus. This transcription factor belongs to a family of regulators that participate in a cell-cell communication process called quorum sensing, which enables bacteria to respond to changes in cell population density by monitoring concentration of self produced autoinducer molecules. Unlike almost all other LuxR-type proteins, VjbR binds to DNA and activates transcription in the absence of any autoinducer signal. To investigate the mechanisms by which Brucella induces VjbR-mediated transcriptional activation, and to determine how inappropriate spatio-temporal expression of the VjbR target genes is prevented, we focused on the study of expression of vjbR itself. By assaying different parameters related to the intracellular lifestyle of Brucella, we identified a restricted set of conditions that triggers VjbR protein expression. Such conditions required the convergence of two signals of different nature: a specific pH value of 5.5 and the presence of urocanic acid, a metabolite involved in the connection between virulence and metabolism of Brucella. In addition, we also observed an urocanic acid, pH-dependent expression of RibH2 and VirB7, two additional intracellular survival-related proteins of Brucella. Analysis of promoter activities and determination of mRNA levels demonstrated that the urocanic acid-dependent mechanisms that induced expression of VjbR, RibH2, and VirB7 act at the post-transcriptional level. Taken together, our findings support a model whereby Brucella induces VjbR-mediated transcription by modulating expression of VjbR in response to specific signals related to the changing environment encountered within the host
Differences in selectivity to natural images in early visual areas (V1âV3)
High-level regions of the ventral visual pathway respond more to intact objects compared to scrambled objects. The aim of this study was to determine if this selectivity for objects emerges at an earlier stage of processing. Visual areas (V1âV3) were defined for each participant using retinotopic mapping. Participants then viewed intact and scrambled images from different object categories (bottle, chair, face, house, shoe) while neural responses were measured using fMRI. Our rationale for using scrambled images is that they contain the same low-level properties as the intact objects, but lack the higher-order combinations of features that are characteristic of natural images. Neural responses were higher for scrambled than intact images in all regions. However, the difference between intact and scrambled images was smaller in V3 compared to V1 and V2. Next, we measured the spatial patterns of response to intact and scrambled images from different object categories. We found higher within-category compared to between category correlations for both intact and scrambled images demonstrating distinct patterns of response. Spatial patterns of response were more distinct for intact compared to scrambled images in V3, but not in V1 or V2. These findings demonstrate the emergence of selectivity to natural images in V3
Apyrase treatment of myocardial infarction according to a clinically applicable protocol fails to reduce myocardial injury in a porcine model
<p>Abstract</p> <p>Background</p> <p>Ectonucleotidase dependent adenosine generation has been implicated in preconditioning related cardioprotection against ischemia-reperfusion injury, and treatment with a soluble ectonucleotidase has been shown to reduce myocardial infarct size (IS) when applied prior to induction of ischemia. However, ectonucleotidase treatment according to a clinically applicable protocol, with administration only after induction of ischemia, has not previously been evaluated. We therefore investigated if treatment with the ectonucleotidase apyrase, according to a clinically applicable protocol, would reduce IS and microvascular obstruction (MO) in a large animal model.</p> <p>Methods</p> <p>A percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 min, in 16 anesthetized pigs (40-50 kg). The pigs were randomized to 40 min of 1 ml/min intracoronary infusion of apyrase (10 U/ml, n = 8) or saline (0.9 mg/ml, n = 8), twenty minutes after balloon inflation. Area at risk (AAR) was evaluated by <it>ex vivo </it>SPECT. IS and MO were evaluated by <it>ex vivo </it>MRI.</p> <p>Results</p> <p>No differences were observed between the apyrase group and saline group with respect to IS/AAR (75.7 ± 4.2% vs 69.4 ± 5.0%, p = NS) or MO (10.7 ± 4.8% vs 11.4 ± 4.8%, p = NS), but apyrase prolonged the post-ischemic reactive hyperemia.</p> <p>Conclusion</p> <p>Apyrase treatment according to a clinically applicable protocol, with administration of apyrase after induction of ischemia, does not reduce myocardial infarct size or microvascular obstruction.</p
Effective Rheology of Bubbles Moving in a Capillary Tube
We calculate the average volumetric flux versus pressure drop of bubbles
moving in a single capillary tube with varying diameter, finding a square-root
relation from mapping the flow equations onto that of a driven overdamped
pendulum. The calculation is based on a derivation of the equation of motion of
a bubble train from considering the capillary forces and the entropy production
associated with the viscous flow. We also calculate the configurational
probability of the positions of the bubbles.Comment: 4 pages, 1 figur
Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at â s = 8 TeV with the ATLAS detector
Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fbâ1 of â s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente
Systems analysis of apoptosis protein expression allows the case-specific prediction of cell death responsiveness of melanoma cells.
Many cancer entities and their associated cell line models are highly heterogeneous in their responsiveness to apoptosis inducers and, despite a detailed understanding of the underlying signaling networks, cell death susceptibility currently cannot be predicted reliably from protein expression profiles. Here, we demonstrate that an integration of quantitative apoptosis protein expression data with pathway knowledge can predict the cell death responsiveness of melanoma cell lines. By a total of 612 measurements, we determined the absolute expression (nM) of 17 core apoptosis regulators in a panel of 11 melanoma cell lines, and enriched these data with systems-level information on apoptosis pathway topology. By applying multivariate statistical analysis and multi-dimensional pattern recognition algorithms, the responsiveness of individual cell lines to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or dacarbazine (DTIC) could be predicted with very high accuracy (91 and 82% correct predictions), and the most effective treatment option for individual cell lines could be pre-determined in silico. In contrast, cell death responsiveness was poorly predicted when not taking knowledge on protein-protein interactions into account (55 and 36% correct predictions). We also generated mathematical predictions on whether anti-apoptotic Bcl-2 family members or x-linked inhibitor of apoptosis protein (XIAP) can be targeted to enhance TRAIL responsiveness in individual cell lines. Subsequent experiments, making use of pharmacological Bcl-2/Bcl-xL inhibition or siRNA-based XIAP depletion, confirmed the accuracy of these predictions. We therefore demonstrate that cell death responsiveness to TRAIL or DTIC can be predicted reliably in a large number of melanoma cell lines when investigating expression patterns of apoptosis regulators in the context of their network-level interplay. The capacity to predict responsiveness at the cellular level may contribute to personalizing anti-cancer treatments in the future
Matching safety to access: global actors and pharmacogovernance in Kenya- a case study
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