Involvement of A pertussis Toxin Sensitive G-Protein in the Inhibition of Inwardly Rectifying K+ Currents by Platelet-Activating Factor in Guinea-Pig Atrial Cardiomyocytes

Platelet-activating factor (PAF) inhibits single inwardly rectifying K+ channels in guinea-pig ventricular cells. There is currently little information as to the mechanism by which these channels are modulated. The effect of PAF on quasi steady-state inwardly rectifying K+ currents (presumably of the IK1 type) of auricular, atrial and ventricular cardiomyocytes from guinea-pig were studied. Applying the patch-clamp technique in the whole-cell configuration, PAF (10 nM) reduced the K+ currents in all three cell types. The inhibitory effect of PAF occurred within seconds and was reversible upon wash-out. It was almost completely abolished by the PAF receptor antagonist BN 50730. Intracellular infusion of atrial cells with guanine 5′-(β-thio)diphosphate (GDPS) or pretreatment of cells with pertussis toxin abolished the PAF dependent reduction of the currents. Neither extracellularly applied isoproterenol nor intracellularly applied adenosine 3′,5′-cyclic monophosphate (cyclic AMP) attenuated the PAF effect. In multicellular preparations of auricles, PAF (10 nM) induced arrhythmias. The arrhythmogenic activity was also reduced by BN 50730. The data indicate that activated PAF receptors inhibit inwardly rectifying K+ currents via a pertussis toxin sensitive G-protein without involvement of a cyclic AMP-dependent step. Since IK1 is a major component in stabilizing the resting membrane potential, the observed inhibition of this type of channel could play an important role in PAF dependent arrhythmogenesis in guinea-pig heart

The Variable Influence of Orthotic Management on Hip and Pelvic Rotation in Children with Unilateral Neurogenic Equinus Deformity

BACKGROUND Equinus deformity with or without concomitant drop foot is a common finding in children with unilateral spastic cerebral palsy and spastic hemiplegia of other causes. Hypothetically, these deformities may lead to pelvic retraction and hip internal rotation during gait. Orthoses are used to reduce pes equinus during gait and to restore hindfoot first contact. OBJECTIVE We aimed to investigate whether the use of orthotic equinus correction reduces rotational hip and pelvic asymmetries. METHODS In a retrospective study, 34 children with unilateral spastic cerebral palsy or spastic hemiplegia of other causes underwent standardized instrumented 3D gait analysis with and without orthotic equinus management. We analyzed the differences in the torsional profile during barefoot walking and while wearing orthoses, as well as investigated the influence of ankle dorsiflexion and femoral anteversion on pelvic and hip kinematics and hip kinetics. RESULTS Wearing orthoses corrected pes equinus and pelvic internal rotation at the end of the stance phase and in the swing phase compared to barefoot walking. Hip rotation and the rotational moment did not significantly change with orthoses. Orthotic management or femoral anteversion did not correlate to pelvic and hip asymmetry. CONCLUSION The findings indicate that the correction of the equinus by using orthoses had a variable effect on the asymmetry of the hip and pelvis and internal rotation; both appear to have a multifactorial cause that is not primarily driven by the equinus component

Scientific and Technical Assistance for the Deployment of a Flexible Airborne Spectrometer System During C-MAPExp and COMEX

The COMEX (CO2 and MEthane eXperiment) campaign supports the mission definition of CarbonSat and HyspIRI (Hyperspectral Infrared Imager) by providing representative airborne remote sensing data MAMAP (Methane Airborne MAPper) for CarbonSat; the Airborne Visual InfraRed Imaging Spectrometer (Classic & Next Generation) AVIRISC/AVIRISNG for HyspIRI as well as ground-based and airborne insitu data. The objectives of the COMEX campaign activities are (see Campaign Implementation Plan (RD4)): 1. Investigate spatial/spectral resolution tradeoffs for CH4 anomaly detection and flux inversion by comparison of MAMAPderived emission estimates with AVIRIS/AVIRISNG derived data. 2. Evaluate sunglint observation geometry on CH4 retrievals for marine sources. 3. Characterize the effect of Surface Spectral Reflectance (SSR) heterogeneity on trace gas retrievals of CO2 and CH4 for medium and lowresolution spectrometry. 4. Identify benefits from joint SWIR/TIR (ShortWave InfraRed/Thermal InfraRed ) data for trace gas detection and retrieval by comparison of MAMAP and AVIRIS/AVIRISNG NIR/SWIR data with MAKO (Aerospace Corp.)TIR data. The ability to derive emission source strength for a range of strong emitting targets by remote sensing will be evaluated from combined AVIRISNG and MAMAP data, adding significant value to the HyspIRI campaign AVIRISNG dataset. The data will be used to quantify anomalies in atmospheric CO2 and CH4 from strong local greenhouse gas sources e.g. localized industrial complexes, landfills, etc. and to derive CO2 and CH4 emissions estimates from atmospheric gradient measurements. The original campaign concept was developed by University of Bremen and BRI. The COMEX campaign is funded bilaterally by NASA and ESA (European Space Agency). Whereas NASA funds the US part of the project via a contract with Dr. Ira Leifer, BRI (Bubbleology Research International), the contribution of MAMAP to the COMEX campaign is funded by ESA within the COMEXE project and NASA with respect to a 50 percent contribution to the flight-related costs of flying MAMAP on a US aircraft. The Data Acquisition Report (RD9) describes the instrumentation used, the measurements made by the team during the COMEX campaign in May/June 2014 and August/September 2014 in California, and an initial assessment of the data quality

Evaluation of simulated CO₂ power plant plumes from six high-resolution atmospheric transport models

Global anthropogenic CO2 sources are dominated by power plants and large industrial facilities. Quantifying the emissions of these point sources is therefore one of the main goals of the planned constellation of anthropogenic CO2 monitoring satellites (CO2M) of the European Copernicus program. Atmospheric transport models may be used to study the capabilities of such satellites through observing system simulation experiments and to quantify emissions in an inverse modelling framework. How realistically the CO2 plumes of power plants can be simulated and how strongly the results may depend on model type and resolution, however, is not well known due to a lack of observations available for benchmarking. Here, we use the unique data set of aircraft in-situ and remote sensing observations collected during the CoMet measurement campaign down-wind of the coal fired power plants at Bełchatów in Poland and Jaenschwalde in Germany in 2018 to evaluate the simulations of six different atmospheric transport models

Hollow silica capsules for amphiphilic transport and sustained delivery of antibiotic and anticancer drugs

Hollow mesoporous silica capsules HMSC are potential drug transport vehicles due to their biocompatibility, high loading capacity and sufficient stability in biological milieu. Herein, we report the synthesis of ellipsoid shaped HMSC aspect ratio amp; 8764;2 performed using hematite particles as solid templates that were coated with a conformal silica shell through cross condensation reactions. For obtaining hollow silica capsules, the iron oxide core was removed by acidic leaching. Gas sorption studies on HMSC revealed mesoscopic pores main pore width amp; 8764;38 and a high surface area of 308.8 m2 g amp; 8722;1. Cell uptake of dye labeled HMSC was confirmed by incubating them with human cervical cancer HeLa cells and analyzing the internalization through confocal microscopy. The amphiphilic nature of HMSC for drug delivery applications was tested by loading antibiotic ciprofloxacin and anticancer curcumin compounds as model drugs for hydrophilic and hydrophobic therapeutics, respectively. The versatility of HMSC in transporting hydrophilic as well as hydrophobic drugs and a pH dependent drug release over several days under physiological conditions was demonstrated in both cases by UV vis spectroscopy. Ciprofloxacin loaded HMSC were additionally evaluated towards Gram negative E. coli bacteria and demonstrated their efficacy even at low concentrations 10 amp; 956;g ml amp; 8722;1 in inhibiting complete bacterial growth over 18 hour

Design of production technology of specified component for conditions of workshop at IME FME Brno university of technology

Diplomová práce se zabývá návrhem a realizací technologie výroby součásti zadané firmou Frentech Aerospace s.r.o. pro podmínky dílny ÚST FSI VUT v Brně (laboratoře C2). Získaných poznatků je využito k návrhu inovované technologie výroby s využitím nástrojů firmy Pramet Tools, s.r.o. Technologie výroby součásti pro dílnu ÚST jsou zpracovány pro duralový materiál EN AW 6082. Součástí práce je technicko-ekonomické zhodnocení všech popsaných technologií výroby. Oba technologické postupy navržené pro podmínky laboratoře C2 jsou zhodnoceny společně a technologický postup firmy Frentech Aerospace s.r.o. je zhodnocen odděleně z důvodu zpracování technologie pro odlišný materiál polotovaru.Diploma thesis deals with design and implementation of manufacturing technology of a part which was given by company Frentech Aerospace s.r.o. Manufacturing technology is prepared for conditions of workshop of Department of Machining FME Brno UT (laboratory C2). Acquired knowledges are used for design of innovative manufacturing technology with cutting tools from company Pramet Tools, s.r.o. Manufacturing technologies of gained part are designed for alloy blank EN AW 6082. Technical-economical assessment of all manufacturing technologies is part of this thesis. Both of manufacturing technologies designed for laboratory C2 are assessed together and manufacturing technology given by company Frentech Aerospace s.r.o. is assessed alone due to using different blank material.

Defining an olfactory receptor function in airway smooth muscle cells

Pathways that control, or can be exploited to alter, the increase in airway smooth muscle (ASM) mass and cellular remodeling that occur in asthma are not well defined. Here we report the expression of odorant receptors (ORs) belonging to the superfamily of G-protein coupled receptors (GPCRs), as well as the canonical olfaction machinery (G olf and AC3) in the smooth muscle of human bronchi. In primary cultures of isolated human ASM, we identified mRNA expression for multiple ORs. Strikingly, OR51E2 was the most highly enriched OR transcript mapped to the human olfactome in lung-resident cells. In a heterologous expression system, OR51E2 trafficked readily to the cell surface and showed ligand selectivity and sensitivity to the short chain fatty acids (SCFAs) acetate and propionate. These endogenous metabolic byproducts of the gut microbiota slowed the rate of cytoskeletal remodeling, as well as the proliferation of human ASM cells. These cellular responses in vitro were found in ASM from non-asthmatics and asthmatics, and were absent in OR51E2-deleted primary human ASM. These results demonstrate a novel chemo-mechanical signaling network in the ASM and serve as a proof-of-concept that a specific receptor of the gut-lung axis can be targeted to treat airflow obstruction in asthma.open0

A Framework for Exploring Functional Variability in Olfactory Receptor Genes

BACKGROUND: Olfactory receptors (ORs) are the largest gene family in mammalian genomes. Since nearly all OR genes are orphan receptors, inference of functional similarity or differences between odorant receptors typically relies on sequence comparisons. Based on the alignment of entire coding region sequence, OR genes are classified into families and subfamilies, a classification that is believed to be a proxy for OR gene functional variability. However, the assumption that overall protein sequence diversity is a good proxy for functional properties is untested. METHODOLOGY: Here, we propose an alternative sequence-based approach to infer the similarities and differences in OR binding capacity. Our approach is based on similarities and differences in the predicted binding pockets of OR genes, rather than on the entire OR coding region. CONCLUSIONS: Interestingly, our approach yields markedly different results compared to the analysis based on the entire OR coding-regions. While neither approach can be tested at this time, the discrepancy between the two calls into question the assumption that the current classification reliably reflects OR gene functional variability

Differential Modulation of Beta-Adrenergic Receptor Signaling by Trace Amine-Associated Receptor 1 Agonists

Trace amine-associated receptors (TAAR) are rhodopsin-like G-protein-coupled receptors (GPCR). TAAR are involved in modulation of neuronal, cardiac and vascular functions and they are potentially linked with neurological disorders like schizophrenia and Parkinson's disease. Subtype TAAR1, the best characterized TAAR so far, is promiscuous for a wide set of ligands and is activated by trace amines tyramine (TYR), phenylethylamine (PEA), octopamine (OA), but also by thyronamines, dopamine, and psycho-active drugs. Unfortunately, effects of trace amines on signaling of the two homologous β-adrenergic receptors 1 (ADRB1) and 2 (ADRB2) have not been clarified yet in detail. We, therefore, tested TAAR1 agonists TYR, PEA and OA regarding their effects on ADRB1/2 signaling by co-stimulation studies. Surprisingly, trace amines TYR and PEA are partial allosteric antagonists at ADRB1/2, whereas OA is a partial orthosteric ADRB2-antagonist and ADRB1-agonist. To specify molecular reasons for TAAR1 ligand promiscuity and for observed differences in signaling effects on particular aminergic receptors we compared TAAR, tyramine (TAR) octopamine (OAR), ADRB1/2 and dopamine receptors at the structural level. We found especially for TAAR1 that the remarkable ligand promiscuity is likely based on high amino acid similarity in the ligand-binding region compared with further aminergic receptors. On the other hand few TAAR specific properties in the ligand-binding site might determine differences in ligand-induced effects compared to ADRB1/2. Taken together, this study points to molecular details of TAAR1-ligand promiscuity and identified specific trace amines as allosteric or orthosteric ligands of particular β-adrenergic receptor subtypes