This article describes novel measurements of the velocity of whole blood flow in a microchannel during coagulation. The blood is imaged volumetrically using a simple optical setup involving a white ...light source and a microscope camera. The images are processed using particle image velocimetry (PIV) and wavelet-based optical flow velocimetry (wOFV), both of which use images of individual blood cells as flow tracers. Measurements of several clinically relevant parameters such as the clotting time, decay rate, and blockage ratio are computed. The high-resolution wOFV results yield highly detailed information regarding thrombus formation and corresponding flow evolution that is the first of its kind.
Background
Common ragweed has been spreading as a neophyte in Europe. Elevated CO2 levels, a hallmark of global climate change, have been shown to increase ragweed pollen production, but their ...effects on pollen allergenicity remain to be elucidated.
Methods
Ragweed was grown in climate‐controlled chambers under normal (380 ppm, control) or elevated (700 ppm, based on RCP4.5 scenario) CO2 levels. Aqueous pollen extracts (RWE) from control‐ or CO2‐pollen were administered in vivo in a mouse model for allergic disease (daily for 3‐11 days, n = 5) and employed in human in vitro systems of nasal epithelial cells (HNECs), monocyte‐derived dendritic cells (DCs), and HNEC‐DC co‐cultures. Additionally, adjuvant factors and metabolites in control‐ and CO2‐RWE were investigated using ELISA and untargeted metabolomics.
Results
In vivo, CO2‐RWE induced stronger allergic lung inflammation compared to control‐RWE, as indicated by lung inflammatory cell infiltrate and mediators, mucus hypersecretion, and serum total IgE. In vitro, HNECs stimulated with RWE increased indistinctively the production of pro‐inflammatory cytokines (IL‐8, IL‐1β, and IL‐6). In contrast, supernatants from CO2‐RWE‐stimulated HNECs, compared to control‐RWE‐stimulated HNECS, significantly increased TNF and decreased IL‐10 production in DCs. Comparable results were obtained by stimulating DCs directly with RWEs. The metabolome analysis revealed differential expression of secondary plant metabolites in control‐ vs CO2‐RWE. Mixes of these metabolites elicited similar responses in DCs as compared to respective RWEs.
Conclusion
Our results indicate that elevated ambient CO2 levels elicit a stronger RWE‐induced allergic response in vivo and in vitro and that RWE increased allergenicity depends on the interplay of multiple metabolites.
Pollen from ragweed grown under elevated CO2 levels (700 ppm, based on RCP4.5 scenario) elicit a stronger allergic inflammatory response in vitro and in vivo by: Enhancing pro‐inflammatory cytokine release in DCs stimulated with RWE or RWE‐conditioned HNEC supernatants and increasing lung inflammatory infiltrate and serum total IgE. Increased allergenicity of CO2‐RWE depends on the interplay of multiple metabolites.
Abbreviations: DC, human monocyte‐derived dendritic cells; HNEC, human nasal epithelial cells; RWE, ragweed pollen extract; ILC, innate lymphoid cells; TNF, tumor necrosis factor; IPCC, Intergovernmental Panel on Climate Change; RCP, representative concentration pathway.
Background
Several microRNAs (miRs) have been described as potential biomarkers in liquid biopsies and in the context of allergic asthma, while therapeutic effects on the airway expression of miRs ...remain elusive. In this study, we investigated epigenetic miR‐associated mechanisms in the sputum of grass pollen‐allergic patients with and without allergen‐specific immunotherapy (AIT).
Methods
Induced sputum samples of healthy controls (HC), AIT‐treated and ‐untreated grass pollen‐allergic rhinitis patients with (AA) and without asthma (AR) were profiled using miR microarray and whole‐transcriptome microarray analysis of the same samples. miR targets were predicted in silico and used to identify inverse regulation. Local PGE2 levels were measured using ELISA.
Results
Two hundred and fifty nine miRs were upregulated in the sputum of AA patients compared with HC, while only one was downregulated. The inverse picture was observed in induced sputum of AIT‐treated patients: while 21 miRs were downregulated, only 4 miRs were upregulated in asthmatics upon AIT. Of these 4 miRs, miR‐3935 stood out, as its predicted target PTGER3, the prostaglandin EP3 receptor, was downregulated in treated AA patients compared with untreated. The levels of its ligand PGE2 in the sputum supernatants of these samples were increased in allergic patients, especially asthmatics, and downregulated after AIT. Finally, local PGE2 levels correlated with ILC2 frequencies, secreted sputum IL‐13 levels, inflammatory cell load, sputum eosinophils and symptom burden.
Conclusions
While profiling the sputum of allergic patients for novel miR expression patterns, we uncovered an association between miR‐3935 and its predicted target gene, the prostaglandin E3 receptor, which might mediate AIT effects through suppression of the PGE2‐PTGER3 axis.
miR‐3935 is upregulated in sputum cells of allergic asthma patients, who received allergen‐specific immunotherapy treatement, while mRNA levels of its predicted target, the prostaglandin E2 receptor, is downregulated as its ligand PGE2 as well. PGE2 is strongly upregulated in sputum supernatants of untreated allergic patients and is reduced in patients, who received allergen‐specific immunotherapy. PGE2 levels correlate with clinical parameters, like eosinophils and symptom score.
Cardiovascular effects of marine omega-3 fatty acids Saravanan, Palaniappan, Dr; Davidson, Neil C, MD; Schmidt, Erik B, Prof ...
The Lancet (British edition),
08/2010, Letnik:
376, Številka:
9740
Journal Article
Recenzirano
Summary Much evidence shows that the marine omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid have beneficial effects in various cardiac disorders, and their use is recommended in ...guidelines for management of patients after myocardial infarction. However, questions have been raised about their usefulness alongside optimum medical therapies with agents proven to reduce risk of cardiac events in high-risk patients. Additionally, there is some evidence for a possible pro-arrhythmic effect in subsets of cardiac patients. Some uncertainly exists about the optimum dose needed to obtain beneficial effects and the relative merit of dietary intake of omega-3 polyunsaturated fatty acids versus supplements. We review evidence for the effects of omega-3 polyunsaturated fatty acids on various cardiac disorders and the risk factors for cardiac disease. We also assess areas of uncertainty needing further research.
This manuscript details recent improvements in a wavelet-based optical flow velocimetry (wOFV) method that represents a more physically sound implementation and results in increased accuracy of the ...velocity estimation. A novel regularization scheme is presented that is based on penalization of directional derivatives of the estimated velocity field or more specifically, second-order penalization of the gradients of divergence and curl, which enforces realistic flow structure. The regularization is performed in the wavelet domain with symmetric boundary conditions for the first time using an alternative wavelet transform approach of matrix multiplications. The method for the computation of full two-dimensional wavelet transforms by a single pair of matrix multiplications is described and shown to be significantly more efficient than a lifting implementation or convolution in MATLAB. Velocity fields are estimated from synthetic tracer particle images generated from 2D DNS of isotropic turbulence and from experimental results from a turbulent flow. Results are compared to an advanced correlation-based PIV algorithm and previous advanced optical flow methods. The velocity results estimated with the new regularization scheme are shown to be more accurate and exhibit a significant reduction in non-physical small-scale artifacts compared to previous results. A significant result from the current method is the ability to generate 2D velocity field images that resolve the dissipative scales in high-Reynolds number, turbulent flows.
Graphic abstract
Climate change impacts on the structure and function of ecosystems will worsen public health issues like allergic diseases. Birch trees (Betula spp.) are important sources of aeroallergens in Central ...and Northern Europe. Birches are vulnerable to climate change as these trees are sensitive to increased temperatures and summer droughts. This study aims to examine the effect of climate change on airborne birch pollen concentrations in Central Europe using Bavaria in Southern Germany as a case study. Pollen data from 28 monitoring stations in Bavaria were used in this study, with time series of up 30 years long. An integrative approach was used to model airborne birch pollen concentrations taking into account drivers influencing birch tree abundance and birch pollen production and projections made according to different climate change and socioeconomic scenarios. Birch tree abundance is projected to decrease in parts of Bavaria at different rates, depending on the climate scenario, particularly in current centres of the species distribution. Climate change is expected to result in initial increases in pollen load but, due to the reduction in birch trees, the amount of airborne birch pollen will decrease at lower altitudes. Conversely, higher altitude areas will experience expansions in birch tree distribution and subsequent increases in airborne birch pollen in the future. Even considering restrictions for migration rates, increases in pollen load are likely in Southwestern areas, where positive trends have already been detected during the last three decades. Integrating models for the distribution and abundance of pollen sources and the drivers that control birch pollen production allowed us to model airborne birch pollen concentrations in the future. The magnitude of changes depends on location and climate change scenario.
Environmental factors that control pollen load occur at multiple spatiotemporal scales, which makes it difficult to determine the direction and intensity of the expected changes. This approach integrated both short‐term meteorological influences on reproductive biology (pollen production) and long‐term bioclimatic changes that lead to vegetation displacements (tree abundance). It was applied to birch under different representative concentration and shared socioeconomic pathways. Pollen load is expected to initially increase, but then, will decrease at lower altitudes. However, increases in pollen load are likely in higher altitudes of Southwestern areas, where positive trends have already been detected during the last three decades.
This study reports the assembly of a DNA barcode reference library for species in the lepidopteran superfamily Noctuoidea from Canada and the USA. Based on the analysis of 69,378 specimens, the ...library provides coverage for 97.3% of the noctuoid fauna (3565 of 3664 species). In addition to verifying the strong performance of DNA barcodes in the discrimination of these species, the results indicate close congruence between the number of species analyzed (3565) and the number of sequence clusters (3816) recognized by the Barcode Index Number (BIN) system. Distributional patterns across 12 North American ecoregions are examined for the 3251 species that have GPS data while BIN analysis is used to quantify overlap between the noctuoid faunas of North America and other zoogeographic regions. This analysis reveals that 90% of North American noctuoids are endemic and that just 7.5% and 1.8% of BINs are shared with the Neotropics and with the Palearctic, respectively. One third (29) of the latter species are recent introductions and, as expected, they possess low intraspecific divergences.
High-harmonic spectroscopy provides a unique insight into the electronic structure of atoms and molecules. Although attosecond science holds the promise of accessing the timescale of ...electron-electron interactions, until now, their signature has not been seen in high-harmonic spectroscopy. We have recorded high-harmonic spectra of atoms to beyond 160 eV, using a new, almost ideal laser source with a wavelength of 1.8 μm and a pulse duration of less than two optical cycles. We show that we can relate these spectra to differential photoionization cross-sections measured with synchrotron sources. In addition, we show that the high-harmonic spectra contain features due to collective multi-electron effects involving inner-shell electrons, in particular the giant resonance in xenon. We develop a new theoretical model based on the strong-field approximation and show that it is in agreement with the experimental observations.
Background
Children with asthma have impaired production of interleukin (IL) 37; in mice, IL‐37 reduces hallmarks of experimental allergic asthma (EAA). However, it remains unclear how IL‐37 exerts ...its inhibitory properties in asthma. This study aimed to identify the mechanism(s) by which IL‐37 controls allergic inflammation.
Methods
IL‐37 target cells were identified by single‐cell RNA‐seq of IL‐1R5 and IL‐1R8. Airway tissues were isolated by laser‐capture microdissection and examined by microarray‐based gene expression analysis. Mononuclear cells (MNC) and airway epithelial cells (AECs) were isolated and stimulated with allergen, IL‐1β, or IL‐33 together with recombinant human (rh) IL‐37. Wild‐type, IL‐1R1– and IL‐33–deficient mice with EAA were treated with rhIL‐37. IL‐1β, IL‐33, and IL‐37 levels were determined in sputum and nasal secretions from adult asthma patients without glucocorticoid therapy.
Results
IL‐37 target cells included AECs, T cells, and dendritic cells. In mice with EAA, rhIL‐37 led to differential expression of >90 genes induced by IL‐1β and IL‐33. rhIL‐37 reduced production of Th2 cytokines in allergen‐activated MNCs from wild‐type but not from IL‐1R1–deficient mice and inhibited IL‐33–induced Th2 cytokine release. Furthermore, rhIL‐37 attenuated IL‐1β– and IL‐33–induced pro‐inflammatory mediator expression in murine AEC cultures. In contrast to wild‐type mice, hIL‐37 had no effect on EAA in IL‐1R1– or IL‐33–deficient mice. We also observed that expression/production ratios of both IL‐1β and IL‐33 to IL‐37 were dramatically increased in asthma patients compared to healthy controls.
Conclusion
IL‐37 downregulates allergic airway inflammation by counterbalancing the disease‐amplifying effects of IL‐1β and IL‐33.
IL‐37 target cells include many cells involved in asthma pathogenesis such as AECs, DCs, ILC2s, and Th2 cells. IL‐37 limits the pro‐inflammatory and disease‐amplifying effects of IL‐1 and IL‐33 on these target cells. Patients with asthma display increased expression/production ratios of both IL‐1β and IL‐33 to IL‐37.
Abbreviations: AEC, airway epithelial cell; DC, dendritic cell; Eos, eosinophil; GC, goblet cell; GM‐CSF, granulocyte‐macrophage colony‐stimulating factor; IL, interleukin; ILC2, innate lymphoid tissue cell 2; Neu, neutrophil; Th2, T helper 2 cell
Mediators involved in the generation of pain in patients with cancer are poorly understood. Using a combined molecular, pharmacologic, behavioral, and genetic approach, we have identified a novel ...mechanism of cancer-dependent allodynia induced by protease-activated receptor 2 (PAR2). Here we show that human head and neck carcinoma cells have increased levels of proteolytic activity compared to normal human cell controls. Supernatant from human carcinoma cells, but not controls, caused marked and prolonged mechanical allodynia in mice, when administered into the hindpaw. This nociceptive effect was abolished by serine protease inhibition, diminished by mast cell depletion and absent in PAR2-deficient mice. In addition, non-contact co-culture of trigeminal ganglion neurons with human head and neck carcinoma cells increased the proportion of neurons that exhibited PAR2-immunoreactivity. Our results point to a direct role for serine proteases and their receptor in the pathogenesis of cancer pain. This previously unrecognized cancer pain pathway has important therapeutic implications wherein serine protease inhibitors and PAR2 antagonists may be useful for the treatment of cancer pain.
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