1,721,524 research outputs found
TLRs bent into shape
No full textToll-like receptors respond to ligands embedded in pathogen-derived macromolecules to induce immune responses. Binding of a stimulatory ligand to preexisting dimers of Toll-like receptor 9 induces conformational changes that lead to their full activation.X112sciescopu
Short Chain Branching Distribution and Thermal Behavior of High Density Polyethylene with Bimodal Molecular Weight Distribution
No full textA novel therapeutic target, GPR43; where it stands in drug discovery.
No full textWith growing interest in human microbiome for its implication in metabolic disorders, inflammatory diseases, immune disorders and so forth, understanding the biology at the interface of the gut flora and the host becomes very important for identifying novel therapeutic avenues. GPR43 has been deorphanized and the metabolites of microbiome, such as short-chain fatty acids, serve as its natural ligands. There are numerous reports that GPR43 might be a crucial link to the novel therapies for the unmet medical needs and many drug discovery organizations are making their moves in response.X118sciescopuskc
Adaptive filtering for noise reduction in hue saturation intensity color space
No full textEven though the hue saturation intensity (HSI) color model has been widely used in color image processing and analysis, the conversion formulas from the RGB color model to HSI are nonlinear and complicated in comparison with the conversion formulas of other color models. When an RGB image is degraded by random Gaussian noise, this nonlinearity leads to a nonuniform noise distribution in HSI, making accurate image analysis more difficult. We have analyzed the noise characteristics of the HSI color model and developed an adaptive spatial filtering method to reduce the magnitude of noise and the nonuniformity of noise variance in the HSI color space. With this adaptive filtering method, the filter kernel for each pixel is dynamically adjusted, depending on the values of intensity and saturation. In our experiments we have filtered the saturation and hue components and generated edge maps from color gradients. We have found that by using the adaptive filtering method, the minimum error rate in edge detection improves by approximately 15%. (C) 2002 Society of Photo-Optical Instrumentation Engineers
UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes
No full textSignalling by means of toll- like receptors ( TLRs) is essential for the development of innate and adaptive immune responses(1-3). UNC93B1, essential for signalling of TLR3, TLR7 and TLR9 in both humans and mice, physically interacts with these TLRs in the endoplasmic reticulum ( ER)(4-6). Here we show that the function of the polytopic membrane protein UNC93B1 is to deliver the nucleotide- sensing receptors TLR7 and TLR9 from the ER to endolysosomes. In dendritic cells of 3d mice, which express an UNC93B1 missense mutant ( H412R) incapable of TLR binding, neither TLR7 nor TLR9 exits the ER. Furthermore, the trafficking and signalling defects of the nucleotide- sensing TLRs in 3d dendritic cells are corrected by expression of wild- type UNC93B1. However, UNC93B1 is dispensable for ligand recognition and signal initiation by TLRs. To our knowledge, UNC93B1 is the first protein to be identified as a molecule specifically involved in trafficking of nucleotide- sensing TLRs. By inhibiting the interaction between UNC93B1 and TLRs it should be possible to achieve specific regulation of the nucleotide- sensing TLRs without compromising signalling via the cell- surface- disposed TLRs.X11412sciescopu
SCATTERING OF LONGITUDINAL-WAVES BY A CYLINDRICAL CAVITY IN AN ATTENUATING SOLID
No full textThis paper deals with the scattering of plane longitudinal elastic waves incident normally on a cylindrical cavity in a solid medium with attenuation. The scattered fields are found by introducing complex wave numbers whose imaginary parts are given by the attenuation coefficients of the solid medium. The impulse responses of the scattered displacement field at various positions of the receivers are obtained. It is seen that the impulse responses in an attenuating medium are different from those in a medium with negligible attenuation. To verify the accuracy of predicted impulse responses, experiments have been carried out for aluminum and acryl specimens as a typical nonattenuating medium and an attenuating one, respectively. Experimental results are in good agreement with predicted ones. Using the results of this study, once the input waveform and the attenuation coefficients are known, it is possible to predict the waveforms of longitudinal waves scattered by a cylindrical cavity. It is also found that the impulse responses of scattered waves can be applicable to finding the size and the position of the cylindrical cavity in a solid
PIKfyve, a class III lipid kinase, is required for TLR-induced type I IFN production via modulation of ATF3
Full text linkType I IFN plays a key role in antiviral responses. It also has been shown that deregulation of type I IFN expression following abnormal activation of TLRs contributes to the pathogenesis of systemic lupus erythematosus. In this study, we find that PIKfyve, a class III lipid kinase, is required for endolysosomal TLR-induced expression of type I IFN in mouse and human cells. PIKfyve binds to phosphatidylinositol 3-phosphate and synthesizes phosphatidylinositol 3,5-bisphosphate, and plays a critical role in endolysosomal trafficking. However, PIKfyve modulates type I IFN production via mechanisms independent of receptor and ligand trafficking in endolysosomes. Instead, pharmacological or genetic inactivation of PIKfyve rapidly induces expression of the transcription repressor ATF3, which is necessary and sufficient for suppression of type I IFN expression by bin'ding to its promoter and blocking its transcription. Thus, we have uncovered a novel phosphoinositide-mediated regulatory mechanism that controls TLR-mediated induction of type I IFN, which may provide a new therapeutic indication for the PIKfyve inhibitor.X111313Ysciescopu
TLR9 regulates adipose tissue inflammation and obesity-related metabolic disorders
Full text linkObjectiveRecent studies have revealed a link between Toll-like receptor (TLR) signaling and the adipose tissue inflammation associated with obesity. Although TLR9 is known to play an important role in inflammation and innate immunity, its role in mediating adipose tissue inflammation has not yet been investigated. Thus, the objective of this study was to determine the role of TLR9 in regulating immune cells in visceral adipose tissue and maintaining the metabolic homeostasis. MethodsWild-type and TLR9-deficient mice were fed with a high-fat diet, and the body weight gain, glucose tolerance, insulin sensitivity, and adipose tissue inflammation were examined. ResultsTLR9-deficient mice gained significantly more weight and body fat under a high-fat diet than wild-type mice and exhibited more severe glucose intolerance and insulin resistance. We also found a dramatic increase of M1 macrophages as well as T(H)1 cells in the adipose tissue of TLR9-deficient mice compared to wild-type mice. Furthermore, the levels of various proinflammatory cytokines and chemokines were higher in TLR9-deficient mice. ConclusionsTLR9 signaling is involved in regulating adipose tissue inflammation and controlling obesity and the metabolic syndrome.1174Ysciescopu
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