TY - JOUR. T1 - Requirement of SH2-containing protein tyrosine phosphatases SHP-1 and SHP-2 for paired immunoglobulin-like receptor B (PIR-B)-mediated inhibitory signal. AU - Maeda, Akito. AU - Kurosaki, Mari. AU - Ono, Masao. AU - Takai, Toshiyuki. AU - Kurosaki, Tomohiro. PY - 1998/4/20. Y1 - 1998/4/20. N2 - Paired immunoglobulin-like receptor B (PIR-B) (p91) molecule has been proposed to function as an inhibitory receptor in B cells and myeloid lineage cells. We demonstrate here that the cytoplasmic region of PIR-B is capable of inhibiting B cell activation. Mutational analysis of five cytoplasmic tyrosines indicate that tyrosine 771 in the motif VxYxxL plays the most crucial role in mediating the inhibitory signal. PIR-B-mediated inhibition was markedly reduced in the SH2-containing protein tyrosine phosphatases SHP- 1 and SHP-2 double-deficient DT40 B cells, whereas this inhibition was unaffected in the inositol polyphosphate 5-phosphatase SHIP-deficient cells. These data demonstrate that ...
NK cells are the first line of defense against infected and transformed cells. Defective NK cell activity was shown to increase susceptibility for viral infections and reduce tumor immune-surveillance. With age, the incidence of infectious diseases and malignancy rises dramatically, suggesting that impaired NK cell function might contribute to disease in these individuals. We found an increased frequency of NK cells with high expression of the inhibitory killer cell lectin-like receptor G1 (KLRG1) in individuals |70 y. The role of KLRG1 in ageing is not known, and the mechanism of KLRG1-induced inhibition of NK cell function is not fully understood. We report that NK cells with high KLRG1 expression spontaneously activate the metabolic sensor AMP-activated protein kinase (AMPK) and that activation of AMPK negatively regulates NK cell function. Pre-existing AMPK activity is further amplified by ligation of KLRG1 in these cells, which leads to internalization of the receptor and allows interaction with
NK cells are the first line of defense against infected and transformed cells. Defective NK cell activity was shown to increase susceptibility for viral infections and reduce tumor immune-surveillance. With age, the incidence of infectious diseases and malignancy rises dramatically, suggesting that impaired NK cell function might contribute to disease in these individuals. We found an increased frequency of NK cells with high expression of the inhibitory killer cell lectin-like receptor G1 (KLRG1) in individuals |70 y. The role of KLRG1 in ageing is not known, and the mechanism of KLRG1-induced inhibition of NK cell function is not fully understood. We report that NK cells with high KLRG1 expression spontaneously activate the metabolic sensor AMP-activated protein kinase (AMPK) and that activation of AMPK negatively regulates NK cell function. Pre-existing AMPK activity is further amplified by ligation of KLRG1 in these cells, which leads to internalization of the receptor and allows interaction with
Leukocyte immunoglobulin-like receptor subfamily B member 3 is a protein that in humans is encoded by the LILRB3 gene. This gene is a member of the leukocyte immunoglobulin-like receptor (LIR) family, which is found in a gene cluster at chromosomal region 19q13.4. The encoded protein belongs to the subfamily B class of LIR receptors which contain two or four extracellular immunoglobulin domains, a transmembrane domain, and two to four cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). The receptor is expressed on immune cells where it binds to MHC class I molecules on antigen-presenting cells and transduces a negative signal that inhibits stimulation of an immune response. It is thought to control inflammatory responses and cytotoxicity to help focus the immune response and limit autoreactivity. Multiple transcript variants encoding different isoforms have been found for this gene. Cluster of differentiation ENSG00000274587, ENSG00000277816, ENSG00000204577 GRCh38: Ensembl ...
TY - JOUR. T1 - Structure of the human NK cell triggering receptor NKp46 ectodomain. AU - Ponassi, Marco. AU - Cantoni, Claudia. AU - Biassoni, Roberto. AU - Conte, Romana. AU - Spallarossa, Andrea. AU - Pesce, Alessandra. AU - Moretta, Alessandro. AU - Moretta, Lorenzo. AU - Bolognesi, Martino. AU - Bordo, Domenico. PY - 2003/9/19. Y1 - 2003/9/19. N2 - NKp46, a natural killer (NK) cell-specific receptor, has been recently identified as one of the triggering receptors involved in NK cell activation mediated by non-HLA class I ligands. The structure of the NKp46 extracellular receptor region, here reported, consists of two Ig-like domains assembled similarly to leukocyte immunoglobulin-like receptors (LIRs) and killer inhibitory receptors (KIRs). The extensive NKp46 residue substitutions at sites structurally related to those mediating interaction with HLA antigens in LIRs and KIRs indicate that NKp46 recognition processes in vivo should involve non-HLA ligands. NKP46 is shown to stem from an ...
Clone REA899 recognizes the B isoform of the mouse paired immunoglobulin-like receptor (PIR-A and PIR-B) antigen, a single-pass type I membrane protein which is also known as leukocyte immunoglobulin-like receptor 3 (LIR-3). Cell surface expression of PIR molecules on myeloid and B lineage cells increase with cellular differentiation and activation. PIR molecules are also expressed on dendritic cells, monocytes/macrophages, and mast cells in varying levels, but not on T cells and NK cells. PIRs functions as receptors for class I MHC antigens. PIR-B down-regulates antigen-induced B cell-activation by recruiting phosphatases to its immunoreceptor tyrosine-based inhibitor motifs (ITIM).Additional information: Clone REA899 displays negligible binding to Fc receptors. | Ireland
LILRA2 [ENSP00000251377]. Leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), member 2; Part of the innate immune responses against microbial infection. Specifically recognizes a set of N-terminally truncated immunoglobulins that are produced via cleavage by proteases from a range of pathogenic bacteria and fungi, including L.pneumophila, M.hyorhinis, S.pneumoniae, S.aureus and C.albicans. Recognizes epitopes that are in part in the variable region of the immunoglobulin light chains, but requires also the constant region for signaling. Binds to a subset of cleaved IgM, IgG3 and IgG4 molecules, but does not bind cleaved IgA1. Binding of N-terminally truncated immunoglobulins mediates activation of neutrophils. In monocytes, activation leads to the release of CSF2, CF3, IL6, CXCL8 and CCL3 and down-regulates responses to bacterial lipopolysaccharide (LPS), possibly via down-regulation of TLR4 expression and reduced signaling via TLR4. In eosinophils, activation by ligand binding ...
UL18 is a human CMV (HCMV) MHC class I (MHCI) homolog that efficiently inhibits leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1)+ NK cells. We found an association of LILRB1 polymorphisms in the regulatory regions and ligand-binding domains with control of HCMV in transplant patients. Naturally occurring LILRB1 variants expressed in model NK cells showed functional differences with UL18 and classical MHCI, but not with HLA-G. The altered functional recognition was recapitulated in binding assays with the binding domains of LILRB1. Each of 4 nonsynonymous substitutions in the first 2 LILRB1 immunoglobulin domains contributed to binding with UL18, classical MHCI, and HLA-G. One of the polymorphisms controlled addition of an N-linked glycan, and that mutation of the glycosylation site altered binding to all ligands tested, including enhancing binding to UL18. Together, these findings indicate that specific LILRB1 alleles that allow for superior immune evasion by HCMV are ...
LILRA4 antibody [N2C2], Internal (leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), member 4) for IHC-P, WB. Anti-LILRA4 pAb (GTX119457) is tested in Human samples. 100% Ab-Assurance.
Recombinant Human LILRB1 is produced by our Mammalian expression system and the target gene encoding Gly24-His458 is expressed with a 6His tag at the C-terminus. Bon Opus Cat.# C484 (BP161)
Among septic patients admitted to the intensive care unit (ICU), early recognition of those with the highest risk of death is of paramount importance. Since clinical judgment is sometimes uncertain biomarkers could provide additional information likely to guide critical illness management. We evaluated the prognostic value of soluble Triggering Receptor Expressed by Myeloid cells 1 (sTREM-1), procalcitonin (PCT) and leucocyte surface expression of CD64. This was a prospective cohort study, which included 190 septic patient admitted to the ICU in two hospitals. Blood samples for biomarker measurements were obtained upon admission and thereafter. The Simplified Acute Physiology Score (SAPS) II and the Sequential Organ Failure Assessment (SOFA) score were calculated. The primary outcome was all-cause death in the ICU. The mortality rate reached 25.8 %. The best predictive value of the three biomarkers was obtained with baseline sTREM-1, although clinical scores outperformed this. Accuracy was greater in
Clone REA1016 recognizes the mouse killer cell lectin-like receptor G1 (KLRG1) antigen. KLRG1 is a homodimeric type II transmembrane glycoprotein of 30-38 kDa subunits. The protein is the mouse homolog of the rat mast cell function-associated antigen (MAFA) and is expressed on a subset of NK cells and T cells. Several members of the cadherin family can interact with KLRG1 leading to inhibition of NK cell and T cell effector functions. Additional information: Clone REA1016 displays negligible binding to Fc receptors. - Belgique
A roundabout is generally known as an efficient, safe, and environmentally friendly intersection. Since 2010, the Korea government has taken the lead in constructing roundabouts as part of a special project. During that time, many ideas have been put forward to improve the safety, operation, and design of such roundabouts. In terms of improvements, it is particularly important to understand roundabout gap acceptance behavior. As such, we investigated gap acceptance behaviors at four roundabouts based on field observation during both good weather and rainy conditions. Based on the observed data, roundabout critical gaps were estimated, and a logit model for gap acceptance using various roundabout variables was developed to investigate gap acceptance maneuvering at roundabouts. A total of 2,421 data events for gap acceptance were collected from the field observation. Out of these events, 64.6% of drivers (1,564 drivers) accepted the given gaps and 35.4% of drivers (857 drivers) rejected them.
PIR-A/B, APC, clone: 10-1-PIR, eBioscience™ 25μg; APC PIR-A/B, APC, clone: 10-1-PIR, eBioscience™ Primary Antibodies Pi to Pm
Day 68 is the most gene-poor of any part of Chromosome 3: only four protein-coding genes (browser view). Two are related: ROBO1 and ROBO2 (roundabout homologs 1 and 2).. Roundabout genes were discovered in fly. The roundabout proteins are on the surface of growing axons in the brain, and help them decide whether to cross between the halves of the brain.. Roundabout genes are found as far away as worm, meaning they are at least 550 million years old.. Click here to see the sequence of Day 68 with ROBO1 underlined.. ...
It is usually my fellow blogger Michel Augsburger of Our House in Provence who chronicles roundabouts but I suppose I might be forgiven if I borrow the idea this one time. We recently went on a short trip to the north western part of France where I saw this roundabout which I absolutely adored. Whoever the creator was he or she had the guts to to go Big, Bold and Beautiful - qualities you do not find very often on roundabout decorations. A true work of art to be found on a roundabout between Rochefort and Marennes ...
分泌型糖蛋白Slit及其受体Robo最初作为一类重要的神经元轴突导向因子被发现。随着对Slit-Robo信号通路作用机制研究的不断深入,该信号通路还参与血管新生、肿瘤血管发生、炎症、白细胞趋化及血管渗漏等过程。
The idea is simple, keep the traffic flowing when the driver reaches a junction. Rather than waiting for a light to change or a policeman to allow progress, the roundabout simply allows traffic to merge and continue onwards. For low flows of traffic, everything works smoothly however when volumes increase, it can cause the same problem that it was designed to prevent - a backup of traffic entering the junction.. In most countries, drivers have to give way to vehicles already using the junction, however in some, it is the opposite - drivers already using the junction have to let others in which increases the traffic in the junction and defeats the purpose of the design! It is also common to see a lack of planning on or near a roundabout ...
package Organism; use strict; use warnings; use feature state; sub count { return scalar keys %{ shift-,{Cells} }; } # Input a list of [ x, y ] coords sub insert_cells { my $cells = shift-,{Cells}; for my $r (@_) { $cells-,{ pack ii, @{$r} } = undef } } # Return sorted list of cells in the Organism. # Used for verification and testing the state of the organism. sub get_live_cells { sort { $a-,[0] ,=, $b-,[0] ,, $a-,[1] ,=, $b-,[1] } map { [ unpack ii, $_ ] } keys %{ shift-,{Cells} }; } # Return the list of dead cells surrounding a cell sub get_dead_cells { my ( $cells, $x0, $y0 ) = ( shift-,{Cells}, @_ ); my ( $x1, $x2, $y1, $y2 ) = ( $x0 - 1, $x0 + 1, $y0 - 1, $y0 + 1 ); state ( $k1, $k2, $k3, $k4, $k5, $k6, $k7, $k8 ); ( ( $k1 = pack ii, $x1, $y1 ) x !( 0 + exists $cells-,{ $k1 } ), ( $k2 = pack ii, $x1, $y0 ) x !( 0 + exists $cells-,{ $k2 } ), ( $k3 = pack ii, $x1, $y2 ) x !( 0 + exists $cells-,{ $k3 } ), ( $k4 = pack ii, $x0, $y1 ) x !( 0 + exists $cells-,{ $k4 } ), ( $k5 = ...
As shown by RNA in situ hybridization in rat (supplemental Figs. 1A-C, 3A, available at www.jneurosci.org as supplemental material) as well as in mouse (data not shown) embryos, Slit2 and Slit3 are highly expressed around the eye in E13 rat and E11.5 mouse embryos (which represent developmentally equivalent stages in the two species). Because Slit1 is not detected there, we first examined Slit2;Slit3 mutant embryos (n = 4). We found that the bottom structure was unaffected in the mutant, but the top structure was dramatically reduced in size when compared with stage-matched littermates (Fig. 1 B). The ratio of the top and the bottom branching areas was reduced by twofold to 0.69 ± 0.30 in the double mutants (Fig. 1 C), and this reduction reflects a change in both branching and neurite growth, because the ratio of the number of branching points or the ratio of branch lengths is also reduced to 0.61 ± 0.36 or 0.56 ± 0.23, respectively, in the mutant from 1.16 ± 0.34 or 1.27 ± 0.22 in the wild ...
Create words, four-letters or more in length, using the Roundabout letters below. Each letter can only be used once in your word and your word must always include the center letter. Do not use proper names or plurals ...
Results. The serum sRAGE (pg/ml) level was significantly lower in patients compared to healthy controls [515 (64-1887) vs 1542 (627-3159); p , 0.0001]. In paired samples, SF had lower levels compared to corresponding plasma level [102 (51-799) vs 481 (134-1006); p , 0.0001]. The level of S100A12 (ng/ml) was higher in SF (1042; 573-1415) than serum (638; 208-779). Serum sRAGE correlated negatively with S100A12 levels (r = −0.474; p , 0.01.), ESR (r = −0.306; p , 0.01), and SJC (r = −0.237; p , 0.05), but not with TJC (r = −0.134; p = NS). The levels of sRAGE remained stable over time in patients with stable disease. ...
Eric, madwifi-lists, I have been able to avoid the AP crashing by using another version of madwifi (I tried using voyage-0.6.5 which contains madwifi in version madwifi-trunk 0.9.4+r4099 as mentioned in the link posted by Eric). It really seemed to be a problem which overloaded the CPU. I come up with this idea, because I have a small display attached via serial line to the ALIX-AP-board and the display was really dull once the error occurred, but sometimes it still reacted - S-L-O-W-L-Y. So now, the error is gone, no more crashing - at least during the last 5 hours, but since the problem usually occurred within 20 minutes, I am very confident. Using a newer version of madwifi solved it. BUT now, I see something else. I am still loading the link heavily with the scp I mentioned before. Roundabout 6 minutes after booting the two ALIX-boards, the connection becomes very laggy. I am pinging the machine, that I am doing the scp to with the very same machine, that does the scp and the ping-times go ...
At the roundabout Rond-Point Kilometre Delta take the 2nd exit Boulevard Pasteur Marc Boegner/N106 towards Alès / Sommières / Le Vigan ...
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Title: Alternative Routes for the Formation of Immunochemically Distinct Advanced Glycation End-products In Vivo. VOLUME: 1 ISSUE: 3. Author(s):Masayoshi Takeuchi and Zenji Makita. Affiliation:Department of Biochemistry, Faculty of Pharmaceutical Science, Hokuriku University, 3-Ho Kanagawa-machi, Kanazawa 920-1181, Japan. Keywords:Advanced Glycation End-products, glycation end-products (AGEs), N-carboxymethyllysine (CML), Pyrraline, Pentosidine, Crossline, Imidazolones, Arg-Lys Imidazole (ALI), Vesperlysine A, Argpyrimidine. Abstract: The advanced stage of the glycation process (also called the Maillard reaction) that leads to the formation of advanced glycation end-products (AGEs) plays an important role in the pathogenesis of angiopathy in diabetic patients and in the aging process. AGEs elicit a wide range of cell-mediated responses that might contribute to diabetic complications, vascular disease, renal disease, and Alzheimer disease. Recently, it has been proposed that AGE are not only ...
Advanced glycation end products (AGEs) are critically involved in atherogenesis in diabetes by binding to receptors for AGE (RAGEs) in vascular cells, thus inducing the expression of proinflammatory mediators. In animal models, interruption of the AGE-RAGE interaction reduces lesion size and plaque development. Therefore, limiting RAGE expression might be an intriguing concept to modulate vascular disease in diabetic patients. The present study investigated whether thiazolidinediones (TZDs), antidiabetic agents clinically used to treat patients with type 2 diabetes, might modulate endothelial RAGE expression. Stimulation of human endothelial cells with rosiglitazone or pioglitazone decreased basal as well as tumor necrosis factor-α-induced RAGE cell surface and total protein expression. In addition, TZDs reduced RAGE mRNA expression in endothelial cells. These effects on RAGE expression were caused by an inhibition of nuclear factor-κB (NF-κB) activation at the proximal NF-κB site of the ...
Title:The Potential of Receptor for Advanced Glycation End Products (RAGE) as a Therapeutic Target for Lung Associated Diseases. VOLUME: 20 ISSUE: 6. Author(s):Tejinder Pal Khaket, Sun Chul Kang* and Tapan Kumar Mukherjee*. Affiliation:Department of Biotechnology, Daegu University, Gyeongsan, Gyeongbuk, Department of Biotechnology, Daegu University, Gyeongsan, Gyeongbuk, Department of Biotechnology, Maharishi Markandeshwar University, Mullana, Haryana. Keywords:Lung, RAGE, inflammation, pulmonary diseases, anti-RAGE therapy, lung epithelial cells.. Abstract:The receptor for advanced glycation end products (RAGE) is a multi-ligand pattern recognition receptor that is highly expressed in lung epithelial cells. It helps alveolar epithelial cells to maintain their morphology and specific architecture. However, in various pathophysiological conditions, pulmonary tissues express a supraphysiological level of RAGE and its ligands including advanced glycation end products, high mobility group box 1 ...
Clinical trial for Pleural Effusion , Use of the Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) in the Diagnosis of Pleural Effusion
This is the second in a series of articles designed to provide important information about key metabolic processes that are really important to understand for optimizing our quality of life - and yet almost no one in the general public has any awareness of them at all.. The first article addressed methylation: an important biochemical process in our bodies that is important for many health issues. Here is a link to the article.. This article addresses another very important metabolic process:. Advanced Glycation End Products (AGEs).. What exactly are Advanced Glycation End Products (AGEs)? Here is a great description of what AGEs are:. Advanced Glycation End Products (AGEs) are basically the nasty by-products of glucose metabolism. The typical Western Diet, coupled with a sedentary lifestyle, too much fat, and insulin resistance, leaves our bodies churning out excess glucose and unable to burn it. It stays in our blood stream too long and there it does incredible damage.. One of the most ...
Clearance of apoptotic cells by macrophages and other phagocytic cells, called efferocytosis, is a central process in the resolution of inflammation. Although the receptor for advanced glycation end products (RAGE) has been shown to participate in a variety of acute and chronic inflammatory processes in the lungs and other organs, a role for RAGE in efferocytosis has not been reported. In the present studies, we examined the potential involvement of RAGE in efferocytosis. Macrophages from transgenic RAGE-/- mice showed a decreased ability to engulf apoptotic neutrophils and thymocytes. Pretreatment of RAGE+/+ macrophages with advanced glycation end products, which competitively bind to RAGE, or Abs against RAGE diminished phagocytosis of apoptotic cells. Overexpression of RAGE in human embryonic kidney 293 cells resulted in an increased ability to engulf apoptotic cells. Furthermore, we found that incubation with soluble RAGE enhances phagocytosis of apoptotic cells by both RAGE+/+ and RAGE-/- ...
TY - JOUR. T1 - Integral role of receptor for advanced glycation end products (RAGE) in nondiabetic atherosclerosis. AU - Uekita, Hironori. AU - Ishibashi, Toshiyuki. AU - Shiomi, Masashi. AU - Koyama, Hidenori. AU - Ohtsuka, Shukuko. AU - Yamamoto, Hiroshi. AU - Yamagishi, Shoichi. AU - Inoue, Hiroyoshi. AU - Itabe, Hiroyuki. AU - Sugimoto, Koichi. AU - Kamioka, Masashi. AU - Ohkawara, Hiroshi. AU - Wada, Ikuo. AU - Yasuchika, Takeishi. PY - 2019/1/1. Y1 - 2019/1/1. N2 - An advanced glycation end products (AGE)/a receptor for AGE (RAGE) axis plays a central role in the pathogenesis of diabetic vascular remodeling. This study was conducted to clarify the role of RAGE in nondiabetic atherosclerosis. We used the aortic and coronary atherosclerotic lesions of Watanabe heritable hyperlipidemic (WHHL) rabbits prone to myocardial infarction (WHHLMI) at 1 to 14 months. Immunohistochemistry demonstrated the significant expression of RAGE as early as at 1 month with the stronger expression at 3 and 7 ...
TY - JOUR. T1 - Anti-RAGE and Aβ immunoglobulin levels are related to dementia level and cognitive performance. AU - Wilson, Jennifer S.. AU - Mruthinti, Shyamala. AU - Buccafusco, Jerry J.. AU - Schade, Rosann F.. AU - Mitchell, Meghan B.. AU - Harrell, Dean U.. AU - Gulati, Nidhi K.. AU - Miller, L. Stephen. PY - 2009/2/1. Y1 - 2009/2/1. N2 - Background. Blood-based immunoglobulins (IgGs) may mark the presence of amyloid plaques characterizing the progression of Alzheimers disease (AD). Previous studies suggest that anti-RAGE and anti-Aβ IgGs increase proportionately with accumulation of amyloid-beta (Aβ) peptides at receptor sites for advanced glycation end products (RAGE), within cortical areas of brain tissue. We assessed the relationship between these potential markers and an AD-type cognitive profile. We hypothesized that these specific IgG levels would be positively correlated with Clinical Dementia Rating (CDR) scores as well as index scores on the Repeatable Battery for the ...
Determine if an acute glucose load (50g) is associated with an in-vivo and in-vitro increase in the concentration of Advanced Glycation End Products (AGEPs) that, in turn, can impact vascular endothelial reactivity and induce an acute increase in blood pressure. Previous studies generated in the investigators laboratory showed that circulating soluble Receptor for Advanced Glycation End Products (sRAGE) and Tumor Necrosis Factor (TNF)-a (mediator of acute inflammation) are considered markers of the extent of maternal RAGE activation and/or systemic inflammation, respectively ...
Advanced glycation end products and diabetes pdf file Protein glycation and formation of advanced glycation end products (AGEs) play an important role in the pathogenesis of diabetic complications. Diabetic vascular complications • Hyperglycemia • Advanced glycation end-​products • Oxidative stress • Inhibitors of glycation. Diabetes mellitus is increasing at.
To the best of our knowledge, our study is the first to demonstrate an association between plasma sRAGE levels and CAD in nondiabetic males. The multivariate-adjusted ORs for CAD revealed that male subjects with sRAGE levels below 776 pg/dL had a 6.719-fold increase in CAD prevalence, independent of established vascular risk factors and lipid parameters. Notably, the independent association between sRAGE levels and CAD was confirmed when analyzing a subgroup of patients with normal levels of LDL cholesterol. This finding appears of interest, because it is estimated that up to half of all CAD cases occur in subjects with moderate to low risk as determined by evaluation of LDL and total cholesterol.3. sRAGE is a soluble receptor produced by alternative splicing of RAGE mRNA21 and is abundantly present in the circulation.22 The mechanism by which plasma sRAGE levels were decreased in CAD patients, however, remains to be clarified. Because sRAGE has been shown to successfully bind to AGEs,30 it has ...
TY - JOUR. T1 - Randomized Trial of an Inhibitor of Formation of Advanced Glycation End Products in Diabetic Nephropathy. AU - Bolton, W. Kline. AU - Cattran, Daniel C.. AU - Williams, Mark E.. AU - Adler, Sharon G.. AU - Appel, Gerald B.. AU - Cartwright, Kenneth. AU - Foiles, Peter G.. AU - Freedman, Barry I.. AU - Raskin, Philip. AU - Ratner, Robert E.. AU - Spinowitz, Bruce S.. AU - Whittier, Frederick C.. AU - Wuerth, Jean Paul. PY - 2004. Y1 - 2004. N2 - Background/Aims: Pimagedine inhibits the formation of advanced glycation end products and slows the progression of diabetic complications in experimental models. This study was undertaken to determine if pimagedine ameliorates nephropathy in type 1 (insulin-dependent) diabetes mellitus. Methods: This was a randomized, double-masked, placebo-controlled study performed in 690 patients with type 1 diabetes mellitus, nephropathy, and retinopathy. The patients received twice daily dosing with placebo, pimagedine 150 mg, or pimagedine 300 mg for ...
Glycation of proteins leads to the formation of early glycation adducts (fructosamine derivatives) and advanced glycation endproducts (AGEs). Formation of AGEs has been linked to the development of cataract, diabetic complications, uraemia, Alzheimers disease and other disorders. AGEs are a group o …
The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface molecules. As a pattern-recognition receptor capable of binding a diverse range of ligands, it is typically expressed at low levels under normal physiological conditions in the majority of tissues. In contrast, the lung exhibits high basal level expression of RAGE localised primarily in alveolar type I (ATI) cells, suggesting a potentially important role for the receptor in maintaining lung homeostasis. Indeed, disruption of RAGE levels has been implicated in the pathogenesis of a variety of pulmonary disorders including cancer and fibrosis. Furthermore, its soluble isoforms, sRAGE, which act as decoy receptors, have been shown to be a useful marker of ATI cell injury. Whilst RAGE undoubtedly plays an important role in the biology of the lung, it remains unclear as to the exact nature of this contribution under both physiological and pathological conditions.
To assess regulation of cell surface expression of ICAM-1 by the interaction of AGEs with RAGE, HSVEC were incubated with AGE albumin. A dose-dependent increase in cell surface expression of ICAM-1 was noted compared with native albumin (Figure 4b, lanes 2, 3, 4, and 1, respectively). This effect was mediated at least in part by RAGE, as demonstrated by decreased AGE-mediated expression of ICAM-1 in the presence of anti-RAGE IgG but not by nonimmune IgG (Figure 4b, lanes 7 and 8, respectively). In vivo-derived uremic AGEs had similar effects; compared with native albumin, incubation of HSVECs with uremic AGEs resulted in an ≈1.7-fold increase in cell surface expression of ICAM-1 (Figure 4b, lanes 9 and 10, respectively). These effects were mediated in part by RAGE, as demonstrated by reduced expression of ICAM-1 in the presence of anti-RAGE IgG but not by nonimmune IgG (Figure 4b, lanes 11 and 12, respectively).. Because E-selectin mediates targeting of inflammatory cells, particularly ...
We have recently shown that the co-expression and interaction of the receptor for advanced glycation end products (RAGE) and its ligand S100B post myocardial infarction play a role in myocyte apoptosis. In other cell types, the S100B/RAGE interaction triggers signaling pathways including NF-kB activation and translocation, MAP kinases, and p53. To determine the signaling pathways modulated by the S100B/RAGE interaction contributing to myocyte apoptosis, rat neonatal cardiac myocyte cultures transfected with a full-length cDNA of the RAGE gene, a dominant-negative cytoplasmic deletion mutant of RAGE, or vector control were treated with nanomolar (1-1000) concentrations of recombinant bovine brain S100B for 48 hrs. 1 μM S100B induced vector alone-transfected myocyte apoptosis, as evidenced by increased terminal deoxynucleotidyltransferase-mediated UTP end labeling (TUNEL) [12.4±0.7% vs. 5.6±0.3% (untreated) of total cells p,0.05], DNA fragmentation, cytochrome C release from the mytochondria to ...
Role of bone-marrow- and non-bone-marrow-derived receptor for advanced glycation end-products (RAGE) in a mouse model of diabetes-associated atherosclerosis. Clin Sci (Lond). 2014 Oct; 127(7):485-97 ...
BACKGROUND/AIMS:Our previous report showed that IgG levels are strongly correlated with the indocyanine green (ICG) retention rate in patients with liver cirrhosis (LC). This correlation suggests that hyperglobulinemia in LC could be explained by impairment of hepatic removal function. To estimate IgG turnover in LC, in the present paper was determined the advanced glycation end-products (AGE) on IgG as a marker of half-life.METHODOLOGY:Serum samples were obtained from patients with LC, rheumatoid arthritis (RA), and Sjögren syndrome (SjS), and from age-matched control patients. IgG was purified from serum by the protein G-based affinity method, concentrated by filtration, and used for assay of Nepsilon-(carboxymethyl) lysine (CML), a predominant AGE, by ELISA.RESULTS:CML on IgG was significantly lower in patients with LC than in control patients, whereas there was no significant difference in total serum CML levels among patients with LC, RA, and SjS, and control patients. CML levels on IgG ...
I have recently read an interesting article in Diabetes Care (1) that showed that the low serum level of the endogenous secretory receptor for advanced glycation end products (esRAGE) was independently associated with the prevalence of vertebral fractures in patients with type 2 diabetes. I totally agreed with the authors opinions that bone quality may be more important than bone density in defining the increased risk for fracture in type 2 diabetic patients and that the advanced glycation end product (AGE)-receptor for AGEs (RAGE) system could play a role in impaired bone quality in these patients. However, it seemed unlikely to me that an insufficient amount of esRAGE to counteract AGEs could intensify the binding of AGEs to RAGE and exert harmful effects on bones, thus being involved in the increased risk of vertebral fractures in their patients.. The endogenous soluble form of RAGE (sRAGE) can generate from the cleavage of cell surface full-length RAGE by sheddase or novel splice variants ...
Advanced glycation end products (AGEs) have been introduced to be involved in the pathogenesis of osteoarthritis (OA). The influence of AGEs on osteoarthritic fibroblast-like synovial cells (FLS) has been incompletely understood as yet. The present study investigates a potential influence of AGE-modified bovine serum albumin (AGE-BSA) on cell growth, and on the expression of proinflammatory and osteoclastogenic markers in cultured FLS. FLS were established from OA joints and stimulated with AGE-BSA. The mRNA expression of p27Kip1, RAGE (receptor for AGEs), nuclear factor kappa B subunit p65 (NFκB p65), tumor necrosis factor alpha (TNF-α, interleukin-6 (IL-6), receptor activator of NFκB ligand (RANKL) and osteoprotegerin was measured by real-time PCR. The respective protein expression was evaluated by western blot analysis or ELISA. NFκB activation was investigated by luciferase assay and electrophoretic mobility shift assay (EMSA). Cell cycle analysis, cell proliferation and markers of necrosis and
Advanced glycation end products (AGEs), the final products of nonenzymatic glycation and oxidation of proteins, are found in the plasma and accumulate in the tissues during aging and at an accelerated rate in diabetes. A novel integral membrane protein, termed receptor for AGE (RAGE), forms a centra …
Kinetics and peptide dependency of the binding of the inhibitory NK receptor CD94/NKG2-A and the activating receptor CD94/NKG2-C to HLA-E. EMBO J. 1999 Aug 02; 18(15):4250-60 ...
Advanced glycation end products naturally form in our bodies from the chemical reaction of sugars with proteins. How can you limit your AGE intake?
Complete information for SIRPA gene (Protein Coding), Signal Regulatory Protein Alpha, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Calcitriol Modulates Cardiac Fibroblasts through Noncanonical Pathway of Receptor for Advanced Glycation End Products and Fibroblast Growth Factor Receptor Signaling: Implicated in Cardiac Fibrosis in ...
Clone TG1 is the first monoclonal antibody detecting TIGIT in routine formalin-fixed paraffin-embedded (FFPE) tissues. TG1 has been validated for the detection of TIGIT positive T-cells with a focus on tumor infiltrating T cells (TILs). Anti-TIGIT clone TG1 allows the identification of TIGIT in the tumor microenvironment under pathological conditions.. TIGIT (T-cell immunoreceptor with Ig and ITIM domains) is a member of the poliovirus receptor (PVR) family. TIGIT is expressed on subsets of T lymphocytes and controls an immune checkpoint. The expression of TIGIT has been reported on NK cells, regulatory T cells, follicular T helper cells, memory CD4+ T cells, and CD8+ T cells, but TIGIT is not expressed on B cells or naive CD4+ T cells. Naive CD4+ T cells may upregulate TIGIT expression upon activation. In many different cancer models, TIGIT has been shown to be upregulated on T cells. The ligands CD155 and CD112 are also highly expressed on dendritic cells and macrophages in different cancer ...
The pathological role of advanced glycation end products (AGEs) and of oxidative-carbonylic stress is well known in the context of diabetes. Moreover, there is also strong evidence that they play a ...
Dr. Medvedik and guests took a look at the recent publication where two forms of advanced glycation end products (AGEs) were successfully cleaved.
Rabbit polyclonal RAGE antibody validated for WB, IHC, Flow Cyt, ICC/IF and tested in Human, Mouse and Rat. Referenced in 36 publications and 11 independent…
TY - JOUR. T1 - Estimation of air pollutant emissions in flower roundabouts and in conventional roundabouts. AU - Corriere, Ferdinando. AU - Guerrieri, Marco. AU - Ticali, Dario. AU - Guerrieri, Marco. AU - Messineo, Antonio. PY - 2013. Y1 - 2013. N2 - The road pollutant emissions, above all in urban context, are correlated to many infrastructuralparameters and to traffi c intensity and typology. The research work on road junction geometry,carried out in European research centres, has recently allowed to design new road intersectiontypes which are of undoubted interest, especially in terms of traffi c functionality and safety, like thefl ower roundabouts (in which right-turn manoeuvres do not confl ict with the circulating fl ow). Themain objective of this paper is to propose a model for the estimation the capacity, delay, levels ofservice and the pollutant emissions into fl ower roundabouts. A comparative analysis between conventionalroundabout and fl ower roundabout has been carried out in ...
The standard treatment for epithelial ovarian carcinoma (EOC) is surgery followed by platinum/paclitaxel-based chemotherapy, but the overall survival rate is poor. The purpose of this study was to investigate the therapeutic potential of chemotherapy combined with inhibition of B and T lymphocyte attenuator (BTLA) for clinical use to treat EOC. Initially, we evaluated the potential application of chemotherapy combined with anti-BTLA antibody in an animal model. We then analyzed the distribution and regulation of BTLA expression on immunocytes in vitro. Finally, we examined the correlation between BTLA expression levels in cancerous tissues and prognosis in 254 EOC cases. The combination of chemotherapy and anti-BTLA antibody for inhibiting BTLA significantly reduced peritoneal tumor volume and extended survival in tumor-bearing mice. In addition, BTLA could be identified mostly on B lymphocytes, especially on CD19hi B cells, rather than on T lymphocytes and natural killer cells. Under regulation of
This gene is a member of the Roundabout (ROBO) gene family that controls neurite outgrowth, growth cone guidance, and axon fasciculation. ROBO proteins are a subfamily of the immunoglobulin transmembrane receptor superfamily. SLIT proteins 1-3, a family of secreted chemorepellants, are ligands for ROBO proteins and SLIT/ROBO interactions regulate myogenesis, leukocyte migration, kidney morphogenesis, angiogenesis, and vasculogenesis in addition to neurogenesis. This gene, ROBO3, has a putative extracellular domain with five immunoglobulin (Ig)-like loops and three fibronectin (Fn) type III motifs, a transmembrane segment, and a cytoplasmic tail with three conserved signaling motifs: CC0, CC2, and CC3 (CC for conserved cytoplasmic). Unlike other ROBO family members, ROBO3 lacks motif CC1. The ROBO3 gene regulates axonal navigation at the ventral midline of the neural tube. In mouse, loss of Robo3 results in a complete failure of commissural axons to cross the midline throughout the spinal cord ...
Mouse gp49 was formerly identified on mast and NK cells. However, in previous studies, only cells cultured in cytokines were examined. In this study, we provide the first comprehensive analysis of the distribution of gp49 on naive, hemopoietic cells. Unexpectedly, we find that resting NK cells lack expression of gp49. Instead, myeloid cells from bone marrow, spleen, and liver, expressing Mac-1 and Gr-1, constitutively express gp49A and B. By contrast, T cells as well as B cells do not express gp49.. Despite that gp49 is not found on naive NK cells, it is induced on NK cells following in vitro and in vivo stimulation. This induced expression is found in NK cell responses to MCMV infection, a notable observation because of the critical role of NK cells in controlling lethality and replication by MCMV (19, 20, 23). Although the mechanism for induction of gp49 expression was not revealed in our studies, NK cells from MCMV-infected IL-12 or IFN-γ-deficient mice were fully capable of gp49 expression. ...
Recombinant protein of human leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), transcript variant a, 20 ug available for purchase from OriGene - Your Gene Company.
The triggering receptor expressed on myeloid cells-1 (TREM-1) is a member of the immunoglobulin superfamily, and its expression is upregulated on phagocytic cells in the presence of bacteria or fungi (1). Several experiments by Bouchon and colleagues showed that TREM-1 mediates the acute inflammatory response to microbial products. Human tissues infected with bacteria are infiltrated with neutrophils and macrophages that express high levels of TREM-1. Conversely, TREM-1 is only weakly expressed in samples from patients with noninfectious inflammatory disorders. In addition, TREM-1 is shed from the membrane of activated phagocytes and can be found in a soluble form in body fluids. The presence of a soluble form of TREM-1 in samples of bronchoalveolar lavage fluid from mechanically ventilated patients has been shown to be a good indicator of infectious pneumonia. During sepsis, a progressive decline of plasma sTREM-1 concentration indicates a favorable clinical evolution during the recovery phase ...
We evaluated the heart using pre- and after-load-independent indices of LV function and found that the blockage of RAGE in diabetic mice from the age of 7 to 12 weeks prevented the development of cardiac dysfunction. dp/dt, which is a complex function influenced by pre- and after-load, was unaffected.[27] Consequently, blockage of RAGE must improve cardiac function by a direct action in the heart.. The function of the heart is dependent on the biophysical properties of the myocardium. As a result, AGE cross-linking has specific consequences for cardiac function. In accordance with this, accumulation of collagen and alterations in myocardial collagen AGEs in the diabetic heart have been demonstrated to decrease myocardial compliance.[15],[28] We found that RAGE blockage normalized LV diastolic chamber stiffness. In addition, the mRNA expression of Col1a1 was normalized in RAGE-blocked diabetic mice. These data indicate that RAGE activation mediates increased collagen AGE formation, which leads to ...
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Inhibitory receptors are crucial immune regulators and are essential to prevent exacerbated responses, thus contributing to immune homeostasis. Leukocyte associated immunoglobulin like receptor 1 (LAIR-1) is an immune inhibitory receptor which has collagen and collagen domain containing proteins as ligands. LAIR-1 is broadly expressed on immune cells and has a large availability of ligands in both circulation and tissues, implicating a need for tight regulation of this interaction. In the current study, we sought to examine the regulation and function of LAIR-1 on monocyte, dendritic cell (DC) and macrophage subtypes, using different in vitro models. We found that LAIR-1 is highly expressed on intermediate monocytes as well as on plasmacytoid DCs. LAIR-1 is also expressed on skin immune cells, mainly on tissue CD14+ cells, macrophages and CD1c+ DCs. In vitro, monocyte and type-2 conventional DC stimulation leads to LAIR-1 upregulation, which may reflect the importance of LAIR-1 as negative regulator
KARAP/DAP12/TYROBP: three names and a multiplicity of biological functions.: The signaling adaptor protein KARAP/DAP12/TYROBP (killer cell activating receptor-a
Roundabouts are safer than intersections because they reduce the number of potential conflicts between road users and lower the driving speed. In the Netherlands, replacing an intersection by a roundabout is estimated to reduce the number of severe casualties by approximately 46%. The traffic flow is usually better on roundabouts than on intersections, and exhaust emission and noise decrease, certainly when compared with signalized intersections. Roundabouts, however, take up more space. ...
Interaction of RAGE with its ligands can promote tumor progression, invasion and angiogenesis. Although blocking RAGE signaling has been proposed as a potential anti-cancer strategy, functional contributions of RAGE expression in the tumor microenvironment (TME) has not been investigated in detail. Here, we evaluated the effect of genetic depletion of RAGE in TME on the growth of gliomas. In both invasive and non-invasive glioma models, animal survival was prolonged in RAGE knockout (Ager-/-) mice. However, the improvement in survival in Ager-/- mice was not due to changes in tumor growth rate but rather to a reduction in tumor-associated inflammation. Furthermore, RAGE ablation in the TME abrogated angiogenesis by downregulating the expression of pro-angiogenic factors which prevented normal vessel formation, thereby generating a leaky vasculature. These alterations were most prominent in non-invasive gliomas, where the expression of VEGF and pro-inflammatory cytokines were also lower in ...
BioVendor - BioVendor Research and Diagnostic Products is a developer and manufacturer of immunoassays, recombinant proteins, antibodies and endotoxin-removal products.
BioVendor - BioVendor Research and Diagnostic Products is a developer and manufacturer of immunoassays, recombinant proteins, antibodies and endotoxin-removal products.
Advanced glycation end-products are considered potent molecules capable of promoting neuronal cell death and participating in the development of neurodegenerative disorders such as Alzheimers disease (Bittencourt LS, et al., 2014). Advanced glycation end-products can be formed several ways. Elevated blood glucose ca
In the current study, we report a crucial role for TLT-1 in regulating leukocyte activation and modulating sepsis-induced acute inflammatory response. A 17-aa residue of its extracellular domain mediates this effect. Whereas treml-1−/− mice are particularly susceptible to infection with the development of an intense inflammatory state that translated into organ damage and rapid mortality, LR17 administration confers a strong protection.. Until recently, the role of TLT-1 has remained unclear. TLT-1 is exclusively expressed in platelets, colocalized with CD62P in α-granules of resting platelets. Upon activation, TLT-1 is quickly exposed on the membrane (24) and subsequently cleaved, leading to the release of a soluble fragment. Structural analysis of the extracellular domain of TLT-1 suggests the existence of several distinct potential ligand binding sites (27). The first TLT-1 ligand was recently identified to be fibrinogen, positioning TLT-1 as a regulator of hemostasis by facilitating ...
TRB conducted a webinar on Monday, May 21, 2018 from 2:00 PM to 3:30 PM ET that identified creative applications of roundabouts to solve intersection problems. Presenters described case studies in which roundabout implementation has provided safer and more efficient travel across various modes. This webinar explored how roundabouts may be effective in easing congestion, prioritizing bicycle and pedestrian safety, and coordinating traffic around railroad crossings. This webinar was organized by the TRB St...
Receptor-Mediated Regulation of the Innate Immune System. Our laboratory studies the molecular regulation and function of multiple receptor systems involved the generation and propagation of the innate immune response with the goal of understanding how the innate immune system can be harnessed for the prevention of and/or treatment of cancer. More specifically, we have been studying the signal transduction of regulatory receptors of innate immune cells including monocytes/macrophages, natural killer (NK) cells, and most recently, platelets. Receptor systems recently or currently under study include the KIR and the TREM and TREM-Like Receptors. Recent findings have driven us to become interested in the regulation of innate cell metabolic pathways by these receptor systems and the pathways with which they interact.. The Triggering Receptors Expressed on Myeloid Cells (TREM) and TREM-Like Receptors. One of the best-characterized myeloid DAP12-coupled receptor systems are the triggering receptors ...
CLM-1 is expressed on myeloid cells in CNS inflammatory lesions. (A) CLM-1 mRNA expression in spinal cord after MOG35-55 immunization. Fold induction is calcula
OBJECTIVE Advanced glycation end products (AGEs) and their specific receptor, the receptor for AGEs (RAGE), play an important role in atherosclerosis. Recently, a soluble form of RAGE (sRAGE) has been identified in human serum. However, the role of sRAGE in cardiovascular disease is still controversial. There is no information on the association between simultaneous measurements of AGEs and sRAGE and vascular function. In this study, we evaluated the associations between serum levels of AGEs and sRAGE, ratio of AGEs to sRAGE, and vascular function. ...