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Sample records for box protein-1 hmgb1

  1. Cloning and characterization of high mobility group box protein 1 (HMGB1) of Wuchereria bancrofti and Brugia malayi

    OpenAIRE

    Thirugnanam, Sivasakthivel; Munirathinam, Gnanasekar; Veerapathran, Anandharaman; Dakshinamoorthy, Gajalakshmi; Reddy, Maryada V.; RAMASWAMY, KALYANASUNDARAM

    2012-01-01

    A human homologue of high mobility group box 1 (HMGB1) protein was cloned and characterized from the human filarial parasites Wuchereria bancrofti and Brugia malayi. Sequence analysis showed that W. bancrofti HMGB1 (WbHMGB1) and B. malayi HMGB1 (BmHMGB1) proteins share 99 % sequence identity. Filarial HMGB1 showed typical architectural sequence characteristics of HMGB family of proteins and consisted of only a single HMG box domain that had significant sequence similarity to the pro-inflammat...

  2. The role of High Mobility Group Box 1 (HMGB1) in colorectal cancer

    OpenAIRE

    Süren, Dinç; Yıldırım, Mustafa; Demirpençe, Özlem; Kaya, Vildan; Alikanoğlu, Arsenal Sezgin; Bülbüller, Nurullah; Yıldız, Mustafa; Sezer, Cem

    2014-01-01

    Background HMGB1, the most important member of the high mobility group box protein family, is a nuclear protein with different functions in the cell; it has a role in cancer progression, angiogenesis, invasion, and metastasis development. We studied the expression of HMGB1 and whether it is a prognostic factor in colorectal carcinoma. Material/Methods The study included 110 cases that were histopathologically diagnosed with colorectal carcinoma from the tissue samples acquired by surgical res...

  3. Serum high mobility group box-1 (HMGB1 is closely associated with the clinical and pathologic features of gastric cancer

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    Chung Jae

    2009-05-01

    Full Text Available Abstract Background High mobility group box-1 (HMGB1 is a newly recognized factor regulating cancer cell tumorigenesis, expansion and invasion. We investigated the correlation between the serum HMGB1 levels and the clinical and pathologic features of gastric cancer and evaluated the validity of HMGB1 as a potential biomarker for the early diagnosis of gastric cancer. Methods A total of 227 subjects were classified into 5 disease groups according to the 'gastritis-dysplasia-carcinoma' sequence of gastric carcinogenesis and their serum levels of HMGB1 were analyzed by an enzyme-linked immunosorbent assay (ELISA method. Clinical parameters, International Union Against Cancer (UICC TNM stage, cancer size, differentiation or lymphatic invasion, vascular or perineural invasion and prognosis were used as analysis variables. Results The serum HMGB1 levels were significantly different among disease groups (ANOVA, p and HMGB1 levels tended to increase according to the progression of gastric carcinogenesis. Serum HMGB1 levels were significantly associated with depth of invasion, lymph node metastasis, tumor size, and poor prognosis (p . However, HMGB1 levels were not associated with patient gender or age, differentiation of tumor cells, or lymphatic, vascular and perineural invasion, or the existence of distant metastasis in advanced cancer (p > 0.05. The sensitivity and specificity of serum HMGB1 was 71% and 67% (cut-off value of 5 ng/ml for the diagnosis of early gastric cancer, and 70% and 64% (cut-off value of 4 ng/ml for the diagnosis of high-risk lesions, respectively. These values were greater than those for carcinoembryonic antigen (CEA (30–40% of sensitivity. Conclusion HMGB1 appears to be a useful serological biomarker for early diagnosis as well as evaluating the tumorigenesis, stage, and prognosis of gastric cancer.

  4. Pivotal role of high-mobility group box 1 (HMGB1) signaling pathways in glioma development and progression.

    Science.gov (United States)

    Angelopoulou, Efthalia; Piperi, Christina; Adamopoulos, Christos; Papavassiliou, Athanasios G

    2016-08-01

    Human gliomas represent the most common type of intracranial tumors, with highest morbidity and mortality. They are characterized by excessive invasiveness and cell proliferation while their unclear boundaries predispose to tumor recurrence soon after conventional treatment. Elucidation of the molecular mechanisms implicated in their development and/or treatment resistance is highly demanded. The high-mobility group box 1 (HMGB1) protein, a highly conserved nuclear protein that functions as a chromatin-binding factor, facilitating nucleosome stabilization and regulating gene transcription, has been implicated in glioma formation and progression. Extracellular released HMGB1 binds to high-affinity receptors, including the receptor for advanced glycation end-products (RAGE) and toll-like receptor (TLR)-2, TLR-4, and TLR-9. Upon receptor binding, HMGB1 triggers the activation of key signaling pathways and immune responses, involved in the regulation of cell growth, differentiation, motility, and apoptosis. Based on the type of receptor and/or cell, HMGB1 is capable to promote oncogenesis or suppress tumor growth, thus affecting treatment efficacy. Herein, we discuss recent evidence implicating HMGB1 in glioma cell differentiation, proliferation, and metastasis with both clinical and prognostic significance. In addition, potential therapeutic approaches to target this protein in order to reduce chemoresistance of glioma cells are also addressed. PMID:27262996

  5. Tolerization with BLP down-regulates HMGB1 a critical mediator of sepsis-related lethality.

    LENUS (Irish Health Repository)

    Coffey, J Calvin

    2012-02-03

    Tolerization with bacterial lipoprotein (BLP) affords a significant survival benefit in sepsis. Given that high mobility group box protein-1 (HMGB1) is a recognized mediator of sepsis-related lethality, we determined if tolerization with BLP leads to alterations in HMGB1. In vitro, BLP tolerization led to a reduction in HMGB1 gene transcription. This was mirrored at the protein level, as HMGB1 protein expression and release were reduced significantly in BLP-tolerized human THP-1 monocytic cells. BLP tolerance in vivo led to a highly significant, long-term survival benefit following challenge with lethal dose BLP in C57BL\\/6 mice. This was associated with an attenuation of HMGB1 release into the circulation, as evidenced by negligible serum HMGB1 levels in BLP-tolerized mice. Moreover, HMGB1 levels in peritoneal macrophages from BLP-tolerized mice were reduced significantly. Hence, tolerization with BLP leads to a down-regulation of HMGB1 protein synthesis and release. The improved survival associated with BLP tolerance could thus be explained by a reduction in HMGB1, were the latter associated with lethality in BLP-related sepsis. In testing this hypothesis, it was noted that neutralization of HMGB1, using anti-HMGB1 antibodies, abrogated BLP-associated lethality almost completely. To conclude, tolerization with BLP leads to a down-regulation of HMGB1, thus offering a novel means of targeting the latter. HMGB1 is also a mediator of lethality in BLP-related sepsis.

  6. Plasma concentration of high-mobility group box 1 (HMGB1) after 100 drop to vertical jumps and after a 1200-km bicycle race.

    Science.gov (United States)

    Behringer, M; Kilian, Y; Montag, J; Geesmann, B; Mester, J

    2016-01-01

    High-mobility group box 1 (HMGB1) has recently been reported to be involved in proinflammation and tissue repair. Therefore, we hypothesized that HMGB1 is released into the bloodstream after eccentric exercises or prolonged endurance activities. Blood samples from 11 participants that performed 100 drop to vertical jumps (DVJ) and from 10 participants that took part in the 1200-km 'Paris-Brest-Paris' bicycle race (PBP) were tested for HMGB1 and creatine kinase (CK) levels. CK increased after both DVJ (pre: 150.6 ± 81.5 U/L; post: 188.8 ± 95.5 U/L 8 h: 790.5 ± 346.4 U/L) and PBP (pre: 81.3 ± 36.4 U/L; post: 725.2 ± 229.5 U/L; 12 h: 535.8 ± 188.6 U/L), indicating membrane damage. However, HMGB1 plasma levels remained below the detection limit (78 pg/mL) of the applied enzyme-linked immunosorbent assay kit for all blood samples analysed. That is, neither high intensity eccentric exercises (DVJ) nor prolonged endurance events (PBP) seemed to affect HMGB1 levels in blood at selected time points. PMID:26880688

  7. Extract of Polygonum cuspidatum Attenuates Diabetic Retinopathy by Inhibiting the High-Mobility Group Box-1 (HMGB1 Signaling Pathway in Streptozotocin-Induced Diabetic Rats

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    Eunjin Sohn

    2016-03-01

    Full Text Available High-mobility group box-1 (HMGB1 is a well-known pro-inflammatory cytokine. We aimed to investigate the effect of the ethanol extract of the root of P. cuspidatum (PCE on retinal inflammation in diabetic retinopathy. PCE (100 or 350 mg/kg/day was administered to diabetic rats for 16 weeks, and hyperglycemia and body weight loss developed in the diabetic rats. The retinal expression levels of HMGB1 and receptor for advanced glycation end products (RAGE and the activity of nuclear factor-kappa B (NF-κB in the retina were examined. Additionally, a chromatin immunoprecipitation assay was performed to analyze the binding of NF-κB binding to the RAGE promoter in the diabetic retinas. The levels of HMGB1 and RAGE expression, NF-κB activity, and NF-κB binding to the RAGE promoter were increased in the diabetic retinas. However, treatment with PCE ameliorated the increases in HMGB1 and RAGE expression, and NF-κB activity in the retina. In addition, in diabetic rats, retinal vascular permeability and the loosening of the tight junctions were inhibited by PCE. These findings suggest that PCE has a preventative effect against diabetes-induced vascular permeability by inhibiting HMGB1-RAGE-NF-κB activation in diabetic retinas. The oral administration of PCE may significantly help to suppress the development of diabetic retinopathy in patients with diabetes.

  8. Anabolic Properties of High Mobility Group Box Protein-1 in Human Periodontal Ligament Cells In Vitro

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    Michael Wolf

    2014-01-01

    Full Text Available High mobility group box protein-1 (HMGB1 is mainly recognized as a chemoattractant for macrophages in the initial phase of host response to pathogenic stimuli. However, recent findings provide evidence for anabolic properties in terms of enhanced proliferation, migration, and support of wound healing capacity of mesenchymal cells suggesting a dual role of the cytokine in the regulation of immune response and subsequent regenerative processes. Here, we examined potential anabolic effects of HMGB1 on human periodontal ligament (PDL cells in the regulation of periodontal remodelling, for example, during orthodontic tooth movement. Preconfluent human PDL cells (hPDL were exposed to HMGB1 protein and the influence on proliferation, migration, osteogenic differentiation, and biomineralization was determined by MTS assay, real time PCR, immunofluorescence cytochemistry, ELISA, and von Kossa staining. HMGB1 protein increased hPDL cell proliferation, migration, osteoblastic marker gene expression, and protein production as well as mineralized nodule formation significantly. The present findings support the dual character of HMGB1 with anabolic therapeutic potential that might support the reestablishment of the structural and functional integrity of the periodontium following periodontal trauma such as orthodontic tooth movement.

  9. Expression and Clinical Significance of HMGB1 and RAGE in Cervical Carcinoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    OBJECTIVE To study the expression level and clinical significance of HMGB1 and RAGE in cervical squamous epithelial carcinoma.METHODS Real time quantitative polymerase chain reaction (qRT-PCR)was employed to examine the expression of HMGB1 (high mobility group box protein1), and RAGE (receptor for advanced glycation endproducts)in 60 cervical squamous epithelial carcinomas (CSEC), their paraneoplastic tissues (PS) and 30 normal cervix tissues (NCS).RESULTS The expression of HMGB1 in the CSEC samples and PS was similar (P>0.05), but higher compared to NCS (P<0.05). Overexpression of HMGB1 in the CESC tissues was significantly correlated with the tumor (P<0.05), and the presence of metastasis (P<0.01), but not correlated with the tumor diameter or tumor grade. RAGE expression was not significantly different among these tissue types, and showed no significant correlation with the the tumor stage, diameter or grade. But there was a significant positive correlation between RAGE expression and CSEC metastasis.CONCLUSION The results suggest that HMGB1 may be related to the proliferation, progression and metastasis of CSEC. The relationship of HMGB1/RAGE may be of importance for CSEC metastasis. HMGB1 presents a new potential gene target for prevention and treatment of CSEC.Study of HMGB1/RAGE expression will offer an experimental foundation for understanding the pathogenesis of CSES.

  10. Toll-like receptor 4 (TLR4) antagonist eritoran tetrasodium attenuates liver ischemia and reperfusion injury through inhibition of high-mobility group box protein B1 (HMGB1) signaling.

    Science.gov (United States)

    Mcdonald, Kerry-Ann; Huang, Hai; Tohme, Samer; Loughran, Patricia; Ferrero, Kimberly; Billiar, Timothy; Tsung, Allan

    2014-01-01

    Toll-like receptor 4 (TLR4) is ubiquitously expressed on parenchymal and immune cells of the liver and is the most studied TLR responsible for the activation of proinflammatory signaling cascades in liver ischemia and reperfusion (I/R). Since pharmacological inhibition of TLR4 during the sterile inflammatory response of I/R has not been studied, we sought to determine whether eritoran, a TLR4 antagonist trialed in sepsis, could block hepatic TLR4-mediated inflammation and end organ damage. When C57BL/6 mice were pretreated with eritoran and subjected to warm liver I/R, there was significantly less hepatocellular injury compared to control counterparts. Additionally, we found that eritoran is protective in liver I/R through inhibition of high-mobility group box protein B1 (HMGB1)-mediated inflammatory signaling. When eritoran was administered in conjunction with recombinant HMGB1 during liver I/R, there was significantly less injury, suggesting that eritoran blocks the HMGB1-TLR4 interaction. Not only does eritoran attenuate TLR4-dependent HMGB1 release in vivo, but this TLR4 antagonist also dampened HMGB1's release from hypoxic hepatocytes in vitro and thereby weakened HMGB1's activation of innate immune cells. HMGB1 signaling through TLR4 makes an important contribution to the inflammatory response seen after liver I/R. This study demonstrates that novel blockade of HMGB1 by the TLR4 antagonist eritoran leads to the amelioration of liver injury. PMID:25375408

  11. HMGB-1 as a Novel Predictor of Disease Severity and Prognosis in Patients with Hemorrhagic Fever with Renal Syndrome

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    Hong Du

    2015-01-01

    Full Text Available Objective. To examine the predictive capacity of the high mobility group box protein-1 (HMGB-1 for disease severity and prognosis of hemorrhagic fever with renal syndrome (HFRS. Methods. One hundred and five HFRS patients and 28 controls were studied. The concentrations of HMGB-1 in the blood were measured with a commercially available ELISA. The levels of white blood cells (WBC, platelets (PLT, hematocrit (HCT, albumin (ALB, blood urea nitrogen (BUN, serum creatinine (Scr, and uric acid (UA were routinely tested in the same time frame. Results. The levels of HMGB-1 increased with the severity of the disease (P<0.001. HMGB-1 was positively correlated with WBC and BUN and negatively correlated with PLT, ALB, and UA (P<0.001. HMGB-1 showed statistical significance for predicting prognosis (AUC = 0.800, P<0.001. The sensitivity and specificity of HMGB-1, WBC, PLT, and ALB used in combination for predicting outcome were better than those of single analyses (AUC = 0.892, P<0.001. Conclusions. HMGB-1 can be considered a novel biomarker for severity and outcome in patients with HFRS. The use of HMGB-1, WBC, PLT, and ALB in combination to predict the outcome in patients with HFRS exhibited an acceptable level of diagnostic capability.

  12. Microglial Amyloid-β1-40 Phagocytosis Dysfunction Is Caused by High-Mobility Group Box Protein-1: Implications for the Pathological Progression of Alzheimer’s Disease

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    Kazuyuki Takata

    2012-01-01

    Full Text Available In Alzheimer disease (AD patient brains, the accumulation of amyloid-β (Aβ peptides is associated with activated microglia. Aβ is derived from the amyloid precursor protein; two major forms of Aβ, that is, Aβ1-40 (Aβ40 and Aβ1-42 (Aβ42, exist. We previously reported that rat microglia phagocytose Aβ42, and high mobility group box protein 1 (HMGB1, a chromosomal protein, inhibits phagocytosis. In the present study, we investigated the effects of exogenous HMGB1 on rat microglial Aβ40 phagocytosis. In the presence of exogenous HMGB1, Aβ40 markedly increased in microglial cytoplasm, and the reduction of extracellular Aβ40 was inhibited. During this period, HMGB1 was colocalized with Aβ40 in the cytoplasm. Furthermore, exogenous HMGB1 inhibited the degradation of Aβ40 induced by the rat microglial cytosolic fraction. Thus, extracellular HMGB1 may internalize with Aβ40 in the microglial cytoplasm and inhibit Aβ40 degradation by microglia. This may subsequently delay Aβ40 clearance. We further confirmed that in AD brains, the parts of senile plaques surrounded by activated microglia are composed of Aβ40, and extracellular HMGB1 is deposited on these plaques. Taken together, microglial Aβ phagocytosis dysfunction may be caused by HMGB1 that accumulates extracellularly on Aβ plaques, and it may be critically involved in the pathological progression of AD.

  13. Early release of high mobility group box nuclear protein 1 after severe trauma in humans: role of injury severity and tissue hypoperfusion

    OpenAIRE

    Cohen, Mitchell J; Brohi, Karim; Calfee, Carolyn S.; Rahn, Pamela; Chesebro, Brian B; Christiaans, Sarah C.; Carles, Michel; Howard, Marybeth; Pittet, Jean-François

    2009-01-01

    Introduction High mobility group box nuclear protein 1 (HMGB1) is a DNA nuclear binding protein that has recently been shown to be an early trigger of sterile inflammation in animal models of trauma-hemorrhage via the activation of the Toll-like-receptor 4 (TLR4) and the receptor for the advanced glycation endproducts (RAGE). However, whether HMGB1 is released early after trauma hemorrhage in humans and is associated with the development of an inflammatory response and coagulopathy is not kno...

  14. 蜂毒素对人肝癌细胞中HMGB1及VEGF-C表达的影响%Effect of melittin on high mobility group box 1 and vascular endothelial growth factors C expressions in hepatocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    曹清心; 汪晨; 刘宇; 赵丹; 凌昌全

    2012-01-01

    目的 观察蜂毒素对人肝癌细胞株HepG2中高迁移率族蛋白B1(high mobility group box 1,HMGB1)及血管内皮生长因子C(vascular endothelial growth factors C,VEGF-C)表达的影响,探讨其抑制肝癌细胞的作用机制.方法 肝癌细胞HepG2体外培养,经蜂毒素处理后,采用四甲基偶氮唑蓝(MTT)法了解蜂毒素对肝癌细胞增殖的影响,用Western-blotting、qRT-PCR方法检测HMGB1、VEGF-C的表达.结果 蜂毒素在体外能够抑制肝癌细胞的增殖活性;Westem-blotting结果显示,蜂毒素可抑制 HMGB1的表达,且呈浓度依赖性,但对VEGF-C的蛋白表达无明显影响;qRT-PCR结果显示,蜂毒素在mRNA水平均具有抑制HMGB1、VEGF-C表达的作用.结论 蜂毒素可降低肝癌细胞的增殖活性,并可能通过HMGB1、VEGF-C的表达发挥抗肝癌作用.%Objective To observe the effect of melittin on the expressions of high mobility group box 1 (HMGB1) and vascular endothelial growth factors C( VEGF-C) in hepatocarcinoma cells in vitro and to study the mechanisms of melittin in hepatocarcinoma cells. Methods HepG2 cell line was treated with melittin in vitro. The inhibition of proliferation was delected by MTT assay. The expressions of HMGB1 and VEGF-C were detected by western-blotting and real-time quantitative PCR{ qRT-PCR) assay. Results Melittin inhibited cell proliferation in vitro. Western-blotting outcome showed that melitlin could down-regulate the protein of HMGB1, while VEGF-C expression did not change. qRT-PCR results showed that HMGBI and VEGF-C mRNA expressions were down-regulate by melittin. Conclusion It is suggested that melittin can inhibit hepatocarcinoma cells proliferation. The effect of melittin in inducing anti-hepatocarcinoma may be related with down-regulation of HMGBI and VEGF-C.

  15. Emerging role of HMGB1 in fibrotic diseases

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    Li, Liu-Cheng; Gao, Jian; Li, Jun

    2014-01-01

    High-mobility group box 1 (HMGB1) is originally identified as a DNA-binding protein that functions as a structural co-factor critical for proper transcriptional regulation in somatic cells. Recent studies indicate that HMGB1 can be passively released from necrotic cells or actively secreted into the extracellular milieu under appropriate signal stimulation. Extracellular HMGB1 is a multifunctional cytokine that contributes to the process of infection, injury, inflammation, apoptosis, and immu...

  16. Expression of HMGB1 in the periodontal tissue subjected to orthodontic force application by Waldo's method in mice.

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    Lv, Shengyu; Li, Juan; Feng, Wei; Liu, Hongrui; Du, Juan; Sun, Jing; Cui, Jian; Sun, Bao; Han, Xiuchun; Oda, Kimimitsu; Amizuka, Norio; Xu, Xin; Li, Minqi

    2015-02-01

    Recent studies indicate that high mobility group box protein 1 (HMGB1) originating from periodontal ligament (PDL) cells can be a potential regulator in the process of orthodontic tooth movement and periodontal tissue remodeling. The aim of this study is to investigate HMGB1 expression in periodontal tissue during orthodontic tooth movement in mice according to Waldo's method. Six 7-week-old C57BL6 mice were used in these experiments. The elastic band was inserted into the teeth space between the right first and second maxillary molars. After 3 days of mechanical loading, mice were fixed with transcardial perfusion of 4 % paraformaldehyde in 0.1 M phosphate buffer (pH 7.4), and the maxillary was extracted for histochemical analyses. The histological examination revealed local PDL tear at the tension side and the formation of extensive cell-free hyaline zones at the compression side. The immunolocalization of HMGB1 was significantly presented at tension side of PDL, apical area and dental pulp, whereas at the compression side of PDL, the labeling of HMGB1 was almost undetectable as the presence of hyaline zone. Taken together, we concluded that the orthodontic tooth movement by Waldo's method leads to histological changes and HMGB1 expression pattern that differ from those of coil spring method, including PDL tear and extensive hyaline zone which may severely destroy periodontal tissue and in turn impede tooth movement. PMID:25523715

  17. The HMGB1/RAGE axis triggers neutrophil-mediated injury amplification following necrosis.

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    Huebener, Peter; Pradere, Jean-Philippe; Hernandez, Celine; Gwak, Geum-Youn; Caviglia, Jorge Matias; Mu, Xueru; Loike, John D; Jenkins, Rosalind E; Antoine, Daniel J; Schwabe, Robert F

    2015-02-01

    In contrast to microbially triggered inflammation, mechanisms promoting sterile inflammation remain poorly understood. Damage-associated molecular patterns (DAMPs) are considered key inducers of sterile inflammation following cell death, but the relative contribution of specific DAMPs, including high-mobility group box 1 (HMGB1), is ill defined. Due to the postnatal lethality of Hmgb1-knockout mice, the role of HMGB1 in sterile inflammation and disease processes in vivo remains controversial. Here, using conditional ablation strategies, we have demonstrated that epithelial, but not bone marrow-derived, HMGB1 is required for sterile inflammation following injury. Epithelial HMGB1, through its receptor RAGE, triggered recruitment of neutrophils, but not macrophages, toward necrosis. In clinically relevant models of necrosis, HMGB1/RAGE-induced neutrophil recruitment mediated subsequent amplification of injury, depending on the presence of neutrophil elastase. Notably, hepatocyte-specific HMGB1 ablation resulted in 100% survival following lethal acetaminophen intoxication. In contrast to necrosis, HMGB1 ablation did not alter inflammation or mortality in response to TNF- or FAS-mediated apoptosis. In LPS-induced shock, in which HMGB1 was considered a key mediator, HMGB1 ablation did not ameliorate inflammation or lethality, despite efficient reduction of HMGB1 serum levels. Our study establishes HMGB1 as a bona fide and targetable DAMP that selectively triggers a neutrophil-mediated injury amplification loop in the setting of necrosis. PMID:25562324

  18. Porcine reproductive and respiratory syndrome virus infection triggers HMGB1 release to promote inflammatory cytokine production

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    Duan, Erzhen; Wang, Dang; Luo, Rui; Luo, Jingyi; Gao, Li; Chen, Huanchun; Fang, Liurong, E-mail: fanglr@mail.hzau.edu.cn; Xiao, Shaobo, E-mail: vet@mail.hzau.edu.cn

    2014-11-15

    The high mobility group box 1 (HMGB1) protein is an endogenous damage-associated molecular pattern (DAMP) molecule involved in the pathogenesis of various infectious agents. Based on meta-analysis of all publicly available microarray datasets, HMGB1 has recently been proposed as the most significant immune modulator during the porcine response to porcine reproductive and respiratory syndrome virus (PRRSV) infection. However, the function of HMGB1 in PRRSV pathogenesis is unclear. In this study, we found that PRRSV infection triggers the translocation of HMGB1 from the nucleus to the extracellular milieu in MARC-145 cells and porcine alveolar macrophages. Although HMGB1 has no effect on PRRSV replication, HMGB1 promotes PRRSV-induced NF-κB activation and subsequent expression of inflammatory cytokines through receptors RAGE, TLR2 and TLR4. Our findings show that HMGB1 release, triggered by PRRSV infection, enhances the efficiency of virus-induced inflammatory responses, thereby providing new insights into the pathogenesis of PRRSV infection. - Highlights: • PRRSV infection triggers HMGB1 release from MARC-145 cells and PAMs. • HMGB1 does not significantly affect PRRSV proliferation. • HMGB1 is involved in PRRSV-induced NF-κB activation and inflammatory responses. • HMGB1 promotes PRRSV-induced inflammatory responses through TLR2/4 and RAGE.

  19. Porcine reproductive and respiratory syndrome virus infection triggers HMGB1 release to promote inflammatory cytokine production

    International Nuclear Information System (INIS)

    The high mobility group box 1 (HMGB1) protein is an endogenous damage-associated molecular pattern (DAMP) molecule involved in the pathogenesis of various infectious agents. Based on meta-analysis of all publicly available microarray datasets, HMGB1 has recently been proposed as the most significant immune modulator during the porcine response to porcine reproductive and respiratory syndrome virus (PRRSV) infection. However, the function of HMGB1 in PRRSV pathogenesis is unclear. In this study, we found that PRRSV infection triggers the translocation of HMGB1 from the nucleus to the extracellular milieu in MARC-145 cells and porcine alveolar macrophages. Although HMGB1 has no effect on PRRSV replication, HMGB1 promotes PRRSV-induced NF-κB activation and subsequent expression of inflammatory cytokines through receptors RAGE, TLR2 and TLR4. Our findings show that HMGB1 release, triggered by PRRSV infection, enhances the efficiency of virus-induced inflammatory responses, thereby providing new insights into the pathogenesis of PRRSV infection. - Highlights: • PRRSV infection triggers HMGB1 release from MARC-145 cells and PAMs. • HMGB1 does not significantly affect PRRSV proliferation. • HMGB1 is involved in PRRSV-induced NF-κB activation and inflammatory responses. • HMGB1 promotes PRRSV-induced inflammatory responses through TLR2/4 and RAGE

  20. The extracellular release of Schistosoma mansoni HMGB1 nuclear protein is mediated by acetylation

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    Coutinho Carneiro, Vitor; Moraes Maciel, Renata de; Caetano de Abreu da Silva, Isabel; Furtado Madeira da Costa, Rodrigo [Instituto de Bioquimica Medica, Programa de Biotecnologia e Biologia Molecular, Universidade Federal do Rio de Janeiro, CCS, Ilha do Fundao, Rio de Janeiro 21941-590 (Brazil); Neto Paiva, Claudia; Torres Bozza, Marcelo [Departamento de Imunologia, Instituto de Microbiologia Professor Paulo de Goes, Universidade Federal do Rio de Janeiro, CCS, Ilha do Fundao, Rio de Janeiro 21941-590 (Brazil); Rosado Fantappie, Marcelo, E-mail: fantappie@bioqmed.ufrj.br [Instituto de Bioquimica Medica, Programa de Biotecnologia e Biologia Molecular, Universidade Federal do Rio de Janeiro, CCS, Ilha do Fundao, Rio de Janeiro 21941-590 (Brazil)

    2009-12-25

    Schistosoma mansoni HMGB1 (SmHMGB1) was revealed to be a substrate for the parasite histone acetyltransferases SmGCN5 and SmCBP1. We found that full-length SmHMGB1, as well as its HMG-box B (but not HMG-box A) were acetylated in vitro by SmGCN5 and SmCBP1. However, SmCBP1 was able to acetylate both substrates more efficiently than SmGCN5. Interestingly, the removal of the C-terminal acidic tail of SmHMGB1 (SmHMGB1{Delta}C) resulted in increased acetylation of the protein. We showed by mammalian cell transfection assays that SmHMGB1 and SmHMGB1{Delta}C were transported from the nucleus to the cytoplasm after sodium butyrate (NaB) treatment. Importantly, after NaB treatment, SmHMGB1 was also present outside the cell. Together, our data suggest that acetylation of SmHMGB1 plays a role in cellular trafficking, culminating with its secretion to the extracellular milieu. The possible role of SmHMGB1 acetylation in the pathogenesis of schistosomiasis is discussed.

  1. Inhibition of HMGB1-induced angiogenesis by cilostazol via SIRT1 activation in synovial fibroblasts from rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Hye Young Kim

    Full Text Available High mobility group box chromosomal protein 1 (HMGB-1 released from injured cells plays an important role in the development of arthritis. This study investigated the anti-angiogenic effects of cilostazol in collagen-induced arthritis (CIA of mice, and the underlying mechanisms involved. The expressions of HIF-1α, VEGF, NF-κB p65 and SIRT1 in synovial fibroblasts obtained from rheumatoid arthritis (RA patients were assessed by Western blotting, and in vitro and in vivo angiogenesis were analyzed. Tube formations by human microvascular endothelial cells (HMVECs were significantly increased by direct exposure to HMGB1 or to conditioned medium derived from HMGB1-stimulated RA fibroblasts, and these increases were attenuated by cilostazol, the latter of which was blocked by sirtinol. HMGB1 increased the expression of HIF-1α and VEGF and concomitantly increased nuclear NF-κB p65 and DNA binding activity, but these effects of HMGB1 were inhibited by cilostazol. SIRT1 protein expression was time-dependently decreased (3-24 hr by HMGB1, which was recovered by pretreatment with cilostazol (1-30 µM or resveratrol, accompanying with increased SIRT1 deacetylase activity. In the tibiotarsal joint tissues of CIA mice treated with vehicle, HIF-1α- and VEGF-positive spots and CD31 staining were markedly exaggerated, whereas SIRT1 immunofluorescence was diminished. These variables were wholly reversed in cilostazol (30 mg/kg/day-treated mice. Furthermore, number of blood vessels stained by von Willebrand factor antibody was significantly lower in cilostazol-treated CIA mice. Summarizing, cilostazol activated SIRT1 and inhibited NF-κB-mediated transcription, thereby suppressing the expression of HIF-1α and VEGF. In addition, cilostazol caused HIF-1α deacetylation by enhancing SIRT1 activity and reduced VEGF production, thereby had an anti-angiogenic effect in vitro studies and in CIA murine model.

  2. HMGB1 Regulates RANKL-Induced Osteoclastogenesis in a Manner Dependent on RAGE

    OpenAIRE

    Zhou, Zheng; Han, Jun-Yan; Xi, Cai-Xia; Xie, Jian-Xin; FENG, XU; Wang, Cong-Yi; Mei, Lin; Xiong, Wen-Cheng

    2008-01-01

    High-mobility group box 1 (HMGB1), a nonhistone nuclear protein, is released by macrophages into the extracellular milieu consequent to cellular activation. Extracellular HMGB1 has properties of a pro-inflammatory cytokine through its interaction with receptor for advanced glycation endproducts (RAGE) and/or toll-like receptors (TLR2 and TLR4). Although HMGB1 is highly expressed in macrophages and differentiating osteoclasts, its role in osteoclastogenesis remains largely unknown. In this rep...

  3. The HMGB1/RAGE axis triggers neutrophil-mediated injury amplification following necrosis

    OpenAIRE

    Huebener, Peter; Pradere, Jean-Philippe; Hernandez, Celine; Gwak, Geum-Youn; Caviglia, Jorge Matias; Mu, Xueru; Loike, John D.; Rosalind E Jenkins; Antoine, Daniel J.; Schwabe, Robert F.

    2014-01-01

    In contrast to microbially triggered inflammation, mechanisms promoting sterile inflammation remain poorly understood. Damage-associated molecular patterns (DAMPs) are considered key inducers of sterile inflammation following cell death, but the relative contribution of specific DAMPs, including high–mobility group box 1 (HMGB1), is ill defined. Due to the postnatal lethality of Hmgb1-knockout mice, the role of HMGB1 in sterile inflammation and disease processes in vivo remains controversial....

  4. Two high-mobility group box domains act together to underwind and kink DNA

    Energy Technology Data Exchange (ETDEWEB)

    Sánchez-Giraldo, R.; Acosta-Reyes, F. J. [Universitat Politecnica de Catalunya, 08028 Barcelona (Spain); Malarkey, C. S. [University of Colorado School of Medicine, Aurora, CO 80045 (United States); Saperas, N. [Universitat Politecnica de Catalunya, 08028 Barcelona (Spain); Churchill, M. E. A., E-mail: mair.churchill@ucdenver.edu [University of Colorado School of Medicine, Aurora, CO 80045 (United States); Campos, J. L., E-mail: mair.churchill@ucdenver.edu [Universitat Politecnica de Catalunya, 08028 Barcelona (Spain)

    2015-06-30

    The crystal structure of HMGB1 box A bound to an unmodified AT-rich DNA fragment is reported at a resolution of 2 Å. A new mode of DNA recognition for HMG box proteins is found in which two box A domains bind in an unusual configuration generating a highly kinked DNA structure. High-mobility group protein 1 (HMGB1) is an essential and ubiquitous DNA architectural factor that influences a myriad of cellular processes. HMGB1 contains two DNA-binding domains, box A and box B, which have little sequence specificity but have remarkable abilities to underwind and bend DNA. Although HMGB1 box A is thought to be responsible for the majority of HMGB1–DNA interactions with pre-bent or kinked DNA, little is known about how it recognizes unmodified DNA. Here, the crystal structure of HMGB1 box A bound to an AT-rich DNA fragment is reported at a resolution of 2 Å. Two box A domains of HMGB1 collaborate in an unusual configuration in which the Phe37 residues of both domains stack together and intercalate the same CG base pair, generating highly kinked DNA. This represents a novel mode of DNA recognition for HMGB proteins and reveals a mechanism by which structure-specific HMG boxes kink linear DNA.

  5. Increased serum HMGB1 levels in patients with Henoch-Schönlein purpura.

    Science.gov (United States)

    Chen, Tao; Guo, Zai-Pei; Wang, Wen-Ju; Qin, Sha; Cao, Na; Li, Meng-Meng

    2014-06-01

    High-mobility group box-1 (HMGB1) has been implicated as a pro-inflammatory cytokine in the pathogenesis of various inflammatory and autoimmune diseases. However, information about HMGB1 in Henoch-Schönlein purpura (HSP) is still unclear. Herein, we investigated the role of HMGB1 in patients with HSP and the pro-inflammatory effects of HMGB1 on human dermal microvascular endothelial cell line (HMEC-1). Serum HMGB1 levels in patients with HSP together with patients with allergic vasculitis (AV) and urticarial vasculitis (UV) were detected by enzyme-linked immunosorbent assay (ELISA). HMEC-1 cells were treated with HMGB1 at concentrations ranging from 4 ng/ml to 100 ng/ml. Serum HMGB1 levels were significantly increased in patients with HSP, AV and UV, when compared with those in control group. Moreover, abundant cytoplasmic expression of HMGB1 was observed in endothelial cells in lesional skin of HSP patients. Using membrane cytokine antibody array, we indicate that HMGB1 markedly induced TNF-α and IL-6 release in cultured supernatant. Furthermore, by real-time quantitative PCR and ELISA, the effects of HMGB1 on these cytokines production in HMEC-1 cells were established. Finally, Western blot data revealed that HMGB1 can induce phosphorylation of inhibitor of κB-α (IκBα) and the nuclear translocation of nuclear factor-κB (NF-κB) p65 in HMEC-1 cells. In conclusion, this study provides first observations on the association of HMGB1 with HSP. We suggest that HMGB1 may be an important mediator of endothelial inflammation through the induction of TNF-α and IL-6 production and may play a crucial role in the pathogenesis of HSP. PMID:24758390

  6. Association of HMGB1 polymorphisms with outcome in patients with systemic inflammatory response syndrome

    DEFF Research Database (Denmark)

    Kornblit, Brian; Munthe-Fog, Lea; Madsen, Hans O;

    2008-01-01

    INTRODUCTION: High mobility group box 1 protein (HMGB1) is a pleiotropic cytokine, recently implicated in the pathophysiology of the systemic inflammatory response syndrome (SIRS) and sepsis. Data from experimental sepsis models show that administration of anti-HMGB1 antibodies significantly...

  7. Anti-HMGB1 Neutralizing Antibody Ameliorates Neutrophilic Airway Inflammation by Suppressing Dendritic Cell-Mediated Th17 Polarization

    Directory of Open Access Journals (Sweden)

    Fang Zhang

    2014-01-01

    Full Text Available We demonstrate that high mobility group box 1 protein (HMGB1 directs Th17 skewing by regulating dendritic cell (DC function. First, our in vitro studies reveal that recombinant HMGB1 (rHMGB1 activates myeloid DCs to produce IL-23 in vitro, and rHMGB1-activated DCs prime naïve lymphocytes to produce the Th17 cytokine IL-17A. Second, we demonstrate that anti-HMGB1 neutralizing antibody attenuates HMGB1 expression, neutrophilic inflammation, airway hyperresponsiveness, and Th17-related cytokine secretion in vivo by using a murine model of neutrophilic asthma induced by ovalbumin (OVA plus lipopolysaccharide (LPS. Furthermore, anti-HMGB1 neutralizing antibody decreases the number of Th17 cells in lung cells and suppresses the production of IL-23 by lung CD11C+ APCs. Finally, we show that intranasal adoptive transfer of rHMGB1-activated DCs was sufficient to restore lung neutrophilic inflammation and the Th17 response in a DC-driven model of asthma, whereas the transfer of rHMGB1 plus anti-HMGB1-treated mDCs significantly reduced these inflammation phenotypes. These data suggest, for the first time, that HMGB1 drives the DC-polarized Th17-type response in allergic lung inflammation and that blocking HMGB1 may benefit the attenuation of neutrophilic airway inflammation in asthma.

  8. Aspirin delays mesothelioma growth by inhibiting HMGB1-mediated tumor progression.

    Science.gov (United States)

    Yang, H; Pellegrini, L; Napolitano, A; Giorgi, C; Jube, S; Preti, A; Jennings, C J; De Marchis, F; Flores, E G; Larson, D; Pagano, I; Tanji, M; Powers, A; Kanodia, S; Gaudino, G; Pastorino, S; Pass, H I; Pinton, P; Bianchi, M E; Carbone, M

    2015-01-01

    High-mobility group box 1 (HMGB1) is an inflammatory molecule that has a critical role in the initiation and progression of malignant mesothelioma (MM). Aspirin (acetylsalicylic acid, ASA) is the most widely used nonsteroidal anti-inflammatory drug that reduces the incidence, metastatic potential and mortality of many inflammation-induced cancers. We hypothesized that ASA may exert anticancer properties in MM by abrogating the carcinogenic effects of HMGB1. Using HMGB1-secreting and -non-secreting human MM cell lines, we determined whether aspirin inhibited the hallmarks of HMGB1-induced MM cell growth in vitro and in vivo. Our data demonstrated that ASA and its metabolite, salicylic acid (SA), inhibit motility, migration, invasion and anchorage-independent colony formation of MM cells via a novel HMGB1-mediated mechanism. ASA/SA, at serum concentrations comparable to those achieved in humans taking therapeutic doses of aspirin, and BoxA, a specific inhibitor of HMGB1, markedly reduced MM growth in xenograft mice and significantly improved survival of treated animals. The effects of ASA and BoxA were cyclooxygenase-2 independent and were not additive, consistent with both acting via inhibition of HMGB1 activity. Our findings provide a rationale for the well documented, yet poorly understood antitumorigenic activity of aspirin, which we show proceeds via HMGB1 inhibition. Moreover, the use of BoxA appears to allow a more efficient HMGB1 targeting while eluding the known gastrointestinal side effects of ASA. Our findings are directly relevant to MM. Given the emerging importance of HMGB1 and its tumor-promoting functions in many cancer types, and of aspirin in cancer prevention and therapy, our investigation is poised to provide broadly applicable information. PMID:26068794

  9. Growth suppression and radiosensitivity increase by HMGB1 in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Yang JIAO; Hai-chao WANG; Sai-jun FAN

    2007-01-01

    Aim: HMGB 1 (high-mobility group box-1) is a nuclear protein containing a con- sensus RB (retinoblastoma)-binding LXCXE motif. In this study, we studied the potential association of HMGB 1 and RB and the in vitro and in vivo activities of HMGB 1 in human breast cancer cells. Methods: The protein-protein interaction was determined by immunoprecipitation-Western blotting and glutathione-S-trans- ferase capture assays; cell growth and radiosensitivity were examined by cell counts, MTT assay, and clonogenic assay; cell cycle progression and apoptosis were evaluated using flow cytometry; and the antitumor activity of HMGB 1 was examined with tumor xenografts in nude mice. Results: HMGB 1 was associated with RB via a LXCXE motif-dependent mechanism. HMGB 1 enhanced the ability of RB for E2F and cyclin A transcription repression. The increased expression of HMGB 1 conferred an altered phenotypes characterized by the suppression of cell growth; G12 arrest and apoptosis was induced in MCF-7 cells containing the wild- type retinoblastoma (Rb) gene, but showed no activities in BT-549 cells contain- ing the Rb gene deletion. The HMGB 1-induced apoptosis accompanied by caspase 3 activation and PARP (poly(ADP-ribose)polymerase) cleavage. HMGB 1 elevated the radiosensitivity of breast cancer cells in both the MCF-7 and BT-549 cell lines. The enhanced expression of HMGB 1 caused a suppression of growth of MCF-7 tumor xenografts in nude mice, while LXCXE-defective HMGB 1 completely lost antitumor growth activity. Conclusion: HMGB 1 functions as a tumor suppressor and radiosensitizer in breast cancer. A HMGB 1-RB interaction is critical for the HMGB1-mediated transcriptional repression, cell growth inhibition, G12 cell cycle arrest, apoptosis induction, and tumor growth suppression, but is not required for radiosensitization. Therefore, it may be possible to design new therapies for the treatment of breast cancer that exert their effects by modulating the HMGB 1 and RB regulatory

  10. Role of high mobility group box-1 on the expression of intestinal epithelial tight junction protein in murine acute necrotizing pancreatitis%HMGB1对急性坏死性胰腺炎大鼠肠上皮细胞紧密连接相关蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    栾正刚; 郭仁宣

    2013-01-01

    目的:观察急性坏死性胰腺炎(ANP)大鼠肠黏膜中高迁移率族蛋白B1 (HMGB1)的表达对肠黏膜上皮细胞紧密连接功能的影响.方法:24只Wistar大鼠随机分为正常对照组、ANP组和丙酮酸乙酯(EP)处理组,分别于建模后24 h取材.测定血浆淀粉酶(AMY)、血浆D-乳酸、肠黏膜髓过氧化物酶(MPO)水平变化;应用Western blot法检测ANP大鼠肠黏膜中HMGB1和occludin蛋白水平的变化.结果:在建模后24 h,大鼠AMY、D-乳酸与肠黏膜MPO水平ANP组明显高于正常对照组和EP处理组(P<0.05),但EP处理组仍高于正常对照组(P< 0.05);ANP组大鼠肠黏膜HMGB1表达水平明显高于正常对照组和EP处理组(P<0.05),EP处理组高于正常对照组(P<0.05);而肠黏膜上皮细胞紧密连接蛋白occludin的表达ANP组较正常对照组和EP处理组下降(P<0.05),EP处理组低于正常对照组(P<0.05).结论:ANP大鼠肠黏膜中HMGB1表达增高,可通过降低occludin蛋白表达,增加肠黏膜屏障通透性.EP能显著抑制HMGB1表达,使occludin蛋白表达升高,对ANP肠黏膜损伤有明显保护作用.%Objective: To investigate the effect of high mobility group box-1 protein (HMGB1) on the expression of intestinal epithelial tight junction protein in murine acute necrotizing pancreatitis(ANP). Methods:Twenty-four male health adult wistar rats were divided randomly into groups: control group, ANP group, and EP treatment group. Specimens were taken at 24h after operation respectively. The concentration of plasma amylase(AMY), plasma D-lactate and the activity of myeloperoxidase(MPO) in the intestinal tissue were determined. The expression of HMGB1 and oc-cludin protein in intestinal mucosa was detected by western blot. Results: In comparison with the control group, levels of plasma D-lactate and MPO in ANP group increased markedly at 24h after operation(P<0.05). The levels of D-lactate and MPO were markedly lowered in EP treatment group 24 h after ANP

  11. Screening of Highly-expressed-HMGB1-Gene Human Lung Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Yi LIU

    2009-09-01

    Full Text Available Background and objective Lung cancer is a type of malignant tumor which threats human health and life. Its morbidity might increase dramatically in a long period. Lung cancer is the leading cause of cancer-related death all over the world. HMGB1 (high mobility group box B 1 is a non-histone chromosome binding protein in the cells. It takes part in many biological processes including genes transcription and DNA repair. HMGB1 overexpression can result in cell apoptosis, differentiation, migration and proliferation. The main purpose of this study was to detect the HMGB1 expression of 4 lung cancer cell lines in order to select the most suitable cell line to do the work next step. Methods Four lung cancer cell lines were cultured by normal method, Western blot and real-time quantitative PCR were used to verify the levels of expression of HMGB1. The cell line which HMGB1 over-expressed was selected. Results HMGB1 expressed in all 4 lung cancer cell lines, the cell line L9981 was the most highly expressed cell line (P < 0.001. Conclusion All 4 lung cancer cell lines expree HMGB1 gene. As the HMGB1 overexpression cell line, L9981 is an ideal material for follow-up research.

  12. High-Mobility Group Box-1 Induces Decreased Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in the Diabetic Retina

    Directory of Open Access Journals (Sweden)

    Ahmed M. Abu El-Asrar

    2013-01-01

    Full Text Available To test the hypothesis that brain-derived neurotrophic factor-(BDNF- mediated neuroprotection is reduced by high-mobility group box-1 (HMGB1 in diabetic retina, paired vitreous and serum samples from 46 proliferative diabetic retinopathy and 34 nondiabetic patients were assayed for BDNF, HMGB1, soluble receptor for advanced glycation end products (sRAGE, soluble intercellular adhesion molecule-1 (sICAM-1, monocyte chemoattractant protein-1 (MCP-1, and TBARS. We also examined retinas of diabetic and HMGB1 intravitreally injected rats. The effect of the HMGB1 inhibitor glycyrrhizin on diabetes-induced changes in retinal BDNF expressions was studied. Western blot, ELISA, and TBARS assays were used. BDNF was not detected in vitreous samples. BDNF levels were significantly lower in serum samples from diabetic patients compared with nondiabetics, whereas HMGB1, sRAGE, sICAM-1, and TBARS levels were significantly higher in diabetic serum samples. MCP-1 levels did not differ significantly. There was significant inverse correlation between serum levels of BDNF and HMGB1. Diabetes and intravitreal administration of HMGB1 induced significant upregulation of the expression of HMGB1, TBARS, and cleaved caspase-3, whereas the expression of BDNF and synaptophysin was significantly downregulated in rat retinas. Glycyrrhizin significantly attenuated diabetes-induced downregulation of BDNF. Our results suggest that HMGB1-induced downregulation of BDNF might be involved in pathogenesis of diabetic retinal neurodegeneration.

  13. Effects of propofol on lipopolysaccharide-induced expression and release of HMGB1 in macrophages

    International Nuclear Information System (INIS)

    This study aimed to determine the effects of different concentrations of propofol (2,6-diisopropylphenol) on lipopolysaccharide (LPS)-induced expression and release of high-mobility group box 1 protein (HMGB1) in mouse macrophages. Mouse macrophage cell line RAW264.7 cells were randomly divided into 5 treatment groups. Expression levels of HMGB1 mRNA were detected using RT-PCR, and cell culture supernatant HMGB1 protein levels were detected using enzyme-linked immunosorbent assay (ELISA). Translocation of HMGB1 from the nucleus to the cytoplasm in macrophages was observed by Western blotting and activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the nucleus was detected using ELISA. HMGB1 mRNA expression levels increased significantly in the cell culture supernatant and in cells after 24 h of stimulating RAW264.7 cells with LPS (500 ng/mL). However, HMGB1 mRNA expression levels in the P2 and P3 groups, which received 500 ng/mL LPS with 25 or 50 μmol/mL propofol, respectively, were significantly lower than those in the group receiving LPS stimulation (P<0.05). After stimulation by LPS, HMGB1 protein levels were reduced significantly in the nucleus but were increased in the cytoplasm (P<0.05). Simultaneously, the activity of NF-κB was enhanced significantly (P<0.05). After propofol intervention, HMGB1 translocation from the nucleus to the cytoplasm and NF-κB activity were inhibited significantly (each P<0.05). Thus, propofol can inhibit the LPS-induced expression and release of HMGB1 by inhibiting HMGB1 translocation and NF-κB activity in RAW264.7 cells, suggesting propofol may be protective in patients with sepsis

  14. Effects of propofol on lipopolysaccharide-induced expression and release of HMGB1 in macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Wang, T.; Wei, X.Y.; Liu, B.; Wang, L.J.; Jiang, L.H. [Department of Anesthesiology, the Third Affiliated Hospital, Zhengzhou University, Zhengzhou (China)

    2015-02-24

    This study aimed to determine the effects of different concentrations of propofol (2,6-diisopropylphenol) on lipopolysaccharide (LPS)-induced expression and release of high-mobility group box 1 protein (HMGB1) in mouse macrophages. Mouse macrophage cell line RAW264.7 cells were randomly divided into 5 treatment groups. Expression levels of HMGB1 mRNA were detected using RT-PCR, and cell culture supernatant HMGB1 protein levels were detected using enzyme-linked immunosorbent assay (ELISA). Translocation of HMGB1 from the nucleus to the cytoplasm in macrophages was observed by Western blotting and activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the nucleus was detected using ELISA. HMGB1 mRNA expression levels increased significantly in the cell culture supernatant and in cells after 24 h of stimulating RAW264.7 cells with LPS (500 ng/mL). However, HMGB1 mRNA expression levels in the P2 and P3 groups, which received 500 ng/mL LPS with 25 or 50 μmol/mL propofol, respectively, were significantly lower than those in the group receiving LPS stimulation (P<0.05). After stimulation by LPS, HMGB1 protein levels were reduced significantly in the nucleus but were increased in the cytoplasm (P<0.05). Simultaneously, the activity of NF-κB was enhanced significantly (P<0.05). After propofol intervention, HMGB1 translocation from the nucleus to the cytoplasm and NF-κB activity were inhibited significantly (each P<0.05). Thus, propofol can inhibit the LPS-induced expression and release of HMGB1 by inhibiting HMGB1 translocation and NF-κB activity in RAW264.7 cells, suggesting propofol may be protective in patients with sepsis.

  15. TLR2 Plays a Critical Role in HMGB1-Induced Glomeruli Cell Proliferation Through the FoxO1 Signaling Pathway in Lupus Nephritis.

    Science.gov (United States)

    Feng, Xiao-Juan; Wu, Chao; Yang, Gui-Fang; Liu, Qing-Juan; Liu, Jin-Xi; Hao, Jun; Xing, Ling-Ling; Yang, Min; Liu, Shu-Xia

    2016-04-01

    The objective of this study was to examine the role and possible mechanisms of toll-like receptor 2 (TLR2) in high-mobility group box chromosomal protein 1 (HMGB1)-induced mouse mesangial cell (MMC) proliferation and glomeruli proliferation of MRL/Fas(lpr) mice. First, the expression of proliferating cell nuclear antigen (PCNA), TLR2 and Forkhead box protein O1 (FoxO1) messenger RNA (mRNA) and protein in the glomeruli of MRL/Fas(lpr) mice was quantified, and the correlation with cell proliferation of glomeruli was analyzed. Then, lipopolysaccharide (LPS), TLR2 neutralization antibody, and small hairpin TLR2 (shTLR2) were used to confirm the role of TLR2 in HMGB1-induced MMC proliferation. Furthermore, wild-type FoxO1 (WT-FoxO1) vector was used to investigate the effect of FoxO1 pathway on HMGB1-induced MMC proliferation. Finally, electroporation was used to knockdown TLR2 in the glomeruli of MRL/Fas(lpr) mice, and renal function, FoxO1, and PCNA expression were detected. The results showed that the TLR2 expression was upregulated and FoxO1 expression was decreased in the glomeruli of MRL/Fas(lpr) mice, and these effects were significantly correlated with cell proliferation of the glomeruli. In vitro, the TLR2 neutralization antibody and the WT-FoxO1 vector, both reduced the MMC proliferation levels induced by HMGB1. The TLR2 neutralization antibody also blocked the HMGB1-dependent activation of the FoxO1 pathway and cell proliferation. In addition, transfection with shTLR2 decreased the proliferation levels and PCNA expression induced by HMGB1. In vivo, treatment with shTLR2 significantly reduced the PCNA expression in the glomeruli of MRL/Fas(lpr) mice and improved renal function. In addition, treatment with shTLR2 or blocking of TLR2 also reduced the translocation of FoxO1. Thus, TLR2 plays a critical role in HMGB1-induced glomeruli cell proliferation through the FoxO1 signaling pathway in lupus nephritis. PMID:26799193

  16. The Emerging Role of HMGB1 in Neuropathic Pain: A Potential Therapeutic Target for Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Wenbin Wan

    2016-01-01

    Full Text Available Neuropathic pain (NPP is intolerable, persistent, and specific type of long-term pain. It is considered to be a direct consequence of pathological changes affecting the somatosensory system and can be debilitating for affected patients. Despite recent progress and growing interest in understanding the pathogenesis of the disease, NPP still presents a major diagnostic and therapeutic challenge. High mobility group box 1 (HMGB1 mediates inflammatory and immune reactions in nervous system and emerging evidence reveals that HMGB1 plays an essential role in neuroinflammation through receptors such as Toll-like receptors (TLR, receptor for advanced glycation end products (RAGE, C-X-X motif chemokines receptor 4 (CXCR4, and N-methyl-D-aspartate (NMDA receptor. In this review, we present evidence from studies that address the role of HMGB1 in NPP. First, we review studies aimed at determining the role of HMGB1 in NPP and discuss the possible mechanisms underlying HMGB1-mediated NPP progression where receptors for HMGB1 are involved. Then we review studies that address HMGB1 as a potential therapeutic target for NPP.

  17. Relationship between HMGB1 and PAI-1 after allogeneic hematopoietic stem cell transplantation

    Science.gov (United States)

    Nomura, Shosaku; Maeda, Yoshinobu; Ishii, Kazuyoshi; Katayama, Yuta; Yagi, Hideo; Fujishima, Naoto; Ota, Shuichi; Moriyama, Masato; Ikezoe, Takayuki; Miyazaki, Yasuhiko; Hayashi, Kunio; Fujita, Shinya; Satake, Atsushi; Ito, Tomoki; Kyo, Taiichi; Tanimoto, Mitsune

    2016-01-01

    Background Conditioning regimens including total body irradiation (TBI) or cyclophosphamide can mobilize high-mobility group box 1 (HMGB1) to peripheral blood. Additionally, increased plasminogen activator inhibitor (PAI)-1 levels are associated with post-allogeneic hematopoietic stem cell transplantation (aHSCT). However, changes to circulating levels of HMGB1 after aHSCT are poorly understood. Materials and methods The study cohort included 289 patients who underwent aHSCT at one of 25 institutions in Japan. We have investigated the relationship between HMGB1 and PAI-1 following aHSCT. A significant increase in HMGB1 levels occurred after conditioning treatment. Additionally, levels of HMGB1 at day 0 were significantly increased in TBI+ patients and cyclophosphamide/TBI patients. Conclusion Our data revealed that an increased level of HMGB1 at day 0 following aHSCT correlates with increased PAI-1 after aHSCT, which is consistent with previous reports. Increased HMGB1 at day 0 after a conditioning regimen may play a role in transplantation-associated coagulopathy following aHSCT, because PAI-1 can accelerate procoagulant activity. PMID:26848281

  18. Minocycline attenuates both OGD-induced HMGB1 release and HMGB1-induced cell death in ischemic neuronal injury in PC12 cells

    International Nuclear Information System (INIS)

    High mobility group box-1 (HMGB1), a non-histone DNA-binding protein, is massively released into the extracellular space from neuronal cells after ischemic insult and exacerbates brain tissue damage in rats. Minocycline is a semisynthetic second-generation tetracycline antibiotic which has recently been shown to be a promising neuroprotective agent. In this study, we found that minocycline inhibited HMGB1 release in oxygen-glucose deprivation (OGD)-treated PC12 cells and triggered the activation of p38mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases (ERK1/2). The ERK kinase (MEK)1/2 inhibitor U-0126 and p38MAPK inhibitor SB203580 blocked HMGB1 release in response to OGD. Furthermore, HMGB1 triggered cell death in a dose-dependent fashion. Minocycline significantly rescued HMGB1-induced cell death in a dose-dependent manner. In light of recent observations as well as the good safety profile of minocycline in humans, we propose that minocycline might play a potent neuroprotective role through the inhibition of HMGB1-induced neuronal cell death in cerebral infarction.

  19. Minocycline attenuates both OGD-induced HMGB1 release and HMGB1-induced cell death in ischemic neuronal injury in PC12 cells

    Energy Technology Data Exchange (ETDEWEB)

    Kikuchi, Kiyoshi [Division of Laboratory and Vascular Medicine, Field of Cardiovascular and Respiratory Disorders, Department of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520 (Japan); Department of Neurosurgery, Omuta City General Hospital, 2-19-1 Takarazaka, Omuta-City, Fukuoka 836-8567 (Japan); Kawahara, Ko-ichi; Biswas, Kamal Krishna; Ito, Takashi [Division of Laboratory and Vascular Medicine, Field of Cardiovascular and Respiratory Disorders, Department of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520 (Japan); Tancharoen, Salunya [Department of Pharmacology, Faculty of Dentistry, Mahidol University, 6 Yothe Rd., Rajthevee Bangkok 10400 (Thailand); Morimoto, Yoko [Department of Periodontology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Matsuda, Fumiyo [Division of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8560 (Japan); Oyama, Yoko; Takenouchi, Kazunori [Division of Laboratory and Vascular Medicine, Field of Cardiovascular and Respiratory Disorders, Department of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520 (Japan); Miura, Naoki [Laboratory of Veterinary Diagnostic Imaging, Department of Veterinary Medicine, Faculty of Agriculture, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065 (Japan); Arimura, Noboru; Nawa, Yuko; Meng, Xiaojie; Shrestha, Binita; Arimura, Shinichiro [Division of Laboratory and Vascular Medicine, Field of Cardiovascular and Respiratory Disorders, Department of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520 (Japan); and others

    2009-07-24

    High mobility group box-1 (HMGB1), a non-histone DNA-binding protein, is massively released into the extracellular space from neuronal cells after ischemic insult and exacerbates brain tissue damage in rats. Minocycline is a semisynthetic second-generation tetracycline antibiotic which has recently been shown to be a promising neuroprotective agent. In this study, we found that minocycline inhibited HMGB1 release in oxygen-glucose deprivation (OGD)-treated PC12 cells and triggered the activation of p38mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases (ERK1/2). The ERK kinase (MEK)1/2 inhibitor U-0126 and p38MAPK inhibitor SB203580 blocked HMGB1 release in response to OGD. Furthermore, HMGB1 triggered cell death in a dose-dependent fashion. Minocycline significantly rescued HMGB1-induced cell death in a dose-dependent manner. In light of recent observations as well as the good safety profile of minocycline in humans, we propose that minocycline might play a potent neuroprotective role through the inhibition of HMGB1-induced neuronal cell death in cerebral infarction.

  20. The effects of high mobility group box-1 protein on the expression of intestinal epithelial tight junction protein occludin in murine severe acute pancreatitis%重症急性胰腺炎大鼠HMGB1对肠上皮细胞occludin表达的影响

    Institute of Scientific and Technical Information of China (English)

    栾正刚; 郭仁宣

    2012-01-01

    目的 观察重症急性胰腺炎(SAP)大鼠肠组织中高迁移率族蛋白B1 (HMGB1)表达对肠黏膜上皮细胞紧密连接occludin蛋白表达的影响.方法 逆行胰胆管注射5%牛磺胆酸钠制作SAP模型.健康Wistar大鼠随机(随机数字法)分为对照组、SAP组、二硫代氨基甲酸吡咯烷(PDTC)处理组.测定血淀粉酶(AMY)、内毒素(LPS)及D-乳酸水平;光镜下观察胰腺和肠组织的病理变化;免疫组织化学法观察occludin分布和表达的变化;RT-PCR法检测大鼠肠组织中HMGB1的表达水平;Western blot法检测大鼠肠组织中HMGB1及occludin蛋白的表达水平.采用SPSS 13.0统计分析软件进行处理,P< 0.05为差异具有统计学意义.结果 在建模后24 h,SAP组大鼠血浆LPS及D-乳酸水平明显高于对照组,提示肠屏障通透性明显增加;PDTC处理组大鼠血浆LPS及D-乳酸水平明显低于SAP组(P<0.05).SAP组大鼠肠组织HMGB1表达水平较对照组明显升高,而occludin蛋白的表达较对照组下降;PDTC组大鼠肠组织HMGB1表达水平明显低于SAP组,occludin水平较SAP组升高(P<0.05).结论 SAP时,大鼠肠组织内HMGB1表达升高,通过降低occludin蛋白表达,来增加肠黏膜屏障通透性;PDTC可抑制HMGB1表达,上调occludin蛋白表达,改善肠黏膜屏障通透性.%Objective To observe the effect of high mobility group box-1 protein (HMGB1) on the expression of intestinal epithelial tight junction protein occludin in murine severe acute pancreatitis (SAP).Methods Rat SAP model was estabilished by retrograde injection of 5 % sodium taurocholate into choledochopancreatic duct.Healthy wistar rats were divided randomly (random number) into three groups:control group,SAP group,pyrrolidine dithiocarbamate (PDTC) therapy group.Levels of plasm amylase,lipopolysaccharide (LPS) and D-lactate were determined.The changes of morphological damage of pancreasand intestinal tissues were observed by microscopy.The distribution

  1. Clinical Value of Serum HMGB1 Levels in Early Detection of Recurrent Squamous Cell Carcinoma of Uterine Cervix: Comparison with Serum SCCA, CYFRA21-1, and CEA Levels

    OpenAIRE

    Sheng, Xiugui; Du, Xuelian; Zhang, Xiaoling; Li, Dapeng; Lu, Chunhua; Li, Qinshui; Ma, Zhifang; Song, Quqing; Wang, Cong

    2009-01-01

    Aim To evaluate the clinical value of serum high mobility group box chromosomal protein 1 (HMGB1) levels in making the early diagnosis of recurrent cervical squamous cell carcinomas (CSCC) and compare it with the value of serum squamous cell carcinoma antigen (SCCA), cytokeratin fragment (CYFRA) 21-1, and carcinoembryonic antigen (CEA) levels. Methods Immunohistochemical staining of tissue from 64 patients with recurrent CSCCs, 72 patients with non-recurrent carcinoma,...

  2. HMGB1 Induces Secretion of Matrix Vesicles by Macrophages to Enhance Ectopic Mineralization

    Science.gov (United States)

    Chen, Qiang; Bei, Jun-Jie; Liu, Chuan; Feng, Shi-Bin; Zhao, Wei-Bo; Zhou, Zhou; Yu, Zheng-Ping; Du, Xiao-Jun; Hu, Hou-Yuan

    2016-01-01

    Numerous clinical conditions have been linked to ectopic mineralization (EM). This process of pathological biomineralization is complex and not fully elucidated, but thought to be started within matrix vesicles (MVs). We hypothesized that high mobility group box 1 (HMGB1), a cytokine associated with biomineralizing process under physiological and pathological conditions, induces EM via promoting MVs secretion from macrophages. In this study, we found that HMGB1 significantly promoted secretion of MVs from macrophages and subsequently led to mineral deposition in elevated Ca/Pi medium in vitro. Transmission electron microscopy of calcifying MVs showed formation of hydroxyapatite crystals in the vesicle interior. Subcutaneous injection into mice with MVs derived from HMGB1-treated cells showed a greater potential to initiate regional mineralization. Mechanistic experiments revealed that HMGB1 activated neutral sphingomyelinase2 (nSMase2) that involved the receptor for advanced glycation end products (RAGE) and p38 MAPK (upstream of nSMase2). Inhibition of nSMase2 with GW4869 or p38 MAPK with SB-239063 prevented MVs secretion and mineral deposition. Collectively, HMGB1 induces MVs secretion from macrophages at least in part, via the RAGE/p38 MAPK/nSMase2 signaling pathway. Our findings thus reveal a novel mechanism by which HMGB1 induces ectopic mineralization. PMID:27243975

  3. Involvement of HMGB1 in Resistance to Tumor Vessel-Targeted, Monoclonal Antibody-Based Immunotherapy

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    Pezzolo, Annalisa

    2016-01-01

    High mobility group box 1 (HMGB1) is a member of the “danger associated molecular patterns” (DAMPs) than can localize in various compartments of the cell (from the nucleus to the cell surface) and subserve different functions accordingly. HMGB1 is implicated in maintenance of genomic stability, autophagy, immune regulation, and tumor growth. HMGB1-induced autophagy promotes tumor resistance to chemotherapy, as shown in different models of malignancy, for example, osteosarcoma, leukemia, and gastric cancer. To the best of our knowledge, there is virtually no information on the relationships between HMGB1 and resistance to immunotherapy. A recent study from our group has shed new light on this latter issue. We have demonstrated that targeting of tumor-derived endothelial cells with an anti-human CD31 monoclonal antibody in a human neuroblastoma model was unsuccessful due to a complex chain of events involving the participation of HMGB1. These results are discussed in detail since they provide the first evidence for a role of HMGB1 in resistance of tumor cells to monoclonal antibody-based immunotherapy. PMID:26925422

  4. HMGB1 interacts with XPA to facilitate the processing of DNA interstrand crosslinks in human cells.

    Science.gov (United States)

    Mukherjee, Anirban; Vasquez, Karen M

    2016-02-18

    Many effective agents used in cancer chemotherapy cause DNA interstrand crosslinks (ICLs), which covalently link both strands of the double helix together resulting in cytotoxicity. ICLs are thought to be processed by proteins from a variety of DNA repair pathways; however, a clear understanding of ICL recognition and repair processing in human cells is lacking. Previously, we found that the high mobility group box 1 (HMGB1) protein bound to triplex-directed psoralen ICLs (TFO-ICLs) in vitro, cooperatively with NER damage recognition proteins, promoted removal of UVC-induced lesions and facilitated error-free repair of TFO-ICLs in mouse fibroblasts. Here, we demonstrate that HMGB1 recognizes TFO-ICLs in human cells, and its depletion increases ICL-induced mutagenesis in human cells without altering the mutation spectra. In contrast, HMGB1 depletion in XPA-deficient human cells significantly altered the ICL-induced mutation spectrum from predominantly T→A to T→G transversions. Moreover, the recruitment of XPA and HMGB1 to the ICLs is co-dependent. Finally, we show that HMGB1 specifically introduces negative supercoils in ICL-containing plasmids in HeLa cell extracts. Taken together, our data suggest that in human cells, HMGB1 functions in association with XPA on ICLs and facilitates the formation of a favorable architectural environment for ICL repair processing. PMID:26578599

  5. HMGB1 Is a Potential Biomarker for Severe Viral Hemorrhagic Fevers.

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    Katarina Resman Rus

    2016-06-01

    Full Text Available Hemorrhagic fever with renal syndrome (HFRS and Crimean-Congo hemorrhagic fever (CCHF are common representatives of viral hemorrhagic fevers still often neglected in some parts of the world. Infection with Dobrava or Puumala virus (HFRS and Crimean-Congo hemorrhagic fever virus (CCHFV can result in a mild, nonspecific febrile illness or as a severe disease with hemorrhaging and high fatality rate. An important factor in optimizing survival rate in patients with VHF is instant recognition of the severe form of the disease for which significant biomarkers need to be elucidated. To determine the prognostic value of High Mobility Group Box 1 (HMGB1 as a biomarker for disease severity, we tested acute serum samples of patients with HFRS or CCHF. Our results showed that HMGB1 levels are increased in patients with CCHFV, DOBV or PUUV infection. Above that, concentration of HMGB1 is higher in patients with severe disease progression when compared to the mild clinical course of the disease. Our results indicate that HMGB1 could be a useful prognostic biomarker for disease severity in PUUV and CCHFV infection, where the difference between the mild and severe patients group was highly significant. Even in patients with severe DOBV infection concentrations of HMGB1 were 2.8-times higher than in the mild group, but the difference was not statistically significant. Our results indicated HMGB1 as a potential biomarker for severe hemorrhagic fevers.

  6. HMGB1 Is a Potential Biomarker for Severe Viral Hemorrhagic Fevers

    Science.gov (United States)

    Resman Rus, Katarina; Fajs, Luka; Korva, Miša; Avšič-Županc, Tatjana

    2016-01-01

    Hemorrhagic fever with renal syndrome (HFRS) and Crimean-Congo hemorrhagic fever (CCHF) are common representatives of viral hemorrhagic fevers still often neglected in some parts of the world. Infection with Dobrava or Puumala virus (HFRS) and Crimean-Congo hemorrhagic fever virus (CCHFV) can result in a mild, nonspecific febrile illness or as a severe disease with hemorrhaging and high fatality rate. An important factor in optimizing survival rate in patients with VHF is instant recognition of the severe form of the disease for which significant biomarkers need to be elucidated. To determine the prognostic value of High Mobility Group Box 1 (HMGB1) as a biomarker for disease severity, we tested acute serum samples of patients with HFRS or CCHF. Our results showed that HMGB1 levels are increased in patients with CCHFV, DOBV or PUUV infection. Above that, concentration of HMGB1 is higher in patients with severe disease progression when compared to the mild clinical course of the disease. Our results indicate that HMGB1 could be a useful prognostic biomarker for disease severity in PUUV and CCHFV infection, where the difference between the mild and severe patients group was highly significant. Even in patients with severe DOBV infection concentrations of HMGB1 were 2.8–times higher than in the mild group, but the difference was not statistically significant. Our results indicated HMGB1 as a potential biomarker for severe hemorrhagic fevers. PMID:27348219

  7. Inhibition of HMGB1 Translocation by Green Tea Extract in Rats Exposed to Environmental Tobacco Smoke

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    Sirintip Chaichalotornkul

    2012-01-01

    Full Text Available Environmental tobacco smoke (ETS exposure is linked to carcinogenic, oxidative and inflammatory cellular reactions. Green tea polyphenol reportedly plays a role in the prevention of inflammation-related diseases. To evaluate the effects of green tea extract (GTE on cellular location of High Mobility Group Box-1 (HMGB1 protein, we studied the lung tissue in rats exposed to cigarette smoke (CS. Rats were divided into three groups; CS, CSG, and C, which were groups of CS-treated only, CS-treated with GTE dietary supplement, and the control, respectively. Our findings by immunocytochemistry showed that abundant HMGB1 translocated from the nucleus to the cytoplasm in the lung tissues of rats that were exposed to CS, whereas HMGB1 was localized to the nuclei of CSG and C group. For in vitro studies, cotinine stimulated the secretion of HMGB1 in a dose and time dependent manner and the HMGB1 level was suppressed by GTE in murine macrophage cell lines. Our results could suggest that GTE supplementation which could suppress HMGB1 may offer a beneficial effect against diseases.

  8. Glycyrrhizin suppresses the expressions of HMGB1 and relieves the severity of traumatic pancreatitis in rats.

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    Ke Xiang

    Full Text Available High mobility group box 1 (HMGB1 plays important roles in a large variety of diseases; glycyrrhizin (GL is recognized as an HMGB1 inhibitor. However, few studies have focused on whether glycyrrhizin can potentially improve the outcome of traumatic pancreatitis (TP by inhibiting HMGB1.A total of 60 male Wistar rats were randomly divided into three groups (n = 20 in each: Control group, TP group and TP-GL group. Pancreatic trauma was established with a custom-made biological impact machine-III, and GL was administered at 15 minutes after the accomplishment of operation. To determine survival rates during the first 7 days after injury, another 60 rats (n = 20 in each were grouped and treated as mentioned above. At 24 hours of induction of TP, the histopathological changes in pancreas were evaluated and serum amylase levels were tested. Serum tumor necrosis factor α (TNF-α, interleukin 6 (IL-6, and HMGB1 were measured using enzyme linked immunosorbent assay. HMGB1 expressions in pancreas were measured using immunohistochemical staining, Western blot and Real-Time PCR analysis.Serum levels of HMGB1, TNF-α and IL-6 were increased dramatically in TP group at 24 hours after induction of TP. However, these indicators were reduced significantly by GL administration in TP-GL group comparing with TP group (P < 0.05. Meanwhile, survival analysis showed that the seven-day survival rate in TP-GL group was significantly higher than that in TP group (85% versus 65%, P < 0.05. GL treatment significantly decreased the pancreatic protein and mRNA expressions of HMGB1 and ameliorated the pancreatic injury in rats with TP.Glycyrrhizin might play an important role in improving survival rates and ameliorating pancreatic injury of TP by suppression of the expressions of HMGB1 and other proinflammatory cytokine.

  9. The potential role of HMGB1 release in peritoneal dialysis-related peritonitis.

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    Shirong Cao

    Full Text Available High mobility group box 1 (HMGB1, a DNA-binding nuclear protein, has been implicated as an endogenous danger signal in the pathogenesis of infection diseases. However, the potential role and source of HMGB1 in the peritoneal dialysis (PD effluence of patients with peritonitis are unknown. First, to evaluate HMDB1 levels in peritoneal dialysis effluence (PDE, a total of 61 PD patients were enrolled in this study, including 42 patients with peritonitis and 19 without peritonitis. Demographic characteristics, symptoms, physical examination findings and laboratory parameters were recorded. HMGB1 levels in PDE were determined by Western blot and ELISA. The concentrations of TNF-α and IL-6 in PDE were quantified by ELISA. By animal model, inhibition of HMGB1 with glycyrrhizin was performed to determine the effects of HMGB1 in LPS-induced mice peritonitis. In vitro, a human peritoneal mesothelial cell line (HMrSV5 was stimulated with lipopolysaccharide (LPS, HMGB1 extracellular content in the culture media and intracellular distribution in various cellular fractions were analyzed by Western blot or immunofluorescence. The results showed that the levels of HMGB1 in PDE were higher in patients with peritonitis than those in controls, and gradually declined during the period of effective antibiotic treatments. Furthermore, the levels of HMGB1 in PDE were positively correlated with white blood cells (WBCs count, TNF-α and IL-6 levels. However, pretreatment with glycyrrhizin attenuated LPS-induced acute peritoneal inflammation and dysfunction in mice. In cultured HMrSV5 cells, LPS actively induced HMGB1 nuclear-cytoplasmic translocation and release in a time and dose-dependent fashion. Moreover, cytosolic HMGB1 was located in lysosomes and secreted via a lysosome-mediated secretory pathway following LPS stimulation. Our study demonstrates that elevated HMGB1 levels in PDE during PD-related peritonitis, at least partially, from peritoneal mesothelial cells

  10. Interference with HMGB1 increases the sensitivity to chemotherapy drugs by inhibiting HMGB1-mediated cell autophagy and inducing cell apoptosis.

    Science.gov (United States)

    Zhang, Ruiguang; Li, Yan; Wang, Zhongliang; Chen, Lingjuan; Dong, Xiaorong; Nie, Xiu

    2015-11-01

    Non-small cell lung cancer is commonly seen with higher morbidity and mortality. High-mobility group protein 1 (HMGB1) is a highly conserved nuclear protein, which is involved in multiple human diseases including cancers. However, the mechanisms of HMGB1 in non-small cell lung cancer remain unclear. The goal of the present study is to identify the relationship between HMGB1 and the progresssion of non-small cell lung cancer and investigate the molecular mechanism of HMGB1 in non-small lung cancer cell lines. Firstly, we detected the expression levels of HMGB1 by by real-time PCR and western blotting analysis, and the results demonstrated that HMGB1 was much higher expressed in non-small cell lung cancer cell lines, including A549, SPC-1-1, NCI-2170, SK-MES-1, and NCI-H1299, compared with that of WI-38. Next, 5 μM of adriamycin (AMD), 20 μM of cisplatin (DDP), and 50 μM of methotrexate (MTX) were used to treat A549 cells and SPC-A-1 cells for 48 h. The results showed that treatment with chemotherapy drugs significantly increased the levels of HMGB1 in A549 cells and SPC-A-1 cells. Moreover, the expression levels of HMGB1 increased in a time-dependent manner being treated with DDP. Then, the endogenous HMGB1 expression was successfully interferred with shRNA specific to HMGB1 in A549 and SPC-A-1 cells, which was detected by western blotting analysis. Then, the cisplatin-sensitive A549 cells and cisplatin-resistant A549/DDP cells were treated with increasing concentrations of cisplatin for 24, 48, and 72 h; cell viability were analyzed by MTT assay; and IC50 values were calculated. The results demonstrated that the expression level of HMGB1 in A549/DDP cells was much higher than that of A549 cells; moreover, transfection with HMGB1 shRNA in A549/DDP cells decreased the IC50 value of cisplatin in A549/DDP cells. The expression levels of autophagy-related proteins beclin-1 and LC3-II were significantly higher in A549/DDP cells or the A549 cells treated with

  11. Stress Induces the Danger-Associated Molecular Pattern HMGB-1 in the Hippocampus of Male Sprague Dawley Rats: A Priming Stimulus of Microglia and the NLRP3 Inflammasome

    Science.gov (United States)

    Frank, Matthew G.; Tracey, Kevin J.; Watkins, Linda R.; Maier, Steven F.

    2015-01-01

    Exposure to acute and chronic stressors sensitizes the proinflammatory response of microglia to a subsequent immune challenge. However, the proximal signal by which stressors prime microglia remains unclear. Here, high mobility group box-1 (HMGB-1) protein was explored as a potential mediator of stress-induced microglial priming and whether HMGB-1 does so via the nucleotide-binding domain, leucine-rich repeat, pyrin domain containing protein 3 (NLRP3) inflammasome. Exposure to 100 inescapable tail shocks (ISs) increased HMGB-1 and NLRP3 protein in the hippocampus and led isolated microglia to release HMGB-1 ex vivo. To determine whether HMGB-1 signaling is necessary for stress-induced sensitization of microglia, the HMGB-1 antagonist BoxA was injected into the cisterna magna before IS. Hippocampal microglia were isolated 24 h later and stimulated with LPS ex vivo to probe for stress-induced sensitization of proinflammatory responses. Previous IS potentiated gene expression of NLRP3 and proinflammatory cytokines to LPS, that is, microglia were sensitized. Treatment with BoxA abolished this effect. To determine whether HMGB-1 is sufficient to prime microglia, IS was replaced with intracerebral administration of disulfide or fully reduced HMGB-1. Intracerebral disulfide HMGB-1 mimicked the effect of the stressor, because microglia isolated from HMGB-1-treated rats expressed exaggerated NLRP3 and proinflammatory cytokine expression after LPS treatment, whereas fully reduced HMGB-1 had no effect. The present results suggest that the CNS innate immune system can respond to an acute stressor as if it were cellular damage, thereby releasing the danger signal HMGB-1 in the brain to prime microglia by acting on the NLRP3 inflammasome, in preparation for a later immune challenge. PMID:25568124

  12. Oxidation of HMGB1 causes attenuation of its pro-inflammatory activity and occurs during liver ischemia and reperfusion.

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    Anding Liu

    Full Text Available High mobility group box 1 (HMGB1 is a nuclear transcription factor. Once HMGB1 is released by damaged cells or activated immune cells, it acts as danger molecule and triggers the inflammatory signaling cascade. Currently, evidence is accumulating that posttranslational modifications such as oxidation may modulate the pro-inflammatory potential of danger signals. We hypothesized that oxidation of HMGB1 may reduce its pro-inflammatory potential and could take place during prolonged ischemia and upon reperfusion.Liver grafts were cold preserved for 24 h and flushed with saline in hourly intervals to collect the effluent. Liver grafts, cold-preserved for 6 h, were transplanted into syngeneic recipients to obtain serum and liver samples 24 h after initiation of reperfusion. Addition of the effluent to a macrophage culture induced the synthesis of tumor necrosis factor-alpha (TNF-α and interleukin (IL-6. The stimulatory activity of graft effluent was reduced after depletion of HMGB1 via immunoprecipitation. Oxidation of the effluent HMGB1 using H(2O(2 attenuated its stimulatory activity as well. Liver transplantation of cold preserved grafts caused HMGB1 translocation and release as determined by immunohistochemistry and ELISA-assay, respectively. Using Western blot with non-reducing conditions revealed the presence of oxidized HMGB1 in liver samples obtained after 12 h and in effluent samples after 16 h of cold preservation as well as in liver and serum samples obtained 24 h after reperfusion.These observations confirm that post-translational oxidation of HMGB1 attenuates its pro-inflammatory activity. Oxidation of HMGB1 as induced during prolonged ischemia and by reoxygenation during reperfusion in vivo might also attenuate its pro-inflammatory activity. Our findings also call for future studies to investigate the mechanism of the inhibitory effect of oxidized HMGB1 on the pro-inflammatory potential.

  13. HMGB1 promotes EC angiogenic behavior in vitro and improves muscle perfusion in vivo in response to ischemic injury

    Science.gov (United States)

    Sachdev, Ulka; Cui, Xiangdong; Hong, Guiying; Namkoong, Seung; Karlsson, Jenny M.; Baty, Catherine J.; Tzeng, Edith

    2013-01-01

    Objectives The angiogenic drive in skeletal muscle ischemia remains poorly understood. Innate inflammatory pathways are activated during tissue injury and repair, suggesting that this highly conserved pathway may be involved in ischemia-induced angiogenesis. We hypothesize that one of the endogenous ligands for innate immune signaling, high mobility group box 1 (HMGB1), in combination with autophagic responses to hypoxia or nutrient deprivation plays an important role in angiogenesis. Methods Human dermal microvascular endothelial cells (EC) were cultured in normoxia or hypoxia (1% oxygen). Immunocytochemical analysis of HMGB1 subcellular localization, evaluation of tube formation, and Western blot analysis of myotubule light-chain 3 (LC3I) conversion to LC3II, as a marker of autophagy, were conducted. 3-methyladenine (3MA), chloroquine (CQ), or rapamycin were administered to inhibit or promote autophagy, respectively. In vivo, a murine hind-limb ischemia model was performed. Muscle samples were collected at 4 hours to evaluate for nuclear HMGB1 and at 14 days to examine endothelial density. Perfusion recovery in the hind-limbs was calculated by laser Doppler perfusion imaging (LDPI). Results Hypoxic EC exhibited reduced nuclear HMGB1 staining compared with normoxic cells (mean fluorescence intensity 186.9 ± 17.1 vs. 236.0 ± 1.6, respectively, P = 0.01) with a concomitant increase in cytosolic staining. HMGB1 treatment of ECs enhanced tube formation, an angiogenic phenotype of ECs. Neutralization of endogenous HMGB1 markedly impaired tube formation and inhibited LC3II formation. Inhibition of autophagy with 3MA or CQ abrogated tube formation while its induction with rapamycin enhanced tubing and promoted HMGB1 translocation. In vivo, ischemic skeletal muscle showed reduced the numbers of HMGB1 positive myocyte nuclei compared with nonischemic muscle (34.9% ± 1.9 vs. 51.7% ± 2.0, respectively, P<0.001). Injection of HMGB1 into ischemic hind-limbs increased

  14. Association of HMGB1 polymorphisms with outcome after allogeneic hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Kornblit, Brian Thomas; Masmas, Tania; Petersen, Søren;

    2010-01-01

    activation of antigen presenting cells (APCs) and propagation of inflammation. HMGB1 is implicated in the pathophysiology of a variety of inflammatory diseases, and we have recently found the variation in the HMGB1 gene to be associated with mortality in patients with systemic inflammatory response syndrome......Several studies have demonstrated that genetic variation in cytokine genes can modulate the immune reactions after allogeneic hematopoietic cell transplantation (HCT). High mobility group box 1 protein (HMBG1) is a pleiotropic cytokine that functions as a pro-inflammatory signal, important for the...

  15. Serum levels of HMGB1, survivin, and VEGF in patients with advanced non-small cell lung cancer during chemotherapy.

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    Wiesława Nilklińska

    2010-05-01

    Full Text Available Recently, several reports have suggested that HMGB1 (the high-mobility group box-1 plays a key role in tumor angiogenesis through multiple mechanisms, including up-regulation of proangiogenic factors. This study was conducted to investigate the prognostic role and the effects of chemotherapy on serum (ELISA angiogenic factors: HMGB1, survivin and VEGF (Vascular Endothelial Growth Factor in patients with advanced stage non-small cell lung cancer (NSCLC. The study entered 40 patients (31 man and 15 healthy volunteers (control group. Peripheral blood samples were taken before and after four cycles of chemotherapy. The mean serum HMGB1 and VEGF levels were significantly higher in patients with advanced NSCLC than in controls (p=0.024, p=0.028, respectively. The levels of survivin in NSCLC patients were comparable to controls. No correlation was found between HMGB1, survivin and VEGF concentrations and the histological type and staging of lung cancer. Similarly, no correlation was revealed between the concentrations of HMGB1, survivin and VEGF and the effect of chemotherapy. However, in patients with NSCLC, HMGB1 positevely correlated with survivin (R=0.814, p=0.007 before chemotherapy, and negatively with VEGF (R=-0.841, p=0.035 after chemotherapy. When the cut-off values of serum HMGB1, survivin and VEGF (2.38 ng/ml, 81.92 pg/ml, 443.26 pg/ml, respectively were used, the prognoses of high and low groups were not different. Concluding, patients with NSCLC have a higher serum concentration of HMGB1 and VEGF, while survivin levels are comparable to healthy individuals. In our opinion, determination of HMGB1, survivin and VEGF concentrations has no clinical significance in the prognosis of the survival time in lung cancer.

  16. Barrier protective effects of withaferin A in HMGB1-induced inflammatory responses in both cellular and animal models

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Wonhwa [College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University (Korea, Republic of); Kim, Tae Hoon [Department of Herbal Medicinal Pharmacology, Daegu Haany University (Korea, Republic of); Ku, Sae-Kwang [Department of Anatomy and Histology, College of Oriental Medicine, Daegu Haany University, Gyeongsan 712-715 (Korea, Republic of); Min, Kyoung-jin [Department of Immunology, School of Medicine, Keimyung University, Daegu 704-701 (Korea, Republic of); Lee, Hyun-Shik [School of Life Sciences, College of Natural Sciences, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Kwon, Taeg Kyu [Department of Immunology, School of Medicine, Keimyung University, Daegu 704-701 (Korea, Republic of); Bae, Jong-Sup, E-mail: baejs@knu.ac.kr [College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701 (Korea, Republic of)

    2012-07-01

    Withaferin A (WFA), an active compound from Withania somnifera, is widely researched for its anti-inflammatory, cardioactive and central nervous system effects. In this study, we first investigated the possible barrier protective effects of WFA against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice induced by high mobility group box 1 protein (HMGB1) and the associated signaling pathways. The barrier protective activities of WFA were determined by measuring permeability, leukocytes adhesion and migration, and activation of pro-inflammatory proteins in HMGB1-activated HUVECs. We found that WFA inhibited lipopolysaccharide (LPS)-induced HMGB1 release and HMGB1-mediated barrier disruption, expression of cell adhesion molecules (CAMs) and adhesion/transendothelial migration of leukocytes to human endothelial cells. WFA also suppressed acetic acid-induced hyperpermeability and carboxymethylcellulose-induced leukocytes migration in vivo. Further studies revealed that WFA suppressed the production of interleukin 6, tumor necrosis factor-α (TNF-α) and activation of nuclear factor-κB (NF-κB) by HMGB1. Collectively, these results suggest that WFA protects vascular barrier integrity by inhibiting hyperpermeability, expression of CAMs, adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases. -- Highlights: ► Withaferin A inhibited LPS induced HMGB1 release. ► Withaferin A reduced HMGB1-mediated hyperpermeability. ► Withaferin A inhibited HMGB1-mediated adhesion and migration of leukocytes. ► Withaferin A inhibited HMGB1-mediated activation of NF-κB, IL-6 and TNF-α.

  17. 高迁移率族蛋白1对狼疮肾炎小鼠肾小球细胞增殖的影响%Effect of shHMGB1 knockdown on renal function improvement and cell proliferation of glomeruli in lupus nephritis mice

    Institute of Scientific and Technical Information of China (English)

    王秋红; 封晓娟; 吴超; 刘淑霞

    2015-01-01

    Objective To investigate the effect of high mobility group box chromosomal protein 1 (HMGB1) knockdown on improving renal function and decreasing cell proliferation of glomeruli in lupus nephritis (LN) MRL/Faslpr mice.Methods Twenty-four MRL/Faslpr mice were randomly divided into 3 groups:LN model group,shHMGB1 group and empty plasmid group.Besides,eight MRL/MpJ mice,age and mass matched to the MRL/Faslpr mice,were chosen as normal control group (shNC group).Electroporation technology was used for in vivo transfection in treatment group.shHMGB1 group and empty plasmid group were transfected by electroporation technology for shHMGB1 plasmids and empty plasmid,LN model group and normal control group were transfected only with saline.Automatic biochemical analyzer was used to detect serum urea nitrogen (BUN) and creatinine (Scr) levels and 24 h urinary protein (UP) was tested.HE staining was used to detect the pathological change of renal tissues; real-time PCR,immunofluorence staining and Western blotting were used to detect the mRNA and protein expression of HMGB1 and PCNA.Results (1) The HMGB1 mRNA and protein expression in LN group increased compared with those in control group,HMGB1 mRNA and protein expression in shHMGB1 group reduced compared with those in LN model group (all P < 0.05).(2) 24 h UP of MRL/Faslpr mice in shHMGB1 group significantly reduced compared with those in LN group (P < 0.05).(3) Immunofluorence and Western blotting showed that positive signal of proliferating cell nuclear antigen (PCNA) was mainly located in nuclei,PCNA mRNA and protein in glomeruli of LN model group increased compared with those of control mice (P < 0.05).Interestingly,PCNA expression in glomeruli of shHMGB1 group remarkably reduced (P < 0.05).Conclusions shHMGB1 significantly improves renal function and decreases cell proliferation of glomeruli in LN MRL/Faslpr mice.%目的 通过敲低肾组织高迁移率族蛋白1(HMGB1)表达,探讨其对改善狼疮肾炎小

  18. Expression of RAGE and HMGB1 in thymic epithelial tumors, thymic hyperplasia and regular thymic morphology.

    Directory of Open Access Journals (Sweden)

    Bernhard Moser

    Full Text Available Recently, a role of the receptor for advanced glycation endproducts (RAGE in myasthenia gravis was described. RAGE and its ligand high mobility group box 1 (HMGB1 play key roles in autoimmunity and cancer. To test whether these molecules are involved in patients with thymic abnormalities we applied immunohistochemical analysis in 33 cases of thymic epithelial tumors, comprising 27 thymomas and 6 thymic carcinomas, and 21 nonneoplastic thymuses. Both molecules were detected in neoplastic epithelial cells: RAGE staining was most intense in WHO type B2 thymomas and thymic carcinomas (pB3>thymic carcinoma (p<0.001. Conversely, HMGB1 cytoplasmic staining intensities were as follows: A and AB (none, B1 (strong, B2 (moderate, B3 and thymic carcinoma (weak; (p<0.001. Fetal thymic tissue showed a distinct expression of RAGE and HMGB1 in subcapsular cortical epithelial cells which was found in 50% of myasthenic patients. Furthermore RAGE and HMGB1 were expressed in thymocytes, macrophages, Hassall's corpuscles, thymic medulla, and germinal center cells in myasthenic patients. Immunohistochemistry results were complemented by systemic measurements (immunosorbent assay: serum levels of soluble RAGE were significantly reduced in patients with epithelial tumors (p = 0.008; and in invasive tumors (p = 0.008. Whereas RAGE was equally reduced in thymic hyperplasia and epithelial tumors (p = 0.003, HMGB1 was only elevated in malignancies (p = 0.036. Results were most pronounced in thymic carcinomas. Thus, RAGE and HMGB1 are involved in the (patho-physiology of thymus, as evidenced by differentiated thymic and systemic expression patterns that may act as diagnostic or therapeutic targets in autoimmune disease and cancer.

  19. HMGB1 Contributes to the Expression of P-Glycoprotein in Mouse Epileptic Brain through Toll-Like Receptor 4 and Receptor for Advanced Glycation End Products.

    Directory of Open Access Journals (Sweden)

    Yan Chen

    Full Text Available The objective of the present study was to investigate the role of high-mobility group box-1 (HMGB1 in the seizure-induced P-glycoprotein (P-gp overexpression and the underlying mechanism. Kainic acid (KA-induced mouse seizure model was used for in vivo experiments. Male C57BL/6 mice were divided into four groups: normal saline control (NS group, KA-induced epileptic seizure (EP group, and EP group pretreated with HMGB1 (EP+HMGB1 group or BoxA (HMGB1 antagonist, EP+BoxA group. Compared to the NS group, increased levels of HMGB1 and P-gp in the brain were observed in the EP group. Injection of HMGB1 before the induction of KA further increased the expression of P-gp while pre-treatment with BoxA abolished this up-regulation. Next, the regulatory role of HMGB1 and its potential involved signal pathways were investigated in mouse microvascular endothelial bEnd.3 cells in vitro. Cells were treated with HMGB1, HMGB1 plus lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS [toll-like receptor 4 (TLR4 antagonist], HMGB1 plus FPS-ZM1 [receptor for advanced glycation end products (RAGE inhibitor], HMGB1 plus SN50 [nuclear factor-kappa B (NF-κB inhibitor], or vehicle. Treatment with HMGB1 increased the expression levels of P-gp, TLR4, RAGE and the activation of NF-κB in bEnd.3 cells. These effects were inhibited by the pre-treatment with either LPS-RS or FPS-ZM1, and were abolished by the pre-treatment of SN50 or a combination treatment of both LPS-RS and FPS-ZM1. Luciferase reporter assays showed that exogenous expression of NF-κB p65 increased the promoter activity of multidrug resistance 1a (P-gp-encoding gene in endothelial cells. These data indicate that HMGB1 contributes to the overexpression of P-gp in mouse epileptic brain tissues via activation of TLR4/RAGE receptors and the downstream transcription factor NF-κB in brain microvascular endothelial cells.

  20. Prognostic value of HMGB1 and oxidative stress markers in multiple trauma patients: A single-centre prospective study.

    Science.gov (United States)

    Polito, Francesca; Cicciu', Marco; Aguennouz, Mohammed; Cucinotta, Maria; Cristani, Mariateresa; Lauritano, Floriana; Sindoni, Alessandro; Gioffre'-Florio, Maria; Fama, Fausto

    2016-09-01

    Serious multiple traumatic injuries may rapidly become fatal or be complicated by a life-threatening sequelae leading to a significant increase of the mortality rate. Trauma scoring systems are used to evaluate the critical status of the patient and recently many different biomarkers have been taken into account to better estimate the potential clinical outcome. The aim of the present study is to analyse the expression pattern of high-mobility group box-1 (HMGB1), oxidative stress markers and nuclear factor erythroid 2-related (Nrf2) in critically ill traumatic patients (at hospital admittance and after 6 and 24 h), in order to find out their potential role as early post-traumatic predictors markers. Forty-seven patients admitted for multiple trauma and 15 healthy participants were prospectively recruited. Eight patients (17%) died within 92 h of admission; this subgroup of patients presented the highest severity scores and their HMGB1 expression levels were significantly correlated with ISS, whereas patients with higher ISS exhibited higher levels of HMGB1 (P <0.001). Our study suggests the role of HMGB1 as a predictive biomarker of outcome in injured patients and hypothesizes the protective role of Nrf2 in bringing down the oxidative stress and HMGB1 release; measuring HMGB1 in combination with Nrf2 might represent a potentially useful tool in the early detection of post-trauma complications. PMID:27343243

  1. MicroRNA-205‑5b inhibits HMGB1 expression in LPS-induced sepsis.

    Science.gov (United States)

    Zhou, Wenhai; Wang, Jing; Li, Zhifeng; Li, Jianguo; Sang, Ming

    2016-07-01

    Inflammatory cytokines belonging to high mobility group box (HMGB)1 play a key role in sepsis through yet unknown mechanisms. The inflammatory response is modulated by microRNAs (miRNAs or miRs) at multiple levels and is poorly understood. In this study, the regulation of HMGB1 by miRNAs was evaluated using 3-(2,4-dimethoxybenzylidene)anabaseine (GTS-21) to activate the cholinergic anti-inflammatory pathway (CAP) and decrease HMGB1 expression in RAW264.7 cells. Microarray-based miRNA expression profiling of RAW264.7 cells was used to screen target miRNAs through genetic screening, GO analysis and hierarchical clustering. The expression of miRNA targets in the serum, colon, spleen, livers and lungs of BALB/c mice was quantified by RT-qPCR. Serum protein levels were quantified by ELISA. Western blot analysis and RT-qPCR were used for verification in vitro. Using miRNA array analysis, we screened 3 miRNAs (miR‑205‑5b, miR‑196a and miR‑193b). Animal experiments with miR‑205‑5b indicated its high degree of expression in the serum, colon, spleen, liver and lungs following the downregulation of HMGB1 in the tissues. RAW264.7 cells transfected with miR‑205‑5b mimics downregulated HMGB1 protein expression, suggesting translational regulation. HMGB1 expression negatively correlated with miR‑205‑5b expression in LPS-induced sepsis. By contrast, HMGB1 expression in LPS-stimulated RAW264.7 cells was increased following transfection with miR‑205‑5b inhibitor. miR‑205‑5b is a critical mediator of cholinergic anti-inflammatory activity in late sepsis. The upregulation of miR‑205‑5b as a potential therapeutic target for the treatment of inflammatory diseases is a possible novel therapeutic strategy against late sepsis. The mechanisms involved include the by post-transcriptional suppression of HMGB1 in cells and tissues. PMID:27246725

  2. Bone marrow stromal cells inhibits HMGB1-mediated inflammation after stroke in type 2 diabetic rats.

    Science.gov (United States)

    Hu, J; Liu, B; Zhao, Q; Jin, P; Hua, F; Zhang, Z; Liu, Y; Zan, K; Cui, G; Ye, X

    2016-06-01

    High-mobility group box 1 (HMGB1), a ligand of receptor for advanced glycation endproducts (RAGE), functions as a proinflammatory factor. It is mainly involved in inflammatory activation and contributes to the initiation and progression of stroke. By using a model of transient middle cerebral artery occlusion (MCAo) in type 2 diabetic rats, we investigated the changes of pro-inflammation mediators, blood-brain barrier (BBB) leakage and functional outcome after stroke. Type 2 diabetic rats did not show an increased lesion volume, but exhibited significantly increased expression of HMGB1 and RAGE, BBB leakage, as well as decreased functional outcome after stroke compared with control rats. Injection of bone marrow stromal cells (BMSCs) into type 2 diabetic rats significantly reduced the expression of HMGB1 and RAGE, attenuated BBB leakage, and improved functional outcome after stroke. BMSCs-treated type 2 diabetic rats inhibited inflammation and improved functional outcome after stroke. Furthermore, in vitro data support the hypothesis that BMSCs-induced reduction of HMGB1 and RAGE in T2DM-MCAo rats contributed to attenuated inflammatory response in the ischemic brain, which may lead to the beneficial effects of BMSCs treatment. Further investigation of BMSCs treatment in type 2 diabetic stroke is warranted. PMID:26946264

  3. HMGB1 interacts with XPA to facilitate the processing of DNA interstrand crosslinks in human cells

    OpenAIRE

    Mukherjee, Anirban; Vasquez, Karen M.

    2015-01-01

    Many effective agents used in cancer chemotherapy cause DNA interstrand crosslinks (ICLs), which covalently link both strands of the double helix together resulting in cytotoxicity. ICLs are thought to be processed by proteins from a variety of DNA repair pathways; however, a clear understanding of ICL recognition and repair processing in human cells is lacking. Previously, we found that the high mobility group box 1 (HMGB1) protein bound to triplex-directed psoralen ICLs (TFO-ICLs) in vitro,...

  4. Systemisk inflammasjon etter traume: Alarminer som aktivatorer av immunresponsen - med fokus på HMGB1.

    OpenAIRE

    Skaga, Erlend

    2014-01-01

    Objectives: Systemic inflammatory response syndrome (SIRS) is commonly seen after sterile traumatic injury and may lead to multiple organ failure and death. Endogenous molecules termed alarmins are released following cellular stress or injury and activate the response. This literature review will discuss the mechanisms in immune system activation after trauma and compare to similar mechanisms in sepsis, with special focus on High mobility group box 1 (HMGB1). Possible future treatment options...

  5. Relationship between HMGB1 content and MHC-Ⅱ expression in circulating monocytes and spleen of mice challenged with zymosan

    Institute of Scientific and Technical Information of China (English)

    L(U) Yi; LU Jiang-yang; ZHAO Min; LI Zhi-hong; YANG Yi

    2009-01-01

    Objective: To observe the regularity of change in high mobility group protein box 1 (HMGB1) content in serum and spleen of mice with multiple organ dysfunction syndrome (MODS), to analyze the correlation between HMGB1 content and major histocompatibility complex (MHC)-Ⅱ-I-Ab expression on monocytes in blood and spleen, and to explore the effect of HMGB1 on immune function of circulating monocytes and splenocytes. Methods: One hundred 8-week-old male 57BL/6 mice were randomly divided into normal group and experimental group subdivided into 8 subgroups: 3, 8, 12 hours, 1, 2, 3, 5-7 days and 10-12 days post zymosan injection (PZI). MODS model was replicated by injecting zymosan into the peritoneal cavity. At each time point, blood and spleen were collected to detect HMGB1 content and the rate of I-Ab positive monocytes. Results: In normal and PZI 3-hour, 8-hour mice, serum HMGB1 was not detected, but it significantly increased at PZI 12 hours. In spleen of normal mice, there was low level of HMGB1 expression. In zymosan-treated mice, HMGB1 started to rise in spleen at PZI 3 hours. Subsequently, HMGB1 content in both serum and spleen significantly increased, and it reached the peak level in 1-2 days, decreased in 5 days, and then increased in 10-12 days. The number of I-Ab positive monocytes in circulating blood and spleen decreased at 1-2 days (t=9.589, 4.432, P<0.01) and 10-12 days following the challenge, forming a two trough like decrease, just corresponding with two-peak increase of HMGB1. However, at 3 hours after zyrnosan challenge, I-Ab expression on circulating monocytes was downregulated (t=5.977, P<0.01), while that in spleen upregulated (t=4.814, P<0.01). Conclusion: In mice with MODS, up-regulated HMGB1 expression can regulate I-Ab expression on monocytes to depress their ability of presenting antigen, which results in immune disturbance contributing development of MODS.

  6. Diet restriction inhibits apoptosis and HMGB1 oxidation and promotes inflammatory cell recruitment during acetaminophen hepatotoxicity.

    Science.gov (United States)

    Antoine, Daniel James; Williams, Dominic P; Kipar, Anja; Laverty, Hugh; Park, B Kevin

    2010-01-01

    Acetaminophen (APAP) overdose is a major cause of acute liver failure and serves as a paradigm to elucidate mechanisms, predisposing factors and therapeutic interventions. The roles of apoptosis and inflammation during APAP hepatotoxicity remain controversial. We investigated whether fasting of mice for 24 h can inhibit APAP-induced caspase activation and apoptosis through the depletion of basal ATP. We also investigated in fasted mice the critical role played by inhibition of caspase-dependent cysteine 106 oxidation within high mobility group box-1 protein (HMGB1) released by ATP depletion in dying cells as a mechanism of immune activation. In fed mice treated with APAP, necrosis was the dominant form of hepatocyte death. However, apoptosis was also observed, indicated by K18 cleavage, DNA laddering and procaspase-3 processing. In fasted mice treated with APAP, only necrosis was observed. Inflammatory cell recruitment as a consequence of hepatocyte death was observed only in fasted mice treated with APAP or fed mice cotreated with a caspase inhibitor. Hepatic inflammation was also associated with loss in detection of serum oxidized-HMGB1. A significant role of HMGB1 in the induction of inflammation was confirmed with an HMGB1-neutralizing antibody. The differential response between fasted and fed mice was a consequence of a significant reduction in basal hepatic ATP, which prevented caspase processing, rather than glutathione depletion or altered APAP metabolism. Thus, the inhibition of caspase-driven apoptosis and HMGB1 oxidation by ATP depletion from fasting promotes an inflammatory response during drug-induced hepatotoxicity/liver pathology. PMID:20811657

  7. Newly identifi ed message for rescue and repair from necrotic cell: Biology and clinical relevance of“endokine, HMGB1

    OpenAIRE

    Maruyama, Ikuro; Ito, Takashi; HASHIGUCHI, Teruto

    2007-01-01

    Responses to stimuli in cellar level are diverse and such hierarchical as secretion of stored factors,synthesis of lipid mediators and protein synthesis through genomic transcription. However, how can the cellsrespond in the case of necrosis? Recently a characteristic intranuclear protein, high-mobility group box 1 protein(HMGB1) is released from necrotic cells. The protein is an abundant nuclear protein with a dual functionboth inside and outside the cells. In physiological state, HMGB1 is p...

  8. Etanercept decreases HMGB1 expression in dorsal root ganglion neuron cells in a rat chronic constriction injury model

    OpenAIRE

    WANG, RUI-KE; Zhang, Qin-Qin; PAN, YUN-DAN; Guo, Qu-Lian

    2012-01-01

    In the present study, we examined the effect of etanercept on high mobility group box 1 (HMGB1) expression in dorsal root ganglion (DRG) neuron cells in a rat model of chronic constriction injury (CCI) of the sciatic nerve, with the aim of exploring the molecular mechanism underlying the therapeutic effect of etanercept on sciatica-related nociception and the potential interaction between tumor necrosis factor-α (TNF-α) and HMGB1 in DRG neuron cells. A rat CCI model was employed and the anima...

  9. Structural aspects of the interaction of anticancer drug Actinomycin-D to the GC rich region of hmgb1 gene.

    Science.gov (United States)

    Lohani, Neelam; Singh, Himanshu Narayan; Moganty, R Rajeswari

    2016-06-01

    The high mobility group box 1 protein has been identified as a key player in chromatin homeostasis including transcription regulation, recombination, repair, and chromatin remodeling. Emerging findings indicate HMGB1 protein over expression in nearly all types of human cancers and inflammatory disorders. Thus it is considered as a potential therapeutic target for treating various malignancies. We screened the promoter region of hmgb1 gene and selected a positive regulatory element of 25 base pair duplex (25RY) (-165 to -183) as a potential target for chemotherapeutic intervention. The molecular interaction of actinomycin (ACT) with the regulatory region of hmgb1 gene was characterized by spectroscopic, calorimetric and molecular docking studies. The hypochromic and bathochromic shift in the absorption spectrum, stabilization of 25RY duplex against thermal denaturation, perturbation of CD spectrum of duplex and enhancement of fluorescence intensity of actinomycin indicate strong binding of actinomycin to the hmgb1 promoter region (25RY).The energetics was characterized to be endothermic and entropy driven. All these results are in good agreement with in silico investigation that suggest minor groove binding with effective intercalation at GC bases of actinomycin to 25RY. This study identifies hmgb1 gene promoter region a potential target for the anticancer therapautiucs. PMID:26923673

  10. HMGB1 mediates endogenous TLR2 activation and brain tumor regression.

    Directory of Open Access Journals (Sweden)

    James F Curtin

    2009-01-01

    Full Text Available BACKGROUND: Glioblastoma multiforme (GBM is the most aggressive primary brain tumor that carries a 5-y survival rate of 5%. Attempts at eliciting a clinically relevant anti-GBM immune response in brain tumor patients have met with limited success, which is due to brain immune privilege, tumor immune evasion, and a paucity of dendritic cells (DCs within the central nervous system. Herein we uncovered a novel pathway for the activation of an effective anti-GBM immune response mediated by high-mobility-group box 1 (HMGB1, an alarmin protein released from dying tumor cells, which acts as an endogenous ligand for Toll-like receptor 2 (TLR2 signaling on bone marrow-derived GBM-infiltrating DCs. METHODS AND FINDINGS: Using a combined immunotherapy/conditional cytotoxic approach that utilizes adenoviral vectors (Ad expressing Fms-like tyrosine kinase 3 ligand (Flt3L and thymidine kinase (TK delivered into the tumor mass, we demonstrated that CD4(+ and CD8(+ T cells were required for tumor regression and immunological memory. Increased numbers of bone marrow-derived, tumor-infiltrating myeloid DCs (mDCs were observed in response to the therapy. Infiltration of mDCs into the GBM, clonal expansion of antitumor T cells, and induction of an effective anti-GBM immune response were TLR2 dependent. We then proceeded to identify the endogenous ligand responsible for TLR2 signaling on tumor-infiltrating mDCs. We demonstrated that HMGB1 was released from dying tumor cells, in response to Ad-TK (+ gancyclovir [GCV] treatment. Increased levels of HMGB1 were also detected in the serum of tumor-bearing Ad-Flt3L/Ad-TK (+GCV-treated mice. Specific activation of TLR2 signaling was induced by supernatants from Ad-TK (+GCV-treated GBM cells; this activation was blocked by glycyrrhizin (a specific HMGB1 inhibitor or with antibodies to HMGB1. HMGB1 was also released from melanoma, small cell lung carcinoma, and glioma cells treated with radiation or temozolomide

  11. Ionizing Radiation Induces HMGB1 Cytoplasmic Translocation and Extracellular Release

    Institute of Scientific and Technical Information of China (English)

    Lili Wang; Li He; Guoqiang Bao; Xin He; Saijun Fan; Haichao Wang

    2016-01-01

    Objective A nucleosomal protein,HMGBI,can be secreted by activated immune cells or passively released by dying cells,thereby amplifying rigorous inflammatory responses.In this study we aimed to test the possibility that radiation similarly induces cytoplasmic HMGB1 translocation and release.Methods Human skin fibroblast (GM0639) and bronchial epithelial (16HBE) cells and rats were exposed to X-ray radiation,and HMGB1 translocation and release were then assessed by immunocytochemistry and immunoassay,respectively.Results At a wide dose range(4.0-12.0 Gy),X-ray radiation induced a dramatic cytoplasmic HMGB1 translocation,and triggered a time-and dose-dependent HMGB1 release both in vitro and in vivo.The radiation-mediated HMGB1 release was also associated with noticeable chromosomal DNA damage and loss of cell viability.Conclusions Radiation induces HMGB1 cytoplasmic translocation and extracellular release through active secretion and passive leakage processes.

  12. Protocatechuic aldehyde ameliorates experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway

    International Nuclear Information System (INIS)

    An abnormal high mobility group box 1 (HMGB1) activation and a decrease in receptor for advanced glycation end-product (RAGE) play a key role in the pathogenesis of pulmonary fibrosis. Protocatechuic aldehyde (PA) is a naturally occurring compound, which is extracted from the degradation of phenolic acids. However, whether PA has anti-fibrotic functions is unknown. In this study, the effects of PA on the transforming growth factor-β1 (TGF-β1)-mediated epithelial–mesenchymal transition (EMT) in A549 cells, on the apoptosis of human type I alveolar epithelial cells (AT I), on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis in vivo were investigated. PA treatment resulted in a reduction of EMT in A549 cells with a decrease in vimentin and HMGB, an increase of E-cadherin and RAGE, a reduction of HLF-1 proliferation with a decrease of fibroblast growth factor 2 (FGF-2) and platelet-derived growth factor (PDGF). Apoptosis of AT I was attenuated with an increase of RAGE. PA ameliorated BLM-induced pulmonary fibrosis in rats with a reduction of histopathological scores and collagen deposition, and a lower FGF-2, PDGF, α-smooth muscle actin (α-SMA) and HMGB1 expression, whereas higher RAGE was found in BLM-instilled lungs. Through the decrease of HGMB1 and the regulation of RAGE, PA reversed the EMT, inhibited HLF-1 proliferation as well as reduced apoptosis in AT I, and prevented pulmonary fibrosis in vivo. Collectively, our results demonstrate that PA prevents experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway. - Highlights: • PA prevents EMT, reduces the apoptosis of AT1 in vitro. • PA decreases proliferation of HLF-1, reduces PDGF and FGF expression in vitro. • PA prevents experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway

  13. Protocatechuic aldehyde ameliorates experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Liang, E-mail: countryspring@sina.com; Ji, Yunxia, E-mail: 413499057@qq.com; Kang, Zechun, E-mail: davidjiangwl@163.com; Lv, Changjun, E-mail: Lucky_lcj@sina.com; Jiang, Wanglin, E-mail: jwl518@163.com

    2015-02-15

    An abnormal high mobility group box 1 (HMGB1) activation and a decrease in receptor for advanced glycation end-product (RAGE) play a key role in the pathogenesis of pulmonary fibrosis. Protocatechuic aldehyde (PA) is a naturally occurring compound, which is extracted from the degradation of phenolic acids. However, whether PA has anti-fibrotic functions is unknown. In this study, the effects of PA on the transforming growth factor-β1 (TGF-β1)-mediated epithelial–mesenchymal transition (EMT) in A549 cells, on the apoptosis of human type I alveolar epithelial cells (AT I), on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis in vivo were investigated. PA treatment resulted in a reduction of EMT in A549 cells with a decrease in vimentin and HMGB, an increase of E-cadherin and RAGE, a reduction of HLF-1 proliferation with a decrease of fibroblast growth factor 2 (FGF-2) and platelet-derived growth factor (PDGF). Apoptosis of AT I was attenuated with an increase of RAGE. PA ameliorated BLM-induced pulmonary fibrosis in rats with a reduction of histopathological scores and collagen deposition, and a lower FGF-2, PDGF, α-smooth muscle actin (α-SMA) and HMGB1 expression, whereas higher RAGE was found in BLM-instilled lungs. Through the decrease of HGMB1 and the regulation of RAGE, PA reversed the EMT, inhibited HLF-1 proliferation as well as reduced apoptosis in AT I, and prevented pulmonary fibrosis in vivo. Collectively, our results demonstrate that PA prevents experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway. - Highlights: • PA prevents EMT, reduces the apoptosis of AT1 in vitro. • PA decreases proliferation of HLF-1, reduces PDGF and FGF expression in vitro. • PA prevents experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.

  14. The repair capacity of lung cancer cell lines A549 and H1299 depends on HMGB1 expression level and the p53 status.

    Science.gov (United States)

    Yusein-Myashkova, Shazie; Stoykov, Ivan; Gospodinov, Anastas; Ugrinova, Iva; Pasheva, Evdokia

    2016-07-01

    Elucidation of the cellular components responsive to chemotherapeutic agents as cisplatin rationalizes the strategy for anticancer chemotherapy. The removal of the cisplatin/DNA lesions gives the chance to the cancer cells to survive and compromises the chemotherapeutical treatment. Therefore, the cell repair efficiency is substantial for the clinical outcome. High mobility group box 1 (HMGB1) protein is considered to be involved in the removal of the lesions as it binds with high affinity to cisplatin/DNA adducts. We demonstrated that overexpression of HMGB1 protein inhibited cis-platinated DNA repair in vivo and the effect strongly depended on its C-terminus. We registered increased levels of DNA repair after HMGB1 silencing only in p53 defective H1299 lung cancer cells. Next, introduction of functional p53 resulted in DNA repair inhibition. H1299 cells overexpressing HMGB1 were significantly sensitized to treatment with cisplatin demonstrating the close relation between the role of HMGB1 in repair of cis-platinated DNA and the efficiency of the anticancer drug, the process being modulated by the C-terminus. In A549 cells with functional p53, the repair of cisplatin/DNA adducts is determined by а complex action of HMGB1 and p53 as an increase of DNA repair capacity was registered only after silencing of both proteins. PMID:26896489

  15. The chaperone like function of the nonhistone protein HMGB1

    Energy Technology Data Exchange (ETDEWEB)

    Osmanov, Taner; Ugrinova, Iva [Institute of Molecular Biology, Bulgarian Academy of Sciences (Bulgaria); Pasheva, Evdokia, E-mail: eva@bio21.bas.bg [Institute of Molecular Biology, Bulgarian Academy of Sciences (Bulgaria)

    2013-03-08

    Highlights: ► The HMGB1 protein strongly enhanced the formation of nucleosome particles. ► The target of HMGB1 action as a chaperone is the DNA not the histone octamer. ► The acetylation of HMGB1 decreases the stimulating effect of the protein. -- Abstract: Almost all essential nuclear processes as replication, repair, transcription and recombination require the chromatin template to be correctly unwound and than repackaged. The major strategy that the cell uses to overcome the nucleosome barrier is the proper removal of the histone octamer and subsequent deposition onto DNA. Important factors in this multi step phenomenon are the histone chaperones that can assemble nucleosome arrays in vitro in the absence of ATP. The nonhistone protein HMGB1 is a good candidate for a chaperone as its molecule consists of two DNA binding motives, Box’s A and B, and a long nonstructured C tail highly negatively charged. HMGB1 protein is known as a nuclear “architectural” factor for its property to bind preferentially to distorted DNA structures and was reported to kink the double helix. Our experiments show that in the classical stepwise dialysis method for nucleosome assembly the addition of HMGB1 protein stimulates more than two times the formation of middle-positioned nucleosomes. The stimulation effect persists in dialysis free experiment when the reconstitution is possible only in the presence of a chaperone. The addition of HMGB1 protein strongly enhanced the formation of a nucleosome in a dose dependant manner. Our results show that the target of HMGB1 action as a chaperone is the DNA fragment not the histone octamer. One possible explanation for the stimulating effect of HMGB1 is the “architectural” property of the protein to associate with the middle of the DNA fragment and to kink it. The acquired V shaped DNA structure is probably conformationals more favorable to wrap around the prefolded histone octamer. We tested also the role of the post

  16. HMGB1 is associated with atherosclerotic plaque composition and burden in patients with stable coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Martin Andrassy

    Full Text Available OBJECTIVES: The role of inflammation in atherosclerosis is widely appreciated. High mobility group box 1 (HMGB1, an injury-associated molecular pattern molecule acting as a mediator of inflammation, has recently been implicated in the development of atherosclerosis. In this study, we sought to investigate the association of plasma HMGB1 with coronary plaque composition in patients with suspected or known coronary artery disease (CAD. DESIGN: HMGB1, high sensitive troponin T (hsTnT and high sensitive C-reactive protein (hsCRP were determined in 152 consecutive patients with suspected or known stable CAD who underwent clinically indicated 256-slice coronary computed tomography angiography (CCTA. Using CCTA, we assessed 1 coronary calcification, 2 non-calcified plaque burden and 3 the presence of vascular remodeling in areas of non-calcified plaques. RESULTS: Using univariate analysis, hsCRP, hsTnT and HMGB1 as well as age, and atherogenic risk factors were associated with non-calcified plaque burden (r = 0.21, p = 0.009; r = 0.48, p<0.001 and r = 0.34, p<0.001, respectively. By multivariate analysis, hsTnT and HMGB1 remained independent predictors of the non-calcified plaque burden (r = 0.48, p<0.01 and r = 0.34, p<0.001, respectively, whereas a non-significant trend was noticed for hs-CRP (r = 0.21, p = 0.07. By combining hsTnT and HMGB1, a high positive predictive value for the presence of non-calcified and remodeled plaque (96% and 77%, respectively was noted in patients within the upper tertiles for both biomarkers, which surpassed the positive predictive value of each marker separately. CONCLUSIONS: In addition to hs-TnT, a well-established cardiovascular risk marker, HMGB1 is independently associated with non-calcified plaque burden in patients with stable CAD, while the predictive value of hs-CRP is lower. Complementary value was observed for hs-TnT and HMGB1 for the prediction of complex coronary plaque.

  17. DETECTION OF EXTRA-NUCLEAR HIGH MOBILITY GROUP BOX-1 PROTEIN IN A CANINE MODEL OF MYOCARDIAL INFARCTION

    Science.gov (United States)

    The high mobility group box-1 protein (HMGB-1) is a well-characterized nuclear protein recently shown to be involved in endotoxin-induced inflammation and injury. Studies have linked HMGB-1 release to the production of pro-inflammatory cytokines; however, a role for HMGB-1 in other disorders involvi...

  18. The Y-Box Binding Protein 1 Suppresses Alzheimer's Disease Progression in Two Animal Models.

    Directory of Open Access Journals (Sweden)

    N V Bobkova

    Full Text Available The Y-box binding protein 1 (YB-1 is a member of the family of DNA- and RNA binding proteins. It is involved in a wide variety of DNA/RNA-dependent events including cell proliferation and differentiation, stress response, and malignant cell transformation. Previously, YB-1 was detected in neurons of the neocortex and hippocampus, but its precise role in the brain remains undefined. Here we show that subchronic intranasal injections of recombinant YB-1, as well as its fragment YB-11-219, suppress impairment of spatial memory in olfactory bulbectomized (OBX mice with Alzheimer's type degeneration and improve learning in transgenic 5XFAD mice used as a model of cerebral amyloidosis. YB-1-treated OBX and 5XFAD mice showed a decreased level of brain β-amyloid. In OBX animals, an improved morphological state of neurons was revealed in the neocortex and hippocampus; in 5XFAD mice, a delay in amyloid plaque progression was observed. Intranasally administered YB-1 penetrated into the brain and could enter neurons. In vitro co-incubation of YB-1 with monomeric β-amyloid (1-42 inhibited formation of β-amyloid fibrils, as confirmed by electron microscopy. This suggests that YB-1 interaction with β-amyloid prevents formation of filaments that are responsible for neurotoxicity and neuronal death. Our data are the first evidence for a potential therapeutic benefit of YB-1 for treatment of Alzheimer's disease.

  19. Thrombin inhibits HMGB1-mediated proinflammatory signaling responses when endothelial protein C receptor is occupied by its natural ligand

    Directory of Open Access Journals (Sweden)

    Jong-Sup Bae

    2013-11-01

    Full Text Available High mobility group box 1 (HMGB1 is involved in thepathogenesis of vascular diseases. Unlike activated protein C(APC, the activation of PAR-1 by thrombin is known to elicitproinflammatory responses. To determine whether the occupancyof EPCR by the Gla-domain of APC is responsible for thePAR-1-dependent antiinflammatory activity of the protease, wepretreated HUVECs with the PC zymogen and then activatedPAR-1 with thrombin. It was found that thrombin downregulatesthe HMGB1-mediated induction of both TNF-α andIL-6 and inhibits the activation of both p38 MAPK and NF-κB inHUVECs pretreated with PC. Furthermore, thrombin inhibitedHMGB1-mediated hyperpermeability and leukocyte adhesion/migration by inhibiting the expression of cell adhesion moleculesin HUVECs if EPCR was occupied. Collectively, theseresults suggest the concept that thrombin can initiate proinflammatoryresponses in vascular endothelial cells through theactivation of PAR-1 may not hold true for normal vesselsexpressing EPCR under in vivo conditions. [BMB Reports 2013;46(11: 544-549

  20. HMGB1 – its role in tumor progression and anticancer therapy 

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    Ryszard Smolarczyk

    2012-11-01

    Full Text Available HMGB1 is an evolutionarily conserved protein with a wide spectrum of action. Its main receptors are RAGE and TLR found on the surface of immune system cells as well as endothelial cells. Although signaling pathways for both receptor groups are different, ultimately they both activate NFκB transcription factor which, in turn, activates genes encoding adhesion proteins, proinflammatory cytokines and proangiogenic factors. Inside cells, HMGB1 is found mainly in the cell nucleus, where it participates in replication, recombination, transcription and DNA repair processes. Following release into the extracellular space, HMGB1 becomes a proinflammatory cytokine which stimulates formation of new blood microvessels, enhances cell migration, activates the inflammatory condition and affects cell proliferation. HMGB1 protein also takes part in regeneration of damaged tissues and stimulates autophagy.HMGB1 plays a potential role in anticancer therapy. Increased amounts of HMGB1 in cancer cells and elevated levels in the bloodstream are noted among patients afflicted with various cancers. HMGB1 protects cells from apoptosis, as it affects telomere stability. HMGB1 also stimulates a number of proteins involved in proliferation of cancer cells and inhibits signals that control cell growth. Ability to arrest HMGB1 release from cells or to inhibit its activity appears to be a promising therapeutic approach. At present, several inhibitors of HMGB1 are known and can be used in anticancer therapy. 

  1. Ethyl pyruvate inhibits proliferation and induces apoptosis of hepatocellular carcinoma via regulation of the HMGB1–RAGE and AKT pathways

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Ping; Dai, Weiqi; Wang, Fan; Lu, Jie; Shen, Miao; Chen, Kan; Li, Jingjing; Zhang, Yan; Wang, Chengfen; Yang, Jing; Zhu, Rong; Zhang, Huawei; Zheng, Yuanyuan; Guo, Chuan-Yong, E-mail: guochuanyong@hotmail.com; Xu, Ling, E-mail: xuling606@sina.com

    2014-01-24

    Highlights: • Ethyl pyruvate inhibits liver cancer. • Promotes apoptosis. • Decreased the expression of HMGB1, p-Akt. - Abstract: Ethyl pyruvate (EP) was recently identified as a stable lipophilic derivative of pyruvic acid with significant antineoplastic activities. The high mobility group box-B1 (HMGB1)–receptor for advanced glycation end-products (RAGE) and the protein kinase B (Akt) pathways play a crucial role in tumorigenesis and development of many malignant tumors. We tried to observe the effects of ethyl pyruvate on liver cancer growth and explored its effects in hepatocellular carcinoma model. In this study, three hepatocellular carcinoma cell lines were treated with ethyl pyruvate. An MTT colorimetric assay was used to assess the effects of EP on cell proliferation. Flow cytometry and TUNEL assays were used to analyze apoptosis. Real-time PCR, Western blotting and immunofluorescence demonstrated ethyl pyruvate reduced the HMGB1–RAGE and AKT pathways. The results of hepatoma orthotopic tumor model verified the antitumor effects of ethyl pyruvate in vivo. EP could induce apoptosis and slow the growth of liver cancer. Moreover, EP decreased the expression of HMGB1, RAGE, p-AKT and matrix metallopeptidase-9 (MMP9) and increased the Bax/Bcl-2 ratio. In conclusion, this study demonstrates that ethyl pyruvate induces apoptosis and cell-cycle arrest in G phase in hepatocellular carcinoma cells, plays a critical role in the treatment of cancer.

  2. Expression and significance of HMGB1, TLR4 and NF-κB p65 in human epidermal tumors

    International Nuclear Information System (INIS)

    High mobility group protein box 1 (HMGB1) is a DNA binding protein located in nucleus. It is released into extracellular fluid where it acts as a novel proinflammatory cytokine which interacts with Toll like receptor 4 (TLR4) to activate nuclear factor-κB (NF-κB). This sequence of events is involved in tumor growth and progression. However, the effects of HMGB1, TLR4 and NF-κB on epidermal tumors remain unclear. Human epidermal tumor specimens were obtained from 96 patients. Immunohistochemistry was used to detect expression of HMGB1, TLR4 and NF-κB p65 in human epidermal tumor and normal skin specimens. Western blot analysis was used to detect the expression of NF-κB p65 in epithelial cell nuclei in human epidermal tumor and normal tissues. Immunohistochemistry and western blot analysis indicated a progressive but statistically significant increase in p65 expression in epithelial nuclei in benign seborrheic keratosis (SK), precancerous lesions (PCL), low malignancy basal cell carcinoma (BCC) and high malignancy squamous cell carcinoma (SCC) (P <0.01). The level of extracellular HMGB1 in SK was significantly higher than in normal skin (NS) (P <0.01), and was higher than in SCC but without statistical significance. The level of TLR4 on epithelial membranes of SCC cells was significantly higher than in SK, PCL, BCC and NS (P <0.01). There was a significant positive correlation between p65 expression in the epithelial nuclei and TLR4 expression on the epithelial cell membranes (r = 0.3212, P <0.01). These findings indicate that inflammation is intensified in parallel with increasing malignancy. They also indicate that the TLR4 signaling pathway, rather than HMGB1, may be the principal mediator of inflammation in high-grade malignant epidermal tumors. Combined detection of p65 in the epithelial nuclei and TLR4 on the epithelial membranes may assist the accurate diagnosis of malignant epidermal tumors

  3. High mobility group box-1 is phosphorylated by protein kinase C zeta and secreted in colon cancer cells

    International Nuclear Information System (INIS)

    Highlights: ► Specific enzyme for HMGB1 phosphorylation and its secretion is proposed. ► Inhibition of PKC-ζ leads to significant reduction of the secreted HMGB1. ► Phosphorylation of specific site of HMGB1 redirects its secretion in cancer cells. ► Activation of PKC-ζ in cancers explains the enhanced HMGB1 secretion. -- Abstract: High mobility group box-1 (HMGB1), a nuclear protein, is overexpressed and secreted in cancer cells. Phosphorylation on two different nuclear localization signal regions are known to be important for the nuclear-to-cytoplasmic transport and secretion of HMGB1. However, little is known about the biochemical mechanism of HMGB1 modifications and its subsequent secretion from cancer cells. To identify the specific enzyme and important sites for HMGB1 phosphorylation, we screened the protein kinase C (PKC) family in a colon cancer cell line (HCT116) for HMGB1 binding by pull-down experiments using a 3XFLAG-HMGB1 construct. Strong interactions between atypical PKCs (PKC-ζ, λ, and ι) and cytoplasmic HMGB1 were observed in HCT116 cells. We further identified the most critical PKC isotype that regulates HMGB1 secretion is PKC-ζ by using PKC inhibitors and siRNA experiments. The serine residues at S39, S53 and S181 of HMGB1 were related to enhancing HMGB1 secretion. We also demonstrated overexpression and activation of PKC-ζ in colon cancer tissues. Our findings suggest that PKC-ζ is involved in the phosphorylation of HMGB1, and the phosphorylation of specific serine residues in the nuclear localization signal regions is related to enhanced HMGB1 secretion in colon cancer cells.

  4. Expression of high mobility group box 1 in inflamed dental pulp and its chemotactic effect on dental pulp cells

    International Nuclear Information System (INIS)

    Highlights: • HMGB1 translocated from nucleus to cytoplasm during dental pulp inflammation. • HMGB1and its receptor RAGE were up-regulated in hDPCs under LPS stimulation. • HMGB1 enhanced hDPCs migration and induces cytoskeleton reorganization. • HMGB1 may play a critical role in dental pulp repair during inflamed state. - Abstract: High mobility group box 1 protein (HMGB1) is a chromatin protein which can be released extracellularly, eliciting a pro-inflammatory response and promoting tissue repair process. This study aimed to examine the expression and distribution of HMGB1 and its receptor RAGE in inflamed dental pulp tissues, and to assess its effects on proliferation, migration and cytoskeleton of cultured human dental pulp cells (DPCs). Our data demonstrated that cytoplasmic expression of HMGB1 was observed in inflamed pulp tissues, while HMGB1 expression was confined in the nuclei in healthy dental pulp. The mRNA expression of HMGB1 and RAGE were significantly increased in inflamed pulps. In in vitro cultured DPCs, expression of HMGB1 in both protein and mRNA level was up-regulated after treated with lipopolysaccharide (LPS). Exogenous HMGB1 enhanced DPCs migration in a dose-dependent manner and induced the reorganization of f-actin in DPCs. Our results suggests that HMGB1 are not only involved in the process of dental pulp inflammation, but also play an important role in the recruitment of dental pulp stem cells, promoting pulp repair and regeneration

  5. Expression of high mobility group box 1 in inflamed dental pulp and its chemotactic effect on dental pulp cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xufang, E-mail: xufang.zhang@student.qut.edu.au [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059 (Australia); Jiang, Hongwei, E-mail: jianghw@163.com [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Gong, Qimei, E-mail: gongqmei@gmail.com [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Fan, Chen, E-mail: c3.fan@student.qut.edu.au [Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059 (Australia); Huang, Yihua, E-mail: enu0701@163.com [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Ling, Junqi, E-mail: lingjq@mail.sysu.edu.cn [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China)

    2014-08-08

    Highlights: • HMGB1 translocated from nucleus to cytoplasm during dental pulp inflammation. • HMGB1and its receptor RAGE were up-regulated in hDPCs under LPS stimulation. • HMGB1 enhanced hDPCs migration and induces cytoskeleton reorganization. • HMGB1 may play a critical role in dental pulp repair during inflamed state. - Abstract: High mobility group box 1 protein (HMGB1) is a chromatin protein which can be released extracellularly, eliciting a pro-inflammatory response and promoting tissue repair process. This study aimed to examine the expression and distribution of HMGB1 and its receptor RAGE in inflamed dental pulp tissues, and to assess its effects on proliferation, migration and cytoskeleton of cultured human dental pulp cells (DPCs). Our data demonstrated that cytoplasmic expression of HMGB1 was observed in inflamed pulp tissues, while HMGB1 expression was confined in the nuclei in healthy dental pulp. The mRNA expression of HMGB1 and RAGE were significantly increased in inflamed pulps. In in vitro cultured DPCs, expression of HMGB1 in both protein and mRNA level was up-regulated after treated with lipopolysaccharide (LPS). Exogenous HMGB1 enhanced DPCs migration in a dose-dependent manner and induced the reorganization of f-actin in DPCs. Our results suggests that HMGB1 are not only involved in the process of dental pulp inflammation, but also play an important role in the recruitment of dental pulp stem cells, promoting pulp repair and regeneration.

  6. Expression and Effects of High-Mobility Group Box 1 in Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Xiaoao Pang

    2014-05-01

    Full Text Available We investigated the significance of high- mobility group box1 (HMGB1 and T-cell-mediated immunity and prognostic value in cervical cancer. HMGB1, forkhead/winged helix transcription factor p3 (Foxp3, IL-2, and IL-10 protein expression was analyzed in 100 cervical tissue samples including cervical cancer, cervical intraepithelial neoplasia (CIN, and healthy control samples using immunohistochemistry. Serum squamous cell carcinoma antigen (SCC-Ag was immunoradiometrically measured in 32 serum samples from 37 cases of squamous cervical cancer. HMGB1 and SCC-Ag were then correlated to clinicopathological characteristics. HMGB1 expression tends to increase as cervical cancer progresses and it was found to be significantly correlated to FIGO stage and lymph node metastasis. These findings suggest that HMGB1 may be a useful prognostic indicator of cervical carcinoma. In addition, there were significant positive relationships between HMGB1 and FOXP3 or IL-10 expression (both p < 0.05. In contrast, HMGB1 and IL-2 expression was negatively correlated (p < 0.05. HMGB1 expression may activate Tregs or facilitate Th2 polarization to promote immune evasion of cervical cancer. Elevated HMGB1 protein in cervical carcinoma samples was associated with a high recurrence of HPV infection in univariate analysis (p < 0.05. HMGB1 expression and levels of SCC-Ag were directly correlated in SCC (p < 0.05. Thus, HMGB1 may be a useful biomarker for patient prognosis and cervical cancer prediction and treatment.

  7. Delivery of the high-mobility group box 1 box A peptide using heparin in the acute lung injury animal models.

    Science.gov (United States)

    Song, Ji Hyun; Kim, Ji Yeon; Piao, Chunxian; Lee, Seonyeong; Kim, Bora; Song, Su Jeong; Choi, Joon Sig; Lee, Minhyung

    2016-07-28

    In this study, the efficacy of the high-mobility group box-1 box A (HMGB1A)/heparin complex was evaluated for the treatment of acute lung injury (ALI). HMGB1A is an antagonist against wild-type high-mobility group box-1 (wtHMGB1), a pro-inflammatory cytokine that is involved in ALIs. HMGB1A has positive charges and can be captured in the mucus layer after intratracheal administration. To enhance the delivery and therapeutic efficiency of HMGB1A, the HMGB1A/heparin complex was produced using electrostatic interactions, with the expectation that the nano-sized complex with a negative surface charge could efficiently penetrate the mucus layer. Additionally, heparin itself had an anti-inflammatory effect. Complex formation with HMGB1A and heparin was confirmed by atomic force microscopy. The particle size and surface charge of the HMGB1A/heparin complex at a 1:1 weight ratio were 113nm and -25mV, respectively. Intratracheal administration of the complex was performed into an ALI animal model. The results showed that the HMGB1A/heparin complex reduced pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, more effectively than HMGB1A or heparin alone. Hematoxylin and eosin staining confirmed the decreased inflammatory reaction in the lungs after delivery of the HMGB1A/heparin complex. In conclusion, the HMGB1A/heparin complex might be useful to treat ALI. PMID:27196743

  8. Binding of histone H1 to DNA is differentially modulated by redox state of HMGB1.

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    Eva Polanská

    Full Text Available HMGB1 is an architectural protein in chromatin, acting also as a signaling molecule outside the cell. Recent reports from several laboratories provided evidence that a number of both the intracellular and extracellular functions of HMGB1 may depend on redox-sensitive cysteine residues of the protein. In this study we demonstrate that redox state of HMGB1 can significantly modulate the ability of the protein to bind and bend DNA, as well as to promote DNA end-joining. We also report a high affinity binding of histone H1 to hemicatenated DNA loops and DNA minicircles. Finally, we show that reduced HMGB1 can readily displace histone H1 from DNA, while oxidized HMGB1 has limited capacity for H1 displacement. Our results suggested a novel mechanism for the HMGB1-mediated modulation of histone H1 binding to DNA. Possible biological consequences of linker histones H1 replacement by HMGB1 for the functioning of chromatin are discussed.

  9. Protective Effects of Berberine on Isoproterenol-Induced Acute Myocardial Ischemia in Rats through Regulating HMGB1-TLR4 Axis

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    Tianzhu Zhang

    2014-01-01

    Full Text Available Berberine, an isoquinoline alkaloid originally isolated from the Chinese herb Coptis chinensis (Huanglian, has been shown to display a wide array of pharmacological activities. The present study was to investigate the effects of berberine against myocardial ischemia produced in rats by isoproterenol. 50 male Sprague-Dawley rats were randomized equally into five groups: a control group, an untreated model group, berberine (30, 60 mg/kg treatment, or propranolol (30 mg/kg. Rats were treated for 12 days and then given isoproterenol, 85 mg/kg for 2 consecutive days by subcutaneous injection. ST-segment elevation was measured after the last administration. Serum levels of creatine kinase isoenzyme (CK-MB, lactate dehydrogenase (LDH, tumor necrosis factor-α (TNF-α, and interleukin-6 (IL-6 were measured after the rats were sacrificed. The hearts were excised for determining heart weight index, microscopic examination, high mobility group box 1 (HMGB1, toll-like receptor (TLR4, prodeath protein (Bax, antideath protein (Bcl-2, and tumor necrosis factor (TNF-α protein were determined by western blot. Berberine decreased the ST elevation induced by acute myocardial ischemia, and decreased serum levels of CK-MB, LDH, TNF-α, and IL-6. Berberine increased total superoxide dismutase (T-SOD activity and decreased malondialdehyde (MDA content in myocardial tissue. Berberine can regulate HMGB1-TLR4 axis to protect myocardial ischemia.

  10. The Role of HMGB1 Signaling Pathway in the Development and Progression of Hepatocellular Carcinoma: A Review

    Directory of Open Access Journals (Sweden)

    Xuanbin Wang

    2015-09-01

    Full Text Available The story of high mobility group protein B1 (HMGB1 in cancer is complicated and the function of HMGB1 in different cancers is uncertain. This review aims to retrieve literature regarding HMGB1 from English electronic resources, analyze and summarize the role of the HMGB1 signaling pathway in hepatocellular carcinoma (HCC, and provide useful information for carcinogenesis and progression of HCC. Results showed that HMGB1 could induce cell proliferation, differentiation, cell death, angiogenesis, metastasis, inflammation, and enhance immunofunction in in vitro and in vivo HCC models. HMGB1 and its downstream receptors RAGE, TLRs and TREM-1 may be potential anticancer targets. In conclusion, HMGB1 plays an important role in oncogenesis and represents a novel therapeutic target, which deserves further study.

  11. Cellular Mechanisms of High Mobility Group 1 (HMGB-1) Protein Action in the Diabetic Retinopathy

    OpenAIRE

    Santos, Andrea Rachelle C.; Dvoriantchikova, Galina; Li, Yiwen; Mohammad, Ghulam; Abu El-Asrar, Ahmed M.; Wen, Rong; Ivanov, Dmitry

    2014-01-01

    Diabetic retinopathy is one of the main microvascular complications of diabetes and remains one of the leading causes of blindness worldwide. Recent studies have revealed an important role of inflammatory and proangiogenic high mobility group 1 (HMGB-1) cytokine in diabetic retinopathy. To elucidate cellular mechanisms of HMGB-1 activity in the retina, we performed this study. The histological features of diabetic retinopathy include loss of blood-vessel pericytes and endothelial cells, as we...

  12. The presence of LC3B puncta and HMGB1 expression in malignant cells correlate with the immune infiltrate in breast cancer.

    Science.gov (United States)

    Ladoire, Sylvain; Enot, David; Senovilla, Laura; Ghiringhelli, François; Poirier-Colame, Vichnou; Chaba, Kariman; Semeraro, Michaela; Chaix, Marie; Penault-Llorca, Frédérique; Arnould, Laurent; Poillot, Marie Laure; Arveux, Patrick; Delaloge, Suzette; Andre, Fabrice; Zitvogel, Laurence; Kroemer, Guido

    2016-05-01

    Several cell-intrinsic alterations have poor prognostic features in human breast cancer, as exemplified by the absence of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β)-positive puncta in the cytoplasm (which indicates reduced autophagic flux) or the loss of nuclear HMGB1 expression by malignant cells. It is well established that breast cancer is under strong immunosurveillance, as reflected by the fact that scarce infiltration of the malignant lesion by CD8(+) cytotoxic T lymphocytes or comparatively dense infiltration by immunosuppressive cell types (such as FOXP3(+) regulatory T cells or CD68(+) tumor-associated macrophages), resulting in low CD8(+):FOXP3(+) or CD8(+):CD68(+) ratios, has a negative prognostic impact. Here, we reveal the surprising finding that cell-intrinsic features may influence the composition of the immune infiltrate in human breast cancer. Thus, the absence of LC3B puncta is correlated with intratumoral (but not peritumoral) infiltration by fewer CD8(+) cells and more FOXP3(+) or CD68(+) cells, resulting in a major drop in the CD8(+):FOXP3(+) or CD8(+):CD68(+) ratios. Moreover, absence of HMGB1 expression in nuclei correlated with a general drop in all immune effectors, in particular FOXP3(+) and CD68(+) cells, both within the tumor and close to it. Combined analysis of LC3B puncta and HMGB1 expression allowed for improved stratification of patients with respect to the characteristics of their immune infiltrate as well as overall and metastasis-free survival. It can be speculated that blocked autophagy in, or HMGB1 loss from, cancer cells may favor tumor progression due to their negative impact on anticancer immunosurveillance. PMID:26979828

  13. Overexpression of Receptor for Advanced Glycation End Products and High-Mobility Group Box 1 in Human Dental Pulp Inflammation

    Directory of Open Access Journals (Sweden)

    Salunya Tancharoen

    2014-01-01

    Full Text Available High mobility group box 1 (HMGB1, a nonhistone DNA-binding protein, is released into the extracellular space and promotes inflammation. HMGB1 binds to related cell signaling transduction receptors, including receptor for advanced glycation end products (RAGE, which actively participate in vascular and inflammatory diseases. The aim of this study was to examine whether RAGE and HMGB1 are involved in the pathogenesis of pulpitis and investigate the effect of Prevotella intermedia (P. intermedia lipopolysaccharide (LPS on RAGE and HMGB1 expression in odontoblast-like cells (OLC-1. RAGE and HMGB1 expression levels in clinically inflamed dental pulp were higher than those in healthy dental pulp. Upregulated expression of RAGE was observed in odontoblasts, stromal pulp fibroblasts-like cells, and endothelial-like cell lining human pulpitis tissue. Strong cytoplasmic HMGB1 immunoreactivity was noted in odontoblasts, whereas nuclear HMGB1 immunoreactivity was seen in stromal pulp fibroblasts-like cells in human pulpitis tissue. LPS stimulated OLC-1 cells produced HMGB1 in a dose-dependent manner through RAGE. HMGB1 translocation towards the cytoplasm and secretion from OLC-1 in response to LPS was inhibited by TPCA-1, an inhibitor of NF-κB activation. These findings suggest that RAGE and HMGB1 play an important role in the pulpal immune response to oral bacterial infection.

  14. High mobility group box1 protein is involved in acute inflammation induced by Clostridium difficile toxin A.

    Science.gov (United States)

    Liu, Ji; Zhang, Bei-Lei; Sun, Chun-Li; Wang, Jun; Li, Shan; Wang, Ju-Fang

    2016-06-01

    High mobility group box1 (HMGB1), as a damage-associated inflammatory factor, contributes to the pathogenesis of numerous chronic inflammatory and autoimmune diseases. In this study, we explored the role of HMGB1 in CDI (Clostridium difficile infection) by in vivo and in vitro experiments. Our results showed that HMGB1 might play an important role in the acute inflammatory responses to C. difficile toxin A (TcdA), affect early inflammatory factors, and induce inflammation via the HMGB1-TLR4 pathway. Our study provides the essential information for better understanding the molecular mechanisms of CDI and the potential new therapeutic strategies for the treatment of this infection. PMID:27151296

  15. A high-mobility group box 1 that binds to DNA, enhances pro-inflammatory activity, and acts as an anti-infection molecule in black rockfish, Sebastes schlegelii.

    Science.gov (United States)

    Xin-Peng, Zhao; Yong-Hua, Hu; Yong, Liu; Jing-Jing, Wang; Guang-Hua, Wang; Ren-Jie, Wang; Min, Zhang

    2016-09-01

    High-mobility group box (HMGB) 1 is a chromosomal protein that plays critical roles in DNA transcription, replication and repair. In addition, HMGB1 functions as a pro-inflammatory molecule in many vertebrates and invertebrates. In teleosts, very limited studies of HMGB1 have been reported. In this study, we identified a HMGB1 homologue (SsHMGB1) from black rockfish (Sebastes schlegelii) and analyzed its structure, expression and biological function. The open reading frame of SsHMGB1 is 621 bp, with a 5'-untranslated region (UTR) of 62 bp and a 3'-UTR of 645 bp. SsHMGB1 contains two typical HMG boxes and an acidic C-terminal tail. The deduced amino acid sequence of SsHMGB1 shares the highest overall identity (89.4%) with the HMGB1 of Anoplopoma fimbria. The expression of SsHMGB1 occurred in multiple tissues and was highest in the brain. Moreover, the mRNA level of SsHMGB1 in head kidney (HK) macrophages could be induced by Listonella anguillarum in a time-dependent manner. Recombinant SsHMGB1 purified from Escherichia coli (i) bound DNA fragments in a dose-dependent manner; and (ii) induced the expression of cytokines in HK macrophages, including a significant increase in TNF-α activity and enhanced mRNA level of TNF13B and IL-1 β, which are known to be involved in antibacterial defense; moreover, (iii) significantly improved the macrophage bactericidal activity together with reduced pathogen dissemination and replication of bacteria in fish kidney. These results indicated that SsHMGB1 is a novel HMGB1 that possesses apparent immunoregulatory properties and is likely to be involved in fighting bacterial infection. PMID:27492120

  16. DNA-HMGB1 interaction: The nuclear aggregates of polyamine mediation.

    Science.gov (United States)

    Iacomino, Giuseppe; Picariello, Gianluca; Sbrana, Francesca; Raiteri, Roberto; D'Agostino, Luciano

    2016-10-01

    Nuclear aggregates of polyamines (NAPs) are supramolecular compounds generated by the self-assembly of protonated nuclear polyamines (spermine, spermidine and putrescine) and phosphate ions. In the presence of genomic DNA, the hierarchical process of self-structuring ultimately produces nanotube-like polymers that envelop the double helix. Because of their modular nature and their aggregation-disaggregation dynamics, NAPs confer plasticity and flexibility to DNA. Through the disposition of charges, NAPs also enable a bidirectional stream of information between the genome and interacting moieties. High mobility group (HMG) B1 is a non-histone chromosomal protein that binds to DNA and that influences multiple nuclear processes. Because genomic DNA binds to either NAPs or HMGB1 protein, we explored the ability of in vitro self-assembled NAPs (ivNAPs) to mediate the DNA-HMGB1 interaction. To this end, we structured DNA-NAPs-HMGB1 and DNA-HMGB1-NAPs ternary complexes in vitro through opportune sequential incubations. Mobility shift electrophoresis and atomic force microscopy showed that the DNA-ivNAPs-HGMB1 complex had conformational assets supposedly more suitable those of the DNA-HGMB1-ivNAPs to comply with the physiological and functional requirements of DNA. Our findings indicated that ivNAPs act as mediators of the DNA-HMGB1 interaction. PMID:27451951

  17. Functional characterization of the ER stress induced X-box-binding protein-1 (Xbp-1 in the porcine system

    Directory of Open Access Journals (Sweden)

    Jin Dong-Il

    2011-05-01

    Full Text Available Abstract Background The unfolded protein response (UPR is an evolutionary conserved adaptive reaction for increasing cell survival under endoplasmic reticulum (ER stress conditions. X-box-binding protein-1 (Xbp1 is a key transcription factor of UPR that activates genes involved in protein folding, secretion, and degradation to restore ER function. The UPR induced by ER stress was extensively studied in diseases linked to protein misfolding and aggregations. However, in the porcine system, genes in the UPR pathway were not investigated. In this study, we isolated and characterized the porcine Xbp1 (pXbp1 gene in ER stress using porcine embryonic fibroblast (PEF cells and porcine organs. ER stress was induced by the treatment of tunicamycin and cell viability was investigated by the MTT assay. For cloning and analyzing the expression pattern of pXbp1, RT-PCR analysis and Western blot were used. Knock-down of pXbp1 was performed by the siRNA-mediated gene silencing. Results We found that the pXbp1 mRNA was the subject of the IRE1α-mediated unconventional splicing by ER stress. Knock-down of pXbp1 enhanced ER stress-mediated cell death in PEF cells. In adult organs, pXbp1 mRNA and protein were expressed and the spliced forms were detected. Conclusions It was first found that the UPR mechanisms and the function of pXbp1 in the porcine system. These results indicate that pXbp1 plays an important role during the ER stress response like other animal systems and open a new opportunity for examining the UPR pathway in the porcine model system.

  18. High prevalence of Y-box protein-1/p18 fragment in plasma of patients with malignancies of different origin

    International Nuclear Information System (INIS)

    Expression of the cold shock protein Y-box protein 1 (YB-1) is associated with deleterious outcome in various malignant diseases. Our group recently showed that the detection of an 18 kDa YB-1 fragment (YB-1/p18) in human plasma identifies patients with malignant diseases. We now tested the prevalence, clinical, and diagnostic value of YB-1/p18 detection in common tumors. A newly established monoclonal YB-1 antibody was used to detect YB-1/p18 by immunoblotting in plasma samples from 151 unselected tumor patients, alongside established tumor markers and various diagnostic measures, during evaluation for a cancerous disease and in follow-up studies after therapeutic interventions. Circulating YB-1/p18 was detected in 78% of patients having a tumor disease. YB-1/p18 positivity was highly prevalent in all examined malignancies, including lung cancer (32/37; 87%), breast cancer (7/10; 70%), cancer of unknown primary (CUP; 5/5, 100%) or hematological malignancies (42/62; 68%). Positivity for YB-1/p18 was independent of other routine laboratory parameters, tumor stage, or histology. In comparison to 13 established tumor markers (cancer antigens 15–3, 19–9, 72–4, and 125; carcinoembryonic antigen; cytokeratin fragments 21–1; neuron-specific enolase; alpha-fetoprotein; beta-2-microglobulin; squamous cell carcinoma antigen; thymidine kinase; tissue polypeptide antigen; pro-gastrin-releasing peptide), YB-1/p18 detection within serum samples was the most sensitive general parameter identifying malignant disorders. YB-1/p18 concentrations altered during therapeutic interventions, but did not predict prognosis. Plasma YB-1/p18 detection has a high specific prevalence in malignancies, thereby providing a novel tool for cancer screening independent of the tumor origin

  19. MicroRNA-24 inhibits high glucose-induced vascular smooth muscle cell proliferation and migration by targeting HMGB1.

    Science.gov (United States)

    Yang, Jian; Chen, Lihua; Ding, Jiawang; Fan, Zhixing; Li, Song; Wu, Hui; Zhang, Jing; Yang, Chaojun; Wang, Huibo; Zeng, Ping; Yang, Jun

    2016-07-25

    Dysfunction of vascular smooth muscle cells (VSMCs) performs a key role in the pathogenesis of diabetic vascular disease. Recent studies have reported that microRNA-24 (miR-24) may be implicated in diabetes and atherosclerotic vascular diseases. This study was designed to explore the role of miR-24 on VSMC proliferation and migration under high glucose conditions mimicking diabetes, and reveal the underlying mechanism. VSMCs were isolated from rat thoracic aortas, treated with normal glucose (NG, 5.5mM) or high glucose (HG, 30mM) during an incubation period. Cell viability, proliferation and migration were detected by trypan blue staining, BrdU incorporation assay and transwell chamber assay. Gene and protein expression were analyzed by qRT-PCR and Western blot respectively. We also used electrophoretic mobility shift assay (EMSA) to detect nuclear factor kappaB (NF-κB) DNA binding. TNF-α and IL-6 levels were determined by enzyme-linked immunosorbent assay. The results showed that adenovirus-mediated miR-24 overexpression significantly inhibited HG-stimulated VSMC proliferation and migration. Meanwhile, high mobility group box-1 (HMGB1) as a target of miR-24, was also markedly suppressed after miR-24 transfection. Additionally, NF-κB nuclear translocation and DNA binding, TNF-α and IL-6 production were all decreased associated with the down-regulation of HMGB1. The above data indicated that miR-24 is a crucial regulator of high glucose-induced proliferation and migration in VSMCs, and suggests that elevation of miR-24 in vascular system may be a novel therapeutic strategy to prevent the development of diabetic atherosclerosis. PMID:27085480

  20. Involvement of spliced X-box binding protein 1 in renal fibrosis induced by unilateral ureteral obstruction in mice.

    Science.gov (United States)

    Shao, D-C; Miao, Nai-Jun; Li, Jia-Jia

    2016-04-25

    Endoplasmic reticulum (ER) stress is involved in the process of kidney fibrosis. Spliced X-box binding protein 1 (XBP1S) is the key mediator of ER stress while its role in fibrosis is still poorly understood. This study was aimed to investigate the role of XBP1S in renal fibrosis and evaluate whether valsartan could alleviate fibrosis through XBP1S. Renal interstitial fibrosis was induced by unilateral ureteral obstruction (UUO) in C57BL/6 mice, and UUO mice were daily administered with valsartan (20 mg/kg) through oral gavage. After 7 days of UUO, at euthanasia, left kidney was collected to examine the histological alteration by using haematoxylin-eosin staining, Masson's trichrome staining, Sirius red staining and immunohistochemistry. Western blot was used to assess XBP1S, targets of XBP1S, fibronectin, α-SMA, BAX and BCL2 protein levels. Real-time polymerase chain reaction was performed to assess NADPH oxidase subunits p47-phox and p67-phox mRNA levels. The results showed that XBP1S expression was decreased by about 70% in the UUO mice compared with that in sham mice (P < 0.01), which was reversed by valsartan administration (P < 0.05). Meanwhile, UUO-induced renal interstitial fibrosis was attenuated by valsartan treatment. In addition, the protein levels of fibronectin and α-SMA were upregulated by UUO induction (P < 0.01), and valsartan administration inhibited the protein levels of fibronectin and α-SMA in UUO mice (P < 0.05). Western blot analysis showed that the ratio of BAX to BCL2 protein level was increased in UUO model compared with that in sham mice, and the increment also was diminished by valsartan treatment (P < 0.05). Finally, UUO-induced mRNA levels of p47-phox and p67-phox were significantly attenuated by valsartan administration (P < 0.05). These results showed that valsartan at least partly restores renal interstitial fibrosis by enhancing XBP1S activation through inhibiting oxidative stress and apoptosis in the UUO mice. These results

  1. Correlation between serum high-mobility group box-1 levels and high-sensitivity C-reactive protein and troponin I in patients with coronary artery disease

    OpenAIRE

    YAO, HENG-CHEN; ZHAO, AI-PING; HAN, QIAN-FENG; Wu, Lei; YAO, DAO-KUO; Wang, Le-Xin

    2013-01-01

    The aim of this study was to evaluate the correlation between levels of serum high-mobility group box-1 (HMGB1) and high-sensitivity C-reactive protein (hs-CRP) and cardiac troponin I in patients with coronary artery disease. The levels of serum HMGB1, hs-CRP and cardiac troponin I were measured in 98 patients with coronary artery disease and in 30 healthy subjects. The correlation between serum HMGB1 levels and hs-CRP and cardiac troponin I levels was analyzed. Serum HMGB1 levels in patients...

  2. Hypoxia induced HMGB1 and mitochondrial DNA interactions mediate tumor growth in hepatocellular carcinoma through Toll Like Receptor 9

    Science.gov (United States)

    Liu, Yao; Yan, Wei; Tohme, Samer; Chen, Man; Fu, Yu; Tian, Dean; Lotze, Michael; Tang, Daolin; Tsung, Allan

    2015-01-01

    Background and aims The mechanisms of hypoxia-induced tumor growth remain unclear. Hypoxia induces intracellular translocation and release of a variety of damage associated molecular patterns (DAMPs) such as nuclear HMGB1 and mitochondrial DNA (mtDNA). In inflammation, Toll-like receptor (TLR)-9 activation by DNA-containing immune complexes has been shown to be mediated by HMGB1. We thus hypothesize that HMGB1 binds mtDNA in the cytoplasm of hypoxic tumor cells and promotes tumor growth through activating TLR9 signaling pathways. Methods C57BL6 mice were injected with Hepa1-6 cancer cells. TLR9 and HMGB1 were inhibited using shRNA or direct antagonists. Huh7 and Hepa1-6 cancer cells were investigated in vitro to investigate how the interaction of HMGB1 and mtDNA activates TLR9 signaling pathways. Results During hypoxia, HMGB1 translocates from the nucleus to the cytosol and binds to mtDNA released from damaged mitochondria. This complex subsequently activates TLR9 signaling pathways to promote tumor cell proliferation. Loss of HMGB1 or mtDNA leads to a defect in TLR9 signaling pathways in response to hypoxia, resulting in decreased tumor cell proliferation. Also, the addition of HMGB1 and mtDNA leads to the activation of TLR-9 and subsequent tumor cell proliferation. Moreover, TLR9 is overexpressed in both hypoxic tumor cells in vitro and in human hepatocellular cancer (HCC) specimens; and, knockdown of either HMGB1 or TLR9 from HCC cells suppressed tumor growth in vivo after injection in mice. Conclusions Our data reveals a novel mechanism by which the interactions of HMGB1 and mtDNA activate TLR9 signaling during hypoxia to induce tumor growth. PMID:25681553

  3. HMGB1 induces an inflammatory response in endothelial cells via the RAGE-dependent endoplasmic reticulum stress pathway

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Ying [Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha 410078 (China); Li, Shu-Jun [Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410078 (China); Yang, Jian [Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha 410078 (China); Qiu, Yuan-Zhen [Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha 410078 (China); Chen, Fang-Ping, E-mail: xychenfp@163.com [Department of Hematology, Xiangya Hospital, Central South University, Changsha 410078 (China)

    2013-09-06

    Highlights: •Mechanisms of inflammatory response induced by HMGB1 are incompletely understood. •We found that endoplasmic reticulum stress mediate the inflammatory response induced by HMGB1. •RAGE-mediated ERS pathways are involved in those processes. •We reported a new mechanism for HMGB1 induced inflammatory response. -- Abstract: The high mobility group 1B protein (HMGB1) mediates chronic inflammatory responses in endothelial cells, which play a critical role in atherosclerosis. However, the underlying mechanism is unknown. The goal of our study was to identify the effects of HMGB1 on the RAGE-induced inflammatory response in endothelial cells and test the possible involvement of the endoplasmic reticulum stress pathway. Our results showed that incubation of endothelial cells with HMGB1 (0.01–1 μg/ml) for 24 h induced a dose-dependent activation of endoplasmic reticulum stress transducers, as assessed by PERK and IRE1 protein expression. Moreover, HMGB1 also promoted nuclear translocation of ATF6. HMGB1-mediated ICAM-1 and P-selectin production was dramatically suppressed by PERK siRNA or IRE1 siRNA. However, non-targeting siRNA had no such effects. HMGB1-induced increases in ICAM-1 and P-selectin expression were also inhibited by a specific eIF2α inhibitor (salubrinal) and a specific JNK inhibitor (SP600125). Importantly, a blocking antibody specifically targeted against RAGE (anti-RAGE antibody) decreased ICAM-1, P-selectin and endoplasmic reticulum stress molecule (PERK, eIF2α, IRE1 and JNK) protein expression levels. Collectively, these novel findings suggest that HMGB1 promotes an inflammatory response by inducing the expression of ICAM-1 and P-selectin via RAGE-mediated stimulation of the endoplasmic reticulum stress pathway.

  4. Macrophage activation by factors released from acetaminophen-injured hepatocytes: Potential role of HMGB1

    International Nuclear Information System (INIS)

    Toxic doses of acetaminophen (AA) cause hepatocellular necrosis. Evidence suggests that activated macrophages contribute to the pathogenic process; however, the factors that activate these cells are unknown. In these studies, we assessed the role of mediators released from AA-injured hepatocytes in macrophage activation. Treatment of macrophages with conditioned medium (CM) collected 24 hr after treatment of mouse hepatocytes with 5 mM AA (CM-AA) resulted in increased production of reactive oxygen species (ROS). Macrophage expression of heme oxygenase-1 (HO-1) and catalase mRNA was also upregulated by CM-AA, as well as cyclooxygenase (COX)-2 and 12/15-lipoxygenase (LOX). CM-AA also upregulated expression of the proinflammatory chemokines, MIP-1α and MIP-2. The effects of CM-AA on expression of COX-2, MIP-1α and MIP-2 were inhibited by blockade of p44/42 MAP kinase, suggesting a biochemical mechanism mediating macrophage activation. Hepatocytes injured by AA were found to release HMGB1, a potent macrophage activator. This was inhibited by pretreatment of hepatocytes with ethyl pyruvate (EP), which blocks HMGB1 release. EP also blocked CM-AA induced ROS production and antioxidant expression, and reduced expression of COX-2, but not MIP-1α or MIP-2. These findings suggest that HMGB1 released by AA-injured hepatocytes contributes to macrophage activation. This is supported by our observation that expression of the HMGB1 receptor RAGE is upregulated in macrophages in response to CM-AA. These data indicate that AA-injured hepatocytes contribute to the inflammatory environment in the liver through the release of mediators such as HMGB1. Blocking HMGB1/RAGE may be a useful approach to limiting classical macrophage activation and AA-induced hepatotoxicity. - Research Highlights: → These studies analyze macrophage activation by mediators released from acetaminophen-damaged hepatocytes. → Factors released from acetaminophen-injured hepatocytes induce macrophage ROS

  5. High-mobility group box-1 in sterile inflammation.

    Science.gov (United States)

    Tsung, A; Tohme, S; Billiar, T R

    2014-11-01

    High-mobility group box 1 (HMGB1) was originally defined as a ubiquitous nuclear protein, but it was later determined that the protein has different roles both inside and outside of cells. Nuclear HMGB1 regulates chromatin structure and gene transcription, whereas cytosolic HMGB1 is involved in inflammasome activation and autophagy. Extracellular HMGB1 has drawn attention because it can bind to related cell signalling transduction receptors, such as the receptor for advanced glycation end products, Toll-like receptor (TLR)2, TLR4 and TLR9. It also participates in the development and progression of a variety of diseases. HMGB1 is actively secreted by stimulation of the innate immune system, and it is passively released by ischaemia or cell injury. This review focuses on the important role of HMGB1 in the pathogenesis of acute and chronic sterile inflammatory conditions. Strategies that target HMGB1 have been shown to significantly decrease inflammation in several disease models of sterile inflammation, and this may represent a promising clinical approach for treatment of certain conditions associated with sterile inflammation. PMID:24935761

  6. HMGB1 Inhibition During Zymosan-Induced Inflammation: The Potential Therapeutic Action of Riboflavin.

    Science.gov (United States)

    Mazur-Bialy, Agnieszka Irena; Pocheć, Ewa

    2016-04-01

    Sepsis, also known as systemic inflammatory response syndrome, is a life-threatening condition caused by a pathogenic agent and leading to multiple organ dysfunction syndrome. One of the factors responsible for the excessive intensification of the inflammatory response in the course of inflammation is high-mobility group protein B1 (HMGB1). HMG-1 is a nuclear protein which, after being released to the intercellular space, has a highly pro-inflammatory effect and acts as a late mediator of lethal damage. The purpose of this study was to examine whether the anti-inflammatory action of riboflavin is accompanied by inhibition of HMGB1 release during peritoneal inflammation and zymosan stimulation of macrophages. Peritonitis was induced in male BALB/c and C57BL/6J mice via intraperitoneal injection of zymosan (40 mg/kg). RAW 264.7 macrophages were activated with zymosan (250 µg/ml). Riboflavin (mice, 50 mg/kg; RAW 264.7, 25 µg/ml) was administered 30 min before zymosan, simultaneously with, or 2, 4, 6 h after zymosan. Additionally, mRNA expression of HMGB1 and its intracellular and serum levels were evaluated. The research showed that riboflavin significantly reduces both the expression and the release of HMGB1; however, the effect of riboflavin was time-dependent. The greatest efficacy was found when riboflavin was given 30 min prior to zymosan, and also 2 and 4 h (C57BL/6J; RAW 264.7) or 4 and 6 h (BALB/c) after zymosan. Research showed that riboflavin influences the level of HMGB1 released in the course of inflammation; however, further study is necessary to determine its mechanisms of action. PMID:26445809

  7. 汉防己甲素对钛颗粒刺激 PBMC 表达 HMGB1的研究%Study on the Expression of HMGB1 in PBMC Stimulated by Tetrandrine on Titanium Particles

    Institute of Scientific and Technical Information of China (English)

    赵丽; 马杏娟; 赵静

    2016-01-01

    Objective The release of HMGB1 of Tetrandrine n on titanium particles stimulate blood mononuclear cell (PBMC) was approached,to supply documentation for prevention artificial knee joint aseptic loosening. Methods The cells were divided into 4 groups ,cells in group 1 were added with nothing, while cells in group 2,3,and 4 were added with titanium particles(0.1%),and the cells in group 3,4 were added with Tetrandrine (1 g/ml,10 g/ml).The contents of HMGB1 protein and HMGB1Mrna of the 4 groups were respectively detected through enzyme linked immunosorbent assay (ELISA)and polymerase chain reaction (PCR) after culturing for 48 hours. Results ①Effect of titanium particles suspension concentration on HMGB1expression: There were statistical differences in the contents of HMGB1 protein and HMGB1 m RNA of macrophages among the 2 groups ( =2600.42,<0.01; =516.55,<0.01).② Effect of titanium particles and Tetrandrine on the expression of HMGB1 protein and HMGB1 m RNA : There were statistical differences in the contents of HMGB1 protein and HMGB1 m RNA of macrophages among the 2 group and 3/4 group ( =17.73,<0.01; =723.45,<0.01); There were statistical differences among the 1 group and 3/4 group ( =2153.03,<0.01; F=1177.804,<0.01).Conclusion Wear particles from joint prosthesis can up-regulate the expression of HMGB1 ,which leads to bone absorption and osteolysis. Tetrandrine could realsed the expression of HMGB1, which would be used to patients for prevention artificial knee joint aseptic loosening.%目的探讨汉防己甲素对钛颗粒刺激人血单个核细胞(PBMC)释放 HMGB1的影响,为临床提供防治人工膝关节无菌松动提供证据。方法将按照密度梯度方法提纯人血单个核细胞分为四组,1组为阴性对照组:不做任何处理;2组为阳性对照组:PBMC+0.1%钛颗粒;3组为低浓度汉防己甲素组:PBMC+0.1%钛颗粒+汉防己甲素1g/ml;4组为高浓度汉防己甲素组:PBMC+0.1%钛颗粒+汉防己甲素10 g

  8. Escape of HIV-1-infected dendritic cells from TRAIL-mediated NK cell cytotoxicity during NK-DC cross-talk--a pivotal role of HMGB1.

    Directory of Open Access Journals (Sweden)

    Marie-Thérèse Melki

    2010-04-01

    Full Text Available Early stages of Human Immunodeficiency Virus-1 (HIV-1 infection are associated with local recruitment and activation of important effectors of innate immunity, i.e. natural killer (NK cells and dendritic cells (DCs. Immature DCs (iDCs capture HIV-1 through specific receptors and can disseminate the infection to lymphoid tissues following their migration, which is associated to a maturation process. This process is dependent on NK cells, whose role is to keep in check the quality and the quantity of DCs undergoing maturation. If DC maturation is inappropriate, NK cells will kill them ("editing process" at sites of tissue inflammation, thus optimizing the adaptive immunity. In the context of a viral infection, NK-dependent killing of infected-DCs is a crucial event required for early elimination of infected target cells. Here, we report that NK-mediated editing of iDCs is impaired if DCs are infected with HIV-1. We first addressed the question of the mechanisms involved in iDC editing, and we show that cognate NK-iDC interaction triggers apoptosis via the TNF-related apoptosis-inducing ligand (TRAIL-Death Receptor 4 (DR4 pathway and not via the perforin pathway. Nevertheless, once infected with HIV-1, DC(HIV become resistant to NK-induced TRAIL-mediated apoptosis. This resistance occurs despite normal amounts of TRAIL released by NK cells and comparable DR4 expression on DC(HIV. The escape of DC(HIV from NK killing is due to the upregulation of two anti-apoptotic molecules, the cellular-Flice like inhibitory protein (c-FLIP and the cellular inhibitor of apoptosis 2 (c-IAP2, induced by NK-DC(HIV cognate interaction. High-mobility group box 1 (HMGB1, an alarmin and a key mediator of NK-DC cross-talk, was found to play a pivotal role in NK-dependent upregulation of c-FLIP and c-IAP2 in DC(HIV. Finally, we demonstrate that restoration of DC(HIV susceptibility to NK-induced TRAIL killing can be obtained either by silencing c-FLIP and c-IAP2 by specific

  9. Plasma high-mobility group box 1 levels predict mortality after ST-segment elevation myocardial infarction

    DEFF Research Database (Denmark)

    Sørensen, Morten V; Pedersen, Sune; Møgelvang, Rasmus;

    2011-01-01

    We evaluated the potential association between plasma high-mobility group box 1 (HMGB1) levels and outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention....

  10. HMGB1 interacts with human topoisomerase IIalpha and stimulates its catalytic activity

    Czech Academy of Sciences Publication Activity Database

    Štros, Michal; Bačíková, Alena; Muselíková Polanská, Eva; Štokrová, Jitka; Strauss, F.

    2007-01-01

    Roč. 35, č. 15 (2007), s. 5001-5013. ISSN 0305-1048 R&D Projects: GA ČR(CZ) GA204/05/2031; GA AV ČR(CZ) IAA400040702 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702; CEZ:AV0Z50520514; CEZ:AV0Z50520701 Keywords : HMGB1 * DNA topoisomerase IIalpha * DNA repair Subject RIV: BO - Biophysics Impact factor: 6.954, year: 2007

  11. High mobility group box-1 protein in patients with suspected community-acquired infections and sepsis: a prospective study

    DEFF Research Database (Denmark)

    Gaïni, Shahin; Pedersen, Svend Stenvang; Koldkjaer, Ole Graesbøll;

    2008-01-01

    INTRODUCTION: Sepsis is a serious condition with a significant morbidity and mortality. New insight into the immunopathogenesis of sepsis could promote the development of new strategies for diagnosis and therapy. High mobility group box-1 protein (HMGB1) has been known for many years as a nuclear...... a department of internal medicine were included in the study in a prospective manner. Demographic data, comorbidity, routine biochemistry, microbiological data, infection focus, severity score, and mortality on day 28 were recorded. Plasma and serum were sampled at the time of admission. HMGB1...... non-infected patients and all infected patients, the area under the curve for HMGB1 was 0.59 (P < 0.0001). HMGB1 correlated only weakly to levels of white blood cell count, neutrophils, C-reactive protein, interleukin-6, procalcitonin, and lipopolysaccharide-binding protein (P < 0.001). HMGB1 did not...

  12. Interaction between DNA and chromosomal proteins HMGB1 and H1 studied by IR/VCD spectroscopy

    Science.gov (United States)

    Polyanichko, Alexander; Chikhirzhina, Elena

    2013-07-01

    Binary complexes of calf thymus DNA with calf thymus non-histone chromosomal protein HMGB1 and linker histone H1 were studied using FTIR/VCD spectroscopy. The spectroscopic data showed that the interaction of the protein HMGB1 and histone H1 with DNA resulted in formation of two different types of the macromolecular complexes. Histone H1 retained its native structure even at high concentrations and induced DNA condensation upon binding at the protein to DNA ratio r (w/w) in the complex r ⩾ 0.3. HMGB1 demonstrated the ability to form soluble complexes at considerably higher protein to DNA ratios. The obtained data suggest that the HMGB1 also participated in the protein-protein interactions via its C-terminal domain.

  13. High-mobility group box 1 expression and lymph node metastasis in intrahepatic cholangiocarcinoma

    Science.gov (United States)

    Xu, Yun-Fei; Ge, Fu-Jun; Han, Bo; Yang, Xiao-Qing; Su, Hong; Zhao, An-Cheng; Zhao, Ming-Hong; Yang, Yu-Bao; Yang, Jie

    2015-01-01

    AIM: To evaluate the prognostic value of high-mobility group box 1 (HMGB1) expression in intrahepatic cholangiocarcinoma (IHCC) and the possible underlying mechanism. METHODS: Tissue microarray was constructed from 65 IHCC patients. Immunohistochemistry was performed to validate expression of HMGB1 and Vascular endothelial growth factor C (VEGF-C). Real-time PCR and Western blot analyses were used to study transcript and protein levels. The interaction between HMGB1 and VEGF-C was evaluated by siRNA, real-time PCR, and enzyme-linked immuno assays. The correlation between HMGB1 expression and other clinicopathologic parameters was analyzed by χ2 test, and the univariate as well as multivariate analyses were accomplished by Kaplan-Meier method and Cox-regression model, respectively. RESULTS: Overall, overexpression of HMGB1 was found in 38/65 (58.8%) IHCCs, whereas VEGF-C overexpression was present in 30/65 (46.2%) cases. Overexpression of HMGB1 was significantly correlated with lymphatic microvessel density (P = 0.031, r = 0.268) and VEGF-C expression (P = 0.041, r = 0.254). With univariate analysis, both HMGB1 (P = 0.001) and VEGF-C (P = 0.004) were identified to be significantly associated with overall survival rate. Multivariate analysis indicated that HMGB1 could be served as an unfavorable independent prognostic factor in IHCCs (P = 0.005). siRNA knockdown of HMGB1 inhibited transforming growth factor-β-induced epithelial-mesenchymal transition (EMT) by elevating E-Cadherin expression and reducing expression of N-Cadherin, Vimentin and Snail in RBE cells. Further in vitro study revealed that HMGB1 silencing significantly decreased the level of VEGF-C, whereas the recombinant HMGB1 increased the VEGF-C level in RBE cells (both P < 0.05), which suggested that HMGB1 could promote lymphatic microvessel density, and subsequently lymphatic invasion, via promoting VEGF-C expression. CONCLUSION: Our results define an important role of HMGB1 in the progression of

  14. Aspirin's Active Metabolite Salicylic Acid Targets High Mobility Group Box 1 to Modulate Inflammatory Responses.

    Science.gov (United States)

    Choi, Hyong Woo; Tian, Miaoying; Song, Fei; Venereau, Emilie; Preti, Alessandro; Park, Sang-Wook; Hamilton, Keith; Swapna, G V T; Manohar, Murli; Moreau, Magali; Agresti, Alessandra; Gorzanelli, Andrea; De Marchis, Francesco; Wang, Huang; Antonyak, Marc; Micikas, Robert J; Gentile, Daniel R; Cerione, Richard A; Schroeder, Frank C; Montelione, Gaetano T; Bianchi, Marco E; Klessig, Daniel F

    2015-01-01

    Salicylic acid (SA) and its derivatives have been used for millennia to reduce pain, fever and inflammation. In addition, prophylactic use of acetylsalicylic acid, commonly known as aspirin, reduces the risk of heart attack, stroke and certain cancers. Because aspirin is rapidly de-acetylated by esterases in human plasma, much of aspirin's bioactivity can be attributed to its primary metabolite, SA. Here we demonstrate that human high mobility group box 1 (HMGB1) is a novel SA-binding protein. SA-binding sites on HMGB1 were identified in the HMG-box domains by nuclear magnetic resonance (NMR) spectroscopic studies and confirmed by mutational analysis. Extracellular HMGB1 is a damage-associated molecular pattern molecule (DAMP), with multiple redox states. SA suppresses both the chemoattractant activity of fully reduced HMGB1 and the increased expression of proinflammatory cytokine genes and cyclooxygenase 2 (COX-2) induced by disulfide HMGB1. Natural and synthetic SA derivatives with greater potency for inhibition of HMGB1 were identified, providing proof-of-concept that new molecules with high efficacy against sterile inflammation are attainable. An HMGB1 protein mutated in one of the SA-binding sites identified by NMR chemical shift perturbation studies retained chemoattractant activity, but lost binding of and inhibition by SA and its derivatives, thereby firmly establishing that SA binding to HMGB1 directly suppresses its proinflammatory activities. Identification of HMGB1 as a pharmacological target of SA/aspirin provides new insights into the mechanisms of action of one of the world's longest and most used natural and synthetic drugs. It may also provide an explanation for the protective effects of low-dose aspirin usage. PMID:26101955

  15. Molecular Cloning of a cDNA Encoding for Taenia solium TATA-Box Binding Protein 1 (TsTBP1 and Study of Its Interactions with the TATA-Box of Actin 5 and Typical 2-Cys Peroxiredoxin Genes.

    Directory of Open Access Journals (Sweden)

    Oscar Rodríguez-Lima

    Full Text Available TATA-box binding protein (TBP is an essential regulatory transcription factor for the TATA-box and TATA-box-less gene promoters. We report the cloning and characterization of a full-length cDNA that encodes a Taenia solium TATA-box binding protein 1 (TsTBP1. Deduced amino acid composition from its nucleotide sequence revealed that encodes a protein of 238 residues with a predicted molecular weight of 26.7 kDa, and a theoretical pI of 10.6. The NH2-terminal domain shows no conservation when compared with to pig and human TBP1s. However, it shows high conservation in size and amino acid identity with taeniids TBP1s. In contrast, the TsTBP1 COOH-terminal domain is highly conserved among organisms, and contains the amino acids involved in interactions with the TATA-box, as well as with TFIIA and TFIIB. In silico TsTBP1 modeling reveals that the COOH-terminal domain forms the classical saddle structure of the TBP family, with one α-helix at the end, not present in pig and human. Native TsTBP1 was detected in T. solium cysticerci´s nuclear extract by western blot using rabbit antibodies generated against two synthetic peptides located in the NH2 and COOH-terminal domains of TsTBP1. These antibodies, through immunofluorescence technique, identified the TBP1 in the nucleus of cells that form the bladder wall of cysticerci of Taenia crassiceps, an organism close related to T. solium. Electrophoretic mobility shift assays using nuclear extracts from T. solium cysticerci and antibodies against the NH2-terminal domain of TsTBP1 showed the interaction of native TsTBP1 with the TATA-box present in T. solium actin 5 (pAT5 and 2-Cys peroxiredoxin (Ts2-CysPrx gene promoters; in contrast, when antibodies against the anti-COOH-terminal domain of TsTBP1 were used, they inhibited the binding of TsTBP1 to the TATA-box of the pAT5 promoter gene.

  16. Molecular Cloning of a cDNA Encoding for Taenia solium TATA-Box Binding Protein 1 (TsTBP1) and Study of Its Interactions with the TATA-Box of Actin 5 and Typical 2-Cys Peroxiredoxin Genes.

    Science.gov (United States)

    Rodríguez-Lima, Oscar; García-Gutierrez, Ponciano; Jiménez, Lucía; Zarain-Herzberg, Ángel; Lazzarini, Roberto; Landa, Abraham

    2015-01-01

    TATA-box binding protein (TBP) is an essential regulatory transcription factor for the TATA-box and TATA-box-less gene promoters. We report the cloning and characterization of a full-length cDNA that encodes a Taenia solium TATA-box binding protein 1 (TsTBP1). Deduced amino acid composition from its nucleotide sequence revealed that encodes a protein of 238 residues with a predicted molecular weight of 26.7 kDa, and a theoretical pI of 10.6. The NH2-terminal domain shows no conservation when compared with to pig and human TBP1s. However, it shows high conservation in size and amino acid identity with taeniids TBP1s. In contrast, the TsTBP1 COOH-terminal domain is highly conserved among organisms, and contains the amino acids involved in interactions with the TATA-box, as well as with TFIIA and TFIIB. In silico TsTBP1 modeling reveals that the COOH-terminal domain forms the classical saddle structure of the TBP family, with one α-helix at the end, not present in pig and human. Native TsTBP1 was detected in T. solium cysticerci´s nuclear extract by western blot using rabbit antibodies generated against two synthetic peptides located in the NH2 and COOH-terminal domains of TsTBP1. These antibodies, through immunofluorescence technique, identified the TBP1 in the nucleus of cells that form the bladder wall of cysticerci of Taenia crassiceps, an organism close related to T. solium. Electrophoretic mobility shift assays using nuclear extracts from T. solium cysticerci and antibodies against the NH2-terminal domain of TsTBP1 showed the interaction of native TsTBP1 with the TATA-box present in T. solium actin 5 (pAT5) and 2-Cys peroxiredoxin (Ts2-CysPrx) gene promoters; in contrast, when antibodies against the anti-COOH-terminal domain of TsTBP1 were used, they inhibited the binding of TsTBP1 to the TATA-box of the pAT5 promoter gene. PMID:26529408

  17. Downregulation of high mobility group box 1 modulates telomere homeostasis and increases the radiosensitivity of human breast cancer cells.

    Science.gov (United States)

    Ke, Shaobo; Zhou, Fuxiang; Yang, Hui; Wei, Yuehua; Gong, Jun; Mei, Zijie; Wu, Lin; Yu, Haijun; Zhou, Yunfeng

    2015-03-01

    The functions of the high mobility group box 1 (HMGB1) in tumor cells include replenishing telomeric DNA and maintaining cell immortality. There is a negative correlation between human telomerase reverse transcriptase (hTERT) and radiosensitivity in tumor cells. Our aim was to elucidate the relationship among HMGB1, telomere homeostasis and radiosensitivity in MCF-7 cells. In this study, we established stably transfected control (MCF-7-NC) and HMGB1 knockdown (MCF-7-shHMGB1) cell lines. The expression of HMGB1 mRNA and the relative telomere length were examined by real-time PCR. Radiosensitivity was detected by clonogenic assay. The protein expressions were determined by western blot analysis. The telomerase activity was detected by PCR-ELISA. Proliferation ability was examined by CCK-8 assay. Cell cycle and apoptosis were examined by flow cytometry. DNA damage foci were detected by immunofluorescence. ShRNA-mediated downregulation of HMGB1 expression increased the radiosensitivity of MCF-7 cells, and reduced the accumulation of hTERT and cyclin D1. Moreover, knockdown of HMGB1 in MCF-7 cells inhibited telomerase activity and cell proliferation, while increasing the extent of apoptosis. Downregulation of HMGB1 modulated telomere homeostasis by changing the level of telomere-binding proteins, such as TPP1 (PTOP), TRF1 and TRF2. This downregulation also inhibited the ATM and ATR signaling pathways. The current data demonstrate that knockdown of HMGB1 breaks telomere homeostasis, enhances radiosensitivity, and suppresses the repair of DNA damage in human breast cancer cells. These results suggested that HMGB1 might be a potential radiotherapy target in human breast cancer. PMID:25501936

  18. Intracellular high mobility group B1 protein (HMGB1) represses HIV-1 LTR-directed transcription in a promoter- and cell-specific manner

    International Nuclear Information System (INIS)

    We investigated whether the high mobility group B 1 (HMGB1), an abundant nuclear protein in all mammalian cells, affects HIV-1 transcription. Intracellular expression of human HMGB1 repressed HIV-1 gene expression in epithelial cells. This inhibitory effect of HMGB1 was caused by repression of long terminal repeat (LTR)-mediated transcription. Other viral promoters/enhancers, including simian virus 40 or cytomegalovirus, were not inhibited by HMGB1. In addition, HMGB1 inhibition of HIV-1 subtype C expression was dependent on the number of NFκB sites in the LTR region. The inhibitory effect of HMGB1 on viral gene expression observed in HeLa cells was confirmed by an upregulation of viral replication in the presence of antisense HMGB1 in monocytic cells. In contrast to what was found in HeLa cells and monocytic cells, endogenous HMGB1 expression did not affect HIV-1 replication in unstimulated Jurkat cells. Thus, intracellular HMGB1 affects HIV-1 LTR-directed transcription in a promoter- and cell-specific manner

  19. Effects of high-mobility group box 1 on the expression of Beclin-1 and LC3 proteins following hypoxia and reoxygenation injury in rat cardiomyocytes.

    Science.gov (United States)

    Xu, Weipan; Jiang, Hong; Hu, Xiaorong; Fu, Wenwen

    2014-01-01

    The mechanisms underlying autophagy during myocardial ischemia and reperfusion remain unclear. The present study investigated the relationship between high-mobility group box 1 protein (HMGB1) and autophagy in hypoxia/reoxygenation (H/R)-induced neonatal rat cardiomyocytes. Neonatal rat cardiomyocytes were treated with recombinant HMGB1 (200 ng/L) or ammonium glycyrrhizinate (100 μM) at appropriate concentrations. Cell viabilities and lactate dehydrogenase (LDH) and creatine kinase (CK) activity levels were measured. HMGB1, LC3 and Beclin-1 expression were assessed by Western blot. The results demonstrated that HMGB1-induced myocardial cells have increased levels of Beclin-1 protein and even higher levels of LC3 protein, while HMGB1-inhibited myocardial cells have decreased levels of Beclin-1 and LC3 proteins. In addition, HMGB1 induction significantly increased LDH and CK levels in the cell culture medium; the inhibition of HMGB1 significantly reduced LDH and CK expression in cardiomyocyte culture medium. In conclusion, the results of the present study suggest that HMGB1 is able to regulate Beclin-1 and LC3 levels following hypoxia and reoxygenation injury in rat cardiomyocytes. PMID:25664043

  20. Eosinophils Modulate CD4+ T Cell Responses via High Mobility Group Box-1 in the Pathogenesis of Asthma

    OpenAIRE

    Shim, Eun-Jin; Chun, Eunyoung; Lee, Hyun-Seung; Bang, Bo-Ram; Cho, Sang-Heon; Min, Kyung-Up; Park, Heung-Woo

    2014-01-01

    Eosinophils have been reported to modulate T cell responses. Previously, we reported that high-mobility group box 1 protein (HMGB1) played a key role in the pathogenesis of asthma. This study was conducted to test our hypothesis that eosinophils could modulate T cell responses via HMGB1 in the pathogenesis of asthma characterized by eosinophilic airway inflammation. We performed in vitro experiments using eosinophils, dendritic cells (DCs), and CD4+ T cells obtained from a murine model of ast...

  1. The integrated endoplasmic reticulum stress response in Leishmania amazonensis macrophage infection: the role of X-box binding protein 1 transcription factor.

    Science.gov (United States)

    Dias-Teixeira, Karina Luiza; Calegari-Silva, Teresa Cristina; Dos Santos, Guilherme R R M; Vitorino Dos Santos, José; Lima, Carolina; Medina, Jorge Mansur; Aktas, Bertal Huseyin; Lopes, Ulisses G

    2016-04-01

    Endoplasmic reticulum (ER) stress triggers the integrated ER-stress response (IERSR) that ensures cellular survival of ER stress and represents a primordial form of innate immunity. We investigated the role of IERSR duringLeishmania amazonensisinfection. Treatment of RAW 264.7 infected macrophages with the ER stress-inducing agent thapsigargin (TG; 1 μM) increasedL. amazonensisinfectivity in an IFN1-α receptor (IFNAR)-dependent manner. In Western blot assays, we showed thatL. amazonensisactivates the inositol-requiring enzyme (IRE1)/ X-box binding protein (XBP)-1-splicing arms of the IERSR in host cells. In chromatin immunoprecipitation (ChIP) assays, we showed an increased occupancy of enhancer and promoter sequences for theIfnbgene by XBP1 in infected RAW 264.7 cells. Knocking down XBP1 expression by transducing RAW 264.7 cells with the short hairpin XBP1 lentiviral vector significantly reduced the parasite proliferation associated with impaired translocation of phosphorylated IFN regulatory transcription factor (IRF)-3 to the nucleus and a decrease in IFN1-β expression. Knocking down XBP1 expression also increased NO concentration, as determined by Griess reaction and reduced the expression of antioxidant genes, such as heme oxygenase (HO)-1, that protect parasites from oxidative stress. We conclude thatL. amazonensisactivation of XBP1 plays a critical role in infection by protecting the parasites from oxidative stress and increasing IFN1-β expression.-Dias-Teixeira, K. L., Calegari-Silva, T. C., Dos Santos, G. R. R. M., Vitorino dos Santos, J., Lima, C., Medina, J. M., Aktas, B. H., Lopes, U. G. The integrated endoplasmic reticulum stress response inLeishmania amazonensismacrophage infection: the role of X-box binding protein 1 transcription factor. PMID:26678450

  2. Adsorption of the Inflammatory Mediator High-Mobility Group Box 1 by Polymers with Different Charge and Porosity

    Directory of Open Access Journals (Sweden)

    Carla Tripisciano

    2014-01-01

    Full Text Available High-mobility group box 1 protein (HMGB1 is a conserved protein with a variety of biological functions inside as well as outside the cell. When released by activated immune cells, it acts as a proinflammatory cytokine. Its delayed release has sparked the interest in HMGB1 as a potential therapeutic target. Here, we studied the adsorption of HMGB1 to anionic methacrylate-based polymers as well as to neutral polystyrene-divinylbenzene copolymers. Both groups of adsorbents exhibited efficient binding of recombinant HMGB1 and of HMGB1 derived from lipopolysaccharide-stimulated peripheral blood mononuclear cells. The adsorption characteristics depended on particle size, porosity, accessibility of the pores, and charge of the polymers. In addition to these physicochemical parameters of the adsorbents, modifications of the molecule itself (e.g., acetylation, phosphorylation, and oxidation, interaction with other plasma proteins or anticoagulants (e.g., heparin, or association with extracellular microvesicles may influence the binding of HMGB1 to adsorbents and lead to preferential depletion of HMGB1 subsets with different biological activity.

  3. Identification of Y-box binding protein 1 as a core regulator of MEK/ERK pathway-dependent gene signatures in colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Karsten Jürchott

    Full Text Available Transcriptional signatures are an indispensible source of correlative information on disease-related molecular alterations on a genome-wide level. Numerous candidate genes involved in disease and in factors of predictive, as well as of prognostic, value have been deduced from such molecular portraits, e.g. in cancer. However, mechanistic insights into the regulatory principles governing global transcriptional changes are lagging behind extensive compilations of deregulated genes. To identify regulators of transcriptome alterations, we used an integrated approach combining transcriptional profiling of colorectal cancer cell lines treated with inhibitors targeting the receptor tyrosine kinase (RTK/RAS/mitogen-activated protein kinase pathway, computational prediction of regulatory elements in promoters of co-regulated genes, chromatin-based and functional cellular assays. We identified commonly co-regulated, proliferation-associated target genes that respond to the MAPK pathway. We recognized E2F and NFY transcription factor binding sites as prevalent motifs in those pathway-responsive genes and confirmed the predicted regulatory role of Y-box binding protein 1 (YBX1 by reporter gene, gel shift, and chromatin immunoprecipitation assays. We also validated the MAPK-dependent gene signature in colorectal cancers and provided evidence for the association of YBX1 with poor prognosis in colorectal cancer patients. This suggests that MEK/ERK-dependent, YBX1-regulated target genes are involved in executing malignant properties.

  4. X-box binding protein 1 (XBP1s is a critical determinant of Pseudomonas aeruginosa homoserine lactone-mediated apoptosis.

    Directory of Open Access Journals (Sweden)

    Cathleen D Valentine

    Full Text Available Pseudomonas aeruginosa infections are associated with high mortality rates and occur in diverse conditions including pneumonias, cystic fibrosis and neutropenia. Quorum sensing, mediated by small molecules including N-(3-oxo-dodecanoyl homoserine lactone (C12, regulates P. aeruginosa growth and virulence. In addition, host cell recognition of C12 initiates multiple signalling responses including cell death. To gain insight into mechanisms of C12-mediated cytotoxicity, we studied the role of endoplasmic reticulum stress in host cell responses to C12. Dramatic protection against C12-mediated cell death was observed in cells that do not produce the X-box binding protein 1 transcription factor (XBP1s. The leucine zipper and transcriptional activation motifs of XBP1s were sufficient to restore C12-induced caspase activation in XBP1s-deficient cells, although this polypeptide was not transcriptionally active. The XBP1s polypeptide also regulated caspase activation in cells stimulated with N-(3-oxo-tetradecanoyl homoserine lactone (C14, produced by Yersinia enterolitica and Burkholderia pseudomallei, and enhanced homoserine lactone-mediated caspase activation in the presence of endogenous XBP1s. In C12-tolerant cells, responses to C12 including phosphorylation of p38 MAPK and eukaryotic initiation factor 2α were conserved, suggesting that C12 cytotoxicity is not heavily dependent on these pathways. In summary, this study reveals a novel and unconventional role for XBP1s in regulating host cell cytotoxic responses to bacterial acyl homoserine lactones.

  5. In vivo binding of hot pepper bZIP transcription factor CabZIP1 to the G-box region of pathogenesis-related protein 1 promoter

    International Nuclear Information System (INIS)

    We find that salicylic acid and ethephon treatment in hot pepper increases the expression of a putative basic/leucine zipper (bZIP) transcription factor gene, CabZIP1. CabZIP1 mRNA is expressed ubiquitously in various organs. The green fluorescent protein-fused transcription factor, CabZIP1::GFP, can be specifically localized to the nucleus, an action that is consistent with the presence of a nuclear localization signal in its protein sequence. Transient overexpression of the CabZIP1 transcription factor results in an increase in PR-1 transcripts level in Nicotiana benthamiana leaves. Using chromatin immunoprecipitation, we demonstrate that CabZIP1 binds to the G-box elements in native promoter of the hot pepper pathogenesis-related protein 1 (CaPR-1) gene in vivo. Taken together, our results suggest that CabZIP1 plays a role as a transcriptional regulator of the CaPR-1 gene

  6. Peroxiredoxins, thioredoxin, and Y-box-binding protein-1 are involved in the pathogenesis and progression of dialysis-associated renal cell carcinoma.

    Science.gov (United States)

    Fushimi, Fumiyoshi; Taguchi, Kenichi; Izumi, Hiroto; Kohno, Kimitoshi; Kuwano, Michihiko; Ono, Mayumi; Nakashima, Yutaka; Takesue, Tetsuro; Naito, Seiji; Oda, Yoshinao

    2013-10-01

    Patients with end-stage renal disease are exposed to increased oxidative stress and impairment of antioxidant mechanisms. We focused on dialysis renal cell carcinoma (RCC), including epithelial hyperplasia in acquired cystic disease of the kidney (ACDK). We attempted to obtain insight into the carcinogenesis and tumor progression in terms of cellular defense mechanisms associated with oxidative stress by investigating the expression of antioxidant proteins by immunohistochemistry. We evaluated retrospectively 43 cases of dialysis RCC and, as a control group, 49 cases of sporadic RCC. Peroxiredoxin (Prx) 1, 3, 4, 5, and 6 expression in dialysis RCC was positively correlated with the duration of dialysis. In epithelial hyperplasia, in 17 cases of acquired cystic disease of the kidney, Prxs and thioredoxin were highly expressed. Moreover, in dialysis RCC, Prx 3, 4, and 5 immunoreactivity and nuclear expression of Y-box-binding protein-1 were higher than in sporadic RCC. In dialysis RCC, Prx 3, 4, and 5 immunoreactivity positively correlated with the Fuhrman nuclear grade. These data suggest that oxidative stress during dialysis enhances antioxidant activity, with an inhibiting effect on carcinogenesis. Once cancer has developed, antioxidant activity might have a stimulating effect on the progression of dialysis RCC. PMID:23907567

  7. [Analysis of the impact of heparin on the affinity of high mobility group box-1 protein and the receptor of advanced glycation end products by surface plasmon resonance technology].

    Science.gov (United States)

    Ling, Yan; Wang, Chun-You; Yang, Zhi-Yong

    2009-11-01

    To investigate the affinity constants of heparin with high mobility group protein 1(HMGB1) and HMGB1 with the receptor of advanced glycation end products (RAGE) and to analyze the impact of heparin on the affinity of HMGB1 and RAGE, the standard BIAcore amine coupling chemistry protocol using EDC and NHS was employed for immobilizing. Surface plasmon resonance biosensor technology was used to detect the affinity constants of heparin/HMGB1, HMGB1/RAGE and heparin/ RAGE. Binding analysis was used to investigate the impact of heparin on the affinity of HMGB1 and RAGE. After the immobilization, 9 000 and 5 000 RU rise of HMGB1 and RAGE respectively were obtained. These meant that the immobilized values of HMGB1 and RAGE were about 9 and 5 ng x mm(-2) respectively. The kinetic constants were k(a) = 1.78 x 10(5) L x mol(-1) x s(-1), kd = 8.02 x 10(-4) s(-1), and the affinity constants were KA = 2.22 x 10(8) L x mol(-1), the equilibrium dissociation constant K(D) = 4.5 x 10(-9) mol x L(-1) for heparin and HMGB1; while the kinetic constants were k(a) = 1.85 x 10(3) L x mol(-1) x s(-1), k(d) = 1.81 x 10(-4) s(-1), K(A) = 1.02 x 10(7) L x mol(-1), K(D) = 9.77 x 10(-8) mol x L(-1) for HMGB1 and RAGE; there was very low affinity of heparin with RAGE. The highest concentration of 10 000 u x L(-1) of heparin in this experiment did not reach the saturation with HMGB1. After 50 mg x L(-1) of HMGB1 was mixed with heparin of 50, 100, 1 000, 10 000 u x L(-1), the combining amount of HMGB1 and RAGE declined from 100 to 50 RU. But there were no significant differences between different concentrations of heparin. It was concluded that heparin can combine with HMGB1 and affect the affinity of HMGB1/RAGE. In addition, this impact was not in a dose-dependent manner. PMID:20101991

  8. Protective effects of ghrelin against oxidative stress, inducible nitric oxide synthase and inflammation in a mouse model of myocardial ischemia/reperfusion injury via the HMGB1 and TLR4/NF-κB pathway.

    Science.gov (United States)

    Sun, Ning; Wang, Hui; Wang, Lin

    2016-09-01

    The present study aimed to investigate the protective effects of ghrelin against oxidative stress, inducible nitric oxide synthase (iNOS) and inflammation in a mouse model of myocardial ischemia/reperfusion injury (MIRI). In addition, the study aimed to determine its underlying mechanisms. A mouse model of MIRI was used in vivo, in order to ascertain the protective effects of ghrelin on MIRI. Commercial kits were used to measure the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) in MIRI mice. Furthermore, Evan's Blue-triphenyltetrazolium chloride solution was used to analyze the protective effects of ghrelin against infarct size in MIRI mice. The underlying mechanisms were determined by measuring MIRI-induced tumor necrosis factor (TNF)‑α, interleukin (IL)‑6, superoxide dismutase (SOD), glutathione (GSH), GSH-peroxidase (GSH‑PX), malondialdehyde (MDA) and caspase‑3/caspase‑9 activities, and iNOS, high mobility group box 1 (HMGB1), Toll‑like receptor 4 (TLR4) and nuclear factor (NF)‑κB protein expression in MIRI mice. The results demonstrated that MIRI led to an increase in infarct size; CK, LDH, TNF‑α, IL‑6, MDA, caspase‑3 and caspase-9 serum levels; and iNOS protein expression. MIRI resulted in inhibition of SOD, FSH and GSH‑PX levels. Conversely, these alterations were significantly inhibited following treatment with ghrelin. In addition, the protective effects of ghrelin against MIRI suppressed HMGB1, TLR4 and NF‑κB protein expression in MIRI mice. The present study revealed that ghrelin exerted protective effects against oxidative stress, iNOS and inflammation in MIRI mice via the HMGB1/TLR4/NF-κB pathway. PMID:27485280

  9. All Trans-Retinoic Acid Mediates MED28/HMG Box-Containing Protein 1 (HBP1)/β-Catenin Signaling in Human Colorectal Cancer Cells.

    Science.gov (United States)

    Lee, Ming-Fen; Hsieh, Nien-Tsu; Huang, Chun-Yin; Li, Chun-I

    2016-08-01

    Vitamin A is required for normal body function, including vision, epithelial integrity, growth, and differentiation. All trans-retinoic acid (ATRA), a family member of vitamin A, has been explored in treating acute promyelocytic leukemia and other types of cancer. Dysregulated Wnt/β-catenin signaling and disrupted cadherin-catenin complex often contribute to colorectal malignancy. MED28, a mammalian Mediator subunit, is found highly expressed in breast and colorectal cancers. Our laboratory has also reported that MED28 regulates cell growth, migration, and invasion in human breast cancer cells. In the current study we investigated the effect of ATRA on MED28 and Wnt/β-catenin signaling in colorectal cancer. HCT116, HT29, SW480, and SW620, four human colorectal cancer cell lines representing different stages of carcinogenesis and harboring critical genetic changes, were employed. Our data indicated that regardless of genetic variations among these cells, suppression of MED28 reduced the expression of cyclin D1, c-Myc, and nuclear β-catenin, but increased the expression of E-cadherin and HMG box-containing protein 1 (HBP1) where HBP1 has been described as a negative regulator of the Wnt/β-catenin signaling. The reporter activity of an HBP1 promoter increased upon MED28 knockdown, but decreased upon MED28 overexpression. ATRA reduced the expression of MED28 and mimicked the effect of MED28 suppression in down-regulating Wnt/β-catenin signaling. Taken together, ATRA can reverse the suppressive effect of MED28 on HBP1 and E-cadherin and inactivate the Wnt/β-catenin pathway in colorectal cancer, suggesting a protective effect of ATRA against colorectal cancer. J. Cell. Physiol. 231: 1796-1803, 2016. © 2015 Wiley Periodicals, Inc. PMID:26660958

  10. Molecular decoy to the Y-box binding protein-1 suppresses the growth of breast and prostate cancer cells whilst sparing normal cell viability.

    Directory of Open Access Journals (Sweden)

    Jennifer H Law

    Full Text Available The Y-box binding protein-1 (YB-1 is an oncogenic transcription/translation factor that is activated by phosphorylation at S102 whereby it induces the expression of growth promoting genes such as EGFR and HER-2. We recently illustrated by an in vitro kinase assay that a novel peptide to YB-1 was highly phosphorylated by the serine/threonine p90 S6 kinases RSK-1 and RSK-2, and to a lesser degree PKCα and AKT. Herein, we sought to develop this decoy cell permeable peptide (CPP as a cancer therapeutic. This 9-mer was designed as an interference peptide that would prevent endogenous YB-1(S102 phosphorylation based on molecular docking. In cancer cells, the CPP blocked P-YB-1(S102 and down-regulated both HER-2 and EGFR transcript level and protein expression. Further, the CPP prevented YB-1 from binding to the EGFR promoter in a gel shift assay. Notably, the growth of breast (SUM149, MDA-MB-453, AU565 and prostate (PC3, LNCap cancer cells was inhibited by ∼90% with the CPP. Further, treatment with this peptide enhanced sensitivity and overcame resistance to trastuzumab in cells expressing amplified HER-2. By contrast, the CPP had no inhibitory effect on the growth of normal immortalized breast epithelial (184htert cells, primary breast epithelial cells, nor did it inhibit differentiation of hematopoietic progenitors. These data collectively suggest that the CPP is a novel approach to suppressing the growth of cancer cells while sparing normal cells and thereby establishes a proof-of-concept that blocking YB-1 activation is a new course of cancer therapeutics.

  11. Activating transcription factor 4 and X box binding protein 1 of Litopenaeus vannamei transcriptional regulated white spot syndrome virus genes Wsv023 and Wsv083.

    Directory of Open Access Journals (Sweden)

    Xiao-Yun Li

    Full Text Available In response to endoplasmic reticulum (ER stress, the signaling pathway termed unfolded protein response (UPR is activated. To investigate the role of UPR in Litopenaeus vannamei immunity, the activating transcription factor 4 (designated as LvATF4 which belonged to a branch of the UPR, the [protein kinase RNA (PKR-like ER kinase, (PERK]-[eukaryotic initiation factor 2 subunit alpha (eIF2α] pathway, was identified and characterized. The full-length cDNA of LvATF4 was 1972 bp long, with an open reading frame of 1299 bp long that encoded a 432 amino acid protein. LvATF4 was highly expressed in gills, intestines and stomach. For the white spot syndrome virus (WSSV challenge, LvATF4 was upregulated in the gills after 3 hpi and increased by 1.9-fold (96 hpi compared to the mock-treated group. The LvATF4 knock-down by RNA interference resulted in a lower cumulative mortality of L. vannamei under WSSV infection. Reporter gene assays show that LvATF4 could upregulate the expression of the WSSV gene wsv023 based on the activating transcription factor/cyclic adenosine 3', 5'-monophosphate response element (ATF/CRE. Another transcription factor of L. vannamei, X box binding protein 1 (designated as LvXBP1, has a significant function in [inositol-requiring enzyme-1(IRE1 - (XBP1] pathway. This transcription factor upregulated the expression of the WSSV gene wsv083 based on the UPR element (UPRE. These results suggest that in L. vannamei UPR signaling pathway transcription factors are important for WSSV and might facilitate WSSV infection.

  12. High Mobility Group Box1 Protein Is Involved in Endoplasmic Reticulum Stress Induced by Clostridium difficile Toxin A.

    Science.gov (United States)

    Liu, Ji; Ma, Yi; Sun, Chun-Li; Li, Shan; Wang, Ju-Fang

    2016-01-01

    High Mobility Group Box1 (HMGB1), a damage-associated inflammatory factor, plays an important role in the pathogenesis of numerous chronic inflammatory and autoimmune diseases. In this study, the role of the HMGB1 in TcdA-induced ER stress was identified. Clostridium difficile toxin A is one of the major virulence factors of C. difficile infection (CDI) and has been proved to induce apoptotic cell death through ER stress. Our results showed that HMGB1 might play an important role in the TcdA-induced ER stress and unfolded protein response. HMGB1 activated molecular markers and induced the C/EBP homologous protein upregulation (CHOP). This study may provide the essential information for better understanding of the molecular mechanisms involved in CDI. PMID:27579314

  13. High-mobility group box-1 release into fetal circulation from umbilical cord tissue and amniotic epithelium in fetal ischemia.

    Science.gov (United States)

    Nakamura, Toshihiko; Yoshioka, Toshirou; Yamada, Shingo; Miyasho, Taku; Sakakibara, Nana; Hatanaka, Daishuke

    2016-07-01

    We report the case of a baby with low birthweight born by emergency caesarean section at 33 weeks 2 days' gestation due to placental abruption. High-mobility group box-1 (HMGB-1) and interleukin-17 concentration in the umbilical cord blood were high at 55.7 ng/mL and 50.7 pg/mL, respectively. On immunostaining of umbilical cord and amniotic epithelium, HMGB-1 was identified in the nuclei of vascular endothelial cells and cytoplasm of the surrounding cells in the umbilical cord. This suggests that, in the present case of placental abruption and subsequent ischemic placenta and fetus, the high level of HMGB-1 observed was due to the release of HMGB-1 into the umbilical cord blood from the vascular endothelial cells of the umbilical cord. PMID:27097754

  14. Effects of high-mobility group box 1 on the expression of Beclin-1 and LC3 proteins following hypoxia and reoxygenation injury in rat cardiomyocytes

    OpenAIRE

    Xu, Weipan; Jiang, Hong; Hu, Xiaorong; Fu, Wenwen

    2014-01-01

    The mechanisms underlying autophagy during myocardial ischemia and reperfusion remain unclear. The present study investigated the relationship between high-mobility group box 1 protein (HMGB1) and autophagy in hypoxia/reoxygenation (H/R)-induced neonatal rat cardiomyocytes. Neonatal rat cardiomyocytes were treated with recombinant HMGB1 (200 ng/L) or ammonium glycyrrhizinate (100 μM) at appropriate concentrations. Cell viabilities and lactate dehydrogenase (LDH) and creatine kinase (CK) activ...

  15. Interplay between human high mobility group protein 1 and replication protein A on psoralen-cross-linked DNA

    DEFF Research Database (Denmark)

    Reddy, Madhava C; Christensen, Jesper; Vasquez, Karen M

    2005-01-01

    Human high mobility group box (HMGB) 1 and -2 proteins are highly conserved and abundant chromosomal proteins that regulate chromatin structure and DNA metabolism. HMGB proteins bind preferentially to DNA that is bent or underwound and to DNA damaged by agents such as cisplatin, UVC radiation, and...... benzo[a]pyrenediol epoxide (BPDE). Binding of HMGB1 to DNA adducts is thought to inhibit nucleotide excision repair (NER), leading to cell death, but the biological roles of these proteins remain obscure. We have used psoralen-modified triplex-forming oligonucleotides (TFOs) to direct a psoralen-DNA...... interstrand cross-link (ICL) to a specific site to determine the effect of HMGB proteins on recognition of these lesions. Our results reveal that human HMGB1 (but not HMGB2) binds with high affinity and specificity to psoralen ICLs, and interacts with the essential NER protein, replication protein A (RPA), at...

  16. Nuclear detection of Y-box protein-1 (YB-1) closely associates with progesterone receptor negativity and is a strong adverse survival factor in human breast cancer

    International Nuclear Information System (INIS)

    Y-box binding protein-1 (YB-1) is the prototypic member of the cold shock protein family that fulfills numerous cellular functions. In the nucleus YB-1 protein orchestrates transcription of proliferation-related genes, whereas in the cytoplasm it associates with mRNA and directs translation. In human tumor entities, such as breast, lung and prostate cancer, cellular YB-1 expression indicates poor clinical outcome, suggesting that YB-1 is an attractive marker to predict patients' prognosis and, potentially, is suitable to individualize treatment protocols. Given these predictive qualities of YB-1 detection we sought to establish a highly specific monoclonal antibody (Mab) for diagnostic testing and its characterization towards outcome prediction (relapse-free and overall survival). Hybridoma cell generation was carried out with recombinant YB-1 protein as immunogen and Mab characterization was performed using immunoblotting and ELISA with recombinant and tagged YB-1 proteins, as well as immunohistochemistry of healthy and breast cancer specimens. Breast tumor tissue array staining results were analyzed for correlations with receptor expression and outcome parameters. YB-1-specific Mab F-E2G5 associates with conformational binding epitopes mapping to two domains within the N-terminal half of the protein and detects nuclear YB-1 protein by immunohistochemistry in paraffin-embedded breast cancer tissues. Prognostic evaluation of Mab F-E2G5 was performed by immunohistochemistry of a human breast cancer tissue microarray comprising 179 invasive breast cancers, 8 ductal carcinoma in situ and 37 normal breast tissue samples. Nuclear YB-1 detection in human breast cancer cells was associated with poor overall survival (p = 0.0046). We observed a close correlation between nuclear YB-1 detection and absence of progesterone receptor expression (p = 0.002), indicating that nuclear YB-1 detection marks a specific subgroup of breast cancer. Likely due to limitation of sample

  17. High mobility group box-1 protein inhibits regulatory T cell immune activity in liver failure in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Lu-WenWang; Hui Chen; Zuo-Jiong Gong

    2010-01-01

    BACKGROUND: Liver failure in chronic hepatitis B (CHB) patients is a severe, life-threatening condition. Intestinal endotoxemia plays a significant role in the progress to liver failure. High mobility group box-1 (HMGB1) protein is involved in the process of endotoxemia. Regulatory T (Treg) cells maintain immune tolerance and contribute to the immunological hyporesponsiveness against HBV infection. However, the roles of HMGB1 and Treg cells in the pathogenesis of liver failure in CHB patients, and whether HMGB1 affects the immune activity of Treg cells are poorly known at present, and so were explored in this study. METHODS: The levels of HMGB1 expression were detected by ELISA, real-time RT-PCR, and Western blotting, and the percentage of CD4+CD25+CD127low Treg cells among CD4+cells was detected by flow cytometry in liver failure patients with chronic HBV infection, CHB patients, and healthy controls. Then, CD4+CD25+CD127low Treg cells isolated from the peripheral blood mononuclear cells from CHB patients were stimulated with HMGB1 at different concentrations or at various intervals. The effect of HMGB1 on the immune activity of Treg cells was assessed by a suppression assay of the allogeneic mixed lymphocyte response. The levels of forkhead box P3 (Foxp3) expression in Treg cells treated with HMGB1 were detected by RT-PCR and Western blotting. RESULTS: A higher level of HMGB1 expression and a lower percentage of Treg cells within the population of CD4+ cells were found in liver failure patients than in CHB patients (82.6±20.1 μg/L vs. 34.2±13.7 μg/L; 4.55±1.34% vs. 9.52± 3.89%, respectively). The immune activity of Treg cells was significantly weakened and the levels of Foxp3 expression were reduced in a dose- or time-dependent manner when Treg cells were stimulated with HMGB1 in vitro. CONCLUSIONS: The high level of HMGB1 and the low percentage of Treg cells play an important role in the pathogenesis of liver failure in patients with chronic HBV infection

  18. Application of hyperthermia in addition to ionizing irradiation fosters necrotic cell death and HMGB1 release of colorectal tumor cells

    International Nuclear Information System (INIS)

    Colorectal cancer is the second leading cause of death in developed countries. Tumor therapies should on the one hand aim to stop the proliferation of tumor cells and to kill them, and on the other hand stimulate a specific immune response against residual cancer cells. Dying cells are modulators of the immune system contributing to anti-inflammatory or pro-inflammatory responses, depending on the respective cell death form. The positive therapeutic effects of temperature-controlled hyperthermia (HT), when combined with ionizing irradiation (X-ray), were the origin to examine whether combinations of X-ray with HT can induce immune activating tumor cell death forms, also characterized by the release of the danger signal HMGB1. Human colorectal tumor cells with differing radiosensitivities were treated with combinations of HT (41.5 oC for 1 h) and X-ray (5 or 10 Gy). Necrotic cell death was prominent after X-ray and could be further increased by HT. Apoptosis remained quite low in HCT 15 and SW480 cells. X-ray and combinations with HT arrested the tumor cells in the radiosensitive G2 cell cycle phase. The amount of released HMGB1 protein was significantly enhanced after combinatorial treatments in comparison to single ones. We conclude that combining X-ray with HT may induce anti-tumor immunity as a result of the predominant induction of inflammatory necrotic tumor cells and the release of HMGB1.

  19. Application of hyperthermia in addition to ionizing irradiation fosters necrotic cell death and HMGB1 release of colorectal tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Schildkopf, Petra, E-mail: petra.schildkopf@uk-erlangen.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuernberg (Germany); Frey, Benjamin, E-mail: benjamin.frey@uk-erlangen.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuernberg (Germany); Mantel, Frederick, E-mail: frederick.mantel@web.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuernberg (Germany); Ott, Oliver J., E-mail: oliver.ott@uk-erlangen.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuernberg (Germany); Weiss, Eva-Maria, E-mail: eva-maria.weiss@uk-erlangen.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuernberg (Germany); Sieber, Renate, E-mail: renate.sieber@uk-erlangen.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuernberg (Germany); Janko, Christina, E-mail: christina.janko@uk-erlangen.de [Department for Internal Medicine 3, Institute for Clinical Immunology, Friedrich-Alexander University of Erlangen-Nuernberg (Germany); Sauer, Rolf, E-mail: rolf.sauer@uk-erlangen.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuernberg (Germany); Fietkau, Rainer, E-mail: rainer.fietkau@uk-erlangen.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuernberg (Germany); Gaipl, Udo S., E-mail: udo.gaipl@uk-erlangen.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuernberg (Germany)

    2010-01-01

    Colorectal cancer is the second leading cause of death in developed countries. Tumor therapies should on the one hand aim to stop the proliferation of tumor cells and to kill them, and on the other hand stimulate a specific immune response against residual cancer cells. Dying cells are modulators of the immune system contributing to anti-inflammatory or pro-inflammatory responses, depending on the respective cell death form. The positive therapeutic effects of temperature-controlled hyperthermia (HT), when combined with ionizing irradiation (X-ray), were the origin to examine whether combinations of X-ray with HT can induce immune activating tumor cell death forms, also characterized by the release of the danger signal HMGB1. Human colorectal tumor cells with differing radiosensitivities were treated with combinations of HT (41.5 {sup o}C for 1 h) and X-ray (5 or 10 Gy). Necrotic cell death was prominent after X-ray and could be further increased by HT. Apoptosis remained quite low in HCT 15 and SW480 cells. X-ray and combinations with HT arrested the tumor cells in the radiosensitive G2 cell cycle phase. The amount of released HMGB1 protein was significantly enhanced after combinatorial treatments in comparison to single ones. We conclude that combining X-ray with HT may induce anti-tumor immunity as a result of the predominant induction of inflammatory necrotic tumor cells and the release of HMGB1.

  20. Soluble HMGB1 is a novel adipokine stimulating IL-6 secretion through RAGE receptor in SW872 preadipocyte cell line: contribution to chronic inflammation in fat tissue.

    Directory of Open Access Journals (Sweden)

    Brice Nativel

    Full Text Available Low-grade inflammation (LGI is a central phenomenon in the genesis of obesity and insulin-resistance characterized by IL-6 in human serum. Whereas this LGI was initially thought to be mainly attributed to macrophage activation, it is now known that pre-adipocytes and adipocytes secrete several adipokines including IL-6 and participate to LGI and associated pathologies. In macrophages, HMGB1 is a nuclear yet secreted protein and acts as a cytokine to drive the production of inflammatory molecules through RAGE and TLR2/4. In this paper we tested the secretion of HMGB1 and the auto- and paracrine contribution to fat inflammation using the human preadipocyte cell line SW872 as a model. We showed that 1 human SW872 secreted actively HMGB1, 2 IL-6 production was positively linked to high levels of secreted HMGB1, 3 recombinant HMGB1 boosted IL-6 expression and this effect was mediated by the receptor RAGE and did not involve TLR2 or TLR4. These results suggest that HMGB1 is a major adipokine contributing to LGI implementation and maintenance, and can be considered as a target to develop news therapeutics in LGI associated pathologies such as obesity and type II diabetes.

  1. Severity of sepsisis is correlated with the elevation of serum high-mobility group box 1 in rats

    Institute of Scientific and Technical Information of China (English)

    HOU Li-chao; XIONG Li-ze; QIN Ming-zhe; ZHENG Li-na; LU Yan; WANG Qiang; PENG Dao-rong; YU Xin-ping; XIN Yu-chang; JI Gen-lin

    2009-01-01

    Background Sepsis is a leading cause of death in the intensive care units. The late inflammatory cytokine,high-mobility group box 1 (HMGB1), plays a critical role in sepsis. In the present study, we investigated the association between the serum HMGB1 levels and the severity of organ injury in the lipopolysaccharide-induced sepsis in rats.Methods To produce an animal model of sepsis with different degree of organ injury, animals were treated with three different doses of lipopolysaccharide (4, 8 and 16 mg/kg), and the animals in control group were treated with the same volume of the vehicle (saline). The levels of serum HMGB1 were measured at 0, 2, 4, 8, 16, 24, 32 and 48 hours after lipopolysaccharide (LPS) or vehicle injection, meanwhile the biochemical and histopathological indicators for the severity of organ injury were assessed.Results The level of HMGB1 had a positive, high correlation with the abnormal changes of serum cardiac troponin Ⅰ, alanine aminotransferase, aspartate aminotransferase, creatinine and blood urea nitrogen, as well as the pathologic scores of heart, lung, liver and kidney.Conclusions The level of serum HMGB1 is highly correlated with the severity of sepsis in rats, suggesting that HMGB1 could serve as a valuable adjunct in the diagnosis and management of sepsis.

  2. Purpurogallin, a Natural Phenol, Attenuates High-Mobility Group Box 1 in Subarachnoid Hemorrhage Induced Vasospasm in a Rat Model

    Directory of Open Access Journals (Sweden)

    Chih-Zen Chang

    2014-01-01

    Full Text Available High-mobility group box 1 (HMGB1 was shown to be an important extracellular mediator involved in vascular inflammation of animals following subarachnoid hemorrhage (SAH. This study is of interest to examine the efficacy of purpurogallin, a natural phenol, on the alternation of cytokines and HMGB1 in a SAH model. A rodent double hemorrhage SAH model was employed. Basilar arteries (BAs were harvested to examine HMGB1 mRNA and protein expression (Western blot. CSF samples were to examine IL-1β, IL-6, IL-8, and TNF-α (rt-PCR. Deformed endothelial wall, tortuous elastic lamina, and necrotic smooth muscle were observed in the vessels of SAH groups but were absent in the purpurogallin group. IL-1β, IL-6, and TNF-α in the SAH only and SAH plus vehicle groups were significantly elevated (P<0.01. Purpurgallin dose-dependently reduced HMGB1 protein expression. Likewise, high dose purpurogallin reduced TNF-α and HMGB1 mRNA levels. In conclusion, purpurogallin exerts its neuroinflammation effect through the dual effect of inhibiting IL-6 and TNF-α mRNA expression and reducing HMGB1 protein and mRNA expression. This study supports purpurogallin could attenuate both proinflammatory cytokines and late-onset inflammasome in SAH induced vasospasm.

  3. Changes of High Mobility Group box 1 in Serum of Pig Acute Hepatic Failure Model and Significance

    Institute of Scientific and Technical Information of China (English)

    Fan ZHANG; Yongwen HE; Zhongping DUAN

    2008-01-01

    The role of the high mobility group box 1 (HMGB-1) in acute hepatic failure and the ef- fect of artificial liver support system treatment on HMGB-1 level were investigated. Pig models of acute hepatic failure were induced by D-galactosamine and randomly divided into two groups with or without artificial liver support system treatment. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were detected by the enzyme linked immunosorbent assay (ELISA), the expression of HMGB-1 by Western blot, and serum levels of HMGB-1, liver function and hepatic pathology were observed after artificial liver support system treatment. The levels of TNF-α and IL-1β were increased and reached the peak at 24th h in the acute hepatic failure group, then quickly decreased. The serum level of HMGB-1 was increased at 24th h in the acute hepatic failure group and reached the peak at 48th h, then kept a stable high level. Significant liver injury appeared at 24th h and was continuously getting worse in the pig models of acute hepatic failure. In contrast, the liver injury was significantly alleviated and serum level of HMGB-1 was significantly decreased in the group treated with artificial liver support system (P<0.05). It was suggested that HMGB-1 may participate in the inflammatory response and liver injury in the late stage of the acute liver failure. Artificial liver support system treatment can reduce serum HMGB-1 level and relieve liver pathological damage.

  4. Expressions of HMGB1 and TLR4 in human glioma tissues of patients combined with epilepsy%伴有癫痫的人脑胶质瘤中HMGB1/TLR4的表达研究

    Institute of Scientific and Technical Information of China (English)

    周少龙; 王新军; 付旭东; 王建业; 寿记新

    2015-01-01

    Objective To investigate the expression of high mobility group protein b 1 (HMGPB1) and toll-like receptors 4 (TLR4) in human glioma tissues of patients with epilepsy and explore the mechanism of glioma-associated epilepsy.Methods Ninety-five glioma specimens,collected during the resection surgery in our hospital firom June 2011 to June 2014,were used in our experiment;among them,55 were low-grade gliomas and 40 were high-grade gliomas.Immunohistochemistry and real time-PCR were used to assay the protein and mRNA expressions of HMGB1 and TLR4 in glioma tissues and peritumoral tissues,and the relation between HMGB1/TLR4 and glioma-associated epilepsy was analyzed.Results The incidence of glioma-associated epilepsy was 35.79% (34/95),and the incidence of glioma-associated epilepsy in low-grade gliomas (49.09%) was significantly higher than that in high-grade gliomas (17.50%)(x2=10.057,P=0.002).Immunohistochemisty and RT-PCR showed that the protein and mRNA expressions of HMGB1/TLR4 in the peritumoral tissues with glioma-associated epilepsy were significantly higher than those in the peritumoral tissues without glioma-associated epilepsy (P<0.05),while no significant difference was noted between glioma tissues with and without epilepsy (P>0.05).Conclusion Over-expression of HMGB1 and TLR4 in peritumoral tissues of glioma patients may be related with the development of glioma-associated epilepsy,which may be a new target in glioma therapy.%目的 研究高迁移率族蛋白B1 (HMGB 1)/Toll样受体4(TLR4)在胶质瘤瘤体及瘤周组织的表达情况,探讨胶质瘤相关性癫痫的发生机制. 方法 收集郑州大学第五附属医院神经外科自2011年6月至2014年6月手术切除的95例胶质瘤标本,其中低级别胶质瘤(WHO Ⅰ~Ⅱ级)55例,高级别胶质瘤(WHOⅢ~Ⅳ)级40例.免疫组化染色、RT-PCR分别检测胶质瘤瘤体、瘤周组织HMGB1及TLR4蛋白和mRNA的表达. 结果 95例胶质瘤患者中,伴癫痫发作34例(35

  5. In-vivo evidence that high mobility group box 1 exerts deleterious effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model and Parkinson's disease which can be attenuated by glycyrrhizin.

    Science.gov (United States)

    Santoro, Matteo; Maetzler, Walter; Stathakos, Petros; Martin, Heather L; Hobert, Markus A; Rattay, Tim W; Gasser, Thomas; Forrester, John V; Berg, Daniela; Tracey, Kevin J; Riedel, Gernot; Teismann, Peter

    2016-07-01

    High-mobility group box 1 (HMGB1) is a nuclear and cytosolic protein that is released during tissue damage from immune and non-immune cells - including microglia and neurons. HMGB1 can contribute to progression of numerous chronic inflammatory and autoimmune diseases which is mediated in part by interaction with the receptor for advanced glycation endproducts (RAGE). There is increasing evidence from in vitro studies that HMGB1 may link the two main pathophysiological components of Parkinson's disease (PD), i.e. progressive dopaminergic degeneration and chronic neuroinflammation which underlie the mechanistic basis of PD progression. Analysis of tissue and biofluid samples from PD patients, showed increased HMGB1 levels in human postmortem substantia nigra specimens as well as in the cerebrospinal fluid and serum of PD patients. In a mouse model of PD induced by sub-acute administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), systemic administration of neutralizing antibodies to HMGB1 partly inhibited the dopaminergic cell death, and reduced the increase of RAGE and tumour necrosis factor-alpha. The small natural molecule glycyrrhizin, a component from liquorice root which can directly bind to HMGB1, both suppressed MPTP-induced HMGB1 and RAGE upregulation while reducing MPTP-induced dopaminergic cell death in a dose dependent manner. These results provide first in vivo evidence that HMGB1 serves as a powerful bridge between progressive dopaminergic neurodegeneration and chronic neuroinflammation in a model of PD, suggesting that HMGB1 is a suitable target for neuroprotective trials in PD. PMID:26921471

  6. High-mobility group box 1 protein and its role in severe acute pancreatitis

    OpenAIRE

    Shen, Xiao; Li, Wei-Qin

    2015-01-01

    The high mobility group box 1 (HMGB1), which belongs to the subfamily of HMG-1/-2, is a highly conserved single peptide chain consisting of 215 amino acid residues with a molecular weight of approximately 24894 Da. HMGB1 is a ubiquitous nuclear protein in mammals and plays a vital role in inflammatory diseases. Acute pancreatitis is one of the most common causes of acute abdominal pain with a poor prognosis. Acute pancreatitis is an acute inflammatory process of the pancreas (duration of less...

  7. Effect of small doses of glucocorticoids on HMGB-1, TERM-1, MPO and BALF in rats with acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Lai-Xu Mu

    2016-01-01

    Objective:To evaluate the effect of small doses of glucocorticoids on HMGB-1, TERM-1, MPO and BALF in rats with acute pancreatitis, and provide theoretical basis for the clinical small doses of glucocorticoids treatment of pancreatitis.Methods: A total of 72 SD rats in the study were randomly divided into the control group (C group), pancreatitis group (AP group) and pancreatitis + methylprednisolone (APM Group), and 5% sodium taurocholate was retrograde injected into pancreaticobiliary duct to establish rat models with acute pancreatitis. 3, 6, 12 h and 24 h after operation, samples were collected respectively, HMGB-1 levels, TERM-1 levels, myeloperoxidase (MPO) activity and the protein contents of bronchoalveolar lavage fluids (BALF) were detected and death rates of all groups was counted.Result:mRNA levels ofTREM-1 of APM group are lower than those of AP group, and the results oft-test are as follows: 3 h (t= 2.787,P<0.05), 6 h (t = 16.241,P<0.01), 12 h (t = 16.892,P<0.01) and 24 h (t= 17.239,P<0.01); compared with the AP group, HMGB-1 levels of APM Group at 12 and 24 h were lower, and the differences are significant, 12 h (t=12.231,P<0.01) and 24 h (t=15.125, P<0.01); compared with the AP group, the MPO activity of APM group significantly reduces at all time phases, and the differences are significant, 3 h (t=2.148,P<0.05), 6 h (t=16.103, P<0.01), 12 h (t=16.476,P<0.01) and 24 h (t=17.219,P<0.01). Compared with AP group, BALF protein contents of APM group significantly increase (P<0.01); compared with AP group, the survival rate of rats in APM group significantly increases, and comparison between two groups by chi-square test shows significant differences (χ2=7.271,P<0.01).Conclusions:Small doses of glucocorticoids can reduce the factors associated with pancreatitis such as TREM-1, HMGB-1, BALF and MPO, it is good for improving clinical therapeutic efficacy and survival rate of AP, and it’s worth popularization and application.

  8. HMGB1, a pathogenic molecule that induces neurite degeneration via TLR4-MARCKS, is a potential therapeutic target for Alzheimer’s disease

    Science.gov (United States)

    Fujita, Kyota; Motoki, Kazumi; Tagawa, Kazuhiko; Chen, Xigui; Hama, Hiroshi; Nakajima, Kazuyuki; Homma, Hidenori; Tamura, Takuya; Watanabe, Hirohisa; Katsuno, Masahisa; Matsumi, Chiemi; Kajikawa, Masunori; Saito, Takashi; Saido, Takaomi; Sobue, Gen; Miyawaki, Atsushi; Okazawa, Hitoshi

    2016-01-01

    Alzheimer’s disease (AD) is the most common neurodegenerative disease, but it remains an intractable condition. Its pathogenesis is predominantly attributed to the aggregation and transmission of two molecules, Aβ and tau; however, other pathological mechanisms are possible. Here, we reveal that phosphorylation of MARCKS, a submembrane protein that regulates the stability of the actin network, occurs at Ser46 prior to aggregation of Aβ and is sustained throughout the course of AD in human and mouse brains. Furthermore, HMGB1 released from necrotic or hyperexcitatory neurons binds to TLR4, triggers the specific phosphorylation of MARCKS via MAP kinases, and induces neurite degeneration, the classical hallmark of AD pathology. Subcutaneous injection of a newly developed monoclonal antibody against HMGB1 strongly inhibits neurite degeneration even in the presence of Aβ plaques and completely recovers cognitive impairment in a mouse model. HMGB1 and Aβ mutually affect polymerization of the other molecule, and the therapeutic effects of the anti-HMGB1 monoclonal antibody are mediated by Aβ-dependent and Aβ-independent mechanisms. We propose that HMGB1 is a critical pathogenic molecule promoting AD pathology in parallel with Aβ and tau and a new key molecular target of preclinical antibody therapy to delay the onset of AD. PMID:27557632

  9. HMGB1, a pathogenic molecule that induces neurite degeneration via TLR4-MARCKS, is a potential therapeutic target for Alzheimer's disease.

    Science.gov (United States)

    Fujita, Kyota; Motoki, Kazumi; Tagawa, Kazuhiko; Chen, Xigui; Hama, Hiroshi; Nakajima, Kazuyuki; Homma, Hidenori; Tamura, Takuya; Watanabe, Hirohisa; Katsuno, Masahisa; Matsumi, Chiemi; Kajikawa, Masunori; Saito, Takashi; Saido, Takaomi; Sobue, Gen; Miyawaki, Atsushi; Okazawa, Hitoshi

    2016-01-01

    Alzheimer's disease (AD) is the most common neurodegenerative disease, but it remains an intractable condition. Its pathogenesis is predominantly attributed to the aggregation and transmission of two molecules, Aβ and tau; however, other pathological mechanisms are possible. Here, we reveal that phosphorylation of MARCKS, a submembrane protein that regulates the stability of the actin network, occurs at Ser46 prior to aggregation of Aβ and is sustained throughout the course of AD in human and mouse brains. Furthermore, HMGB1 released from necrotic or hyperexcitatory neurons binds to TLR4, triggers the specific phosphorylation of MARCKS via MAP kinases, and induces neurite degeneration, the classical hallmark of AD pathology. Subcutaneous injection of a newly developed monoclonal antibody against HMGB1 strongly inhibits neurite degeneration even in the presence of Aβ plaques and completely recovers cognitive impairment in a mouse model. HMGB1 and Aβ mutually affect polymerization of the other molecule, and the therapeutic effects of the anti-HMGB1 monoclonal antibody are mediated by Aβ-dependent and Aβ-independent mechanisms. We propose that HMGB1 is a critical pathogenic molecule promoting AD pathology in parallel with Aβ and tau and a new key molecular target of preclinical antibody therapy to delay the onset of AD. PMID:27557632

  10. Localization and Differential Expression of the Krüppel-Associated Box Zinc Finger Proteins 1 and 54 in Early Mouse Development

    DEFF Research Database (Denmark)

    Albertsen, Maria; Teperek, Marta; Elholm, Grethe;

    2010-01-01

    -fused reporter gene into zygotes demonstrated the intracellular distribution of ZFP1-green fluorescent protein (GFP) and ZFP54-GFP colocalized with a DNA marker in the two-cell embryo. The KRAB domain was essential to colocalize with DNA, and deletion of the KRAB domain in ZFP1-GFP and ZFP54-GFP localized...... transcriptional repressors, zinc finger protein (ZFP1) and ZFP54, belonging to the Krüppel-associated box (KRAB) zinc finger family, were isolated. ZFP1 and ZFP54 contain an N-terminally located KRAB repressor domain followed by 8 and 12 repeats of Krüppel zinc-finger motifs, respectively. Reverse transcription...

  11. 高迁移率族蛋白B1在创伤免疫功能紊乱中的作用及其调节机制%The potential role of high mobility group box 1 protein in immune dysfunction and its regulatory mechanism after major trauma

    Institute of Scientific and Technical Information of China (English)

    姚咏明; 林洪远

    2008-01-01

    Objective To investigate the potential effect of high mobility group box 1 protein (HMGB1) on host immune response and its molecular regulation mechanism as well as its interventional pathway following major burns/trauma. Methods With both animal experiments and clinical investigation, serial studies were conducted to observe the effects of HMGB1 on changes in immune function of T lymphoeytes, dendritic cells, and macrophages both in vivo and in vitro. Results It was found that thermal injury or trauma induced a delayed and persistent increase in HMGB1 expression as well as its release in various tissues.HMGB1 formation could markedly influence the cell-mediated immunity, including the changes in T lymphocytes, dendritic cells, and macrophages following major trauma or burns. These effects were closely related with dysfunction of various organs in the course of sepsis. Conclusion These data proved that HMGB1 not only acts as a novel "late" inflammatory mediator but is also closely associated with immunosuppression after acute insults. HMGB1 might play an important role in inducing systemic inflammatory response together with host immunological dissonance, resulting in the development of septic complications. Intervention of HMGB1 expression and release presumably provides a potentially effective way to regulate both excessive inflammatory and immune response, thereby as a measure to improve the prognosis of severe sepsis secondary to major trauma.

  12. Spinal high-mobility group box 1 contributes to mechanical allodynia in a rat model of bone cancer pain

    International Nuclear Information System (INIS)

    Mechanisms underlying bone cancer-induced pain are largely unknown. Previous studies indicate that neuroinflammation in the spinal dorsal horn is especially involved. Being first reported as a nonhistone chromosomal protein, high-mobility group box 1 (HMGB1) is now implicated as a mediator of inflammation. We hypothesized that HMGB1 could trigger the release of cytokines in the spinal dorsal horn and contribute to bone cancer pain. To test this hypothesis, we first built a bone cancer pain model induced by intratibal injection of Walker 256 mammary gland carcinoma cells. The structural damage to the tibia was monitored by radiological analysis. The mechanical allodynia was measured and the expression of spinal HMGB1 and IL-1β was evaluated. We observed that inoculation of cancer cells, but not heat-killed cells, induced progressive bone destruction from 9 d to 21 d post inoculation. Behavioral tests demonstrated that the significant nociceptive response in the cancer cells-injected rats emerged on day 9 and this kind of mechanical allodynia lasted at least 21 d following inoculation. Tumor cells inoculation significantly increased HMGB1 expression in the spinal dorsal horn, while intrathecal injecting a neutralizing antibody against HMGB1 showed an effective and reliable anti-allodynia effect with a dose-dependent manner. IL-1β was significantly increased in caner pain rats while intrathecally administration of anti-HMGB1 could decrease IL-1β. Together with previous reports, we predict that bone cancer induces HMGB1 production, enhancing spinal IL-1β expression and thus modulating spinal excitatory synaptic transmission and pain response.

  13. Inhibition of high-mobility group box 1 as therapeutic option in autoimmune disease : lessons from animal models

    NARCIS (Netherlands)

    Schaper, Fleur; Heeringa, Peter; Bijl, Marc; Westra, Johanna

    2013-01-01

    Purpose of review High-mobility group box 1 (HMGB1) is a molecule that has gained much attention in the last couple of years as an important player in innate immune responses and modulating factor in several (auto) immune diseases. Furthermore, advancements have been made in identifying the diverse

  14. Histone H1 Differentially Inhibits DNA Bending by Reduced and Oxidized HMGB1 Protein

    Czech Academy of Sciences Publication Activity Database

    Štros, Michal; Muselíková Polanská, Eva; Kučírek, Martin; Pospíšilová, Š.

    2015-01-01

    Roč. 10, č. 9 (2015). E-ISSN 1932-6203 R&D Projects: GA ČR GAP305/12/2475; GA ČR GA15-01354S Institutional support: RVO:68081707 Keywords : GROUP BOX DOMAINS * BINDING PROTEINS * LINKER HISTONES Subject RIV: BO - Biophysics Impact factor: 3.234, year: 2014

  15. Effects of Ethyl Pyruvate on High Mobility Group Box1 gene expression in septic lung of rat

    Institute of Scientific and Technical Information of China (English)

    Lian Zeng; Shanglong Yao; Dong Liu; Yuelan Wang

    2005-01-01

    Objective: Ethyl Pyruvate (EP) has been shown to be an effective anti-inflammatory agent in a variety of model systems. The aim of this study was to investigate the effects of EP on High Mobility Group Box1 (HMGB1) genes expression and the possible mechanisms of EP protecting against acute lung injury induced by sepsis. Methods: Forty Wistar rats were randomly divided into normal controls, sham operation, acute lung injury, and EP treatment (40 mg/kg intra-peritoneally every 6 hrs ) groups. At the time points of 24 hours the animals in each group were sacrificed, and the lungs were harvested. Wet/dry lung weight ratio, the protein in the bronchoalveolar lavage fluid(BALF), and pulmonary permeability index(PPI) were determined. The histological morphology of lung was observed under microscope. The expression of HMGB1 mRNA was measured using semi-quantitative RT-PCR. Results: EP treatment decreased wet/dry lung weight ratio, the protein in the BALF, and PPI ( P < 0.01 ). The histological morphology of lung injury was ameliorated. EP significantly inhibited the HMGB1 mRNA expression (P < 0.01 ). HMGB1 mRNA expression in lungs positivelycorrelation with wet/dry lung weight ratio, the protein in the BALF, and PPI. Conclusion: EP administered inhibits HMGB1 mRNAexpression, and protects the lungs against acute injury induced by sepsis.

  16. Local and systemic occurrences of HMGB1 in gnotobiotic piglets infected with E. coli O55 are related to bacterial translocation and inflammatory cytokines

    Czech Academy of Sciences Publication Activity Database

    Šplíchalová, Alla; Šplíchal, Igor

    2012-01-01

    Roč. 60, č. 3 (2012), s. 597-600. ISSN 1043-4666 R&D Projects: GA ČR GA524/09/0365 Institutional support: RVO:61388971 Keywords : HMGB1 * Enteric infection * E. coli Subject RIV: EC - Immunology Impact factor: 2.518, year: 2012

  17. Alarmin HMGB1 is released in the small intestine of gnotobiotic piglets infected with enteric pathogens and its level in plasma reflects severity of sepsis

    Czech Academy of Sciences Publication Activity Database

    Šplíchalová, Alla; Šplíchal, Igor; Chmelařová, Petra; Trebichavský, Ilja

    2011-01-01

    Roč. 31, č. 3 (2011), s. 488-497. ISSN 0271-9142 R&D Projects: GA MŠk ME 915 Institutional research plan: CEZ:AV0Z50200510 Keywords : HMGB1 * enteric infection * cytokines Subject RIV: EE - Microbiology, Virology Impact factor: 3.077, year: 2011

  18. Melatonin relieves neuropathic allodynia through spinal MT2-enhanced PP2Ac and downstream HDAC4 shuttling-dependent epigenetic modification of hmgb1 transcription.

    Science.gov (United States)

    Lin, Tzer-Bin; Hsieh, Ming-Chun; Lai, Cheng-Yuan; Cheng, Jen-Kun; Wang, Hsueh-Hsiao; Chau, Yat-Pang; Chen, Gin-Den; Peng, Hsien-Yu

    2016-04-01

    Melatonin (MLT; N-acetyl-5-methoxytryptamine) exhibits analgesic properties in chronic pain conditions. While researches linking MLT to epigenetic mechanisms have grown exponentially over recent years, very few studies have investigated the contribution of MLT-associated epigenetic modification to pain states. Here, we report that together with behavioral allodynia, spinal nerve ligation (SNL) induced a decrease in the expression of catalytic subunit of phosphatase 2A (PP2Ac) and enhanced histone deacetylase 4 (HDAC4) phosphorylation and cytoplasmic accumulation, which epigenetically alleviated HDAC4-suppressed hmgb1 gene transcription, resulting in increased high-mobility group protein B1 (HMGB1) expression selectively in the ipsilateral dorsal horn of rats. Focal knock-down of spinal PP2Ac expression also resulted in behavioral allodynia in association with similar protein expression as observed with SNL. Notably, intrathecal administration with MLT increased PP2Ac expression, HDAC4 dephosphorylation and nuclear accumulation, restored HDAC4-mediated hmgb1 suppression and relieved SNL-sensitized behavioral pain; these effects were all inhibited by spinal injection of 4P-PDOT (a MT2 receptor antagonist, 30 minutes before MLT) and okadaic acid (OA, a PP2A inhibitor, 3 hr after MLT). Our findings demonstrate a novel mechanism by which MLT ameliorates neuropathic allodynia via epigenetic modification. This MLT-exhibited anti-allodynia is mediated by MT2-enhanced PP2Ac expression that couples PP2Ac with HDAC4 to induce HDAC4 dephosphorylation and nuclear import, herein increases HDAC4 binding to the promoter of hmgb1 gene and upregulates HMGB1 expression in dorsal horn neurons. PMID:26732138

  19. High-mobility group box 1 inhibits HCO(3)(-) absorption in medullary thick ascending limb through a basolateral receptor for advanced glycation end products pathway.

    Science.gov (United States)

    Good, David W; George, Thampi; Watts, Bruns A

    2015-10-15

    High-mobility group box 1 (HMGB1) is a damage-associated molecule implicated in mediating kidney dysfunction in sepsis and sterile inflammatory disorders. HMGB1 is a nuclear protein released extracellularly in response to infection or injury, where it interacts with Toll-like receptor 4 (TLR4) and other receptors to mediate inflammation. Previously, we demonstrated that LPS inhibits HCO(3)(-) absorption in the medullary thick ascending limb (MTAL) through a basolateral TLR4-ERK pathway (Watts BA III, George T, Sherwood ER, Good DW. Am J Physiol Cell Physiol 301: C1296-C1306, 2011). Here, we examined whether HMGB1 could inhibit HCO(3)(-) absorption through the same pathway. Adding HMGB1 to the bath decreased HCO(3)(-) absorption by 24% in isolated, perfused rat and mouse MTALs. In contrast to LPS, inhibition by HMGB1 was preserved in MTALs from TLR4(-/-) mice and was unaffected by ERK inhibitors. Inhibition by HMGB1 was eliminated by the receptor for advanced glycation end products (RAGE) antagonist FPS-ZM1 and by neutralizing anti-RAGE antibody. Confocal immunofluorescence showed expression of RAGE in the basolateral membrane domain. Inhibition of HCO(3)(-) absorption by HMGB1 through RAGE was additive to inhibition by LPS through TLR4 and to inhibition by Gram-positive bacterial molecules through TLR2. Bath amiloride, which selectively prevents inhibition of MTAL HCO(3)(-) absorption mediated through Na⁺/H⁺ exchanger 1 (NHE1), eliminated inhibition by HMGB1. We conclude that HMGB1 inhibits MTAL HCO(3)(-) absorption through a RAGE-dependent pathway distinct from TLR4-mediated inhibition by LPS. These studies provide new evidence that HMGB1-RAGE signaling acts directly to impair the transport function of renal tubules. They reveal a novel paradigm for sepsis-induced renal tubule dysfunction, whereby exogenous pathogen-associated molecules and endogenous damage-associated molecules act directly and independently to inhibit MTAL HCO(3)(-) absorption through

  20. The high-mobility group box 1 cytokine induces transporter-mediated release of glutamate from glial subcellular particles (gliosomes) prepared from in situ-matured astrocytes.

    Science.gov (United States)

    Bonanno, Giambattista; Raiteri, Luca; Milanese, Marco; Zappettini, Simona; Melloni, Edon; Pedrazzi, Marco; Passalacqua, Mario; Tacchetti, Carlo; Usai, Cesare; Sparatore, Bianca

    2007-01-01

    The multifunctional protein high-mobility group box 1 (HMGB1) is expressed in restricted areas of adult brain where it can act as a proinflammatory cytokine. We report here that HMGB1 affects CNS transmission by inducing glutamatergic release from glial (gliosomes) but not neuronal (synaptosomes) resealed subcellular particles isolated from mouse cerebellum and hippocampus. Confocal microscopy showed that gliosomes are enriched with glia-specific proteins such as GFAP and S-100, but not with neuronal proteins such as PSD-95, MAP-2, and beta-tubulin III. Furthermore, gliosomes exhibit labeling neither for integrin-alphaM nor for myelin basic protein, specific for microglia and oligodendrocytes, respectively. The gliosomal fraction contains proteins of the exocytotic machinery coexisting with GFAP. Consistent with ultrastructural analysis, several approximately 30-nm nonclustered vesicles are present in the gliosome cytoplasm. Finally, gliosomes represent functional organelles that actively export glutamate when subjected to releasing stimuli, such as ionomycin or ATP, by mechanisms involving extracellular Ca(2+) and Ca(2+) release from intracellular stores. HMGB1-induced release of the stable glutamate analogue [(3)H]d-aspartate and endogenous glutamate form gliosomes, whereas nerve terminals were insensitive to the protein. The HMGB1-evoked release of glutamate was independent on modifications of cytosolic Ca(2+) concentration, but it was blocked by dl-threo-beta-benzyloxyaspartate, suggesting the involvement of transporter-mediated release mechanisms. Moreover, dihydrokainic acid, a selective inhibitor of glutamate transporter 1 does not block the HMGB1 effect, indicating a role for the glial glutamate-aspartate transporter (GLAST) subtype in this response. HMGB1 bind to gliosomes but not to synaptosomes and can physically interact with GLAST and receptor for advanced glycation end products (RAGE). Taken together, these results suggest that the HMGB1 cytokine

  1. Metformin protects against hyperglycemia-induced cardiomyocytes injury by inhibiting the expressions of receptor for advanced glycation end products and high mobility group box 1 protein.

    Science.gov (United States)

    Zhang, Ting; Hu, Xiaorong; Cai, Yuli; Yi, Bo; Wen, Zhongyuan

    2014-03-01

    Metformin (MET), an anti-diabetic oral drug with antioxidant properties, has been proved to provide cardioprotective effects in patients with diabetic disease. However, the mechanism is unclear. This study aimd to investigate the effects of MET on the expressions of receptor for advanced glycation end products (RAGE) and high mobility group box 1 protein (HMGB1) in hyperglycemia-treated neonatal rat ventricular myocytes. Cardiocytes were prepared and cultured with high glucose and different concentrations of MET. The expressions of RAGE and HMGB1 were evaluated by Western blot analysis. The superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), lactate dehydrogenase (LDH) and creatine kinase (CK) were measured. After 12 h-incubation, MET significantly inhibited the increase of MDA, TNF-α, LDH and CK levels induced by high glucose, especially at the 5 × 10(-5) to 10(-4 )mol/L concentrations while inhibiting the decrease of SOD level. Meanwhile, RAGE and HMGB1 expression were significantly increased induced by hyperglycaemia for 24 h (P < 0.05). MET inhibited the expressions of RAGE and HMGB1 in a dose-dependent manner, especially at the 5 × 10(-5) to 10(-4 )mol/L concentrations (P < 0.05). In conclusion, our study suggested that MET could reduce hyperglycemia-induced cardiocytes injury by inhibiting the expressions of RAGE and HMGB1. PMID:24420848

  2. The inflammatory molecules IL-1β and HMGB1 can rapidly enhance focal seizure generation in a brain slice model of temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Giorgio Carmignoto

    2014-06-01

    Full Text Available Epilepsy is a neurological disorder characterized by a hyperexcitable brain tissue and unpredictable seizures, i.e., aberrant firing discharges in large neuronal populations. It is well established that proinflammatory cytokines, in addition to their canonical involvement in the immune response, have a crucial role in the mechanism of seizure generation. The purpose of the present study was to investigate the role of interleukin-1β (IL-1β and high mobility group B1 (HMGB1 in the generation of seizure-like discharges using two models of focal epilepsy in a rat entorhinal cortex slice preparation. Seizure like-discharges were evoked by either slice perfusion with low Mg2+ and picrotoxin or with a double NMDA local stimulation in the presence of the proconvulsant 4-amino-pyridine. The effects of IL-1β or HMGB1 were evaluated by monitoring seizure discharge generation through laser scanning microscope imaging of Ca2+ signals from neurons and astrocytes. In the picrotoxin model, we revealed that both cytokines increased the mean frequency of spontaneous ictal-like discharges, whereas only IL-1β reduced the latency and prolonged the duration of the first ictal-like event. In the second model, a single NMDA pulse, per se ineffective, became successful when it was performed after IL-β or HMGB1 local applications. These findings demonstrate that both IL-1β and HMGB1 can rapidly lower focal ictal event threshold and strengthen the possibility that targeting these inflammatory pathways may represent an effective therapeutic strategy to prevent seizures.

  3. In vitro research on the molecular mechanism of the functions of HSF1, HMGB1 and IL-10%HSF1与HMGB1和IL-10作用分子机制的体外研究及意义

    Institute of Scientific and Technical Information of China (English)

    艾云智; 陈丹; 罗文福; 张先安; 罗成群

    2012-01-01

    目的:本研究以RAW264.7细胞系为研究对象,烧伤血清刺激建立烧伤细胞模型,在体外研究HSF1的抗炎症机制.方法:Western blot法检测烧伤血清刺激前后RAW264.7细胞中HSF1与NF-κB表达,凝胶阻滞法(EMSA)检测HSF1与炎症因子HMGB1和抗炎症因子IL-10基因启动子区相互作用,同时检测NF-κB是否参与上述的相互作用.结果:正常培养条件下的RAW264.7细胞几乎不表达HSF1,少量表达NF-κB,加入烧伤血清刺激后大量表达HSF1和NF-κB.HSF1与HMGB1和IL-10基因的启动子区HSE有相互作用.NF-κB不参与HSF1与HMGB1和IL-10基因启动子区HSE的结合.结论:HSF1与HMGB1和IL-10的启动子区HSE结合,抑制HMGB1的表达,促进IL-10的表达.在炎症反应中HMGB1和IL-10的表达不直接受NF-κB的调节.

  4. Extracellular Signal-regulated Kinase (ERK)-dependent Phosphorylation of Y-Box-binding Protein 1 (YB-1) Enhances Gene Expression in Granulosa Cells in Response to Follicle-stimulating Hormone (FSH).

    Science.gov (United States)

    Donaubauer, Elyse M; Hunzicker-Dunn, Mary E

    2016-06-01

    Within the ovarian follicle, immature oocytes are surrounded and supported by granulosa cells (GCs). Stimulation of GCs by FSH leads to their proliferation and differentiation, events that are necessary for fertility. FSH activates multiple signaling pathways to regulate genes necessary for follicular maturation. Herein, we investigated the role of Y-box-binding protein-1 (YB-1) within GCs. YB-1 is a nucleic acid binding protein that regulates transcription and translation. Our results show that FSH promotes an increase in the phosphorylation of YB-1 on Ser(102) within 15 min that is maintained at significantly increased levels until ∼8 h post treatment. FSH-stimulated phosphorylation of YB-1(Ser(102)) is prevented by pretreatment of GCs with the PKA-selective inhibitor PKA inhibitor (PKI), the MEK inhibitor PD98059, or the ribosomal S6 kinase-2 (RSK-2) inhibitor BI-D1870. Thus, phosphorylation of YB-1 on Ser(102) is PKA-, ERK-, and RSK-2-dependent. However, pretreatment of GCs with the protein phosphatase 1 (PP1) inhibitor tautomycin increased phosphorylation of YB-1(Ser(102)) in the absence of FSH; FSH did not further increase YB-1(Ser(102)) phosphorylation. This result suggests that the major effect of RSK-2 is to inhibit PP1 rather than to directly phosphorylate YB-1 on Ser(102) YB-1 coimmunoprecipitated with PP1β catalytic subunit and RSK-2. Transduction of GCs with the dephospho-adenoviral-YB-1(S102A) mutant prevented the induction by FSH of Egfr, Cyp19a1, Inha, Lhcgr, Cyp11a1, Hsd17b1, and Pappa mRNAs and estradiol-17β production. Collectively, our results reveal that phosphorylation of YB-1 on Ser(102) via the ERK/RSK-2 signaling pathway is necessary for FSH-mediated expression of target genes required for maturation of follicles to a preovulatory phenotype. PMID:27080258

  5. Nuclear expression of Y-box binding protein-1 is associated with poor prognosis in patients with pancreatic cancer and its knockdown inhibits tumor growth and metastasis in mice tumor models.

    Science.gov (United States)

    Shinkai, Kentaro; Nakano, Kenji; Cui, Lin; Mizuuchi, Yusuke; Onishi, Hideya; Oda, Yoshinao; Obika, Satoshi; Tanaka, Masao; Katano, Mitsuo

    2016-07-15

    The objective of this study was to examine the implication of Y-box-binding protein-1 (YB-1) for the aggressive phenotypes, prognosis and therapeutic target in pancreatic ductal adenocarcinoma (PDAC). YB-1 expression in PDAC, pancreatic intraepithelial neoplasia (PanIN) and normal pancreas specimens was evaluated by immunohistochemistry, and its correlation with clinicopathological features was assessed in patients with PDAC. The effects of YB-1 on proliferation, invasion and expressions of cell cycle-related proteins and matrix metalloproteinases (MMPs) were analyzed by WST-8, cell cycle and Matrigel invasion assays, Western blotting and quantitative RT-PCR in PDAC cells transfected with YB-1-siRNAs. To verify the significance of YB-1 for tumor progression in vivo, the growth and metastasis were monitored after intrasplenic implantation of ex vivo YB-1 siRNA-transfected PDAC cells, and YB-1-targeting antisense oligonucleotides were intravenously administered in nude mice harboring subcutaneous tumor. The intensity of YB-1 expression and positivity of nuclear YB-1 expression were higher in PDAC than PanIN and normal pancreatic tissues. Nuclear YB-1 expression was significantly associated with dedifferentiation, lymphatic/venous invasion and unfavorable prognosis. YB-1 knockdown inhibited cell proliferation via cell cycle arrest by S-phase kinase-associated protein 2 downregulation and consequent p27 accumulation, and decreased the invasion due to downregulated membranous-type 2 MMP expression in PDAC cells. Tumor growth and liver metastasis formation were significantly suppressed in nude mice after implantation of YB-1-silenced PDAC cells, and the YB-1 targeting antisense oligonucleotide significantly inhibited the growth of subcutaneous tumors. In conclusion, YB-1 may be involved in aggressive natures of PDAC and a promising therapeutic target. PMID:26939718

  6. 重症急性胰腺炎大鼠肝损伤HMGB1/TLR4mRNA的表达%Changes of HMGB1 and Toll-like receptor gene expression of livers in acute liver injury complicated with severe acute pancreatitis rats

    Institute of Scientific and Technical Information of China (English)

    黄鹏; 吴河水; 王春友

    2012-01-01

    目的 研究重症急性胰腺炎(SAP)大鼠肝损伤中高迁移率族蛋白B1(HMGB1)和Toll 样受体(TLR)4 mRNA的表达.方法 采用十二指肠闭襻法制作大鼠SAP模型.50只动物分为假手术组(S组)、胰腺炎组(P组).P组于建模后6、12、24、48 h分批剖杀,S组于术后6 h剖杀.观察血清淀粉酶、CRP、ALT和AST及肝组织IL-6和TNF-α的变化,RT-PCR方法检测各组不同时点肝组织HMGBl mRNA 和TLR4 mRNA的表达.结果 与S组比较,P组血清淀粉酶、CRP、ALT、AST、肝组织IL-6和TNF-α浓度升高(P<0.05).与S组比较,P组大鼠6 h肝组织TLR4 mRNA表达开始增高,术后12 h肝组织TLR4 mRNA表达迅速达到峰值(P<0.05);同时,P组HMGB1 mRNA于12 h快速上升,24~48 h时一直保持上升趋势(P<0.05);结论 SAP大鼠肝组织内HMGB1和TLR4的基因表达上调;其表达增高可能在SAP肝损伤的发生、发展中起重要作用.%Objective To investigate the changes of HMGB1 and Toll-like receptor 4 gene expression of livers in a-cute liver injury complicated with severe acute pancreatitis ( SAP ) rats. Methods Fifty SD male rats were randomly divided into Sham-operated group ( n = 10 ) and P group ( n =40 ). Levels of amylase, ALT, AST, CRP, IL-6 and TNF-α were observed. HMGB1 mRNA and TLR4 mRNA expression in the livers were measured by RT-PCR. Results Liver injuries were aggravated, the levels of serum amylase, CRP, ALT, AST, IL-6 and TNF-α were increased in livers ( P < 0.05 ). TLR4 mRNA could be detected in livers with low values in sham-operated group, but they were significantly increased at 6 hours in SAP group, peaking at 12 hours ( P <0. 05 ). HMGB1 mRNA were significantly increased at 12 hours in SAP group, peaking at 48 hours ( P <0. 05 ). Conclusion These data suggested that expression of HMGB1 mRNA and TLR4 mRNA were increased in livers in SAP, which may play an important role in mediating pro-inflammatory cytokine synthesis and release. Up-regula-tion of HMGB1 mRNA and TLR4 m

  7. Biphasic Modulation of NOS Expression, Protein and Nitrite Products by Hydroxocobalamin Underlies Its Protective Effect in Endotoxemic Shock: Downstream Regulation of COX-2, IL-1β, TNF-α, IL-6, and HMGB1 Expression

    Science.gov (United States)

    Sampaio, André L. F.; Dalli, Jesmond; Brancaleone, Vincenzo; D'Acquisto, Fulvio; Perretti, Mauro; Wheatley, Carmen

    2013-01-01

    Background. NOS/•NO inhibitors are potential therapeutics for sepsis, yet they increase clinical mortality. However, there has been no in vivo investigation of the (in vitro) •NO scavenger, cobalamin's (Cbl) endogenous effects on NOS/•NO/inflammatory mediators during the immune response to sepsis. Methods. We used quantitative polymerase chain reaction (qPCR), ELISA, Western blot, and NOS Griess assays, in a C57BL/6 mouse, acute endotoxaemia model. Results. During the immune response, pro-inflammatory phase, parenteral hydroxocobalamin (HOCbl) treatment partially inhibits hepatic, but not lung, iNOS mRNA and promotes lung eNOS mRNA, but attenuates the LPS hepatic rise in eNOS mRNA, whilst paradoxically promoting high iNOS/eNOS protein translation, but relatively moderate •NO production. HOCbl/NOS/•NO regulation is reciprocally associated with lower 4 h expression of TNF-α, IL-1β, COX-2, and lower circulating TNF-α, but not IL-6. In resolution, 24 h after LPS, HOCbl completely abrogates a major late mediator of sepsis mortality, high mobility group box 1 (HMGB1) mRNA, inhibits iNOS mRNA, and attenuates LPS-induced hepatic inhibition of eNOS mRNA, whilst showing increased, but still moderate, NOS activity, relative to LPS only. experiments (LPS+D-Galactosamine) HOCbl afforded significant, dose-dependent protection in mice Conclusions. HOCbl produces a complex, time- and organ-dependent, selective regulation of NOS/•NO during endotoxaemia, corollary regulation of downstream inflammatory mediators, and increased survival. This merits clinical evaluation. PMID:23781123

  8. Role of high mobility group box-1 and protection of growth hormone and somatostatin in severe acute pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Y.F. [Department of Surgery, Huashan Hospital, Fudan University, Shanghai (China); Wu, M. [Department of Surgery, Jinshan Pavilion Forest Hospital, Shanghai (China); Ma, B.J.; Cai, D.A.; Yin, B.B. [Department of Surgery, Huashan Hospital, Fudan University, Shanghai (China)

    2014-09-12

    In this study, we investigated the potential role of high-mobility group box 1 (HMGB1) in severe acute pancreatitis (SAP) and the effects of growth hormone (G) and somatostatin (S) in SAP rats. The rats were randomly divided into 6 groups of 20 each: sham-operated, SAP, SAP+saline, SAP+G, SAP+S and SAP+G+S. Ileum and pancreas tissues of rats in each group were evaluated histologically. HMGB1 mRNA expression was measured by reverse transcription-PCR. Levels of circulating TNF-α, IL-1, IL-6, and endotoxin were also measured. In the SAP group, interstitial congestion and edema, inflammatory cell infiltration, and interstitial hemorrhage occurred in ileum and pancreas tissues. The levels of HMGB1, TNF-α, IL-1, IL-6 and endotoxin were significantly up-regulated in the SAP group compared with those in the sham-operated group, and the 7-day survival rate was 0%. In the SAP+G and SAP+S groups, the inflammatory response of the morphological structures was alleviated, the levels of HMGB1, TNF-α, IL-1, IL-6, and endotoxin were significantly decreased compared with those in the SAP group, and the survival rate was increased. Moreover, in the SAP+G+S group, all histological scores were significantly improved and the survival rate was significantly higher compared with the SAP group. In conclusion, HMGB1 might participate in pancreas and ileum injury in SAP. Growth hormone and somatostatin might play a therapeutic role in the inflammatory response of SAP.

  9. Study of Transcription Activity of X-Box Binding Protein 1 Gene in Human Different Cell Lines%人类不同类型细胞中X-盒结合蛋白1转录活性研究

    Institute of Scientific and Technical Information of China (English)

    郭风劲; 宋方洲; 张静; 李婧; 唐勇

    2007-01-01

    Human X-box binding protein 1 (XBP1), an important transcription factor, participates in many signal transduction processes. To further investigate the biological function of XBP1, sequences of XBP1 promoter and its two deletion mutants were first determined using bioinformatic analysis. The report vectors containing XBP1 promoter and its deletion mutants were then constructed, namely, p1-XBP1p, p2-XBP1p, and p3-XBP1p. Each reporter vector was separately transfected into HepG2, L02, K562,SMMC-7721, HSF, and Lipocyte Ito Cell line using FuGENE 6 transfection reagents. The activity of chloramphenicol acetyltransferase (CAT) in each group of transfected cells was detected by ELISA assay, which in turn reflects the transcription activity of the XBP1 gene promoter. The activity involving p3-XBP1p was the highest in HepG2, which was 12.4-fold of that of pCAT3-Basic. The activities of p3-XBP1p in K562 and SMMC-7721 were the second and the third highest, which were 10.9-fold and 10.0-fold of that of the pCAT3-Basic, respectively. The CAT activity in L02 was lower than that in the above-mentioned abnormal cell, and no reporter activity was detected in HSF and Ito Cell. The XBP1 transcription and expression in K562, HepG2 and SMMC-7721 were found to be higher than that in L02, HSF and Ito cells, based on the results of real-time RT-PCR and Western blot. The XBP1 transcription and expression in L02, HSF was lower, whereas that in Ito cells was totally lacking. The result was similar to that of CAT-ELISA. Therefore, the XBP1 gene promoter can drive its downstream gene expression and its activity is cell line-dependent.The core sequence of XBP1 promoter was found between -227bp and 66bp sequence. This sequence was closely associated with the transcriptional activity of XBP1 promoter.%人类X-盒结合蛋白1(X-box binding protein1,XBP1)作为一种重要的转录因子,在细胞中涉及了广泛的信号调控过程.为进一步研究XBP1的生物学功能,首先利用

  10. PDGFRα-positive cells in bone marrow are mobilized by high mobility group box 1 (HMGB1) to regenerate injured epithelia

    OpenAIRE

    Tamai, Katsuto; Yamazaki, Takehiko; Chino, Takenao; Ishii, Masaru; Otsuru, Satoru; Kikuchi, Yasushi; Iinuma, Shin; Saga, Kotaro; Nimura, Keisuke; Shimbo, Takashi; Umegaki, Noriko; Katayama, Ichiro; Miyazaki, Jun-ichi; Takeda, Junji; McGrath, John A.

    2011-01-01

    The role of bone marrow cells in repairing ectodermal tissue, such as skin epidermis, is not clear. To explore this process further, this study examined a particular form of cutaneous repair, skin grafting. Grafting of full thickness wild-type mouse skin onto mice that had received a green fluorescent protein-bone marrow transplant after whole body irradiation led to an abundance of bone marrow-derived epithelial cells in follicular and interfollicular epidermis that persisted for at least 5 ...

  11. Mucosal immunization with high-mobility group box 1 in chitosan enhances DNA vaccine-induced protection against coxsackievirus B3-induced myocarditis.

    Science.gov (United States)

    Wang, Maowei; Yue, Yan; Dong, Chunsheng; Li, Xiaoyun; Xu, Wei; Xiong, Sidong

    2013-11-01

    Coxsackievirus B3 (CVB3), a small single-stranded RNA virus, belongs to the Picornaviridae family. Its infection is the most common cause of myocarditis, with no vaccine available. Gastrointestinal mucosa is the major entry port for CVB3; therefore, the induction of local immunity in mucosal tissues may help control initial viral infections and alleviate subsequent myocardial injury. Here we evaluated the ability of high-mobility group box 1 (HMGB1) encapsulated in chitosan particles to enhance the mucosal immune responses induced by the CVB3-specific mucosal DNA vaccine chitosan-pVP1. Mice were intranasally coimmunized with 4 doses of chitosan-pHMGB1 and chitosan-pVP1 plasmids, at 2-week intervals, and were challenged with CVB3 4 weeks after the last immunization. Compared with chitosan-pVP1 immunization alone, coimmunization with chitosan-pHMGB1 significantly (P loads, decreased myocardial injury, and increased survival rates. Flow cytometric analysis indicated that HMGB1 enhanced dendritic cell (DC) recruitment to mesenteric lymph nodes and promoted DC maturation, which might partly account for its mucosal adjuvant effect. This strategy may represent a promising approach to candidate vaccines against CVB3-induced myocarditis. PMID:24027262

  12. The Transcription Regulation and Molecular Mechanism of HSF1 on HMGB1%热休克转录因子1对高迁移率族蛋白B1的转录调控作用及机制

    Institute of Scientific and Technical Information of China (English)

    欧阳华伟; 罗成群

    2010-01-01

    目的:探讨烧伤血清诱导下热休克转录因子1(HSF1)对高迁移率族蛋白B1(HMGB1)的转录调控作用及其机制.方法:构建热休克转录因子1真核表达载体pcDNA3.1-HSF1,HMGB1野生型启动子荧光素酶报告基因pGL3-HMGB1-Y,HMGB1突变型启动子荧光素酶报告基因pGL3-HMGB1-T.pcDNA3.1-HSF1转染巨噬细胞RAW264.7,烧伤血清诱导后,半定量RT-PCR检测HMGB1 mRNA的表达.pcDNA3.1-HSF1,HMGB1启动子荧光素酶报告基因共转染RAW264.7,烧伤血清诱导后,检测并比较pGL3-HMGB1-Y和 pGL3-HMGB1-T的相对萤光素酶活性.结果:烧伤血清诱导下,HSF1可以下调RAW264.7 HMGB1mRNA的表达.pGL3-HMGB1-T的相对荧光素酶值较pGL3-HMGB1-Y明显下降,P<0.01,差异有显著统计学意义.结论:烧伤血清诱导下,HSF1可能通过与HMGB1启动子区HSE的结合下调小鼠巨噬细胞RAW264.7 HMGB1mRNA的表达.

  13. Carbon-ion beams induce production of an immune mediator protein, high mobility group box 1, at levels comparable with X-ray irradiation

    International Nuclear Information System (INIS)

    X-ray radiotherapy activates tumor antigen-specific T-cell responses, and increases in the serum levels of high mobility group box 1 (HMGB1) induced by X-ray irradiation play a pivotal role in activating anti-tumor immunity. Here, we examined whether carbon-ion beams, as well as X-rays, can induce HMGB1 release from human cancer cell lines. The study examined five human cancer cell lines: TE2, KYSE70, A549, NCI-H460 and WiDr. The proportion of cells surviving X- or carbon-ion beam irradiation was assessed in a clonogenic assay. The D10, the dose at which 10% of cells survive, was calculated using a linear–quadratic model. HMGB1 levels in the culture supernatants were assessed by an ELISA. The D10 dose for X-rays in TE2, KYSE70, A549, NCI-H460 and WiDr cells was 2.1, 6.7, 8.0, 4.8 and 7.1 Gy, respectively, whereas that for carbon-ion beams was 0.9, 2.5, 2.7, 1.8 and 3.5 Gy, respectively. X-rays and carbon-ion beams significantly increased HMGB1 levels in the culture supernatants of A549, NCI-H460 and WiDr cells at 72 h post-irradiation with a D10 dose. Furthermore, irradiation with X-rays or carbon-ion beams significantly increased HMGB1 levels in the culture supernatants of all five cell lines at 96 h post-irradiation. There was no significant difference in the amount of HMGB1 induced by X-rays and carbon-ion beams at any time-point (except at 96 h for NCI-H460 cells); thus we conclude that comparable levels of HMGB1 were detected after irradiation with iso-survival doses of X-rays and carbon-ion beams. (author)

  14. MicroRNA‑451 protects against cardiomyocyte anoxia/reoxygenation injury by inhibiting high mobility group box 1 expression.

    Science.gov (United States)

    Xie, Jing; Hu, Xiaorong; Yi, Chunfeng; Hu, Gangying; Zhou, Xiaoya; Jiang, Hong

    2016-06-01

    High mobility group box 1 (HMGB1) protein serves an important role in myocardial ischemia/reperfusion (I/R) injury. MicroRNAs (miRNAs) are a group of small non‑coding RNAs that regulate numerous signaling pathways involved in myocardial I/R injury. The present study aimed to investigate whether miR‑451 protects against cardiomyocyte anoxia/reoxygenation (A/R) injury by attenuating HMGB1 expression. Neonatal rat ventricular cardiomyocytes were prepared and then subjected to A/R injury. The effect of upregulation or downregulation of miR‑451 on cell viability, apoptosis, superoxide dismutase (SOD) activity, and the expression of cleaved‑caspase‑3 and HMGB1 were measured accordingly. A luciferase assay was performed to further confirm whether miR‑451 can directly recognize the 3'‑untranslated region of HMGB1 in HEK293 cells. The expression of miR‑451 was significantly decreased in the cardiomyocytes during A/R, and upregulation of miR‑451 led to increased miR‑451 expression (P<0.05). Upregulation of miR‑451 significantly attenuated the loss of cardiomyocyte viability (P<0.05) and increased the intracellular levels of SOD during A/R (P<0.05). Furthermore, upregulation of miR‑451 significantly decreased the apoptosis of cardiomyocytes during A/R (P<0.05). The HMGB1 mRNA and protein expression levels were significantly downregulated in the Ad‑miR‑451 group compared with those in the A/R group (P<0.05). In addition, upregulation of miR‑451 reduced its translocation from the nucleus to the cytoplasm. The luciferase assay confirmed that HMGB1 mRNA is a direct target of miR‑451 in cardiomyocytes. In conclusion, the present study suggested that upregulation of miR‑451 could protect against A/R‑induced cardiomyocyte injury by inhibiting HMGB1 expression. PMID:27121079

  15. Poly(ADP-ribose) polymerase activation induces high mobility group box 1 release from proximal tubular cells during cisplatin nephrotoxicity.

    Science.gov (United States)

    Kim, J

    2016-06-20

    Cisplatin is one of the most potent chemotherapy drugs against cancer, but its major side effect such as nephrotoxicity limits its use. Inhibition of poly(ADP-ribose) polymerase (PARP) protects against various renal diseases via gene transactivation and/or ADP-ribosylation. However, the role of PARP in necrotic cell death during cisplatin nephrotoxicity remains an open question. Here we demonstrated that pharmacological inhibition of PARP by postconditioning dose-dependently prevented tubular injury and renal dysfunction following cisplatin administration in mice. PARP inhibition by postconditioning also attenuated ATP depletion during cisplatin nephrotoxicity. Systemic release of high mobility group box 1 (HMGB1) protein in plasma induced by cisplatin administration was significantly diminished by PARP inhibition by postconditioning. In in vitro kidney proximal tubular cell lines, PARP inhibition by postconditioning also diminished HMGB1 release from cells. These data demonstrate that cisplatin-induced PARP1 activation contributes to HMGB1 release from kidney proximal tubular cells, resulting in the promotion of inflammation during cisplatin nephrotoxicity. PMID:26447520

  16. Tumor Necrosis Factor Receptor-associated Protein 1 (TRAP1) Mutation and TRAP1 Inhibitor Gamitrinib-triphenylphosphonium (G-TPP) Induce a Forkhead Box O (FOXO)-dependent Cell Protective Signal from Mitochondria.

    Science.gov (United States)

    Kim, Hyunjin; Yang, Jinsung; Kim, Min Ju; Choi, Sekyu; Chung, Ju-Ryung; Kim, Jong-Min; Yoo, Young Hyun; Chung, Jongkyeong; Koh, Hyongjong

    2016-01-22

    TRAP1 (tumor necrosis factor receptor-associated protein 1), a mitochondrial Hsp90 family chaperone, has been identified as a critical regulator of cell survival and bioenergetics in tumor cells. To discover novel signaling networks regulated by TRAP1, we generated Drosophila TRAP1 mutants. The mutants successfully developed into adults and produced fertile progeny, showing that TRAP1 is dispensable in development and reproduction. Surprisingly, mutation or knockdown of TRAP1 markedly enhanced Drosophila survival under oxidative stress. Moreover, TRAP1 mutation ameliorated mitochondrial dysfunction and dopaminergic (DA) neuron loss induced by deletion of a familial Parkinson disease gene PINK1 (Pten-induced kinase 1) in Drosophila. Gamitrinib-triphenylphosphonium, a mitochondria-targeted Hsp90 inhibitor that increases cell death in HeLa and MCF7 cells, consistently inhibited cell death induced by oxidative stress and mitochondrial dysfunction induced by PINK1 mutation in mouse embryonic fibroblast cells and DA cell models such as SH-SY5Y and SN4741 cells. Additionally, gamitrinib-triphenylphosphonium also suppressed the defective locomotive activity and DA neuron loss in Drosophila PINK1 null mutants. In further genetic analyses, we showed enhanced expression of Thor, a downstream target gene of transcription factor FOXO, in TRAP1 mutants. Furthermore, deletion of FOXO almost nullified the protective roles of TRAP1 mutation against oxidative stress and PINK1 mutation. These results strongly suggest that inhibition of the mitochondrial chaperone TRAP1 generates a retrograde cell protective signal from mitochondria to the nucleus in a FOXO-dependent manner. PMID:26631731

  17. Toll-like receptor 4 and high-mobility group box 1 are critical mediators of tissue injury and survival in a mouse model for heatstroke.

    Directory of Open Access Journals (Sweden)

    Mohammed Dehbi

    Full Text Available The molecular mechanisms that initiate the inflammatory response in heatstroke and their relation with tissue injury and lethality are not fully elucidated. We examined whether endogenous ligands released by damaged/stressed cells such as high-mobility group box 1 (HMGB1 signaling through Toll-like receptor 4 (TLR4 may play a pathogenic role in heatstroke. Mutant TLR4-defective (C3H/HeJ and wild type (C3H/HeOuJ mice were subjected to heat stress in an environmental chamber pre-warmed at 43.5 °C until their core temperature reached 42.7°C, which was taken as the onset of heatstroke. The animals were then allowed to recover passively at ambient temperature. A sham-heated group served as a control. Mutant mice displayed more histological liver damage and higher mortality compared with wild type mice (73% vs. 27%, respectively, P<0.001. Compared to wild type mice, mutant mice exhibited earlier plasma release of markers of systemic inflammation such as HMGB1 (206 ± 105 vs. 63 ± 21 ng/ml; P = 0.0018 and 209 ± 100 vs. 46 ± 32 ng/ml; P<0.0001, IL-6 (144 ± 40 vs. 46 ± 20 pg/ml; P<0.001 and 184 ± 21 vs. 84 ± 54 pg/ml; P = 0.04, and IL-1β (27 ± 4 vs. 1.7 ± 2.3 pg/ml; P<0.0001 at 1 hour. Both strains of mice displayed early release of HMGB1 into the circulation upstream of IL-1β and IL-6 responses which remained elevated up to 24 h. Specific inhibition of HMGB1 activity with DNA-binding A Box (600 µg/mouse protected the mutant mice against the lethal effect of heat stress (60% A Box vs. 18% GST protein, P = 0.04. These findings suggest a protective role for the TLR4 in the host response to severe heat stress. They also suggest that HMGB1 is an early mediator of inflammation, tissue injury and lethality in heatstroke in the presence of defective TLR4 signaling.

  18. High-mobility group box-1 protein and keratin-18, circulating serum proteins informative of acetaminophen-induced necrosis and apoptosis in vivo.

    Science.gov (United States)

    Antoine, Daniel J; Williams, Dominic P; Kipar, Anja; Jenkins, Rosalind E; Regan, Sophie L; Sathish, Jean G; Kitteringham, Neil R; Park, B Kevin

    2009-12-01

    Drug-induced hepatotoxicity represents a major clinical problem and an impediment to new medicine development. Serum biomarkers hold the potential to provide information about pathways leading to cellular responses within inaccessible tissues, which can inform the medicinal chemist and the clinician with respect to safe drug design and use. Hepatocyte apoptosis, necrosis, and innate immune activation have been defined as features of the toxicological response associated with the hepatotoxin acetaminophen (APAP). Within this investigation, we have unambiguously identified and characterized by liquid chromatography-tandem mass spectrometry differing circulating molecular forms of high-mobility group box-1 protein (HMGB1) and keratin-18 (K18), which are linked to the mechanisms and pathological changes induced by APAP in the mouse. Hypoacetylated HMGB1 (necrosis indicator), caspase-cleaved K18 (apoptosis indicator), and full-length K18 (necrosis indicator) present in serum showed strong correlations with the histological time course of cell death and was more sensitive than alanine aminotransferase activity. We have further identified a hyperacetylated form of HMGB1 (inflammatory indicator) in serum, which indicated that hepatotoxicity was associated with an inflammatory response. The inhibition of APAP-induced apoptosis and K18 cleavage by the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(OMe) fluoromethyl ketone are associated with increased hepatic damage, by a shift to necrotic cell death only. These findings illustrate the initial verification of K18 and HMGB1 molecular forms as serum-based sensitive tools that provide insights into the cellular dynamics involved in APAP hepatotoxicity within an inaccessible tissue. Based on these findings, potential exists for the qualification and measurement of these proteins to further assist in vitro, in vivo, and clinical bridging in toxicological research. PMID:19783637

  19. 高迁移率族蛋白B1对小鼠调节性T细胞与CD4+CD25-T细胞相互作用的影响%Influence of high mobility group box-1 protein on the correlation between regulatory T cells and CD4+CD25-T cells of spleen in mice

    Institute of Scientific and Technical Information of China (English)

    张莹; 姚咏明; 于燕; 吴瑶; 盛志勇

    2008-01-01

    Objective To investigate the influence of high mobility group box-1 protein(HMGB1)on the immunosuppression function of splenic regulatory T cells(Tregs)and its potential regulatory mechanism underlying the effect on CD4+CD25-T cells in mice.nethods CD4+CD25+Tregs isolated from the spleens of male BALB/c mice by magnetic beads were seeded on 96-well(1×105 cells/well)cell culture plates coated with 1 μg/ml anti-CD3 and soluble CD28.After being stimulated with HMGB1 for different time and concentrations,the secretions of IL-2 and IL-10 were analyzed by ELISA.Tregs stimulated for 72 hours were cultured with CD4+CD25-T cells together.The suppressive activity of CD4+CD25+Treg to CD4+CD25-T cells was analyzed by MTT test.IL-2,IL-10,IL-4,and interferon(IFN)-γ in the cell suspensions were determined by ELISA.Resuits After stimulation with HMGB1,the suppressive activity of splenic Tregs in mice were significantly down-regulated at 72 hours,when the proportion of Tregs to CD4+CD25-T cells was 1:1.The secretion of IL-2 of Tregs stimulated by HMGB1 was not markedly changed(P>0.05).while a dose-dependent decrease between IL-10 induction and HMGB1 concentration was obviously(P<0.05).When CD4+CD25-T cells were cultured with stimulated Tregs,comparing with unstimulated-Treg group,levels of IL-2 and IFN-γ were elevated following the increased concentration of HMGB1(P<0.05 or P<0.01).Meanwhile the secretion of IL-4 and IL-10 significantly decreased when cultured with stimulated Tregs(P<0.05).Conclusions These data suggested that HMGB1 stimulation can result in significant down-regulation of immunosuppression of splenic Tregs in mice.HMGB1 might be a potential immunoregnlatory signal that influences the proliferation of effector T cells,secretion of IL-2 and cells-polarization by inhibiting CD4+CD25+Tregs activity.%目的 观察高迁移率族蛋白B1(HMGB1)对调节性T细胞(Treg)与CD4+CD25-T细胞相互作用的影响,并初步探讨其影

  20. A Genome-wide Association Study Provides Evidence of Sex-specific Involvement of Chr1p35.1 (ZSCAN20-TLR12P and Chr8p23.1 (HMGB1P46 With Diabetic Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Weihua Meng

    2015-10-01

    Full Text Available Neuropathic pain is defined as pain arising as a direct consequence of a lesion or a disease affecting the somatosensory system and it affects around 1 in 4 diabetic patients in the UK. The purpose of this genome-wide association study (GWAS was to identify genetic contributors to this disorder. Cases of neuropathic pain were defined as diabetic patients with a multiple prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain. Controls were diabetic individuals who were not prescribed any of these drugs, nor amitriptyline, carbamazepine, or nortriptyline. Overall, 961 diabetic neuropathic pain cases and 3260 diabetic controls in the Genetics of Diabetes Audit and Research Tayside (GoDARTS cohort were identified. We found a cluster in the Chr1p35.1 (ZSCAN20-TLR12P with a lowest P value of 2.74 × 10−7 at rs71647933 in females and a cluster in the Chr8p23.1, next to HMGB1P46 with a lowest P value of 8.02 × 10−7 at rs6986153 in males. Sex-specific narrow sense heritability was higher in males (30.0% than in females (14.7%. This GWAS on diabetic neuropathic pain provides evidence for the sex-specific involvement of Chr1p35.1 (ZSCAN20-TLR12P and Chr8p23.1 (HMGB1P46 with the disorder, indicating the need for further research.

  1. An arginine-rich motif of ring finger protein 4 (RNF4) oversees the recruitment and degradation of the phosphorylated and SUMOylated Krüppel-associated box domain-associated protein 1 (KAP1)/TRIM28 protein during genotoxic stress.

    Science.gov (United States)

    Kuo, Ching-Ying; Li, Xu; Kong, Xiang-Qian; Luo, Cheng; Chang, Che-Chang; Chung, Yiyin; Shih, Hsiu-Ming; Li, Keqin Kathy; Ann, David K

    2014-07-25

    Krüppel-associated box domain-associated protein 1 (KAP1) is a universal transcriptional corepressor that undergoes multiple posttranslational modifications (PTMs), including SUMOylation and Ser-824 phosphorylation. However, the functional interplay of KAP1 PTMs in regulating KAP1 turnover during DNA damage response remains unclear. To decipher the role and cross-talk of multiple KAP1 PTMs, we show here that DNA double strand break-induced KAP1 Ser-824 phosphorylation promoted the recruitment of small ubiquitin-like modifier (SUMO)-targeted ubiquitin E3 ligase, ring finger protein 4 (RNF4), and subsequent RNF4-mediated, SUMO-dependent degradation. Besides the SUMO interacting motif (SIM), a previously unrecognized, but evolutionarily conserved, arginine-rich motif (ARM) in RNF4 acts as a novel recognition motif for selective target recruitment. Results from combined mutagenesis and computational modeling studies suggest that RNF4 utilizes concerted bimodular recognition, namely SIM for Lys-676 SUMOylation and ARM for Ser(P)-824 of simultaneously phosphorylated and SUMOylated KAP1 (Ser(P)-824-SUMO-KAP1). Furthermore, we proved that arginines 73 and 74 within the ARM of RNF4 are required for efficient recruitment to KAP1 or accelerated degradation of promyelocytic leukemia protein (PML) under stress. In parallel, results of bimolecular fluorescence complementation assays validated the role of the ARM in recognizing Ser(P)-824 in living cells. Taken together, we establish that the ARM is required for RNF4 to efficiently target Ser(P)-824-SUMO-KAP1, conferring ubiquitin Lys-48-mediated proteasomal degradation in the context of double strand breaks. The conservation of such a motif may possibly explain the requirement for timely substrate selectivity determination among a myriad of SUMOylated proteins under stress conditions. Thus, the ARM dynamically regulates the SIM-dependent recruitment of targets to RNF4, which could be critical to dynamically fine-tune the

  2. Einstein's Boxes

    CERN Document Server

    Norsen, T

    2005-01-01

    At the 1927 Solvay conference, Einstein presented a thought experiment intended to demonstrate the incompleteness of the quantum mechanical description of reality. In the following years, the thought experiment was picked up and modified by Einstein, de Broglie, and several other commentators into a simple scenario involving the splitting in half of the wave function of a single particle in a box. In this paper we collect together several formulations of this thought experiment from the existing literature; analyze and assess it from the point of view of the Einstein-Bohr debates, the EPR dilemma, and Bell's theorem; and generally lobby for Einstein's Boxes taking its rightful place alongside similar but historically better-known quantum mechanical thought experiments such as EPR and Schroedinger's Cat.

  3. Einstein's Boxes

    OpenAIRE

    Norsen, Travis

    2004-01-01

    At the 1927 Solvay conference, Einstein presented a thought experiment intended to demonstrate the incompleteness of the quantum mechanical description of reality. In the following years, the thought experiment was picked up and modified by Einstein, de Broglie, and several other commentators into a simple scenario involving the splitting in half of the wave function of a single particle in a box. In this paper we collect together several formulations of this thought experiment from the exist...

  4. 高迁移率蛋白-1对多发伤后全身炎症反应综合征的预警价值%The relationship between high-mobility group box-1 protein and the prognosis of patients with systemic inflammatory response syndrome after multiple trauma

    Institute of Scientific and Technical Information of China (English)

    唐伦先; 孙志扬

    2008-01-01

    Objective To observe the relationship between high-mobility group box-1 protein HMGB-1 andthe prognosis of systemic inflammatory response syndrome (SIRS) patients after multiple trauma. Method Sixtypatients with SIRS after multiple trauma in the emergency trauma center were divided into multiple organ dysfunc-tion syndrome (MODS) group and non-MODS group according to the MODS diagnostic criteria, and were followedup for 28 days and then assigned to survival group and fatal group, respectively. Another 20 healthy people wereera-oiled in the conrtol group. The levels of HMGB-1 were measured by ELISA at 24 hours, 3 days, 5 days and 7days after admission. APACHE Ⅱ scores were calculated. Results The concentrations of HMGB- 1 in the patientswith SIRS after trauma at every time point were higher than those in control group (P<0.01). The concentrationsof HMGB-1 and APACHEⅡ scores in the MODS group and the fatal group were higher than those in non-MODSgroup and the survival group (P<0.05 and P<0.01 separately). There was positive correlation between theconcentrations of HMGB-1 and APACHE Ⅱ scores (r=0.7938, P<0.05). Conclusions As an importantpro-inflammatory cytokine in sepsis, HMGB-1 may play a role in the development of SIRS after multiple trauma andcan be used to assess the severity of illness and prognosis.%目的 探讨血清HNGB-1水平对多发伤后全身炎症反应综合征(SIRS)患者病情发生发展的预警价值.方法 将60例入住上海市东方医院急诊创伤中心的多发伤后SIRS患者分为多器官功能障碍综合征组(MODS组)和非MODS组、存活组和死亡组,选择健康体检者20例作为对照组.检测试验组入院24 h、第3、5、7天和对照组血清HMGB-1浓度,并进行APACHE Ⅱ评分.结果 SIRS组入院后HNGB-1浓度进行性上升,各时间点浓度均明显高于对照组(P<0.01);NODS组和死亡组HMGB-1浓度分别明显高于非MODS组和存活组(P<0.05).MODS组的APACHEⅡ评分明显高于非MODS组(P<0

  5. 外源性一氧化碳释放分子对脓毒症大鼠肺组织高迁移率族蛋白B1表达的影响%Effect of extrinsic carbon monoxide releasing-molecule-2 on the expression of high mobility group box 1 in rats with sepsis-induced lung injury

    Institute of Scientific and Technical Information of China (English)

    徐丽; 鲍红光; 张勇; 刘晨辉; 张蕊

    2013-01-01

    Objective To investigate the effect of extrinsic carbon monoxide releasing-molecule-2 (CORM-2) on the expression of high mobility group box 1 (HMGB1) in rats with sepsis-induced lung injury.Methods The animal model of sepsis was established by ceal ligation and puncture (CLP) in 150 Wistar male rats,which were randomly divided into 3 groups:C group,CLP group and CORM-2 group.At 6,12,24,48,72 h,HMGB1 concentration in lung homogenate was detected by ELISA.Lung HMGB1 mRNA was detected with real-time fluorescent quantitative polymerase chain reaction (real-time RT-PCR),DNA-binding activity of STAT3 was analyzed by electrophoretic mobility shift assay (EMSA).Malonaldehyde (MDA) content in lung tissue and the wet-to-dry (W/D) weight ratio of lung tissue were determined.The extent of cell apoptosis was determined by flow cytometry.Results Compared with C group,gene and protein expression of HMGB1 in groups CLP,CORM-2 were increased,DNA-binding activity of STAT3 and MDA content in lung homogenate were raise,as well as the rates of apoptosis and lung W/D weight ratio.Compared with CLP group,gene and protein expression of HMGB1 in group CORM-2 was decreased,DNA-binding activity of STAT3 and MDA content in lung homogenate were lower,as well as the rates of apoptosis and lung W/D weight ratio.Conclusions CORM-2 intervention may down-regnlate HMGB 1 expression and attenuate lung injury in CLP-induced septic rats.%目的 研究外源性一氧化碳释放分子(CORM-2)对脓毒症大鼠肺组织高迁移率族蛋白B1(HMGB1)表达的影响.方法 盲肠结扎穿孔(CLP)法制备脓毒症动物模型,150只雄性Wistar大鼠,随机分为对照组(C组)、脓毒症模型组(CLP组)和CORM-2组(n=50),分别于术后6、12、24、48、72 h处死,采用酶联免疫吸附法(ELISA)检测肺组织匀浆中HMGB1表达水平,实时荧光定量聚合酶链反应(real-time PCR)法检测肺组织匀浆中HMGB1 mRNA的表达水平;凝胶阻滞电泳分析技术(EMSA)检测肺组织STAT3

  6. High Mobility Group Box-1 Promotes Inflammation-Induced Lymphangiogenesis via Toll-Like Receptor 4-Dependent Signalling Pathway

    Science.gov (United States)

    Zhao, Miying; Fan, Yiming; Li, Xiaorong

    2016-01-01

    Lymphangiogenesis in inflammation has received considerable attention in recent years. Administration of modulating lymphangiogenesis provides more possibilities of treating inflammation-associated diseases. However, the main mediators and factors governing inflammation-induced lymphangiogenesis (ILA) are yet to be defined. Here, we explored the role of HMGB1-TLR4 signalling pathway in modulating inflammation-induced lymphangiogenesis and its underlying mechanisms using an ILA mouse model and 2 cell lines. Our results show that HMGB1 promoted VEGF-C-induced HDLECs proliferation in a dose-dependent manner and TLR4 mediates HMGB1-induced LECs proliferation and tube formation in vitro. And in vivo, rHMGB1 treatment significantly promoted ILA, and the promoting effects was inhibited notably when HMGB1-TLR4 was blocked. HMGB1-associated ILA is primarily dependent on TLR4 but not on TLR2. In mechanisms, the recruitment and activation of CD11b+ cells are important cellular mechanisms in HMGB1-TLR4 associated ILA, and multiple key pro-lymphangiogenesis molecules mediates HMGB1-TLR4 associated ILA, including VEGF-C/VEGFR3, inflammatory factors IL-1β and TNF-α, MMP-2 and MMP-9 and NF-κB p65. In conclusion, HMGB1-associated ILA is primarily dependent on TLR4, and CD11b+ cells and multiple molecular mechanisms mediate HMGB1-TLR4 associated ILA. Furthermore, the ILA can be effectively modulated by HMGB1-TLR4 signalling. Consequently, administration of modulating ILA through HMGB1-TLR4 pathway may provide us more possibilities of treating inflammation and lymphangiogenesis associated diseases. PMID:27100831

  7. Laryngeal (Voice Box) Cancer

    Science.gov (United States)

    ... Meeting Calendar Find an ENT Doctor Near You Voice Box (Laryngeal) Cancer Voice Box (Laryngeal) Cancer Patient Health Information News media ... laryngeal cancer can be severe with respect to voice, breathing, or swallowing. It is fundamentally a preventable ...

  8. IFN-γ induces lipogenesis in mouse mesangial cells via the JAK2/STAT1 pathway.

    Science.gov (United States)

    Hao, Jun; Zhang, Yu-jun; Lv, Xin; Xu, Ning; Liu, Qin-juan; Zhao, Song; Feng, Xiao-juan; Xing, Ling-ling; Kang, Peng-peng; Li, Gui-ying; Liu, Shu-xia

    2013-04-15

    The objective is to investigate the effect of high mobility group box-1 (HMGB1) on lipid deposition in γ-interferon (IFN-γ)-stimulated mouse mesangial cell line (MMC) and to determine whether the Janus kinase 2 and signal transducer and activator of transcription 1 (JAK2/STAT1) signaling pathway plays an important role in this process. We employed a control group, an IFN-γ stimulation group, and an IFN-γ + AG490 (JAK2 inhibitor) group. RNA interference aimed at sterol regulatory element-binding protein-1 (SREBP-1) or HMGB1 was used to investigate the effect of these proteins on IFN-γ-induced lipid deposition. Western blotting was used to detect phospho (p)-JAK2, JAK2, p-STAT1, STAT1, SREBP-1, fatty acid synthase (FAS), and HMGB1 protein expression. RT-PCR was used to detect SREBP-1, FAS, and HMGB1 mRNA. Oil Red O staining and the triglyceride assay were used to detect lipid deposition and triglyceride content. Results were as follows: 1) IFN-γ increased MMC cell lipid deposition, triglyceride content, and p-JAK2, p-STAT1, SREBP-1, and FAS expression; 2) SREBP-1 inhibition prevented FAS upregulation and attenuated IFN-γ-induced MMC cell lipid deposition and triglyceride content; 3) HMGB1 upregulated SREBP-1 and FAS mRNA and protein levels, which increased lipid deposition in MMC cells. Small interfering RNA-mediated inhibition of HMGB1 decreased SREBP-1 and FAS expression and lipid accumulation; 4) AG490 decreased upregulation of HMGB1 and p-JAK2/p-STAT1, as well as IFN-γ-induced lipogenesis. In conclusion, the JAK2/STAT1 pathway mediates IFN-γ-induced lipogenesis in MMC cells through regulation of HMGB1/SREBP-1/FAS. PMID:23407880

  9. Fragile X mental retardation protein interactions with the microtubule associated protein 1B RNA

    OpenAIRE

    Menon, Lakshmi; Mader, Samantha Ann; Mihailescu, Mihaela-Rita

    2008-01-01

    Fragile X mental retardation syndrome, the most common form of inherited mental retardation, is caused by the absence of the fragile X mental retardation protein (FMRP). FMRP has been shown to use its arginine–glycine–glycine (RGG) box to bind to a subset of RNA targets that form a G quadruplex structure. We performed a detailed analysis of the interactions between the FMRP RGG box and the microtubule associated protein 1B (MAP1B) mRNA, a relevant in vivo FMRP target. We show that MAP1B RNA f...

  10. Shaping 3-D boxes

    DEFF Research Database (Denmark)

    Stenholt, Rasmus; Madsen, Claus B.

    2011-01-01

    Enabling users to shape 3-D boxes in immersive virtual environments is a non-trivial problem. In this paper, a new family of techniques for creating rectangular boxes of arbitrary position, orientation, and size is presented and evaluated. These new techniques are based solely on position data...

  11. The Maine Music Box

    OpenAIRE

    Lutz, Marilyn; Gallucci, Laura

    2005-01-01

    The paper describes the Maine Music Box and examines its potential as a tool for teaching and learning music. Pedagogical concepts are demonstrated using MIDI, Scorch, image and streaming video files.

  12. Voice box (image)

    Science.gov (United States)

    The larynx, or voice box, is located in the neck and performs several important functions in the body. The larynx is involved in swallowing, breathing, and voice production. Sound is produced when the air which ...

  13. The BOXES Methodology Black Box Dynamic Control

    CERN Document Server

    Russell, David W

    2012-01-01

    Robust control mechanisms customarily require knowledge of the system’s describing equations which may be of the high order differential type.  In order to produce these equations, mathematical models can often be derived and correlated with measured dynamic behavior.  There are two flaws in this approach one is the level of inexactness introduced by linearizations and the other when no model is apparent.  Several years ago a new genre of control systems came to light that are much less dependent on differential models such as fuzzy logic and genetic algorithms. Both of these soft computing solutions require quite considerable a priori system knowledge to create a control scheme and sometimes complicated training program before they can be implemented in a real world dynamic system. Michie and Chambers’ BOXES methodology created a black box system that was designed to control a mechanically unstable system with very little a priori system knowledge, linearization or approximation.  All the method need...

  14. Opto-Box

    CERN Document Server

    Bertsche, David; The ATLAS collaboration; Welch, Steven; Smith, Dale Shane; Che, Siinn; Gan, K.K.; Boyd, George Russell Jr

    2015-01-01

    The opto-box is a custom mini-crate for housing optical modules, which process and transfer optoelectronic data. The system tightly integrates electrical, mechanical, and thermal functionality into a small package of size 35x10x8 cm^3. Special attention was given to ensure proper shielding, grounding, cooling, high reliability, and environmental tolerance. The custom modules, which incorporate Application Specific Integrated Circuits (ASICs), were developed through a cycle of rigorous testing and redesign. In total, fourteen opto-boxes have been installed and loaded with modules on the ATLAS detector. They are currently in operation as part of the LHC run 2 data read-out chain.

  15. Teaching with Box Tops.

    Science.gov (United States)

    Raiser, Lynne; D'Zamko, Mary Elizabeth

    1984-01-01

    Using environmental materials (such as the phone book and placemats from fast food restaurants) can be a motivating way to teach learning disabled students skills and concepts, as shown in an approach to reading, math, science and nutrition, and social studies instruction using a JELL-O brand gelatin box. (CL)

  16. Hydrophobic, Porous Battery Boxes

    Science.gov (United States)

    Bragg, Bobby J.; Casey, John E., Jr.

    1995-01-01

    Boxes made of porous, hydrophobic polymers developed to contain aqueous potassium hydroxide electrolyte solutions of zinc/air batteries while allowing air to diffuse in as needed for operation. Used on other types of batteries for in-cabin use in which electrolytes aqueous and from which gases generated during operation must be vented without allowing electrolytes to leak out.

  17. Glove box posting system

    International Nuclear Information System (INIS)

    A system for posting objects into closed containers, such as glove boxes, is described in which the bag used, preferably made of plastic, does not have to be fitted and sealed by the operator during each posting operation. (U.K.)

  18. Cereal Box Totems.

    Science.gov (United States)

    Jones, AnnMarie

    2002-01-01

    Presents a multicultural project used with fourth-grade students in which they created a three-dimensional totem pole using leftover cereal boxes. Discusses in detail how to create the totem pole. Explains that students learned about Northwest American Indians in class. (CMK)

  19. PHOTOCHEMICAL BOX MODEL (PBM)

    Science.gov (United States)

    This magnetic tape contains the FORTRAN source code, sample input data, and sample output data for the Photochemical Box Model (PBM). The PBM is a simple stationary single-cell model with a variable height lid designed to provide volume-integrated hour averages of O3 and other ph...

  20. Decommissioning a small glove box

    International Nuclear Information System (INIS)

    An account is given of dismantling a fuel fabrication glove box using simple tooling. The fissile content of the box was first measured by several non-destructive techniques. After cleaning, the box was dismantled using hand tools and finally packed for disposal. A record of operator radiation doses, the time taken for each stage of the operation and packing information is given. (author)

  1. Opto-Box

    CERN Document Server

    Bertsche, David; The ATLAS collaboration

    2015-01-01

    The opto-box is a custom mini-crate for housing optical modules, which process and transfer optoelectronic data. Many novel solutions were developed for the custom design and manufacturing. The system tightly integrates electrical, mechanical, and thermal functionality into a small package of size 35x10x8 cm$^{3}$. Special attention was given to ensure proper shielding, grounding, cooling, high reliability, and environmental tolerance. The custom modules, which incorporate Application Specific Integrated Circuits (ASICs), were developed through a cycle of rigorous testing and redesign. In total, fourteen opto-boxes have been installed and loaded with modules on the ATLAS detector. They are currently in operation as part of the LHC run 2 data read-out chain.

  2. The Box Method

    DEFF Research Database (Denmark)

    Nielsen, Peter Vilhelm

    The velocity level in a room ventilated by jet ventilation is strongly influenced by the supply conditions. The momentum flow in the supply jets controls the air movement in the room and, therefore, it is very important that the inlet conditions and the numerical method can generate a satisfactor...... description of this momentum flow. The Box Method is a practical method for the description of an Air Terminal Device which will save grid points and ensure the right level of the momentum flow....

  3. Learning with box kernels.

    Science.gov (United States)

    Melacci, Stefano; Gori, Marco

    2013-11-01

    Supervised examples and prior knowledge on regions of the input space have been profitably integrated in kernel machines to improve the performance of classifiers in different real-world contexts. The proposed solutions, which rely on the unified supervision of points and sets, have been mostly based on specific optimization schemes in which, as usual, the kernel function operates on points only. In this paper, arguments from variational calculus are used to support the choice of a special class of kernels, referred to as box kernels, which emerges directly from the choice of the kernel function associated with a regularization operator. It is proven that there is no need to search for kernels to incorporate the structure deriving from the supervision of regions of the input space, because the optimal kernel arises as a consequence of the chosen regularization operator. Although most of the given results hold for sets, we focus attention on boxes, whose labeling is associated with their propositional description. Based on different assumptions, some representer theorems are given that dictate the structure of the solution in terms of box kernel expansion. Successful results are given for problems of medical diagnosis, image, and text categorization. PMID:24051728

  4. Inflammation and Epilepsy: The Foundations for a New Therapeutic Approach in Epilepsy?

    OpenAIRE

    Walker, Lauren; Sills, Graeme J.

    2012-01-01

    Emerging data from experimental epilepsy models and resected human brain tissue support the proposed involvement of innate immune system activation and consequent inflammation in epilepsy. Key mediators of this process include interleukin-1β, high-mobility group box protein 1 (HMGB1), and Toll-like receptor (TLR) signaling. These recent findings constitute the basis for a novel avenue of drug development in epilepsy, one that is not only distinct from previous approaches but uniquely based on...

  5. Projection optics box

    Science.gov (United States)

    Hale, Layton C.; Malsbury, Terry; Hudyma, Russell M.; Parker, John M.

    2000-01-01

    A projection optics box or assembly for use in an optical assembly, such as in an extreme ultraviolet lithography (EUVL) system using 10-14 nm soft x-ray photons. The projection optics box utilizes a plurality of highly reflective optics or mirrors, each mounted on a precision actuator, and which reflects an optical image, such as from a mask, in the EUVL system onto a point of use, such as a target or silicon wafer, the mask, for example, receiving an optical signal from a source assembly, such as a developed from laser system, via a series of highly reflective mirrors of the EUVL system. The plurality of highly reflective optics or mirrors are mounted in a housing assembly comprised of a series of bulkheads having wall members secured together to form a unit construction of maximum rigidity. Due to the precision actuators, the mirrors must be positioned precisely and remotely in tip, tilt, and piston (three degrees of freedom), while also providing exact constraint.

  6. Glove-box filters

    International Nuclear Information System (INIS)

    Description is given of a device for simply and rapidly assembling and dissassembling the filters used inside sealed enclosures, such as glove-boxes and shielded cells equipped with nippers or manipulators, said filters being of the type comprising a cylindrical casing containing a filtering member, the upper portion of said casing being open so as to allow the gases to be cleaned to flow in, whereas the casing bottom is centrally provided with a hole extended outwardly by a threaded collar on which is screwed a connecting-sleeve to be fixed to the mouth of a gas outlet pipe. To a yoke transverse bar is welded a pin which can be likened to a bent spring-blade, one arm of which welded to said transverse bar, is rectilinear whereas its other arm is provided with a boss cooperating with a cavity made in a protrusion of said pipe, right under the mouth thereof

  7. ACSYS in a box

    CERN Document Server

    Briegel, C; Hendricks, B; King, C; Lackey, S; Neswold, R; Nicklaus, D; Patrick, J; Petrov, A; Rechenmacher, R; Schumann, C; Smedinghoff, J

    2012-01-01

    The Accelerator Control System at Fermilab has evolved to enable this relatively large control system to be encapsulated into a "box" such as a laptop. The goal was to provide a platform isolated from the "online" control system. This platform can be used internally for making major upgrades and modifications without impacting operations. It also provides a standalone environment for research and development including a turnkey control system for collaborators. Over time, the code base running on Scientific Linux has enabled all the salient features of the Fermilab's control system to be captured in an off-the-shelf laptop. The anticipated additional benefits of packaging the system include improved maintenance, reliability, documentation, and future enhancements.

  8. Cardboard Boxes: Learning Concepts Galore!

    Science.gov (United States)

    Warner, Laverne; Wilmoth, Linda

    2007-01-01

    Mrs. Keenan, a preschool teacher, observed her 3-year-old granddaughter Riley pull, tug, and stack piles of holiday boxes on the floor. She remembered that her child care director had suggested using boxes as a curriculum theme, but she hadn't given much thought about the idea until now. She said to herself, "I wonder if my children would be as…

  9. Students' approaches to mathematical tasks using software as a black-box, glass-box or open-box

    OpenAIRE

    Hosein, Anesa

    2009-01-01

    Three mathematical software modes are investigated in this thesis: black-box software showing no mathematical steps; glass-box software showing the intermediate mathematical steps; and open-box software showing and allowing interaction at the intermediate mathematical steps. The glass-box and open-box software modes are often recommended over the black-box software to help understanding but there is limited research comparing all three. This research investigated students' performance and the...

  10. Method of positioning channel box

    International Nuclear Information System (INIS)

    Upon measuring the dimension of a channel box by disposing ultrasonic sensors to the uppermost portion of a measuring device main body, the deviation of the channel box from the center of the device main body is detected by measuring the distance betwen the sensors at the uppermost portion of the device main body and the lower end of the channel box for four surfaces simultaneously. The direction and the distance for moving the channel box to the center of the device main body are calculated based on the results to feedback tham for the operation of a fuel exchanger, thereby positioning the channel box upon insertion to the device main body. That is, a fuel assembly loaded with the channel box is gradually brought down being suspended from a crane and the position of the channel box is recognized by the ultrasonic sensors, thereafter, the position of the center is corrected and it is brought down again and the outer dimension is measured. Accurate positioning in a short periodof time is enabled and operator's burden can be mitigated to prevent the danger of indury. (N.H.)

  11. Microclimate boxes for panel paintings

    DEFF Research Database (Denmark)

    Wadum, Jørgen

    The use of microclimate boxes to protect vulnerable panel paintings is, therefore, not a new phenomenon of the past two or three decades. Rather, it has been a concern for conservators and curators to protect these objects of art at home and in transit since the end of the nineteenth century. The...... increased number of travelling exhibitions in recent years has heightened the need to protect paintings during circulation (Thomson 1961; Mecklenburg 1991). The use and design of microclimate boxes have been evolving since 1892. These boxes may be divided into three broad groups: those using an active...

  12. Two-dimensional box plot

    OpenAIRE

    Phattrawan Tongkumchum

    2005-01-01

    In this paper we propose a two-dimensional box plot, a simple bivariate extension of the box plot and the scatter plot. This plot comprises a pair of trapeziums oriented in the direction of a fitted straight line, with symbols denoting extreme values. The choice for the fitted straight resistant line showing the relationship between the two variables is Tukey’s resistance line. The main components of the plot are an inner box containing 50% of the projection points of the observations on the ...

  13. Genistein Increase Intracellular Distribution of the High Motility Group Box - 1 through p38 Pathway in HeLa culture cells induced by Tumor Necrosis Factor - α

    Directory of Open Access Journals (Sweden)

    Merlita Herbani

    2014-05-01

    Full Text Available Cervical cancer is one kind of many cancers that cause death to women around the world. Many studies had support the statement that inflammation has a strong linkage with cancer development. Several factors like proinflammatory factor can influence tumor cell microenvironment, and induce a faster proliferation. TNF-α is suspected can induce proliferation. While cancer itself can induce inflammation, which is marked by several marker. One of them is HMGB1, released from the cell as active secretory lysosomes or passive diffusion. Genistein has demonstrated growth inhibitory effects of various types of cancer cells. It inhibits tyrosine kinase pathway, which can be activated by TNF-α. One of those pathways that have the link with proliferation is p38. This study tries to reveal about inhibitory effect of genistein toward p38 pathway that had been activated by TNF-α. This research was conducted by exposing cultured HeLa cells with various doses of genistein for 90 minutes, and then exposed to TNF-α 10 ng / mL for 20 minutes. Observations were made with a confocal microscope, by staining the cells with pp38-TRITC and HMGB1 antibody. The intensity was measured and analyzed by Fluoview software. The results suggest that there be significant differences between pp38 intranuclear intensity and HMGB1 extranuclear intensity of each dose of genistein (p = 0.000, ANOVA. pp38 and HMGB1 intensity were increased along with increasing genistein dose, but at high dose there were noted decreasing of pp38 and HMGB1 intensity. At apoptotic dose, pp38 and HMGB1 intensity were increased markedly, showing the effect of apoptosis. In general, increasing doses of genistein increase intranuclear p38 activation and HMGB1 extranuclear translocation. So there were a strong linkage between p38 activation and HMGB1 translocation in this study.

  14. HMGB1 associates with TERT and stimulates telomerase activity

    Czech Academy of Sciences Publication Activity Database

    Kunická, Zuzana; Muselíková Polanská, Eva; Dvořáčková, Martina; Štros, Michal; Fajkus, Jiří

    Cold Spring Harbor, 2007. s. 85-85. [Telomeres & Telomerase. 02.05.2007-06.05.2007, Cold Spring Harbor] R&D Projects: GA ČR(CZ) GA521/05/0055; GA ČR(CZ) GA204/05/2031 Institutional research plan: CEZ:AV0Z50040507 Keywords : telomere * chromatin * high-mobility-group protein Subject RIV: BO - Biophysics

  15. Myiasis in two box turtles.

    Science.gov (United States)

    Gould, W J; Georgi, M E

    1991-10-15

    Two eastern box turtles (Terrapene carolina carolina) were treated for myiasis caused by Sarcophaga cistudinis. The tortoises were examined because of swellings of the proximal cervical regions. Both fully recovered following surgical removal of multiple larvae. PMID:1748614

  16. Thinking Outside the Box

    International Nuclear Information System (INIS)

    The World Nuclear Transport Institute was formed to fill a need to provide a dedicated vehicle for the radioactive transport and packaging industry sectors worldwide, to exchange information and ideas, all with a view to working toward consolidated industry positions on the key issues affecting safe, efficient and reliable transport. WNTI was also intended to be a strong voice for industry in those international and national bodies where deliberations on such transport safety issues take place. The very fact that companies, sometimes in competition with each other, were prepared to come together in this way, reflects two important points: firstly, it represents an acknowledgement on industry's part that safe, effective and reliable transport is the sine qua non, the absolute essential. And second, it is a recognition that it is enhanced to the extent that industry is able to collaborate to this end. This is thinking outside the box. Another important attribute of safety is 'stability'. Everyone likes to know where he or she stands. The radioactive materials packaging and transport industry thrives within a stable regulatory framework for safety. For a stable regulatory regime allows operators to be properly trained; it allows operators to become familiar with safety requirements, and to be at ease with them. Stability is conducive to safety and efficiency. Stability is good for business too - for stability in package and transport requirements allows sufficient time for a fair return on investment in expensive package design, manufacture, licensing and use over time. Stability should not, however, be opposed to creativity. From experience we can develop new thinking to improve efficiency as illustrated in examples of work related to the packaging and transport of Uranium Concentrates for instance.. Another example is work within WNTI on the thermal test requirements for the packaging of uranium hexafluoride. The robustness of packages is based on the risk factors

  17. Comparison of black-box, glass-box and open-box software for aiding conceptual understanding

    OpenAIRE

    Hosein, Anesa; Aczel, James; Clow, Doug; Richardson, John T. E.

    2008-01-01

    Three mathematical software types: black-box (no steps shown), glass-box (steps shown) and open-box (interactive steps) were used by 32 students to solve conceptual and procedural tasks on the computer via remote observation. Comparison of the three software types suggests that there is no difference in the scores that students receive for conceptual understanding tasks. Students using the black-box are more likely to explore answers than students using the glass and open-box software.

  18. Plate forming and break down pizza box

    Science.gov (United States)

    Pantisano, Frank; Devine, Scott M.

    1992-01-01

    A standard corrugated paper pizza box is provided with slit cuts cut through the top panel of the pizza box in a shape to form four circular serving plates with a beveled raised edge and cross slit cuts through the bottom panel of the pizza box separating the box into four essentially equal portions for easy disposal.

  19. First-aid boxes - Reminder

    CERN Multimedia

    GS Department

    2010-01-01

    With a view to ensuring optimum use of the first-aid boxes on the CERN site, we should like to remind you of various changes introduced in March 2009: The TSO of the buildings concerned is responsible for the first-aid boxes, including checking their contents.   First-aid boxes may be restocked ONLY at the CERN stores (SCEM No. 54.99.80). This is no longer possible at the Infirmary. The associated cost is charged to the Departments.   First-aid boxes should be used only for mild injuries. All other cases should be referred to the Medical Service Infirmary (Bldg. 57 – ground-floor, tel. 73802) between 8.00 a.m. and 5.30 p.m. or to the Fire and Rescue Service (tel. 74444). N.B.: This information does not apply to the red emergency first-aid boxes in the underground areas or to the emergency kits for use in the event of being splashed with hydrofluoric acid.

  20. Asymptotic Symmetries from finite boxes

    CERN Document Server

    Andrade, Tomas

    2015-01-01

    It is natural to regulate an infinite-sized system by imposing a boundary condition at finite distance, placing the system in a "box." This breaks symmetries, though the breaking is small when the box is large. One should thus be able to obtain the asymptotic symmetries of the infinite system by studying regulated systems. We provide concrete examples in the context of Einstein-Hilbert gravity (with negative or zero cosmological constant) by showing in 4 or more dimensions how the Anti-de Sitter and Poincar\\'e asymptotic symmetries can be extracted from gravity in a spherical box with Dirichlet boundary conditions. In 2+1 dimensions we obtain the full double-Virasoro algebra of asymptotic symmetries for AdS$_3$ and, correspondingly, the full Bondi-Metzner-Sachs (BMS) algebra for asymptotically flat space. In higher dimensions, a related approach may continue to be useful for constructing a good asymptotically flat phase space with BMS asymptotic symmetries.

  1. Asymptotic symmetries from finite boxes

    Science.gov (United States)

    Andrade, Tomás; Marolf, Donald

    2016-01-01

    It is natural to regulate an infinite-sized system by imposing a boundary condition at finite distance, placing the system in a 'box.' This breaks symmetries, though the breaking is small when the box is large. One should thus be able to obtain the asymptotic symmetries of the infinite system by studying regulated systems. We provide concrete examples in the context of Einstein-Hilbert gravity (with negative or zero cosmological constant) by showing in 4 or more dimensions how the anti-de Sitter and Poincaré asymptotic symmetries can be extracted from gravity in a spherical box with Dirichlet boundary conditions. In 2 + 1 dimensions we obtain the full double-Virasoro algebra of asymptotic symmetries for AdS3 and, correspondingly, the full Bondi-Metzner-Sachs (BMS) algebra for asymptotically flat space. In higher dimensions, a related approach may continue to be useful for constructing a good asymptotically flat phase space with BMS asymptotic symmetries.

  2. Identifying competencies of boxing coaches

    Directory of Open Access Journals (Sweden)

    Ioannis Tasiopoulos

    2014-10-01

    Full Text Available The purpose of this study was to find out the management skills required by boxing coaches to administrate their clubs. For the purposes of this study a scale was constructed which was answered by 98 boxing coaches. Explanatory factor analysis revealed seven factors: Communication-public relations (5 items, event management (4 items, management techniques (4 items, new technologies (4 items, prevention-safety (2 items, sport (5 items and sports facilities (2 items. The Cronbach of the scale was 0.85. The five competencies that rated by the coaches were: Supervisors of the area of training, maintaining excellent communication with athletes, using new technologies (e-mail, internet, handling disciplinary matters, accidents, complaints and reports on some sporting games and promoted harmony among athletes. We concluded that boxing coaches understand that the competencies required for meeting their obligations, were related to sports, prevention, safety and communications-public relations.

  3. Innovations in Los Alamos alpha box design

    International Nuclear Information System (INIS)

    Destructive examinations of irradiated fuel pins containing plutonium fuel must be performed in shielded hot cells with strict provisions for containing the plutonium. Alpha boxes provide containment for the plutonium, toxic fission products, and other hazardous highly radioactive materials. The alpha box contains windows for viewing and a variety of transfer systems specially designed to allow transfers in and out of the alpha box without spread of the hazardous materials that are contained in the box. Alpha boxes have been in use in the Wing 9 hot cells at Los Alamos National Laboratory for more than 20 years. Features of the newly designed alpha boxes are presented

  4. Innovations in Los Alamos alpha box design

    Energy Technology Data Exchange (ETDEWEB)

    Ledbetter, J.M.; Dowler, K.E.; Cook, J.H.

    1985-01-01

    Destructive examinations of irradiated fuel pins containing plutonium fuel must be performed in shielded hot cells with strict provisions for containing the plutonium. Alpha boxes provide containment for the plutonium, toxic fission products, and other hazardous highly radioactive materials. The alpha box contains windows for viewing and a variety of transfer systems specially designed to allow transfers in and out of the alpha box without spread of the hazardous materials that are contained in the box. Alpha boxes have been in use in the Wing 9 hot cells at Los Alamos National Laboratory for more than 20 years. Features of the newly designed alpha boxes are presented.

  5. Partons of a spherical box

    International Nuclear Information System (INIS)

    Calculation of parton distributions in the 'cavity approximation' to the MIT bag model gives a divergent sum of positive terms. In this version of the model the flexible movable bag is replaced by an inflexible immovable box. This suggests that Bjorken scaling does not hold for the deep inelastic scattering in this version of the model. (K.A.)

  6. On the Dirichlet's Box Principle

    Science.gov (United States)

    Poon, Kin-Keung; Shiu, Wai-Chee

    2008-01-01

    In this note, we will focus on several applications on the Dirichlet's box principle in Discrete Mathematics lesson and number theory lesson. In addition, the main result is an innovative game on a triangular board developed by the authors. The game has been used in teaching and learning mathematics in Discrete Mathematics and some high schools in…

  7. A Box Full of Kisses

    Institute of Scientific and Technical Information of China (English)

    崔增印

    2008-01-01

    The story goes that some time ago,a man pun- ished his 3-year-old daughter for wasting a roll of gold wrapping paper.Money was tight and he became infuriated when the child tried to decorate a box to put under the Christmas tree.Nevertheless,the little girl brought the gift to

  8. Legionella pneumophila infection induces programmed cell death, caspase activation, and release of high-mobility group box 1 protein in A549 alveolar epithelial cells: inhibition by methyl prednisolone

    Directory of Open Access Journals (Sweden)

    Koide Michio

    2008-05-01

    Full Text Available Abstract Background Legionella pneumophila pneumonia often exacerbates acute lung injury (ALI and acute respiratory distress syndrome (ARDS. Apoptosis of alveolar epithelial cells is considered to play an important role in the pathogenesis of ALI and ARDS. In this study, we investigated the precise mechanism by which A549 alveolar epithelial cells induced by L. pneumophila undergo apoptosis. We also studied the effect of methyl prednisolone on apoptosis in these cells. Methods Nuclear deoxyribonucleic acid (DNA fragmentation and caspase activation in L. pneumophila-infected A549 alveolar epithelial cells were assessed using the terminal deoxyribonucleotidyl transferase-mediated triphosphate (dUTP-biotin nick end labeling method (TUNEL method and colorimetric caspase activity assays. The virulent L. pneumophila strain AA100jm and the avirulent dotO mutant were used and compared in this study. In addition, we investigated whether methyl prednisolone has any influence on nuclear DNA fragmentation and caspase activation in A549 alveolar epithelial cells infected with L. pneumophila. Results The virulent strain of L. pneumophila grew within A549 alveolar epithelial cells and induced subsequent cell death in a dose-dependent manner. The avirulent strain dotO mutant showed no such effect. The virulent strains of L. pneumophila induced DNA fragmentation (shown by TUNEL staining and activation of caspases 3, 8, 9, and 1 in A549 cells, while the avirulent strain did not. High-mobility group box 1 (HMGB1 protein was released from A549 cells infected with virulent Legionella. Methyl prednisolone (53.4 μM did not influence the intracellular growth of L. pneumophila within alveolar epithelial cells, but affected DNA fragmentation and caspase activation of infected A549 cells. Conclusion Infection of A549 alveolar epithelial cells with L. pneumophila caused programmed cell death, activation of various caspases, and release of HMGB1. The dot/icm system, a

  9. Cosmetic Foot Surgery: Fashion's Pandora's Box

    Science.gov (United States)

    ... News, Videos & Podcasts » Articles » Text Size Print Bookmark Cosmetic Foot Surgery: Fashion’s Pandora’s Box? Cosmetic Foot Surgery: Fashion’s Pandora’s Box? Foot and Ankle Surgeons Warn ...

  10. The Heuristic Interpretation of Box Plots

    Science.gov (United States)

    Lem, Stephanie; Onghena, Patrick; Verschaffel, Lieven; Van Dooren, Wim

    2013-01-01

    Box plots are frequently used, but are often misinterpreted by students. Especially the area of the box in box plots is often misinterpreted as representing number or proportion of observations, while it actually represents their density. In a first study, reaction time evidence was used to test whether heuristic reasoning underlies this…

  11. Expression of high mobility group box 1 in the lung protection of oxygen controlled reperfusion against early ischemia-reperfusion injury with cardiopulmonary bypass in canines%氧控制性再灌注抗犬体外循环肺缺血再灌注早期损伤过程中高迁移族蛋白1的表达

    Institute of Scientific and Technical Information of China (English)

    荣健; 叶升; 吴钟凯; 陈光献; 梁孟亚; 刘海; 黄伟明; 王治平

    2010-01-01

    Objective To observe the expression of high mobility group box 1 (HMGB1)in the lung protection of oxygen controlled reperfusion against ischemia-reperfusion (I/R) with cardiopulmonary bypass (CPB) in canine. Methods Fourteen healthy canines were randomly divided into two groups:control group (n=7) and test group (n=7), and received CPB. The animals in the control group received 80% FiO2 throughout the whole procedure, whereas those in the test group received 40% immediately at the declamping of aorta, and an additional 10% every 5 min later until 80% FiO2 was reached. Other procedures were the same with control group. Arterial oxygen partial pressure (PaO2) was recorded after anesthesia was completed, before and at 5, 10, 15, 20, 25 min after sternotomy, and before withdrawal of CPB. HMGB1 expression by RT-PCR and Western blot, NF-κB expression by Western blot, IL-6 and TNF-α by ELISA were analyzed just after sternotomy(T1 ), 25 min after declamping(T2) and 90 min after declamping(T3). At the same time points, malondialdehyde, myeloperoxidase activity, wet/dry mass (Mw/MD) gnd tissue pathology were analyzed. Results PaO2 was significantly lower in the test group than that in the control group at 5, 10, 15 and 20 min after aortic declamping (all P<0.05). Compared with the control group at T2 and T3, the test group was found to have lower levels in HMGB1 mRNA and protein expressions (T2:0.926 0±0.013 9 vs 1.049 6±0.030 6;T3:0.832 5±0.015 4 vs 0.989 4±0.014 4, both P<0.05; T2:0.434 5±0.074 8 vs 0.551 2±0.047 4;T3:0.449 0±0.054 1vs 0.545 5±0.040 6, both P<0.05), NF-κB protein expression in the lung tissues, IL-6 and TNF-α in serum, Mw/MD ratio, MDA level and MPO activity (all P<0.05).Pathological scores in test group at T2 and T3 were significantly lower than those in control group (T2:2.0±0.7vs 3.8 ±0.5; T3:2.6±0.6 vs 4.2 ±0.8, both P<0.05). Conclusion Oxygen controlled reperfusion possesses lung protection in early stage of I/R injury with

  12. Box-shaped halophilic bacteria.

    OpenAIRE

    Javor, B; Requadt, C; Stoeckenius, W

    1982-01-01

    Three morphologically similar strains of halophilic, box-shaped procaryotes have been isolated from brines collected in the Sinai, Baja California (Mexico), and southern California (United States). Although the isolates in their morphology resemble Walsby's square bacteria, which are a dominant morphological type in the Red Sea and Baja California brines, they are probably not identical to them. The cells show the general characteristics of extreme halophiles and archaebacteria. They contain ...

  13. Broken links and black boxes

    DEFF Research Database (Denmark)

    Sindbæk, Søren Michael

    2013-01-01

    Long-distance communication has emerged as a particular focus for archaeological exploration using network theory, analysis, and modelling. Initial attempts to adapt methods from social network analysis to archaeological data have, however, struggled to produce decisive results. This paper argues...... ruined network from observable distributions and patterns of association in the archaeological record. In formal terms this is not a problem of network analysis, but network synthesis: the classic problem of cracking codes or reconstructing black-box circuits....

  14. Das k-Box-Produkt

    OpenAIRE

    Elser, Stefan

    2011-01-01

    Ziel dieser Doktorarbeit ist es, bekannte und oft verwendete Eigenschaften des Tychonow-Produkts in analoger Form für das k-Box-Produkt zu beweisen, was bisher noch nicht geschehen ist, und die Verbindung zwischen der Infinitären Kombinatorik und der Topologie zu vertiefen. In der Infinitären Kombinatorik, ein Zweig der modernen Mengenlehre, bedient man sich gerne topologischer Begriffe, um einerseits Ergebnisse zu verdeutlichen und um andererseits den sehr abstrakten kombinatorischen Be...

  15. Vascular barrier protective effects of baicalin, baicalein and wogonin in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Kwak, Soyoung [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Ku, Sae-Kwang [Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 712-715 (Korea, Republic of); Han, Min-Su [Laboratory for Arthritis and Bone Biology, Fatima Research Institute, Fatima Hospital, Daegu 701-600 (Korea, Republic of); Bae, Jong-Sup, E-mail: baejs@knu.ac.kr [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701 (Korea, Republic of)

    2014-11-15

    Inhibition of high mobility group box 1 (HMGB1) protein and restoration of endothelial integrity is emerging as an attractive therapeutic strategy in the management of sepsis. Here, three structurally related polyphenols found in the Chinese herb Huang Qui, baicalin (BCL), baicalein (BCN), and wogonin (WGN), were examined for their effects on lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-mediated release of HMGB1 and on modulation of HMGB1-mediated inflammatory responses. According to our data, BCL, BCN, and WGN inhibited the release of HMGB1 and down-regulated HMGB1-dependent inflammatory responses in human endothelial cells. BCL, BCN, and WGN also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with BCL, BCN, and WGN reduced CLP-induced release of HMGB1 and sepsis-related mortality and pulmonary injury in mice. These results indicate that BCL, BCN, and WGN could be candidate therapeutic agents for various severe vascular inflammatory diseases owing to their inhibition of the HMGB1 signaling pathway. - Highlights: • HMGB1 is an inflammatory mediator for vascular inflammation. • Baicalin, baicalein and wogonin inhibited HMGB1-induced hyperpermeability in vitro and in vivo. • Baicalin, baicalein and wogonin inhibited HMGB1-mediated inflammatory responses. • Baicalin, baicalein and wogonin suppressed the activation of NF-κB and ERK1/2 and production of TNF-α and IL-6. • Baicalin, baicalein and wogonin prevent CLP-induced septic mortality.

  16. Ionization box type radiation detector

    International Nuclear Information System (INIS)

    An ionization box for monitoring radiation rays, a first amplification circuit of a multi-stage amplification circuit employing a MOS type FET as an initial stage amplification device, a second amplification circuit employing a junction type FET as an initial stage amplification device, a first change-over switch for switching ionization current depending on input signals, a second change-over switch for switching output signals, and a signal level discrimination circuit are constituted integrally. When radiation dose rate is low, the ionization current is inputted to the first amplification circuit and outputted as a radiation ray monitor signal and, when the radiation dose rate is increased to higher than a predetermined value, the ionization current is inputted to the second amplification circuit and outputted as a radiation ray monitor signal. That is, monitoring accuracy is high when the ionization current is low since the MOS type FET of high input impedance is used. If the ionization current is higher than a predetermined value, there is no worry that the detection becomes impossible since the junction type FET having less worry of causing characteristic change due to high radiation dose rate is used. Accordingly, ionization box type monitor at a high monitoring reliability can be obtained. (N.H.)

  17. F-box proteins in flowering plants

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    In eukaryotes, the ubiquitin-mediated protein degradation pathway has been shown to control several key biological processes such as cell division, development, metabolism and immune response. F-box proteins, as a part of SCF (Skp1-Cullin (or Cdc53)-F-box) complex, functioned by interacting with substrate proteins, leading to their subsequent degradation by the 26S proteasome. To date, several F-box proteins identified in Arabidopsis and Antirrhinum have been shown to play important roles in auxin signal transduction, floral organ formation, flowering and leaf senescence. Arabidopsis genome sequence analysis revealed that it encodes over 1000 predicted F-box proteins accounting for about 5% of total predicted proteins. These results indicate that the ubiquitin-mediated protein degradation involving the F-box proteins is an important mechanism controlling plant gene expression. Here, we review the known F-box proteins and their functionsin flowering plants.

  18. Understanding Recommender Dynamics driving Box Office Revenues

    CERN Document Server

    Yeung, C H; Jin, C -H

    2010-01-01

    We introduce a simple model to investigate the underlying dynamics driving movie box office. Without an explicit reliance on time, the box office of movies evolves naturally by movie-movie competition through reviews listed on a centralized recommender system. A simple mean-field approximation is employed which assumes an average interaction between the competing movies, and describes the interesting box office dynamics. Box office hits are found for movies with quality beyond a critical value, leading to booms in gross box office. Such critical value is dependent on the reviewing behaviors, intention of movie goers for new movies, and the quality of the peer competing movies. Finally we compare our analytical results with simulations and real system and obtain qualitative agreements, suggesting the present model in describing the fundamental dynamics of box office.

  19. Metod of black box and their us

    OpenAIRE

    Novotný, Martin

    2013-01-01

    This thesis on a topic "black-box method and its use" deals with the description of the method of solving problematic tasks as a black box and its use in teaching. Using the theory of systems and cybernetics disciplines, especially cybernetic-pedagogy attempts to describe this method so that it is as efficient as possible and to maximize the benefits for students. Besides, the implementation of selected black box that will be suitable and used for teaching subjects electrotechnics, automatiza...

  20. Repackaging SRS Black Box TRU Waste

    International Nuclear Information System (INIS)

    Historically, large items of TRU Waste, which were too large to be packaged in drums for disposal have been packaged in various sizes of custom made plywood boxes at the Savannah River Site (SRS), for many years. These boxes were subsequently packaged into large steel ''Black Boxes'' for storage at SRS, pending availability of Characterization and Certification capability, to facilitate disposal of larger items of TRU Waste. There are approximately 107 Black Boxes in inventory at SRS, each measuring some 18' x 12' x 7', and weighing up to 45,000 lbs. These Black Boxes have been stored since the early 1980s. The project to repackage this waste into Standard Large Boxes (SLBs), Standard Waste Boxes (SWB) and Ten Drum Overpacks (TDOP), for subsequent characterization and WIPP disposal, commenced in FY04. To date, 10 Black Boxes have been repackaged, resulting in 40 SLB-2's, and 37 B25 overpack boxes, these B25's will be overpacked in SLB-2's prior to shipping to WIPP. This paper will describe experience to date from this project

  1. Interchangeable breech lock for glove boxes

    Energy Technology Data Exchange (ETDEWEB)

    Lemonds, David Preston

    2015-11-24

    A breech lock for a glove box is provided that may be used to transfer one or more items into the glove box. The breech lock can be interchangeably installed in place of a plug, glove, or other device in a port or opening of a glove box. Features are provided to aid the removal of items from the breech lock by a gloved operator. The breech lock can be reused or, if needed, can be replaced with a plug, glove, or other device at the port or opening of the glove box.

  2. Immunohistochemical localization of dentin matrix protein 1 in human dentin

    OpenAIRE

    G Orsini; Ruggeri, A.; Mazzoni, A.; Nato, F; Falconi, M; Putignano, A; Di Lenarda, R.; A Nanci; Breschi, L.

    2009-01-01

    Dentin matrix protein 1 (DMP1) is a non-collagenous matrix protein with a recognized role in the formation of mineralized tissues such as dentin. The aim of this study was to analyze the distribution of DMP1 in human dentin by means of immunofluorescence and high-resolution immunogold labeling. Fully developed, sound human dentin specimens were submitted to fluorescence labeling and post-embedding immunolabeling techniques with a rabbit polyclonal antihuman DMP1 antibody followed by correspon...

  3. Model Equations: "Black Box" Reconstruction

    Science.gov (United States)

    Bezruchko, Boris P.; Smirnov, Dmitry A.

    Black box reconstruction is both the most difficult and the most tempting modelling problem when any prior information about an appropriate model structure is lacking. An intriguing thing is that a model capable of reproducing an observed behaviour or predicting further evolution should be obtained only from an observed time series, i.e. "from nothing" at first sight. Chances for a success are not large. Even more so, a "good" model would become a valuable tool to characterise an object and understand its dynamics. Lack of prior information causes one to utilise universal model structures, e.g. artificial neural networks, radial basis functions and algebraic polynomials are included in the right-hand sides of dynamical model equations. Such models are often multi-dimensional and involve quite many free parameters.

  4. Unification of box shapes in molecular simulations

    NARCIS (Netherlands)

    Bekker, H.

    1997-01-01

    In molecular simulations with periodic boundary conditions the computational box may have five different shapes: triclinic; the hexagonal prism; two types of dodecahedrons; and the truncated octahedron. In this article, we show that every molecular simulation, formulated in one of these boxes, can b

  5. Black-Box Search by Unbiased Variation

    DEFF Research Database (Denmark)

    Lehre, Per Kristian; Witt, Carsten

    2012-01-01

    The complexity theory for black-box algorithms, introduced by Droste, Jansen, and Wegener (Theory Comput. Syst. 39:525–544, 2006), describes common limits on the efficiency of a broad class of randomised search heuristics. There is an obvious trade-off between the generality of the black-box model...

  6. Cosmetic Foot Surgery: Fashion's Pandora's Box

    Science.gov (United States)

    ... Fashion’s Pandora’s Box? A A A | Print | Share Cosmetic Foot Surgery: Fashion’s Pandora’s Box? Foot and ankle ... extreme and imprudent as it may sound, the cosmetic surgery craze isn't just for faces anymore- ...

  7. Modern biotechnology Panacea or new Pandora's box?

    NARCIS (Netherlands)

    Tramper, J.; Yang Zhu, Yang

    2011-01-01

    According to Greek mythology Pandora was sent down to earth upon the orders of Zeus. She was given a mysterious box which she was not allowed to open. However, Pandora was very curious and when she arrived on earth she couldn?t help taking a peek inside the box. She saw that it was filled with gifts

  8. Box Plots in the Australian Curriculum

    Science.gov (United States)

    Watson, Jane M.

    2012-01-01

    This article compares the definition of "box plot" as used in the "Australian Curriculum: Mathematics" with other definitions used in the education community; describes the difficulties students experience when dealing with box plots; and discusses the elaboration that is necessary to enable teachers to develop the knowledge necessary to use them…

  9. 49 CFR 178.515 - Standards for reconstituted wood boxes.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Standards for reconstituted wood boxes. 178.515... wood boxes. (a) The identification code for a reconstituted wood box is 4F. (b) Construction requirements for reconstituted wood boxes are as follows: (1) The walls of boxes must be made of...

  10. Myocardial ischemic preconditioning upregulated protein 1(Mipu1):zinc finger protein 667 - a multifunctional KRAB/C2H2 zinc finger protein

    International Nuclear Information System (INIS)

    Myocardial ischemic preconditioning upregulated protein 1 (Mipu1) is a newly discovered upregulated gene produced in rats during the myocardial ischemic preconditioning process. Mipu1 cDNA contains a 1824-base pair open reading frame and encodes a 608 amino acid protein with an N-terminal Krüppel-associated box (KRAB) domain and classical zinc finger C2H2 motifs in the C-terminus. Mipu1 protein is located in the cell nucleus. Recent studies found that Mipu1 has a protective effect on the ischemia-reperfusion injury of heart, brain, and other organs. As a nuclear factor, Mipu1 may perform its protective function through directly transcribing and repressing the expression of proapoptotic genes to repress cell apoptosis. In addition, Mipu1 also plays an important role in regulating the gene expression of downstream inflammatory mediators by inhibiting the activation of activator protein-1 and serum response element

  11. Myocardial ischemic preconditioning upregulated protein 1(Mipu1):zinc finger protein 667 - a multifunctional KRAB/C{sub 2}H{sub 2} zinc finger protein

    Energy Technology Data Exchange (ETDEWEB)

    Han, D.; Zhang, C. [Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, Post-doctoral Mobile Stations for Basic Medicine, University of South China, Hengyang City, Hunan Province (China); Fan, W.J. [Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, Post-doctoral Mobile Stations for Basic Medicine, University of South China, Hengyang City, Hunan Province (China); The Second Affiliated Hospital, University of South China, Hengyang City, Hunan Province (China); Pan, W.J.; Feng, D.M.; Qu, S.L.; Jiang, Z.S. [Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, Post-doctoral Mobile Stations for Basic Medicine, University of South China, Hengyang City, Hunan Province (China)

    2014-10-31

    Myocardial ischemic preconditioning upregulated protein 1 (Mipu1) is a newly discovered upregulated gene produced in rats during the myocardial ischemic preconditioning process. Mipu1 cDNA contains a 1824-base pair open reading frame and encodes a 608 amino acid protein with an N-terminal Krüppel-associated box (KRAB) domain and classical zinc finger C{sub 2}H{sub 2} motifs in the C-terminus. Mipu1 protein is located in the cell nucleus. Recent studies found that Mipu1 has a protective effect on the ischemia-reperfusion injury of heart, brain, and other organs. As a nuclear factor, Mipu1 may perform its protective function through directly transcribing and repressing the expression of proapoptotic genes to repress cell apoptosis. In addition, Mipu1 also plays an important role in regulating the gene expression of downstream inflammatory mediators by inhibiting the activation of activator protein-1 and serum response element.

  12. Improvements relating to glove boxes

    International Nuclear Information System (INIS)

    It is stated that radiation problems with glove boxes can only be partly overcome by adding shielding to their working faces, since about 25% of the working face may be taken up with glove ports at which the only shielding provided is that of the glove. A glove port cover is here described, mountable above the port, comprising a number of flaps of lead-loaded flexible material. The flaps can be pushed aside by hand to permit access to a glove fixed in the port, but overlap to close off the port when the hand is withdrawn. The lead loaded flexible material preferably has a natural or synthetic rubber base. Constructional details are given. Only the flaps need to be lead-loaded, and to facilitate manufacture and handling the surfaces of the cover are preferably lead-free. Three flaps can suffice, but five or six are preferred. For mounting purposes a cover may have beading at its periphery for clamped location in a groove round the glove port. (U.K.)

  13. Packing a cake into a box

    KAUST Repository

    Skopenkov, Mikhail

    2011-05-01

    Given a triangular cake and a box in the shape of its mirror image, how can the cake be cut into a minimal number of pieces so that it can be put into the box? The cake has icing, so we are not allowed to put it into the box upside down. V. G. Boltyansky asked this question in 1977 and showed that three pieces always suffice. In this paper we provide examples of cakes that cannot be cut into two pieces to be put into the box. This shows that three is the answer to Boltyansky\\'s question. We also give examples of cakes which can be cut into two pieces. © THE MATHEMATICAL ASSOCIATION OF AMERICA.

  14. Spacer for supporting fuel element boxes

    International Nuclear Information System (INIS)

    A spacer plate unit arranged externally on each side and at a predetermined level of a polygonal fuel element box for mutually supporting, with respect to one another, a plurality of the fuel element boxes forming a fuel element bundle, is formed of a first and a second spacer plate part each having the same length and the same width and being constituted of unlike first and second materials, respectively. The first and second spacer plate parts of the several spacer plate units situated at the predetermined level are arranged in an alternating continuous series when viewed in the peripheral direction of the fuel element box, so that any two spacer plate units belonging to face-to-face oriented sides of two adjoining fuel element boxes in the fuel element bundle define interfaces of unlike materials

  15. Mystery Boxes, X Rays, and Radiology.

    Science.gov (United States)

    Thomson, Norman

    2000-01-01

    Indicates the difficulties of teaching concepts beyond light and color and creating memorable learning experiences. Recommends sequential activities using the mystery box approach to explain how scientists and doctors use photon applications. (YDS)

  16. Packing a cake into a box

    CERN Document Server

    Skopenkov, Mikhail

    2010-01-01

    Given a cake in form of a triangle and a box that fits the mirror image of the cake, how to cut the cake into a minimal number of pieces so that it can be put into the box? The cake has an icing, so that we are not allowed to put it into the box upside down. V.G. Boltyansky asked this question in 1977 and showed that three pieces always suffice. In this paper we provide examples of cakes that cannot be cut into two pieces to put into the box. This shows that three is the answer to V.G. Boltyansky's question. Also we give examples of cakes which can be cut into two pieces.

  17. Structural studies of human glioma pathogenesis-related protein 1

    International Nuclear Information System (INIS)

    Structural analysis of a truncated soluble domain of human glioma pathogenesis-related protein 1, a membrane protein implicated in the proliferation of aggressive brain cancer, is presented. Human glioma pathogenesis-related protein 1 (GLIPR1) is a membrane protein that is highly upregulated in brain cancers but is barely detectable in normal brain tissue. GLIPR1 is composed of a signal peptide that directs its secretion, a conserved cysteine-rich CAP (cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 proteins) domain and a transmembrane domain. GLIPR1 is currently being investigated as a candidate for prostate cancer gene therapy and for glioblastoma targeted therapy. Crystal structures of a truncated soluble domain of the human GLIPR1 protein (sGLIPR1) solved by molecular replacement using a truncated polyalanine search model of the CAP domain of stecrisp, a snake-venom cysteine-rich secretory protein (CRISP), are presented. The correct molecular-replacement solution could only be obtained by removing all loops from the search model. The native structure was refined to 1.85 Å resolution and that of a Zn2+ complex was refined to 2.2 Å resolution. The latter structure revealed that the putative binding cavity coordinates Zn2+ similarly to snake-venom CRISPs, which are involved in Zn2+-dependent mechanisms of inflammatory modulation. Both sGLIPR1 structures have extensive flexible loop/turn regions and unique charge distributions that were not observed in any of the previously reported CAP protein structures. A model is also proposed for the structure of full-length membrane-bound GLIPR1

  18. Structural studies of human glioma pathogenesis-related protein 1

    Energy Technology Data Exchange (ETDEWEB)

    Asojo, Oluwatoyin A., E-mail: oasojo@unmc.edu [College of Medicine, Nebraska Medical Center, Omaha, NE 68198-6495 (United States); Koski, Raymond A.; Bonafé, Nathalie [L2 Diagnostics LLC, 300 George Street, New Haven, CT 06511 (United States); College of Medicine, Nebraska Medical Center, Omaha, NE 68198-6495 (United States)

    2011-10-01

    Structural analysis of a truncated soluble domain of human glioma pathogenesis-related protein 1, a membrane protein implicated in the proliferation of aggressive brain cancer, is presented. Human glioma pathogenesis-related protein 1 (GLIPR1) is a membrane protein that is highly upregulated in brain cancers but is barely detectable in normal brain tissue. GLIPR1 is composed of a signal peptide that directs its secretion, a conserved cysteine-rich CAP (cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 proteins) domain and a transmembrane domain. GLIPR1 is currently being investigated as a candidate for prostate cancer gene therapy and for glioblastoma targeted therapy. Crystal structures of a truncated soluble domain of the human GLIPR1 protein (sGLIPR1) solved by molecular replacement using a truncated polyalanine search model of the CAP domain of stecrisp, a snake-venom cysteine-rich secretory protein (CRISP), are presented. The correct molecular-replacement solution could only be obtained by removing all loops from the search model. The native structure was refined to 1.85 Å resolution and that of a Zn{sup 2+} complex was refined to 2.2 Å resolution. The latter structure revealed that the putative binding cavity coordinates Zn{sup 2+} similarly to snake-venom CRISPs, which are involved in Zn{sup 2+}-dependent mechanisms of inflammatory modulation. Both sGLIPR1 structures have extensive flexible loop/turn regions and unique charge distributions that were not observed in any of the previously reported CAP protein structures. A model is also proposed for the structure of full-length membrane-bound GLIPR1.

  19. Decommissioning a tritium glove-box facility

    Energy Technology Data Exchange (ETDEWEB)

    Folkers, C.L.; Homann, S.G.; Nicolosi, A.S.; Hanel, S.L.; King, W.C.

    1979-08-08

    A large glove-box facility for handling reactive metal tritides was decommissioned. Major sections of the glove box were decontaminated and disassembled for reuse at another tritium facility. To achieve the desired results, decontamnation required repeated washing, first with organic liquids, then with water and detergents. Worker protection was provided by simple ventilation combined with careful monitoring of the work areas and employees. Several innovative techniques are described.

  20. Decommissioning a tritium glove-box facility

    International Nuclear Information System (INIS)

    A large glove-box facility for handling reactive metal tritides was decommissioned. Major sections of the glove box were decontaminated and disassembled for reuse at another tritium facility. To achieve the desired results, decontamnation required repeated washing, first with organic liquids, then with water and detergents. Worker protection was provided by simple ventilation combined with careful monitoring of the work areas and employees. Several innovative techniques are described

  1. SET Backaction on the Single Electron Box

    OpenAIRE

    Turek, B. A.; Lehnert, K. W.; Clerk, A.; Gunnarsson, D.; Bladh, K.; Delsing, P.; Schoelkopf, R. J.

    2005-01-01

    We report an experimental observation of the backaction of a Single Electron Transistor (SET) measuring the Coulomb staircase of a single electron box. As current flows through the SET, the charge state of the SET island fluctuates. These fluctuations capacitively couple to the box and cause changes in the position, width, and asymmetry of the Coulomb staircase. A sequential tunnelling model accurately recreates these effects, confirming this mechanism of the backaction of an SET. This is a f...

  2. Random Young diagrams in a Rectangular Box

    DEFF Research Database (Denmark)

    Beltoft, Dan; Boutillier, Cédric; Enriquez, Nathanaël

    We exhibit the limit shape of random Young diagrams having a distribution proportional to the exponential of their area, and confined in a rectangular box. The Ornstein-Uhlenbeck bridge arises from the fluctuations around the limit shape.......We exhibit the limit shape of random Young diagrams having a distribution proportional to the exponential of their area, and confined in a rectangular box. The Ornstein-Uhlenbeck bridge arises from the fluctuations around the limit shape....

  3. A comparison of high-mobility group-box 1 protein, lipopolysaccharide-binding protein and procalcitonin in severe community-acquired infections and bacteraemia: a prospective study

    DEFF Research Database (Denmark)

    Gaïni, Shahin; Koldkjaer, Ole G; Møller, Holger J;

    2008-01-01

    immune response when the host is challenged by bacterial pathogens. Procalcitonin (PCT) has been suggested as a marker of severe bacterial infections and sepsis. The aim of the present study was to investigate levels of HMGB1, LBP and PCT in a well-characterised sepsis cohort. The study plan included...

  4. HYDROGEN AND VOC RETENTION IN WASTE BOXES

    Energy Technology Data Exchange (ETDEWEB)

    PACE ME; MARUSICH RM

    2008-11-21

    The Hanford Waste Management Project Master Documented Safety Analysis (MDSA) (HNF-14741, 2003) identifies derived safety controls to prevent or mitigate the risks of a single-container deflagration during operations requiring moving, venting or opening transuranic (TRU)-waste containers. The issue is whether these safety controls are necessary for operations involving TRU-waste boxes that are being retrieved from burial at the Hanford Site. This paper investigates the potential for a deflagration hazard within these boxes and whether safety controls identified for drum deflagration hazards should be applied to operations involving these boxes. The study evaluates the accumulation of hydrogen and VOCs within the waste box and the transport of these gases and vapors out of the waste box. To perform the analysis, there were numerous and major assumptions made regarding the generation rate and the transport pathway dimensions and their number. Since there is little actual data with regards to these assumptions, analyses of three potential configurations were performed to obtain some indication of the bounds of the issue (the concentration of hydrogen or flammable VOCs within a waste box). A brief description of each of the three cases along with the results of the analysis is summarized.

  5. Toll-Like Receptor 4 Is Essential in the Development of Abdominal Aortic Aneurysm.

    Directory of Open Access Journals (Sweden)

    Chao-Han Lai

    Full Text Available Toll-like receptor (TLR family plays a key role in innate immunity and various inflammatory responses. TLR4, one of the well-characterized pattern-recognition receptors, can be activated by endogenous damage-associated molecular pattern molecules such as high mobility group box 1 (HMGB1 to sustain sterile inflammation. Evidence suggested that blockade of TLR4 signaling may confer protection against abdominal aortic aneurysm (AAA. Herein we aimed to obtain further insight into the mechanism by which TLR4 might promote aneurysm formation. Characterization of the CaCl2-induced AAA model in mice revealed that upregulation of TLR4 expression, localized predominantly to vascular smooth muscle cells (VSMCs, was followed by a late decline during a 28-day period of AAA development. In vitro, TLR4 expression was increased in VSMCs treated with HMGB1. Knockdown of TLR4 by siRNA attenuated HMGB1-enhanced production of proinflammatory cytokines, specifically interleukin-6 and monocyte chemoattractant protein-1 (MCP-1, and matrix-degrading matrix metalloproteinase (MMP-2 from VSMCs. In vivo, two different strains of TLR4-deficient (C57BL/10ScNJ and C3H/HeJ mice were resistant to CaCl2-induced AAA formation compared to their respective controls (C57BL/10ScSnJ and C3H/HeN. Knockout of TLR4 reduced interleukin-6 and MCP-1 levels and HMGB1 expression, attenuated macrophage accumulation, and eventually suppressed MMP production, elastin destruction and VSMC loss. Finally, human AAA exhibited higher TLR4 expression that was localized to VSMCs. These data suggest that TLR4 signaling contributes to AAA formation by promoting a proinflammatory status of VSMCs and by inducing proteinase release from VSMCs during aneurysm initiation and development.

  6. 49 CFR 178.517 - Standards for plastic boxes.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Standards for plastic boxes. 178.517 Section 178... PACKAGINGS Non-bulk Performance-Oriented Packaging Standards § 178.517 Standards for plastic boxes. (a) The following are identification codes for plastic boxes: (1) 4H1 for an expanded plastic box; and (2) 4H2 for...

  7. 49 CFR 230.101 - Steam locomotive driving journal boxes.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Steam locomotive driving journal boxes. 230.101... Locomotives and Tenders Running Gear § 230.101 Steam locomotive driving journal boxes. (a) Driving journal boxes. Driving journal boxes shall be maintained in a safe and suitable condition for service. Not...

  8. Effect of an odor eliminator on feline litter box behavior.

    Science.gov (United States)

    Cottam, Nicole; Dodman, Nicholas H

    2007-02-01

    Decreasing litter box odor may be an important treatment component in addressing feline inappropriate elimination. A three-phase study was conducted to determine if the use of Zero Odor litter box spray increases the preference of litter boxes to cats, presumably by its odor-eliminating quality. In the first phase, cats were given a litter box preference test between a litter box sprayed with Zero Odor and one without. In the second phase, the number of occurrences of behaviors indicative of a cat's dissatisfaction with the litter box (scratching at the sides of the box, floor or wall, hesitating when entering the litter box, balancing on the side of the box and eliminating outside of the litter box) was compared before and after the use of Zero Odor. Last, the frequency of eliminations that occurred outside the litter box was measured during a baseline phase and a test phase, in which Zero Odor was sprayed into all litter boxes in the home. Significantly fewer behaviors associated with feline litter box dissatisfaction and fewer undesirable eliminations were observed in phases 2 and 3, respectively. These findings suggest that use of Zero Odor litter box spray appears to decrease litter box odor and increases the attractiveness of litter box to cats. PMID:17049291

  9. 49 CFR 178.514 - Standards for plywood boxes.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Standards for plywood boxes. 178.514 Section 178... PACKAGINGS Non-bulk Performance-Oriented Packaging Standards § 178.514 Standards for plywood boxes. (a) The identification code for a plywood box is 4D. (b) Construction requirements for plywood boxes are as follows:...

  10. MAVS protein is attenuated by rotavirus nonstructural protein 1.

    Directory of Open Access Journals (Sweden)

    Satabdi Nandi

    Full Text Available Rotavirus is the single, most important agent of infantile gastroenteritis in many animal species, including humans. In developing countries, rotavirus infection attributes approximately 500,000 deaths annually. Like other viruses it establishes an intimate and complex interaction with the host cell to counteract the antiviral responses elicited by the cell. Among various pattern recognition receptors (PAMPs of the host, the cytosolic RNA helicases interact with viral RNA to activate the Mitochondrial Antiviral Signaling protein (MAVS, which regulates cellular interferon response. With an aim to identify the role of different PAMPs in rotavirus infected cell, MAVS was found to degrade in a time dependent and strain independent manner. Rotavirus non-structural protein 1 (NSP1 which is a known IFN antagonist, interacted with MAVS and degraded it in a strain independent manner, resulting in a complete loss of RNA sensing machinery in the infected cell. To best of our knowledge, this is the first report on NSP1 functionality where a signaling protein is targeted unanimously in all strains. In addition NSP1 inhibited the formation of detergent resistant MAVS aggregates, thereby averting the antiviral signaling cascade. The present study highlights the multifunctional role of rotavirus NSP1 and reinforces the fact that the virus orchestrates the cellular antiviral response to its own benefit by various back up strategies.

  11. Heterochromatin protein 1 secures survival and transmission of malaria parasites.

    Science.gov (United States)

    Brancucci, Nicolas M B; Bertschi, Nicole L; Zhu, Lei; Niederwieser, Igor; Chin, Wai Hoe; Wampfler, Rahel; Freymond, Céline; Rottmann, Matthias; Felger, Ingrid; Bozdech, Zbynek; Voss, Till S

    2014-08-13

    Clonally variant expression of surface antigens allows the malaria parasite Plasmodium falciparum to evade immune recognition during blood stage infection and secure malaria transmission. We demonstrate that heterochromatin protein 1 (HP1), an evolutionary conserved regulator of heritable gene silencing, controls expression of numerous P. falciparum virulence genes as well as differentiation into the sexual forms that transmit to mosquitoes. Conditional depletion of P. falciparum HP1 (PfHP1) prevents mitotic proliferation of blood stage parasites and disrupts mutually exclusive expression and antigenic variation of the major virulence factor PfEMP1. Additionally, PfHP1-dependent regulation of PfAP2-G, a transcription factor required for gametocyte conversion, controls the switch from asexual proliferation to sexual differentiation, providing insight into the epigenetic mechanisms underlying gametocyte commitment. These findings show that PfHP1 is centrally involved in clonally variant gene expression and sexual differentiation in P. falciparum and have major implications for developing antidisease and transmission-blocking interventions against malaria. PMID:25121746

  12. Cadmium-induced aggregation of iron regulatory protein-1

    International Nuclear Information System (INIS)

    Iron regulatory protein-1 (IRP-1) is central to regulation of iron homeostasis, and has been shown to be sensitive to Cd2+ in vitro. Although Cd2+ induces disulfide-bond formation in many proteins, the critical cysteine residues for iron binding in IRP-1 were shown not to be involved in Cd-induced IRP-1 aggregation in vitro. Here we show that Cd2+ causes polymerization and aggregation of IRP-1 in vitro and in vivo, and decreases in a dose-dependent manner both its RNA-binding and aconitase enzymatic activities, as well as its cytosolic expression. We have used two-dimensional electrophoresis to demonstrate thiol-dependent self-association of purified recombinant IRP-1 treated with Cd2+, as well as self-association in Cd2+-exposed mesangial cells. Circular dichroism spectra confirm significant conformational changes in the purified protein upon Cd2+ exposure. Following Cd2+ treatment, there is increased translocation of inactive IRP-1 to the actin cytoskeletal fraction, and this translocation is diminished by both antioxidant (BHA) treatment and inhibition of CaMK-II. These changes differ from those elicited by manipulation of iron levels. Cadmium-induced translocation of proteins to cellular compartments, and particularly to the cytoskeleton, is becoming a recognized event in Cd2+ toxicity. Polymer-dependent translocation of IRP-1 in Cd2+-exposed cells may underlie effects of Cd2+ on iron homeostasis

  13. Bending analysis of laminated composite box beams

    Energy Technology Data Exchange (ETDEWEB)

    Tripathy, A.K.; Patel, H.J.; Pang, S.S. (Louisiana State Univ., Baton Rouge, LA (United States). Dept. of Mechanical Engineering)

    1994-01-01

    Box beams are widely used in weight reduction structures such as aircraft wings. The use of composite box beams further reduces the weight factor for such structures with the same deflection and stress as that of isotropic box beams. The difference in the behavior of composite box beam with different fiber orientation, number of plies, and number of stringers also provides a wide range of designing parameters to achieve the required performance for a given problem. A bending analysis has been carried out for the study of deflections and stresses for box beams of different material (isotropic and laminated composites), size, and number of stringers subjected to different kinds of loading conditions. A finite element model has been developed based on the strain energy principle, and the results are compared with an available commercial code COSMOS/M.'' Experiments using aluminum and scotchply composite laminates were conducted to verify the results. An optimal design for size and number of stiffeners for a given loading condition has been achieved. Investigations have also been carried out to find the effect of transverse shear on the span-wise normal stress.

  14. Pharmacy Students’ Knowledge of Black Box Warnings

    Science.gov (United States)

    Shireman, Theresa I.; Generali, Joyce; Rigler, Sally; Mayorga, Angela

    2010-01-01

    Objective To evaluate the progression of pharmacy students’ knowledge of black box warnings across 3 years of didactic training, and to determine how they stay current with new warnings. Methods A cross-sectional survey instrument was administered to pharmacy students in their first (P1), second (P2), and third (P3) professional years. The survey assessed student awareness of medications possessing a black box warning and familiarity with the warning content for 20 medications (15 with and 5 without warnings). Results Mean number of correct responses identifying the presence or absence of a black box warning among the 20 medications were 5.8 ± 3.3, 9.6 ± 4.0, and 14.8 ± 2.8 for the P1, P2, and P3 students, respectively. Knowledge of black box warning content was variable. Students were least aware of the warning content for stavudine and enoxaparin. Students were most familiar with the warning content for paroxetine and estrogen. Conclusion Students’ awareness and understanding of black box warnings was proportional to their educational progression, but their knowledge level was inconsistent across drug groups. PMID:20221356

  15. MEIOTIC F-BOX Is Essential for Male Meiotic DNA Double-Strand Break Repair in Rice[OPEN

    Science.gov (United States)

    Wang, Chong; Yu, Junping; Zong, Jie; Lu, Pingli

    2016-01-01

    F-box proteins constitute a large superfamily in plants and play important roles in controlling many biological processes, but the roles of F-box proteins in male meiosis in plants remain unclear. Here, we identify the rice (Oryza sativa) F-box gene MEIOTIC F-BOX (MOF), which is essential for male meiotic progression. MOF belongs to the FBX subfamily and is predominantly active during leptotene to pachytene of prophase I. mof meiocytes display disrupted telomere bouquet formation, impaired pairing and synapsis of homologous chromosomes, and arrested meiocytes at late prophase I, followed by apoptosis. Although normal, programmed double-stranded DNA breaks (DSBs) form in mof mutants, foci of the phosphorylated histone variant γH2AX, a marker for DSBs, persist in the mutant, indicating that many of the DSBs remained unrepaired. The recruitment of Completion of meiosis I (COM1) and Radiation sensitive51C (RAD51C) to DSBs is severely compromised in mutant meiocytes, indicating that MOF is crucial for DSB end-processing and repair. Further analyses showed that MOF could physically interact with the rice SKP1-like Protein1 (OSK1), indicating that MOF functions as a component of the SCF E3 ligase to regulate meiotic progression in rice. Thus, this study reveals the essential role of an F-box protein in plant meiosis and provides helpful information for elucidating the roles of the ubiquitin proteasome system in plant meiotic progression. PMID:27436711

  16. Nearly Seamless Vacuum-Insulated Boxes

    Science.gov (United States)

    Stepanian, Christopher J.; Ou, Danny; Hu, Xiangjun

    2010-01-01

    A design concept, and a fabrication process that would implement the design concept, have been proposed for nearly seamless vacuum-insulated boxes that could be the main structural components of a variety of controlled-temperature containers, including common household refrigerators and insulating containers for shipping foods. In a typical case, a vacuum-insulated box would be shaped like a rectangular parallelepiped conventional refrigerator box having five fully closed sides and a hinged door on the sixth side. Although it is possible to construct the five-closed-side portion of the box as an assembly of five unitary vacuum-insulated panels, it is not desirable to do so because the relatively high thermal conductances of the seams between the panels would contribute significant amounts of heat leakage, relative to the leakage through the panels themselves. In contrast, the proposal would make it possible to reduce heat leakage by constructing the five-closed-side portion of the box plus the stationary portion (if any) of the sixth side as a single, seamless unit; the only remaining seam would be the edge seal around the door. The basic cross-sectional configuration of each side of a vacuum-insulated box according to the proposal would be that of a conventional vacuum-insulated panel: a low-density, porous core material filling a partially evacuated space between face sheets. However, neither the face sheets nor the core would be conventional. The face sheets would be opposite sides of a vacuum bag. The core material would be a flexible polymer-modified silica aerogel of the type described in Silica/Polymer and Silica/Polymer/Fiber Composite Aero - gels (MSC-23736) in this issue of NASA Tech Briefs. As noted in that article, the stiffness of this core material against compression is greater than that of prior aerogels. This is an important advantage because it translates to greater retention of thickness and, hence, of insulation performance when pressure is

  17. Advances in the theory of box integrals

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, David H.; Borwein, J.M.; Crandall, R.E.

    2009-06-25

    Box integrals - expectations <|{rvec r}|{sup s}> or <|{rvec r}-{rvec q}|{sup s}> over the unit n-cube (or n-box) - have over three decades been occasionally given closed forms for isolated n,s. By employing experimental mathematics together with a new, global analytic strategy, we prove that for n {le} 4 dimensions the box integrals are for any integer s hypergeometrically closed in a sense we clarify herein. For n = 5 dimensions, we show that a single unresolved integral we call K{sub 5} stands in the way of such hyperclosure proofs. We supply a compendium of exemplary closed forms that naturally arise algorithmically from this theory.

  18. Fire test of DOT 7A Boxes

    International Nuclear Information System (INIS)

    The primary objective of conducting the full-scale fire tests of the DOT (Department of Transportation) 7A FRP Boxes was to provide information to assist in quantifying the fire hazard of the storage located at the Radioactive Waste Management Complex (RWMC), and to learn if changing the storage array will decrease the fire risk. Also, the level of fire fighting and fire protection required to maintain the risk at the RWMC within acceptable DOE guidelines was investigated. Two full-scale fire tests were conducted at Southwest Research Institute (SwRI) in June 1978, using the DOE 7A FRP Plywood Storage Containers. The fire tests showed that when subjected to a substantial ignition source, the boxes will propagate fire as long as no fire-suppression measures are taken. Fire will breach the boxes and spread the radioactive contaminated waste if it is not extinguished. As the fire progresses, additional boxes will become involved, and eventually the entire storage array will ignite. It is recommended that the use of DOT 7A Boxes be discontinued and replaced with noncombustible storage containers. In the event this is not practicable, guidance recommendations are presented to minimize the large fire loss potential. It is also recommended that an investigation be conducted into the number of boxes that can be destroyed and still maintain a safe environment for employees and the public. This investigation should include how far radioactive contamination will spread, what cleanup will be required, anticipated exposure of the people within the area, and the public impact of such a fire

  19. Testing of packings for stuffing boxes

    International Nuclear Information System (INIS)

    The stuffing box packings function when they are sealed tight and do not obstruct the movement of the spindle. Characteristic values are necessary to characterise the materials properties of stuffing box packings. Essentially, the definitions of the characteristic values are known and can be calculated in experimental setups. It is absolutely necessary to standardise the characteristic values as well as the testing procedures in order to be able to provide comparable and reproduceable characteristic values. Depending upon the importance of the fittings, it is necessary to guarantee sufficiently exact and reliable assembly for defined operating conditions. (orig.)

  20. Circulating monocyte chemoattractant protein-1 in women with gestational diabetes.

    Directory of Open Access Journals (Sweden)

    Mariusz Kuzmicki

    2008-04-01

    Full Text Available Monocyte chemoattractant protein 1 (MCP-1 has been implicated as a key factor in the recruitment and activation of peripheral blood leukocytes in atherosclerotic lesions and adipose tissue. Elevated levels of circulating MCP-1 have been found in patients with type 1 and type 2 diabetes, as well as with coronary artery disease. In this study we compared serum MCP-1 concentrations between pregnant women with normal glucose tolerance (NGT, gestational diabetes mellitus (GDM and non-pregnant healthy women. The group studied consisted of 62 patients with GDM (mean age 30.1 +/- 5.0 years at 29.0 +/- 3.5 week of gestation, 64 pregnant women with NGT (mean age 30.0 +/- 4.7 years at 29.2 +/- 2.9 week of gestation and 34 non-pregnant healthy women (mean age 29.8 +/- 4.7 years. Serum MCP-1 concentration was measured using an enzyme - linked immunosorbent assay. Median MCP-1 concentrations did not differ significantly between women with GDM (median 342.3 [interquartile range 267.9-424.4] pg/ml and NGT (338.0 [274.7-408.2] pg/ml, but were markedly lower than those found in non-pregnant women (485.2 [409.6-642.4] pg/ml, p<0.0001. After adjusting for glucose, the difference between pregnant and non-pregnant women remained highly significant (p<0.0001. In GDM patients MCP-1 levels correlated significantly with fasting glucose (r=0.2665, p=0.0363, insulin (r=0.4330, p=0.0004, HOMA-IR (r=0.4402, p=0.0003, ISQUICKI (r=-0.4402, p=0.0003, HbA1c (r=0.2724, p=0.0322, as well as with prepregnancy and current BMI (r=0.3501, p=0.0057 and r=0.3250, p=0.0106, respectively. Multiple regression analysis revealed that MCP1 concentrations were significantly predicted only by plasma glucose ( beta=0.3489, p=0.00004. Our results suggest that MCP1 levels are decreased in pregnant women, irrespective of their glucose tolerance status.

  1. Cereal Box Design: An Interdisciplinary Graphics Activity

    Science.gov (United States)

    Fitzgerald, Mike; Tsosie, Teri

    2012-01-01

    The cereal box design activity is intriguing both for its simplicity and the resourcefulness that it can generate in young people. Also, it lends itself to a variety of curriculums. It covers both consumerism and Design for the Environment (DfE) concepts broadly and in depth. The activity introduces a wide range of topics. They include graphic…

  2. Study of WATCH GRB error boxes

    DEFF Research Database (Denmark)

    Gorosabel, J.; Castro-Tirado, A. J.; Lund, Niels;

    1995-01-01

    We have studied the first WATCH GRB Catalogue ofγ-ray Bursts in order to find correlations between WATCH GRB error boxes and a great variety of celestial objects present in 33 different catalogues. No particular class of objects has been found to be significantly correlated with the WATCH GRBs....

  3. Black hole formation in a box

    International Nuclear Information System (INIS)

    Evidence is presented for Hawking's viewpoint that in an insulated box in thermal equilibrium, black holes should form and evaporate in a statistically time-symmetric way. In particular, it is shown that if a black hole can evaporate adiabatically, it is much more likely to form adiabatically than by Jeans instability. (author)

  4. Safety evaluation for packaging CPC metal boxes

    International Nuclear Information System (INIS)

    This Safety Evaluation for Packaging (SEP) provides authorization for the use of Container Products Corporation (CPC) metal boxes, as described in this document, for the interarea shipment of radioactive contaminated equipment and debris for storage in the Central Waste Complex (CWC) or T Plant located in the 200 West Area. Authorization is granted until November 30, 1995. The CPC boxes included in this SEP were originally procured as US Department of Transportation (DOT) Specification 7A Type A boxes. A review of the documentation provided by the manufacturer revealed the documentation did not adequately demonstrate compliance to the 4 ft drop test requirement of 49 CFR 173.465(c). Preparation of a SEP is necessary to document the equivalent safety of the onsite shipment in lieu of meeting DOT packaging requirements until adequate documentation is received. The equivalent safety of the shipment is based on the fact that the radioactive contents consist of contaminated equipment and debris which are not dispersible. Each piece is wrapped in two layers of no less than 4 mil plastic prior to being placed in the box which has an additional 10 mil liner. Pointed objects and sharp edges are padded to prevent puncture of the plastic liner and wrapping

  5. Choreographies with Secure Boxes and Compromised Principals

    DEFF Research Database (Denmark)

    Carbone, Marco; Guttman, Joshua

      We equip choreography-level session descriptions with a simple abstraction of a security infrastruc- ture. Message components may be enclosed within (possibly nested) ”boxes” annotated with the intended source and destination of those components. The boxes are to be implemented with cryp...

  6. RELIABILITY BASED DESIGN OF A GEAR BOX

    Directory of Open Access Journals (Sweden)

    D.MADHUSEKHAR

    2014-08-01

    Full Text Available Reliability is the probability that a system, component or device will perform without failure for a specified period of time under specified operating conditions. The concept of reliability is of great importance in the design of various machine members. Conventional engineering design uses a deterministic approach. It disregards the fact that the material properties, the dimensions of the components and the externally applied loads are statistical in nature. In conventional design this uncertainties are covered with a factor of safety, which is not always successful. The growing trend towards reducing uncertainty and increasing reliability is to use the probabilistic approach. In the present work a three shaft four speed gear box and six speed gear box are designed using reliability principles. For the specified reliability of the system (Gear box, component reliability (Gear pair is calculated by considering the system as a series system. Design is considered to be safe and adequate if the probability of failure of gear box is less than or equal to a specified quantity in each of the two failure modes. . All the parameters affecting the design are considered as random variables and all the random variables are assumed to follow normal distribution. A computer program in C++ is developed to calculate the face widths in bending and surface failure modes. The larger one out of the two values is considered. By changing the variations in the design parameters, variations in the face widths are studied.

  7. Nondestructive assay of boxed radioactive waste

    International Nuclear Information System (INIS)

    This paper describes the problems related to the nondestructive assay (NDA) of boxed radioactive waste at the Hanford Site and how Westinghouse Hanford company (WHC) is solving the problems. The waste form and radionuclide content are described. The characteristics of the combined neutron and gamma-based measurement system are described

  8. A white box perspective on behavioural adaptation

    DEFF Research Database (Denmark)

    Bruni, Roberto; Corradini, Andrea; Gadducci, Fabio; Lluch Lafuente, Alberto; Vandin, Andrea

    We present a white-box conceptual framework for adaptation developed in the context of the EU Project ASCENS coordinated by Martin Wirsing. We called it CoDA, for Control Data Adaptation, since it is based on the notion of control data. CoDA promotes a neat separation between application and...

  9. PVC posting bags for glove boxes

    International Nuclear Information System (INIS)

    This specification covers the materials, measurements and manufacture of unpigmented PVC posting bags for use on glove boxes, together with methods of testing the materials. These bags are used in the handling of radioactive and toxic materials of a hazardous nature and therefore must be of the highest standard of mechanical strength, leak tightness and general finish. (author)

  10. Grey-box modelling of pharmacokinetic/pharmacodynamic systems

    DEFF Research Database (Denmark)

    Tornøe, Christoffer Wenzel; Jacobsen, Judith L; Pedersen, Oluf;

    2004-01-01

    Grey-box pharmacokinetic/pharmacodynamic (PK/PD) modelling is presented as a promising way of modelling PK/PD systems. The concept behind grey-box modelling is based on combining physiological knowledge along with information from data in the estimation of model parameters. Grey-box modelling...

  11. 49 CFR 230.103 - Tender roller bearing journal boxes.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Tender roller bearing journal boxes. 230.103... Locomotives and Tenders Running Gear § 230.103 Tender roller bearing journal boxes. Tender roller bearing journal boxes shall be maintained in a safe and suitable condition....

  12. 49 CFR 230.102 - Tender plain bearing journal boxes.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Tender plain bearing journal boxes. 230.102... Locomotives and Tenders Running Gear § 230.102 Tender plain bearing journal boxes. Plain bearing journal boxes... expected to damage the bearing; or have a detrimental effect on the lubrication of the journal and...

  13. Application of Defense Technology Commonly Used in Boxing Match

    Institute of Scientific and Technical Information of China (English)

    Zhixiao Li[1; Jianjun Liu[2

    2015-01-01

    Boxing defense technology is a kind of techniques to prevent the opponent from attacking successfully. Boxing is a kind of sports that needs close cooperation between attack and defense. Attack is used for defense, where there is no attack, there will be no defense, and vice versa. Defense technology is the foundation of attack technology, therefore, defense is of vital importance in boxing match.

  14. High expression of Y-box-binding protein 1 correlates with poor prognosis and early recurrence in patients with small invasive lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Zhao S

    2016-05-01

    Full Text Available Shilei Zhao,1,* Wei Guo,1,* Jinxiu Li,1 Wendan Yu,1 Tao Guo,1 Wuguo Deng,2,3 Chundong Gu1 1The First Affiliated Hospital, Institute of Cancer Stem Cell, Lung Cancer Diagnosis and Treatment Center, Dalian Medical University, Dalian, 2Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University, Guangzhou, 3State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: Prognosis of small (≤2 cm invasive lung adenocarcinoma remains poor, and identification of high-risk individuals from the patients after complete surgical resection of lung adenocarcinoma has become an urgent problem. YBX1 has been reported to be able to predict prognosis in many cancers (except lung adenocarcinoma that are independent of TNM (tumor, nodes, metastases staging, especially small invasive lung adenocarcinoma. Therefore, we examined the significance of YBX1 expression on prognosis and recurrence in patients with small invasive lung adenocarcinoma. Material and methods: A total of 75 patients with small invasive lung adenocarcinoma after complete resection were enrolled from January 2008 to December 2010. Immunohistochemical staining was used to detect the expression of YBX1, and receiver operating characteristic curve analysis was performed to precisely assess the overall expression of YBX1. Meanwhile, primary lesions were identified based on the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society’s classification of lung adenocarcinoma. The effect of different clinicopathological factors on patients’ survival was examined. Furthermore, Western blot analysis was used to show the expression of YBX1 in vitro. Results: Sensitivity and specificity of YBX1 for detecting small invasive lung adenocarcinoma from normal surrounding tissue were 66.7% and 74.7% (area under the receiver operating characteristic curve =0.731; P<0.001, respectively. High YBX1 expression was detected in 31 (41.3% patients, and in A549, H322, Hcc827, and H1299 lung adenocarcinoma cells but not in HLF cells. In addition to sex, age, tumor size, TNM staging, pleural invasion, and lymph node metastasis, the expression of YBX1 was associated with the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society pathological grade risk (P=0.026 and differentiation (P=0.009. The patients with low YBX1 expression lived longer than those with high expression (5-year overall survival: 52.3% vs 79.0%; P=0.039 and showed fewer recurrences (P=0.024. In multivariate analyses, high YBX1 expression (odds ratio =2.737; 95% confidence interval: 1.058–7.082; P=0.038 was shown as an independent risk factor of overall survival but not of disease-free survival (odds ratio =1.696; 95% confidence interval: 0.616–4.673; P=0.307. Conclusion: YBX1 is an important predictor for the prognosis in patients with small invasive lung adenocarcinoma after complete resection. Keywords: YBX1, lung adenocarcinoma, prognosis

  15. Association of X-box binding protein 1 (XBP1) genotype with morning cortisol and 1-year clinical course after a major depressive episode

    OpenAIRE

    Grunebaum, Michael F.; Galfalvy, Hanga C.; Huang, Yung-Yu; Cooper, Thomas B.; Burke, Ainsley K.; Agnello, Melissa; Oquendo, Maria A.; Mann, J. John

    2009-01-01

    Brain diseases including Alzheimer’s and Parkinson’s involve the cellular ‘unfolded protein’ (UPR) stress response. Psychiatric illnesses such as depressive disorders are thought to involve brain stress-response pathways. The XBP1 gene encodes a key transcription factor in the UPR stress response and therefore could be involved in the pathophysiology of depressive disorders. A functional polymorphism (−116C→G) in the XBP1 promoter was linked in some studies to bipolar disorder. Among 132 adul...

  16. Y-box-binding protein-1 (YB-1) promotes cell proliferation, adhesion and drug resistance in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Miao, Xiaobing; Wu, Yaxun; Wang, Yuchan; Zhu, Xinghua; Yin, Haibing; He, Yunhua; Li, Chunsun; Liu, Yushan; Lu, Xiaoyun; Chen, Yali; Shen, Rong; Xu, Xiaohong; He, Song

    2016-08-15

    YB-1 is a multifunctional protein, which has been shown to correlate with resistance to treatment of various tumor types. This study investigated the expression and biologic function of YB-1 in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical analysis showed that the expression statuses of YB-1 and pYB-1(S102) were reversely correlated with the clinical outcomes of DLBCL patients. In addition, we found that YB-1 could promote the proliferation of DLBCL cells by accelerating the G1/S transition. Ectopic expression of YB-1 could markedly increase the expression of cell cycle regulators cyclin D1 and cyclin E. Furthermore, we found that adhesion of DLBCL cells to fibronectin (FN) could increase YB-1 phosphorylation at Ser102 and pYB-1(S102) nuclear translocation. In addition, overexpression of YB-1 could increase the adhesion of DLBCL cells to FN. Intriguingly, we found that YB-1 overexpression could confer drug resistance through cell-adhesion dependent and independent mechanisms in DLBCL. Silencing of YB-1 could sensitize DLBCL cells to mitoxantrone and overcome cell adhesion-mediated drug resistance (CAM-DR) phenotype in an AKT-dependent manner. PMID:27397581

  17. Grey Box Modelling of Hydrological Systems

    DEFF Research Database (Denmark)

    Thordarson, Fannar Ørn

    intervals. The thesis illustrates three performance measures for this performance evaluations: reliability, sharpness and resolution. For decision making, a performance criterion is preferred that quantifies all of these measures in a single number, and for that the quantile skill score criterion is...... equations, and a black box model, which relates to models that are obtained statistically from input-output relations. Grey box model consists of a system description, defined by a finite set of stochastic differential equations, and an observation equation. Together, system and observation equations...... lack of fit in state space formulation, and further support decisions for a model expansion. By using stochastic differential equations to formulate the dynamics of the hydrological system, either the complexity of the model can be increased by including the necessary hydrological processes in the...

  18. Fatal exit the automotive black box debate

    CERN Document Server

    Kowalick, Tom

    2005-01-01

    "Fatal Exit: The Automotive Black Box Debate cuts through thirty years of political wrangling and institutional biases to provide an argument for the Motor Vehicle Event Data Recorder (MVEDR). This automotive equivalent of an airplane's flight recorder or black box is intended to solve the mysteries of car crashes and improve the safety of our roads. The reader is taken inside the automotive industry and the government highway safety establishment to foster an understanding of the politics and the positions on all sides of this safety debate. The author takes an unbiased approach, chronologically presenting each argument and uncovering the agendas and mandates of each of the stakeholders." "This publication is essential reading for all consumers who need to have their voices heard on this critical issue, as well as for attorneys, public safety advocates, public policy administrators, engineers, automotive professionals, journalists, and insurance executives."--Jacket.

  19. The Central Nervous System of Box Jellyfish

    DEFF Research Database (Denmark)

    Garm, Anders Lydik; Ekström, Peter

    2008-01-01

    nervous system is described. Each rhopalium holds a separate part of the CNS with 1,000 nerve cells and a large amount of neuropil. The rhopalial nervous system has several subsystems defined by the anatomy, location, and immunocytochemistry of the cells. Most of the subsystems connect to one or more of...... behaviors in the box jellyfish such as obstacle avoidance and navigation. The need to process the visual information and turn it into the appropriate behavior puts strong demands on the nervous system of box jellyfish, which appears more elaborate than in other cnidarians. Here, the central part of this...... the eye types, and it is likely that the rhopalial nervous system accounts for most of the visual processing. The major part of the CNS is made up of a ring nerve encircling the bell shaped body. The ring nerve holds around 10,000 cells and is directly connected to all four rhopalial nervous systems...

  20. The gradient flow in a twisted box

    Energy Technology Data Exchange (ETDEWEB)

    Ramos, Alberto [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany). John von Neumann-Inst. fuer Computing NIC

    2013-08-15

    We study the perturbative behavior of the gradient flow in a twisted box. We apply this information to define a running coupling using the energy density of the flow field. We study the step-scaling function and the size of cutoff effects in SU(2) pure gauge theory. We conclude that the twisted gradient flow running coupling scheme is a valid strategy for step-scaling purposes due to the relatively mild cutoff effects and high precision.

  1. Dry boxes and inert atmosphere techniques

    International Nuclear Information System (INIS)

    Practitioners need to conduct experiments with molten salts in an inert atmosphere owing to the chemical reactivity of these media. Most fused salt solvent systems show reactivity to water and/or oxygen, which results in significant chemical changes in the properties of these solvents. Although several studies on the nature of an oxygen/oxide electrode in this melt have been reported, the reactions have not been fully understood because of apparent water contamination in many cases. Nitrate melt systems are also hygroscopic; for example, the LiNO3-KNO3 eutectic (1770C) absorbs water to at least 0.2% by weight. The result is that the electrochemistry of heavier, electropositive metal ions has been significantly altered. In addition, trace amounts of water have been shown to significantly affect the oxygen-oxide redox chemistry in NaNO3-KNO3 melts (2500C). The haloaluminates, which include AlCl3-NaCl (1750C), as well as AlCl3-organic salt binaries are particularly sensitive to the presence of both oxygen and moisture. Oxygen is a strong oxidant in the fused hydroxide systems with formation of superoxide ion from either oxide or water. This chapter describes general, inert atmosphere techniques which can be used by the molten salt experimentalist. Because of the limitations of volatility, vacuum manipulations are not considered. Rather, the use of glove boxes, glove bags, and inert bench-top techniques are discussed. The areas covered are: glove box and bag equipment, operation and maintenance of glove boxes and glove bags, and common operations conducted inside glove boxes

  2. Adaptive Techniques to find Optimal Planar Boxes

    CERN Document Server

    Barbay, J; Pérez-Lantero, P

    2012-01-01

    Given a set $P$ of $n$ planar points, two axes and a real-valued score function $f()$ on subsets of $P$, the Optimal Planar Box problem consists in finding a box (i.e. axis-aligned rectangle) $H$ maximizing $f(H\\cap P)$. We consider the case where $f()$ is monotone decomposable, i.e. there exists a composition function $g()$ monotone in its two arguments such that $f(A)=g(f(A_1),f(A_2))$ for every subset $A\\subseteq P$ and every partition $\\{A_1,A_2\\}$ of $A$. In this context we propose a solution for the Optimal Planar Box problem which performs in the worst case $O(n^2\\lg n)$ score compositions and coordinate comparisons, and much less on other classes of instances defined by various measures of difficulty. A side result of its own interest is a fully dynamic \\textit{MCS Splay tree} data structure supporting insertions and deletions with the \\emph{dynamic finger} property, improving upon previous results [Cort\\'es et al., J.Alg. 2009].

  3. Changes in position and quality of preferred nest box: effects on nest box use by laying hens

    DEFF Research Database (Denmark)

    Riber, Anja Brinch; Nielsen, Birte L.

    2013-01-01

    Using laying hens, we investigated whether position of a nest box, both within the pen and relative to other nest boxes, influenced the preference for a nest box, and how a sudden and marked change to the preferred box influenced the use of nest boxes by the hens. Groups (n=12) of 15 Isa Warren...... hens were housed in pens, each with five identical nest boxes in different positions: Two single (in a corner or not) and a triplet of nest boxes (one of which in a corner). The use of nest boxes was determined by the number of eggs laid daily in each box. Three experiments, each lasting 10 days, were...... carried out. First, the undisturbed use of each of the nest box types was investigated, and a strong preference (P<0.001) was found for single nest boxes in a corner, with 62% of the nest box eggs laid there. Second, each of the hen groups was moved to another pen allocated at random, and where the...

  4. Business plan PME.Box: internationalization to Spain

    OpenAIRE

    Pinto, Diogo José Gomes Ferreira

    2011-01-01

    The document herein described, provides detailed information of the development of PME.BOX Business Plan regarding the expansion to a detailed overview of the business model and strategies that PME.BOX looks to implement in order to maximize its business reach and in turn generate revenue. PME.BOX (firm) is an IT start up firm based in Madan Par the commercial rights of pme.box (software). Pme.box is a touch management solution intended to help small and medium enterprises (SMEs) in ...

  5. Reconciling White-Box and Black-Box Perspectives on Behavioral Self-adaptation

    DEFF Research Database (Denmark)

    Bruni, Roberto; Corradini, Andrea; Gadducci, Fabio; Hölzl, Matthias; Lluch Lafuente, Alberto; Vandin, Andrea; Wirsing, Martin

    This paper proposes to reconcile two perspectives on behavioral adaptation commonly taken at different stages of the engineering of autonomic computing systems. Requirements engineering activities often take a black-box perspective: A system is considered to be adaptive with respect to an...... environment whenever the system is able to satisfy its goals irrespectively of the environment perturbations. Modeling and programming engineering activities often take a white-box perspective: A system is equipped with suitable adaptation mechanisms and its behavior is classified as adaptive depending on...... whether the adaptation mechanisms are enacted or not. The proposed approach reconciles black- and white-box perspectives by proposing several notions of coherence between the adaptivity as observed by the two perspectives: These notions provide useful criteria for the system developer to assess and...

  6. 49 CFR 178.512 - Standards for steel or aluminum boxes.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Standards for steel or aluminum boxes. 178.512... aluminum boxes. (a) The following are identification codes for steel or aluminum boxes: (1) 4A for a steel box; and (2) 4B for an aluminum box. (b) Construction requirements for steel or aluminum boxes are...

  7. The expression of selenium-binding protein 1 is decreased in uterine leiomyoma

    Directory of Open Access Journals (Sweden)

    Quddus M Ruhul

    2010-12-01

    Full Text Available Abstract Background Selenium has been shown to inhibit cancer development and growth through the mediation of selenium-binding proteins. Decreased expression of selenium-binding protein 1 has been reported in cancers of the prostate, stomach, colon, and lungs. No information, however, is available concerning the roles of selenium-binding protein 1 in uterine leiomyoma. Methods Using Western Blot analysis and immunohistochemistry, we examined the expression of selenium-binding protein 1 in uterine leiomyoma and normal myometrium in 20 patients who had undergone hysterectomy for uterine leiomyoma. Results and Discussion The patient age ranged from 34 to 58 years with a mean of 44.3 years. Proliferative endometrium was seen in 8 patients, secretory endometrium in 7 patients, and atrophic endometrium in 5 patients. Two patients showed solitary leiomyoma, and eighteen patients revealed 2 to 5 tumors. Tumor size ranged from 1 to 15.5 cm with a mean of 4.3 cm. Both Western Blot analysis and immunohistochemistry showed a significant lower level of selenium-binding protein 1 in leiomyoma than in normal myometrium. Larger tumors had a tendency to show a lower level of selenium-binding protein 1 than smaller ones, but the difference did not reach a statistical significance. The expression of selenium-binding protein 1 was the same among patients with proliferative, secretory, and atrophic endometrium in either leiomyoma or normal myometrium. Also, we did not find a difference of selenium-binding protein 1 level between patients younger than 45 years and older patients in either leiomyoma or normal myometrium. Conclusions Decreased expression of selenium-binding protein 1 in uterine leiomyoma may indicate a role of the protein in tumorigenesis. Our findings may provide a basis for future studies concerning the molecular mechanisms of selenium-binding protein 1 in tumorigenesis as well as the possible use of selenium in prevention and treatment of uterine

  8. Adaptation of Black-Box Software Components

    Directory of Open Access Journals (Sweden)

    Rolf Andreas Rasenack

    2008-01-01

    Full Text Available The globalization of the software market leads to crucial problems for software companies. More competition between software companies arises and leads to the force on companies to develop ever newer software products in ever shortened time interval. Therefore the time to market for software systems is shortened and obviously the product life cycle is shortened too. Thus software companies shortened the time interval for research and development. Due to the fact of competition between software companies software products have to develop low-priced and this leads to a smaller return on investment. A big challenge for software companies is the use of an effective research and development process to have these problems under control. A way to control these problems can be the reuse of existing software components and adapt those software components to new functionality or accommodate mismatched interfaces. Complete redevelopment of software products is more expensive and time consuming than to develop software components. The approach introduced here presents novel technique together with a supportive environment that enables developers to cope with the adaptability of black-box software components. A supportive environment will be designed that checks the compatibility of black-box software components with the assistance of their specifications. Generated adapter software components can take over the part of adaptation and advance the functionality. Besides, a pool of software components can be used to compose an application to satisfy customer needs. Certainly this pool of software components consists of black-box software components and adapter software components which can be connected on demand.

  9. Box codes of lengths 48 and 72

    Science.gov (United States)

    Solomon, G.; Jin, Y.

    1993-11-01

    A self-dual code length 48, dimension 24, with Hamming distance essentially equal to 12 is constructed here. There are only six code words of weight eight. All the other code words have weights that are multiples of four and have a minimum weight equal to 12. This code may be encoded systematically and arises from a strict binary representation of the (8,4;5) Reed-Solomon (RS) code over GF (64). The code may be considered as six interrelated (8,7;2) codes. The Mattson-Solomon representation of the cyclic decomposition of these codes and their parity sums are used to detect an odd number of errors in any of the six codes. These may then be used in a correction algorithm for hard or soft decision decoding. A (72,36;15) box code was constructed from a (63,35;8) cyclic code. The theoretical justification is presented herein. A second (72,36;15) code is constructed from an inner (63,27;16) Bose Chaudhuri Hocquenghem (BCH) code and expanded to length 72 using box code algorithms for extension. This code was simulated and verified to have a minimum distance of 15 with even weight words congruent to zero modulo four. The decoding for hard and soft decision is still more complex than the first code constructed above. Finally, an (8,4;5) RS code over GF (512) in the binary representation of the (72,36;15) box code gives rise to a (72,36;16*) code with nine words of weight eight, and all the rest have weights greater than or equal to 16.

  10. Keller-box method and its application

    CERN Document Server

    Prasad, Kerehalli V

    2014-01-01

    Most of the problems arising in science and engineering are nonlinear. They are inherently difficult to solve. Traditional analytical approximations are valid only for weakly nonlinear problems, and often break down for problems with strong nonlinearity. This book presents the current theoretical developments and applications of Keller-Box method to nonlinear problems. The first half of the bookaddresses basic concepts to understand the theoretical framework for the method. In the second half of the book, the authorsgive a number of examples of coupled nonlinear problems that have been solved

  11. Mirror box therapy: seeing is believing.

    Science.gov (United States)

    Lamont, Kelly; Chin, May; Kogan, Mikhail

    2011-01-01

    Working with patients with different chronic pain syndromes can be challenging. Pharmacological therapies are often associated with variety of side effects. Mind-body modalities are thought to play a role; however, the lack of clear consensus and large body of clinical experience makes it hard to provide good evidence-based recommendation to most of our chronic pain patients. In recent years the Phantom Limb Pain (PLP) and to some degree Complex Regional Pain Syndrome (CRPS) may prove to be an exception. In this review we summarize the current evidence supporting use of Mirror Box Therapy and its successor, Immersive Virtual Reality. PMID:22051561

  12. The Transformation of the "Black Box"

    OpenAIRE

    JIMENEZ DOMENECH, LUCIA

    2012-01-01

    The idea of this project is to convert an old office building downtown into an energy-neutral high-rise village. The assignment contained the office building located in the city centre of Groningen at Eendrachtskade 2, commonly called the "Black Box". It was built in 1976, and the actual technical condition is poor with inadequate insulation. When the building remains empty in 2014, the most obvious next thing to happen is the demolition. But, due to climate impact, the objective is to reuse ...

  13. Test procedure for boxed waste assay system

    International Nuclear Information System (INIS)

    This document, prepared by Los Alamos National Laboratory's NMT-4 group, details the test methodology and requirements for Acceptance/Qualification testing of a Boxed Waste Assay System (BWAS) designed and constructed by Pajarito Scientific Corporation. Testing of the BWAS at the Plutonium Facility (TA55) at Los Alamos National Laboratory will be performed to ascertain system adherence to procurement specification requirements. The test program shall include demonstration of conveyor handling capabilities, gamma ray energy analysis, and imaging passive/active neutron accuracy and sensitivity. Integral to these functions is the system's embedded operating and data reduction software

  14. Box model for channels of human migration

    CERN Document Server

    Vitanov, Nikolay K

    2016-01-01

    We discuss a mathematical model of migration channel based on the truncated Waring distribution. The truncated Waring distribution is obtained for a more general model of motion of substance through a channel containing finite number of boxes. The model is applied then for case of migrants moving through a channel consisting of finite number of countries or cities. The number of migrants in the channel strongly depends on the number of migrants that enter the channel through the country of entrance. It is shown that if the final destination country is very popular then large percentage of migrants may concentrate there.

  15. Radiometry of radiochemical processing plant box

    International Nuclear Information System (INIS)

    Radiometry method is used to detect shielding losses in the newly designed processing plants, to control the personnel exposure handling the radioactivity. The acceptable radiation level in occupied area at the working place, as per AERB regulatory guidelines is 1 μSv/h (0.1mR/h). Hence a stringent control on the shielding is mandatory. The shielding integrity was evaluated using a sealed source of 900 mCi 60Co (1.17 MeV and 1.33 MeV g photons of 100% abundance), by radiometry at -the newly designed 100 mm lead shielded SS 6 cell -plant box used for processing 5 -10Ci of 32P, 51Cr,153Sm, 177Lu, 166Ho etc. The radiometry source introduced into plant box through the loading chamber in H2 can (Dia. 25 mm and length 40 mm) was loaded in the plant. MS stand was fabricated and used for housing the radiometry source at different elevations (300, 600 and 900 mm). The stand was kept in the center of the plant at different locations viz., 845 mm, 1445 mm and 2045 mm distance from one side. The transmitted radiation field was mapped using radiation survey meter at marked grid segments of 100 mm x 100 mm in all sides and top of the plant box. The transmitted radiation field in all sides and top of the plant box were mapped using radiation survey meter. At certain grids the radiation levels indicated shielding losses, all such cavities were filled up, the gap was plugged and the radiometry dose mapping was repeated. Due to this rectification, radiation level at most of the places was reduced and the results showed that the shielding had improved. There was higher transmitted radiation field on the plant during opening of sliding doors. Whenever doors are opened during some work, alarm of audio alarm system indicates door opening condition. Installation of the same had been made mandatory to control occupational exposure. The radiation level may not exceed the limit of 1 μ iSv/h for the permanent occupancy of lab personnel at the working place

  16. Smart Distribution Boxes, Complete Energy Management

    Energy Technology Data Exchange (ETDEWEB)

    Platise, Uros

    2010-09-15

    Present households demand side management implementations are turning conventional appliances into smart ones to support auto demand (AutoDR) response function. Present concept features a direct link between the power meters and appliances. In this paper new concept and example of implementation of a so-called Smart Distribution Box (SmartDB) is represented for complete energy and power management. SmartDBs, as an intermediate layer, are extending smart grid power meter functionality to support AutoDR with fast and guaranteed response times, distributed power sources, and besides provide full control over energy management and extra safety functions to the consumers.

  17. LHC Crab Cavity Coupler Test Boxes

    CERN Document Server

    Mitchell, James; Burt, Graeme; Calaga, Rama; Macpherson, Alick; Montesinos, Eric; Silva, Subashini; Tutte, Adam; Xiao, Binping

    2016-01-01

    The LHC double quarter wave (DQW) crab cavities have two different types of Higher Order Mode (HOM) couplers in addition to a fundamental power coupler (FPC). The FPC requires conditioning, so to achieve this we have designed a radio-frequency (RF) quarter wave resonator to provide high transmission between two opposing FPCs. For the HOM couplers we must ensure that the stop-band filter is positioned at the cavity frequency and that peak transmission occurs at the same frequencies as the strongest HOMs. We have designed two test boxes which preserve the cavity spectral response in order to test the couplers.

  18. Slepton pair production in the POWHEG BOX

    International Nuclear Information System (INIS)

    We present an implementation for slepton pair production at hadron colliders in the POWHEG BOX, a framework for combining next-to-leading order QCD calculations with parton-shower Monte-Carlo programs. Our code provides a SUSY Les Houches Accord interface for setting the supersymmetric input parameters. Decays of the sleptons and parton-shower effects are simulated with PYTHIA. Our Monte-Carlo program allows the generation of events, and thus of arbitrary distributions with appropriate selection cuts. Kinematic distributions of experimentally observable quantities are shown for a representative point in the supersymmetric parameter space.

  19. Seismic stability of a standalone glove box structure

    International Nuclear Information System (INIS)

    Highlights: • Glove box is a leak tight, safety related structure used for handling radiotoxic materials. • To study the seismic performance of a freestanding glove box, extensive shake table testing has been carried out. • Glove box maintained structural integrity and leak tightness up to design basis earthquake loading. • Detailed three-dimensional finite element model of the structure is developed and analyzed by using direct time integration methods. • Simplified numerical method is proposed and successfully applied, to quickly estimate sliding displacement and determine upper bounds for it. - Abstract: In a nuclear fuel cycle facility, radiotoxic materials are being handled in freestanding leak tight enclosures called glove boxes (GBs). These glove boxes act as a primary confinement for the radiotoxic materials. Glove boxes are designed as per codal requirements for class I component. They are designed to withstand extreme level of earthquake loading with a return period of 10,000 years. To evaluate seismic performance of the glove box, there is a need to check the stability (sliding and overturning), structural integrity (stresses and strains) and leak tightness under earthquake loading. Extensive shake table experiments were conducted on a single standalone glove box. Actual laboratory conditions were simulated during testing to check the response. After extensive shake table testing, glove box structure was also analyzed using finite element (FE) software. Detailed three-dimensional model of glove box structure was developed and analyzed using nonlinear time history method. It was observed that finite element methods could be utilized to accurately predict dynamic response of glove box structure. This paper discusses the details and results of shake table testing and methodology used for modelling and analysing freestanding glove box structure under seismic loading. In addition, simplified numerical procedure, developed using energy conservation

  20. Seismic stability of a standalone glove box structure

    Energy Technology Data Exchange (ETDEWEB)

    Saraswat, A., E-mail: anupams@barc.gov.in [Bhabha Atomic Research Centre, Mumbai (India); Reddy, G.R. [Bhabha Atomic Research Centre, Mumbai (India); Ghosh, S. [Indian Institute of Technology Bombay, Mumbai (India); Ghosh, A.K.; Kumar, Arun [Bhabha Atomic Research Centre, Mumbai (India)

    2014-09-15

    Highlights: • Glove box is a leak tight, safety related structure used for handling radiotoxic materials. • To study the seismic performance of a freestanding glove box, extensive shake table testing has been carried out. • Glove box maintained structural integrity and leak tightness up to design basis earthquake loading. • Detailed three-dimensional finite element model of the structure is developed and analyzed by using direct time integration methods. • Simplified numerical method is proposed and successfully applied, to quickly estimate sliding displacement and determine upper bounds for it. - Abstract: In a nuclear fuel cycle facility, radiotoxic materials are being handled in freestanding leak tight enclosures called glove boxes (GBs). These glove boxes act as a primary confinement for the radiotoxic materials. Glove boxes are designed as per codal requirements for class I component. They are designed to withstand extreme level of earthquake loading with a return period of 10,000 years. To evaluate seismic performance of the glove box, there is a need to check the stability (sliding and overturning), structural integrity (stresses and strains) and leak tightness under earthquake loading. Extensive shake table experiments were conducted on a single standalone glove box. Actual laboratory conditions were simulated during testing to check the response. After extensive shake table testing, glove box structure was also analyzed using finite element (FE) software. Detailed three-dimensional model of glove box structure was developed and analyzed using nonlinear time history method. It was observed that finite element methods could be utilized to accurately predict dynamic response of glove box structure. This paper discusses the details and results of shake table testing and methodology used for modelling and analysing freestanding glove box structure under seismic loading. In addition, simplified numerical procedure, developed using energy conservation

  1. Teaching Outside the Box: ARL Librarians' Integration of the "One- Box" into Student Instruction

    Science.gov (United States)

    Kulp, Christina; McCain, Cheryl; Scrivener, Laurie

    2014-01-01

    This article reports the results of a survey that targeted reference and instruction librarians who work at libraries that are members of the Asso- ciation of Research Libraries (ARL). Respondents were asked to indicate whether or not they teach students to use the one-box tool, and why or why not. Based on the responses of the 352 librarians who…

  2. Hairy Black Holes in a Box

    CERN Document Server

    Basu, Pallab; Subramanian, P N Bala

    2016-01-01

    We do a systematic study of the phases of gravity coupled to an electromagnetic field and charged scalar in flat space, with box boundary conditions. The scalar-less box has previously been investigated by Braden, Brown, Whiting and York (and others) before AdS/CFT and we elaborate and extend their results in a language more familiar from holography. The phase diagram of the system is analogous to that of AdS black holes, but we emphasize the differences and explain their origin. Once the scalar is added, we show that the system admits both boson stars as well as hairy black holes as solutions, providing yet another way to evade flat space no-hair theorems. Furthermore both these solutions can exist as stable phases in regions of the phase diagram. The final picture of the phases that emerges is strikingly similar to that found recently for holographic superconductors in global AdS, arXiv: 1602.07211. Our construction lays bare certain previously unnoticed subtleties associated to the definition quasi-local c...

  3. Expression of monocyte chemoattractant protein-1 in the pancreas of mice

    Institute of Scientific and Technical Information of China (English)

    LI Dong; ZHU Su-wen; LIU Dong-juan; LIU Guo-liang; SHAN Zhong-yan

    2005-01-01

    Background Type 1 diabetes has been recognized as an organ specific autoimmune disease owing to the immune destruction of pancreatic islet β cells in genetically susceptible individuals.In both human and rodent models of type 1 diabetes, such as nonobese diabetic (NOD) mice, biobreeding rats, the disease has a distinct stage characterized by immune cells infiltrating in the pancreas (insulitis).The major populations of infiltrating cells are macrophages and T lymphocytes.Therefore, immune cell infiltration of pancreatic islets may be a crucial step in the pathogenesis of type 1 diabetes.Monocyte chemoattractant protein-1 can specifically attract monocytes in vivo.Interferon induced protein-10 has chemoattractant effects on the activated lymphocytes.In this study, we analysed the expression of monocyte chemoattractant protein-1 in the pancreas of mice and interferon inducible protein-10 mRNA in the pancreas of NOD mice, and discussed their possible role in the pathogenesis of type 1 diabetes.Methods The immunohistochemical method and immunoelectronmicroscopy were used to evaluate the expression of monocyte chemoattractant protein-1 in the pancreas of NOD mice and BALB/c mice.RT-PCR was used to evaluate the expression of monocyte chemoattractant protein-1 and interferon inducible protein mRNA in NOD mice.Results Monocyte chemoattractant protein-1 was positive in the pancreas of NOD mice, whereas negative in the pancreas of BALB/C mice.RT-PCR showed that monocyte chemoattractant protein-1 and interferon inducible protein-10 mRNA could be found in the pancreas of NOD mice.Immunoelectronmicroscopy demonstrated that monocyte chemoattractant protein-1 was produced by β cells and stored in the cytoplasm of the cells.Conclusions Pancreatic islet β cells produce monocyte chemoattractantprotein-1 in NOD mice.Monocyte chemoattractant protein-1 may play an important part in the pathogenesis of type 1 diabetes by attracting monocytes/macrophages to infiltrate pancreatic

  4. Roles of F-box Proteins in Plant Hormone Responses

    Institute of Scientific and Technical Information of China (English)

    Haichuan YU; Jiao WU; Nanfei XU; Ming PENG

    2007-01-01

    The F-box protein is an important component of the E3 ubiquitin ligase Skpl-Cullin-F-box protein complex. It binds specific substrates for ubiquitin-mediated proteolysis. The F-box proteins contain a signature F-box motif at their amino-terminus and some protein-protein interaction motifs at their carboxyterminus, such as Trp-Asp repeats or leucine rich repeats. Many F-box proteins have been identified to be involved in plant hormone response as receptors or important medial components. These breakthrough findings shed light on our current understanding of the structure and function of the various F-box proteins,their related plant hormone signaling pathways, and their roles in regulating plant development.

  5. Software sensors based on the grey-box modelling approach

    DEFF Research Database (Denmark)

    Carstensen, J.; Harremoës, P.; Strube, Rune

    1996-01-01

    In recent years the grey-box modelling approach has been applied to wastewater transportation and treatment Grey-box models are characterized by the combination of deterministic and stochastic terms to form a model where all the parameters are statistically identifiable from the on......-box model for the specific dynamics is identified. Similarly, an on-line software sensor for detecting the occurrence of backwater phenomena can be developed by comparing the dynamics of a flow measurement with a nearby level measurement. For treatment plants it is found that grey-box models applied to on......-line measurements. With respect to the development of software sensors, the grey-box models possess two important features. Firstly, the on-line measurements can be filtered according to the grey-box model in order to remove noise deriving from the measuring equipment and controlling devices. Secondly, the grey...

  6. C-terminal binding protein (CtBP activates the expression of E-box clock genes with CLOCK/CYCLE in Drosophila.

    Directory of Open Access Journals (Sweden)

    Taichi Q Itoh

    Full Text Available In Drosophila, CLOCK/CYCLE heterodimer (CLK/CYC is the primary activator of circadian clock genes that contain the E-box sequence in their promoter regions (hereafter referred to as "E-box clock genes". Although extensive studies have investigated the feedback regulation of clock genes, little is known regarding other factors acting with CLK/CYC. Here we show that Drosophila C-terminal binding protein (dCtBP, a transcriptional co-factor, is involved in the regulation of the E-box clock genes. In vivo overexpression of dCtBP in clock cells lengthened or abolished circadian locomotor rhythm with up-regulation of a subset of the E-box clock genes, period (per, vrille (vri, and PAR domain protein 1ε (Pdp1ε. Co-expression of dCtBP with CLK in vitro also increased the promoter activity of per, vri, Pdp1ε and cwo depending on the amount of dCtBP expression, whereas no effect was observed without CLK. The activation of these clock genes in vitro was not observed when we used mutated dCtBP which carries amino acid substitutions in NAD+ domain. These results suggest that dCtBP generally acts as a putative co-activator of CLK/CYC through the E-box sequence.

  7. Cash Flow Prediction Using a Grey-Box Model

    OpenAIRE

    Pang, Yang; Opong, Kwaku; Moutinho, Luia; Li, Yun

    2015-01-01

    This paper tackles the problem of financial forecasting by extending methods developed in automation, engineering and computing science. Current methods existing in the literature for firm-level cash flows are first analysed. Then a grey-box modelling method is developed to elevate the performance of cash-flow prediction. Linear panel data modelling is used as a benchmark model. Experiments with out-of-sample tests are used to validate the grey-box approach. Encouragingly, nonlinear grey-box ...

  8. Binding of Histone H1 to DNA Is Differentially Modulated by Redox State of HMGB1

    Czech Academy of Sciences Publication Activity Database

    Muselíková Polanská, Eva; Pospíšilová, Š.; Štros, Michal

    2014-01-01

    Roč. 9, č. 2 (2014). E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GAP305/12/2475; GA MŠk(CZ) ED1.1.00/02.0068 Institutional support: RVO:68081707 Keywords : CHROMOSOMAL-PROTEIN HMG1 * MOBILITY GROUP-1 PROTEIN * LINKER HISTONES Subject RIV: BO - Biophysics Impact factor: 3.234, year: 2014

  9. Reduction in circulating level of HMGB-1 following continuous renal replacement therapy in sepsis.

    Science.gov (United States)

    Ueno, Takuya; Ikeda, Toshiaki; Yokoyama, Takayoshi; Kihara, Yu; Konno, Osamu; Nakamura, Yuki; Iwamoto, Hitoshi; Shimizu, Tetsunosuke; McGrath, Martina M; Chandraker, Anil

    2016-07-01

    Early recovery from shock improves prognosis in patients with severe sepsis and septic shock. During this period, cytokine imbalances mediate the development of organ damage and mortality. In Japan, we have access to hemoperfusion using an immobilized polymyxin B fiber column for endotoxin removal (PMX-DHP) and continuous hemodiafiltration (CHDF) as artificial support for patients with septic shock, with the aim of improving hemodynamics and organ dysfunction caused by elevated inflammatory cytokines and mediators. In this Short communication, we discuss recent findings showing anti-inflammatory treatment following these continuous renal replacement therapies in sepsis. PMID:27155819

  10. HMGB1 Mediates Endogenous TLR2 Activation and Brain Tumor Regression

    OpenAIRE

    Curtin, James; Liu, Naiyou; Candolfi, Marianela; Xiong, Weidong; Assi, Hikmat; Yagiz, Kader; Edwards, Matthew; Michelsen, Kathrin; Kroeger, Kurt; Liu, Chunyan; Muhammad, AKM Ghulam; Clark, Mary; Arditi, Moshe; Comin-Anduix, Begonya; Ribas, Antoni

    2009-01-01

    Editors' Summary Background. Every year, more than 175,000 people develop a primary brain tumor (a cancer that starts in the brain rather than spreading in from elsewhere). Like all cancers, brain tumors develop when a cell acquires genetic changes that allow it to grow uncontrollably and that change other aspects of its behavior, including the proteins it makes. There are many different types of cells in the brain and, as a result, there are many different types of brain tumors. However, one...

  11. On the role of HMGB1 and IL-1 in tissue barrier defense

    OpenAIRE

    Zetterström, Cecilia

    2001-01-01

    The specialized epithelial surfaces of the lymphoepithelial tissue in the airways and the seminiferous epithelium of the testis are sites of host-environmental interaction at the same time as they serve important physiological functions in gas exchange and reproduction. The host response of a broken epithelial barrier requires rapid mechanisms to control the microflora and to prevent invasion of pathogens. Cytokines are a heterogeneous group of proteins originally described ...

  12. Diet Restriction Inhibits Apoptosis and HMGB1 Oxidation and Promotes Inflammatory Cell Recruitment during Acetaminophen Hepatotoxicity

    OpenAIRE

    Antoine, Daniel James; Williams, Dominic P.; Kipar, Anja; Laverty, Hugh; Park, B. Kevin

    2010-01-01

    Acetaminophen (APAP) overdose is a major cause of acute liver failure and serves as a paradigm to elucidate mechanisms, predisposing factors and therapeutic interventions. The roles of apoptosis and inflammation during APAP hepatotoxicity remain controversial. We investigated whether fasting of mice for 24 h can inhibit APAP-induced caspase activation and apoptosis through the depletion of basal ATP. We also investigated in fasted mice the critical role played by inhibition of caspase-depende...

  13. Recognition of DNA interstrand cross-link of antitumor cisplatin by HMGB1 protein

    Czech Academy of Sciences Publication Activity Database

    Kašpárková, Jana; Delalande, Olivier; Štros, Michal; Elizondo-Riojas, M.A.; Vojtíšková, Marie; Kozelka, J.; Brabec, Viktor

    2003-01-01

    Roč. 42, č. 5 (2003), s. 1234-1244. ISSN 0006-2960 R&D Projects: GA ČR GA305/02/1552; GA ČR GA305/01/0418; GA MZd NL6058; GA AV ČR IAA5004105 Institutional research plan: CEZ:AV0Z5004920 Keywords : platinum complexes * nucleic-acids * base pairs Subject RIV: BO - Biophysics Impact factor: 3.922, year: 2003

  14. Three Essays on Big-Box Retailers and Regional Economics

    OpenAIRE

    Peralta, Denis

    2016-01-01

    The big-box retail stores such as Wal-Mart and Target have become the focus of many studies researching their impacts on local economic outcomes. This dissertation studies three related topics: (i) the dynamic interrelationship among the presence of the big-box stores, retail wage, and employment, (ii) the impact of the big-box retailers on personal income growth, and (iii) the dynamic interrelationship between the presence of big-box retailers and personal income growth. The research draws i...

  15. Ion-wake Field inside a Glass Box

    CERN Document Server

    Chen, Mudi; Zhang, Bo; Matthews, Lorin S; Hyde, Truell W

    2016-01-01

    The confinement provided by a glass box is proving ideal for the formation of vertically aligned structures and a convenient method for controlling the number of dust particles comprising these dust structures, as well as their size and shape. In this paper, the electronic confinement of the glass box is mapped and the particle interactions between the particle pairs inside the glass box are measured. The ion-wake field is shown to exist within the glass box and its vertical and horizontal extent is measured.

  16. New approaches to glove box design at Hanford

    International Nuclear Information System (INIS)

    Glove boxes provide the primary environmental containment system for plutonium processing operations at US Dept. of Energy (DOE)-owned facilities such as Rockwell Hanford. As noted in previous presentations, glove box designs and operations have evolved through stages that are a result of advances in processing techniques, new regulatory requirements, and cost escalation. These factors will continue to influence the current glove box designs and operations. The purpose of this presentation is to discuss required upgrades and changes that are being incorporated into glove boxes being installed at Rockwell Hanford and other DOE installations or are being evaluated for future upgrades

  17. Dream Box Learning. What Works Clearinghouse Intervention Report

    Science.gov (United States)

    What Works Clearinghouse, 2013

    2013-01-01

    "DreamBox Learning" is a supplemental online mathematics program that provides adaptive instruction for students in grades K-5 and focuses on number and operations, place value, and number sense. The What Works Clearinghouse (WWC) identified one study of "DreamBox Learning" that both falls within the scope of the Elementary…

  18. Effect of auricular acupuncture on oxygen consumption of boxing athletes

    Institute of Scientific and Technical Information of China (English)

    LIN Zen-Pin; WANG Chung-Yuan; JANO Tsong-Rong; MA Tso-chiang; CHIA Fan; LIN Jaung-Geng; HSU Jen-Jeng; HO Tsung-Jung

    2009-01-01

    @@ Boxing is an official sport at the 2008 Beijing Olympic Games and the fast development of world-class high strength training and sport science has made a significant impact on scientific training. Boxing needs high cardio-respiratory function, speed, muscle strength, and anaerobic and intensive physical demands including weight control covering the grading of athlete's.

  19. Wind Speed Prediction Using Box-Jenkins Method

    Directory of Open Access Journals (Sweden)

    Helga Silaghi

    2008-05-01

    Full Text Available This paper presents the Box-Jenkins method used for wind speed prediction. Box-Jenkins methodology finds the best fit of a time series to past values in order to make forecasts. This methodology uses the autocorrelation and partial autocorrelation functions.

  20. Olympic Sports(ⅩⅣ):Boxing

    Institute of Scientific and Technical Information of China (English)

    姜全红

    2004-01-01

    Boxing has a long sporting history.The earliest evidence of boxing is found in Egypt around 3000 B.C.The sport was introduced to the Olympic Games by the Greeks in the late 7th century B.C.. Greek boxers used thongs of soft leather to bind their hands

  1. Decontamination and dismantling of large plutonium-contamined glove boxes

    International Nuclear Information System (INIS)

    This report describes the work performed in the frame of two C.E.C. - Contracts FI1D-002400-B Decommissioning of very large glove boxes and FI1D-0058 Decommissioning of a complex glove box structure to be dismounted partially on place. Detailed information is given about each glove box. The selection of the solution Transportation of the glove boxes to a specialized dismantling plant is justified. The necessary contacts inside the BELGONUCLEAIRE MOX plant and between the latter and other organizations are explained. The problems of manipulating large gloves are listed and the retained solution of building a so called Stiffening frame around each glove box is described. Furthermore information is given concerning required operators time for cleaning, manipulating, packing and dismantling together with received doses and quantities of waste produced. Concerning the glove box unit partially to be dismounted on place, detailed information is given about the way the glove boxes have been treated prior to this partial dismantling on place and about the way this partial dismantling has been performed. From these results one can conclude that such a delicate task can be performed without major difficulties. Finally information is given of the decontamination test of a highly Pu contaminated glove box with freon with rather poor results and of the preliminary CO2 blasting tests on non active samples

  2. Faster Black-Box Algorithms Through Higher Arity Operators

    DEFF Research Database (Denmark)

    Doerr, Benjamin; Johannsen, Daniel; Kötzing, Timo; Lehre, Per Kristian; Wagner, Markus; Winzen, Carola

    We extend the work of Lehre and Witt (GECCO 2010) on the unbiased black-box model by considering higher arity variation operators. In particular, we show that already for binary operators the black-box complexity of LeadingOnes drops from (n2) for unary operators to O(n log n). For OneMax, the (n...

  3. Getting started with Oracle VM VirtualBox

    CERN Document Server

    Dash, Pradyumna

    2013-01-01

    A step-by-step guide that will show you how to install, configure, and manage VirtualBox.This book is for system administrators, technical architects, and virtualization enthusiasts who want to learn how to set up a virtual machine. Knowledge of the Linux environment is expected. Prior experience with VirtualBox or knowledge of virtualization is not required.

  4. A System for Cooling inside a Glove Box

    Science.gov (United States)

    Sanz, Martial

    2010-01-01

    An easy, efficient, reliable, and low-cost method of constructing a cooling system using a simple circulating pump is described. The system is employed in conjunction with an inert atmosphere glove box to achieve the synthesis of air- and moisture-sensitive compounds inside the glove box at controlled, low temperatures without contaminating the…

  5. The effect and mechanism of Astragaloside IV on immune function of regulatory T cell mediated by high mobility group box 1 protein in vitro%黄芪甲苷对体外高迁移率族蛋白B1介导小鼠调节性T细胞免疫功能的影响

    Institute of Scientific and Technical Information of China (English)

    黄立锋; 李金凤; 姚咏明; 张淑文; 李文雄

    2014-01-01

    Objective Based the previous studies, the present study was performed to investigate the antagonistic effects of different doses of Astragaloside IV on the immune function of Treg mediated by HMGB1 in vitro and its potential mechanism.Methods CD4+CD25-T cells isolated from the spleens of male BABL/c mice by magnetic beads were seeded on 48-well cell culture plates and were randomly divided into four groups as follows(12 holes per group). Normal control group: CD4+CD25-T cells were cultured merely. Treg group: Tregs(100μl) and CD4+CD25-T cells were co-cultured in ratio of 1:10. HMGB1+Treg group: Tregs(100μl) stimulated by HMGB1(1μg/ml) for 72 h and CD4+CD25-T cells were co-cultured in ratio of 1∶10. HMGB1+AST IV+Treg group: Tregs(100μl) stimulated by HMGB1(1μg/ml) and AST IV(100μg/ml)for 72 h were co-cultured with CD4+CD25-T cells in ratio of 1:10. CD4+CD25-T cells and supernatants were again collected on post-culture 72 hour. The proliferation of CD4+CD25- T cells was analyzed by MTT test, the activity of NFAT and the contents of cytokines of IL-2 released into supernatants were also determined by means of ELISA. Results When CD4+CD25-T cells were co-cultured with Tregs, the cell proliferation(0.166±0.039) and the levels of NFAT(0.156±0.035) and IL-2(2.38±0.58) in supernatant were markedly decreased as compared with those in the control group(P<0.01). However, the contrary results were found when CD4+CD25-T cells were co-cultured with Treg stimulated by HMGB1. Compared with those in the(HMGB1+Treg) group, the contrary results were showed with a dose-dependent in the(HMGB1+ASTⅣ+Treg) group.Conclusion ASTⅣcan rivalry the effects of HMGB1 on immune function of Treg in vitro, this result indicate that ASTⅣhas the therapeutic action on inflammation promoted by HMGB1.%目的:观察高迁移率族蛋白B1(HMGB1)刺激的小鼠调节性T细胞(CD4+CD25+Treg)对CD4+CD25-T细胞免疫功能的影响及黄芪甲苷(AST Ⅳ)对HMGB1

  6. Aspect ratio dependence in magnetorotational instability shearing box simulations

    CERN Document Server

    Bodo, G; Cattaneo, F; Rossi, P; Ferrari, A

    2008-01-01

    Aims: We study the changes in the properties of turbulence driven by the magnetorotational instability in a shearing box, as the computational domain size in the radial direction is varied relative to the height Methods: We perform 3D simulations in the shearing box approximation, with a net magnetic flux, and we consider computational domains with different aspect ratios Results: We find that in boxes of aspect ratio unity the transport of angular momentum is strongly intermittent and dominated by channel solutions in agreement with previous work. In contrast, in boxes with larger aspect ratio, the channel solutions and the associated intermittent behavior disappear. Conclusions: There is strong evidence that, as the aspect ratio becomes larger, the characteristics of the solution become aspect ratio independent. We conclude that shearing box calculations with aspect ratio unity or near unity may introduce spurious effects.

  7. Getting started with Citrix VDI-in-a-Box

    CERN Document Server

    Brown, Stuart Arthur

    2013-01-01

    A practical and fast-paced guide that gives you all the information you need to simplify and streamline virtual desktops so you get a production-quality solution while instantly lowering your costs and improving security.Getting Started with Citrix VDI-in-a-Box is great for IT professionals who are new to VDI-in-a-Box and who are looking for a good grounding in the product. You may be planning to research VDI-in-a-Box in more detail, or you may be tasked with researching how VDI-in-a-Box could improve the productivity of your organization. No prior knowledge of VDI-in-a-Box is required, just a

  8. Opening up a Colourful Cosmic Jewel Box

    Science.gov (United States)

    2009-10-01

    The combination of images taken by three exceptional telescopes, the ESO Very Large Telescope on Cerro Paranal , the MPG/ESO 2.2-metre telescope at ESO's La Silla observatory and the NASA/ESA Hubble Space Telescope, has allowed the stunning Jewel Box star cluster to be seen in a whole new light. Star clusters are among the most visually alluring and astrophysically fascinating objects in the sky. One of the most spectacular nestles deep in the southern skies near the Southern Cross in the constellation of Crux. The Kappa Crucis Cluster, also known as NGC 4755 or simply the "Jewel Box" is just bright enough to be seen with the unaided eye. It was given its nickname by the English astronomer John Herschel in the 1830s because the striking colour contrasts of its pale blue and orange stars seen through a telescope reminded Herschel of a piece of exotic jewellery. Open clusters [1] such as NGC 4755 typically contain anything from a few to thousands of stars that are loosely bound together by gravity. Because the stars all formed together from the same cloud of gas and dust their ages and chemical makeup are similar, which makes them ideal laboratories for studying how stars evolve. The position of the cluster amongst the rich star fields and dust clouds of the southern Milky Way is shown in the very wide field view generated from the Digitized Sky Survey 2 data. This image also includes one of the stars of the Southern Cross as well as part of the huge dark cloud of the Coal Sack [2]. A new image taken with the Wide Field Imager (WFI) on the MPG/ESO 2.2-metre telescope at ESO's La Silla Observatory in Chile shows the cluster and its rich surroundings in all their multicoloured glory. The large field of view of the WFI shows a vast number of stars. Many are located behind the dusty clouds of the Milky Way and therefore appear red [3]. The FORS1 instrument on the ESO Very Large Telescope (VLT) allows a much closer look at the cluster itself. The telescope's huge mirror

  9. On (2,3)-agreeable Box Societies

    CERN Document Server

    Abrahams, Michael; Zell, Thierry

    2009-01-01

    The notion of $(k,m)$-agreeable society was introduced by Deborah Berg et al.: a family of convex subsets of $\\R^d$ is called $(k,m)$-agreeable if any subfamily of size $m$ contains at least one non-empty $k$-fold intersection. In that paper, the $(k,m)$-agreeability of a convex family was shown to imply the existence of a subfamily of size $\\beta n$ with non-empty intersection, where $n$ is the size of the original family and $\\beta\\in[0,1]$ is an explicit constant depending only on $k,m$ and $d$. The quantity $\\beta(k,m,d)$ is called the minimal \\emph{agreement proportion} for a $(k,m)$-agreeable family in $\\R^d$. If we only assume that the sets are convex, simple examples show that $\\beta=0$ for $(k,m)$-agreeable families in $\\R^d$ where $kboxes, i.e. cuboids with sides parallel to the coordinates hyperplanes. We derive explicit formulas for the first non-trivial case: the case...

  10. A formula for lubrication of journal boxes

    Energy Technology Data Exchange (ETDEWEB)

    Gimayev, R.N.; Aliyev, R.A.; Dolukhanov, R.Ts.; Kondrasheva, N.K.; Ol' kov, P.L.; Rogacheva, O.I.; Spivak, Ye.A.

    1982-01-01

    In order to improve lubricating properties of oils used for journal boxes, an extract that boils off at 275-470/sup 0/, 60-75, is used, with a thermal cracking residue that is ADS 25-40. The latter consists of oil fraction extracts in a mixture with a catalytically cracked heavy gasoil (low-coking). Thus, content of aromatic hydrocarbons and asphalt-tar substances determines its positive lubricating properties. Example: the lubricant derived by direct compounding of a selectively cleaned oil fraction extract (SE), having a boiling temp. of 275-470/sup 0/, thermal ADS cracking residue and density of 1.100 is prepared with a component ratio 75:25. The derived oil has a viscosity of 42.0 sSt/50/sup 0/; dynamic viscosity 110 pz/-10/sup 0/; boiling temp. in an open crucible is 140/sup 0/; congelation temp. -42/sup 0/; critical loading, determined by a four-bearing friction machine, 85 kgs; thickness of lubricating layer, determined by centrifuge, 3.35 mkm. Comparison of physicochemical properties of the given and known lubricants shows that the tested item has better viscosity and lubricating characteristics. Oil test samples satisfy all GOST 610-72 requirements for summer-type axle oils.

  11. Non-signaling boxes and quantum logics

    International Nuclear Information System (INIS)

    Using a quantum logic approach we analyze the structure of the so-called non-signaling theories respecting relativistic causality, but allowing correlations violating bounds imposed by quantum mechanics such as CHSH inequality. We discuss the relations among such theories, quantum mechanics, and classical physics. Our main result is the construction of a probability theory adequate for the simplest instance of a non-signaling theory—the two non-signaling boxes world—in which we exhibit its differences in comparison with classical and quantum probabilities. We show that the question of whether such a theory can be treated as a kind of ‘generalization’ of the quantum theory of the two-qubit system cannot be answered positively. Some of its features put it closer to the quantum world—on the one hand, for example, the measurements are destructive, though on the other hand the Heisenberg uncertainty relations are not satisfied. Another interesting property contrasting it from quantum mechanics is that the subset of ‘classically correlated states’, i.e. the states with only classical correlations, does not reproduce the classical world of the two two-state systems. Our results establish a new link between quantum information theory and the well-developed theory of quantum logics. (paper)

  12. Probability boxes on totally preordered spaces for multivariate modelling

    CERN Document Server

    Troffaes, Matthias C M; 10.1016/j.ijar.2011.02.001

    2011-01-01

    A pair of lower and upper cumulative distribution functions, also called probability box or p-box, is among the most popular models used in imprecise probability theory. They arise naturally in expert elicitation, for instance in cases where bounds are specified on the quantiles of a random variable, or when quantiles are specified only at a finite number of points. Many practical and formal results concerning p-boxes already exist in the literature. In this paper, we provide new efficient tools to construct multivariate p-boxes and develop algorithms to draw inferences from them. For this purpose, we formalise and extend the theory of p-boxes using Walley's behavioural theory of imprecise probabilities, and heavily rely on its notion of natural extension and existing results about independence modeling. In particular, we allow p-boxes to be defined on arbitrary totally preordered spaces, hence thereby also admitting multivariate p-boxes via probability bounds over any collection of nested sets. We focus on t...

  13. Measure Guideline: Optimizing the Configuration of Flexible Duct Junction Boxes

    Energy Technology Data Exchange (ETDEWEB)

    Beach, R.; Burdick, A.

    2014-03-01

    This measure guideline offers additional recommendations to heating, ventilation, and air conditioning (HVAC) system designers for optimizing flexible duct, constant-volume HVAC systems using junction boxes within Air Conditioning Contractors of America (ACCA) Manual D guidance (Rutkowski, H. Manual D -- Residential Duct Systems, 3rd edition, Version 1.00. Arlington, VA: Air Conditioning Contractors of America, 2009.). IBACOS used computational fluid dynamics software to explore and develop guidance to better control the airflow effects of factors that may impact pressure losses within junction boxes among various design configurations (Beach, R., Prahl, D., and Lange, R. CFD Analysis of Flexible Duct Junction Box Design. Golden, CO: National Renewable Energy Laboratory, submitted for publication 2013). These recommendations can help to ensure that a system aligns more closely with the design and the occupants' comfort expectations. Specifically, the recommendations described herein show how to configure a rectangular box with four outlets, a triangular box with three outlets, metal wyes with two outlets, and multiple configurations for more than four outlets. Designers of HVAC systems, contractors who are fabricating junction boxes on site, and anyone using the ACCA Manual D process for sizing duct runs will find this measure guideline invaluable for more accurately minimizing pressure losses when using junction boxes with flexible ducts.

  14. Alterations in expression levels of deafness dystonia protein 1 affect mitochondrial morphology

    DEFF Research Database (Denmark)

    Engl, Gertraud; Florian, Stefan; Tranebjærg, Lisbeth;

    2012-01-01

    Deafness-Dystonia-Optic Neuropathy (DDON) Syndrome is a rare X-linked progressive neurodegenerative disorder resulting from mutations in the TIMM8A gene encoding for the deafness dystonia protein 1 (DDP1). Despite important progress in identifying and characterizing novel mutations in this gene...

  15. Expression of Plasmodium falciparum erythrocyte membrane protein 1 in experimentally infected humans

    DEFF Research Database (Denmark)

    Lavstsen, Thomas; Magistrado, Pamela; Hermsen, Cornelus C;

    2005-01-01

    -encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family, which is expressed on the surface of infected erythrocytes where it mediates binding to endothelial receptors. Thus, severe malaria may be caused by parasites expressing PfEMP1 variants that afford parasites optimal sequestration in...

  16. Analyzing Plasmodium falciparum erythrocyte membrane protein 1 gene expression by a next generation sequencing based method

    DEFF Research Database (Denmark)

    Jespersen, Jakob S.; Petersen, Bent; Seguin-Orlando, Andaine;

    2013-01-01

    Plasmodium falciparum is responsible for most cases of severe malaria and causes >1 million deaths every year. The particular virulence of this Plasmodium species is highly associated with the expression of certain members of the Plasmodium falciparum erythrocyte membrane protein 1(PfEMP1) family...

  17. Plasmodium falciparum Erythrocyte Membrane Protein 1 Diversity in Seven Genomes – Divide and Conquer

    DEFF Research Database (Denmark)

    Rask, Thomas Salhøj; Hansen, Daniel Aaen; Theander, Thor G.;

    2010-01-01

    The var gene encoded hyper-variable Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family mediates cytoadhesion of infected erythrocytes to human endothelium. Antibodies blocking cytoadhesion are important mediators of malaria immunity acquired by endemic populations. The development...

  18. *611540 SH3-DOMAIN GRB2-LIKE (ENDOPHILIN)-INTERACTING PROTEIN 1; SGIP1 [OMIM

    Lifescience Database Archive (English)

    Full Text Available FIELD NO 611540 FIELD TI 611540 SH3-DOMAIN GRB2-LIKE (ENDOPHILIN)-INTERACTING PROTEIN 1; SGIP1 F ... differential-display PCR of hypothalamic RNA from lean ... and obese Psammomys obesus (Israeli sand rats), a ... nhibition of Sgip1 hypothalamic expression in both lean ... P. obesus and Sprague-Dawley rats caused a signifi ...

  19. Bayesian spatio-temporal kriging with misspecified black-box

    OpenAIRE

    Faye, Papa-Abdulaye; faye, Papa Abdoulaye; Druilhet, Pierre; Azzaoui, Nourddine; Yao, Anne-Françoise

    2015-01-01

    We propose a new algorithm for spatio-temporal prediction. At a given time t, we use a Bayesian kriging model for spatial prediction. The temporal evolution from t to t + 1 is given by a deterministic black-box which can be a complex numerical code or a partial differential equation. As often in practice, the black-box is misspecified, in the sense that its parameters are imprecisely known or may be varying randomly over time. At time t, we use the black-box to obtain a rough prediction at ti...

  20. Patent Boxes Design, Patents Location and Local R&D

    OpenAIRE

    Annette Alstadsæter; Salvador Barrios; Nicodème, Gaëtan J.A.; Agnieszka Skonieczna; Antonio Vezzani

    2015-01-01

    Patent boxes have been heavily debated for their role in corporate tax competition. This paper uses firm-level data for the period 2000-2011 for the top 2,000 corporate research and development (R&D) investors worldwide to consider the determinants of patent registration across a large sample of countries. Importantly, we disentangle the effects of corporate income taxation from the tax advantage of patent boxes. We also exploit a new and original dataset on patent box features such as the co...

  1. Patent Boxes Design, Patents Location and Local R&D

    OpenAIRE

    Annette Alstadsæter; Salvador Barrios; Gaëtan Nicodème; Agnieszka Maria Skonieczna; Antonio Vezzani

    2015-01-01

    Patent boxes have been heavily debated for their role in corporate tax competition.This paper uses firm-level data for the period 2000-2011 for the top 2,000 corporate R&D investors worldwide to consider the determinants of patent registration across a large sample of countries. Importantly, we disentangle the effects of corporate income taxation from the tax advantage of patent boxes. We also exploit a new and original dataset on patent box features such as the conditionality on performing r...

  2. The AirQuality SenseBox

    Science.gov (United States)

    Demuth, Dustin; Nuest, Daniel; Bröring, Arne; Pebesma, Edzer

    2013-04-01

    In the past year, a group of open hardware enthusiasts and citizen scientists had large success in the crowd-funding of an open hardware-based sensor platform for air quality monitoring, called the Air Quality Egg. Via the kickstarter platform, the group was able to collect triple the amount of money than needed to fulfill their goals. Data generated by the Air Quality Egg is pushed to the data logging platform cosm.com, which makes the devices a part of the Internet of Things. The project aims at increasing the participation of citizens in the collection of data, the development of sensors, the operation of sensor stations, and, as data on cosm is publicly available, the sharing, visualization and analysis of data. Air Quality Eggs can measure NO2 and CO concentrations, as well as relative humidity and temperature. The chosen sensors are low-cost and have limited precision and accurracy. The Air Quality Egg consists of a stationary outdoor and a stationary indoor unit. Each outdoor unit will wirelessly transmit air quality measurements to the indoor unit, which forwards the data to cosm. Most recent versions of the Air Quality Egg allow a rough calibration of the gas sensors and on-the-fly conversion from raw sensor readings (impedance) to meaningful air quality data expressed in units of parts per billion. Data generated by these low-cost platforms are not intended to replace well-calibrated official monitoring stations, but rather augment the density of the total monitoring network with citizen sensors. To improve the usability of the Air Quality Egg, we present a new and more advanced concept, called the AirQuality SenseBox. We made the outdoor platform more autonomous and location-aware by adding solarpanels and rechargeable batteries as a power source. The AirQuality SenseBox knows its own position from a GPS device attached to the platform. As a mobile sensor platform, it can for instance be attached to vehicles. A low-cost and low-power wireless chipset

  3. Release of Danger Signals during Ischemic Storage of the Liver: A Potential Marker of Organ Damage?

    Directory of Open Access Journals (Sweden)

    Anding Liu

    2010-01-01

    Full Text Available Liver grafts suffer from unavoidable injury due to ischemia and manipulation before implantation. Danger signals such as high-mobility group box -1(HMGB1 and macrophage migration inhibitory factor (MIF play a pivotal role in the immune response. We characterized the kinetics of their release into the effluent during cold/warm ischemia and additional manipulation-induced mechanical damage. Furthermore, we evaluated the relationship between HMGB1/MIF release and ischemic/mechanical damage. Liver enzymes and protein in the effluent increased with increasing ischemia time. HMGB1/MIF- release correlated with the extent of hepatocellular injury. With increasing ischemia time and damage, HMGB1 was translocated from the nucleus to the cytoplasma as indicated by weak nuclear and strong cytoplasmic staining. Enhancement of liver injury by mechanical damage was indicated by an earlier HMGB1 translocation into the cytoplasm and earlier release of danger signals into the effluent. Our results suggest that determination of HMGB1 and MIF reflects the extent of ischemic injury. Furthermore, HMGB1and MIF are more sensitive than liver enzymes to detect the additional mechanical damage inflicted on the organ graft during surgical manipulation.

  4. Experts’ Misinterpretation of Box Plots – a Dual Processing Approach

    Directory of Open Access Journals (Sweden)

    Stephanie Lem

    2014-11-01

    Full Text Available Recent studies have shown that students often misinterpret the area of the box in box plots as representing the frequency or proportion of observations in that interval, while it actually represents density. This misinterpretation has been shown to be based on the saliency of this area and can be explained by heuristic reasoning as defined by dual process theories. In this study we tested whether expert users of box plots also display this misinterpretation and show signs of the same heuristic reasoning as found in students. Using a reaction time test, we found signs of heuristic reasoning in experts, both with respect to accuracy and reaction times. If even experts have difficulty interpreting box plots, one can question whether these are an appropriate form of representation to use when reporting data and deserve the prominent place they currently have in the statistics curriculum.

  5. Gray-box modelling approach for description of storage tunnel

    DEFF Research Database (Denmark)

    Harremoës, Poul; Carstensen, Jacob

    1999-01-01

    The dynamics of a storage tunnel is examined using a model based on on-line measured data and a combination of simple deterministic and black-box stochastic elements. This approach, called gray-box modeling, is a new promising methodology for giving an on-line state description of sewer systems. ...... and implemented in a SCADA system because the most important information on the specific system is provided on-line......The dynamics of a storage tunnel is examined using a model based on on-line measured data and a combination of simple deterministic and black-box stochastic elements. This approach, called gray-box modeling, is a new promising methodology for giving an on-line state description of sewer systems...

  6. BoxLib with Tiling: An AMR Software Framework

    CERN Document Server

    Zhang, Weiqun; Day, Marcus; Nguyen, Tan; Shalf, John; Unat, Didem

    2016-01-01

    In this paper we introduce a block-structured adaptive mesh refinement (AMR) software framework that incorporates tiling, a well-known loop transformation. Because the multiscale, multiphysics codes built in BoxLib are designed to solve complex systems at high resolution, performance on current and next generation architectures is essential. With the expectation of many more cores per node on next generation architectures, the ability to effectively utilize threads within a node is essential, and the current model for parallelization will not be sufficient. We describe a new version of BoxLib in which the tiling constructs are embedded so that BoxLib-based applications can easily realize expected performance gains without extra effort on the part of the application developer. We also discuss a path forward to enable future versions of BoxLib to take advantage of NUMA-aware optimizations using the TiDA portable library.

  7. Confirmation test on confinement performance of improved glove box

    International Nuclear Information System (INIS)

    Glove boxes are used at nuclear facilities to confine radioactive materials by ensuring a high level of airtightness and negative internal pressure. The allowable rate of air leakage is 0.1% vol/hr or less at the pre-service inspection. The negative pressure value is normally maintained at about -30 mm H2 O. Structural strength and confinement reliability of glove boxes during earthquake are major concerns, and most important glove boxes are designed to withstand seismic class A events is Japan. This paper describes vibration tests done to confirm that improve large-sized glove boxes maintain their confinement performance and structural strength even during earthquake and that the design analysis methods used are appropriate. (author). 1 ref., 6 figs., 3 tabs

  8. Sizing Procedures for a Fibre Reinforced Plastic Box

    Directory of Open Access Journals (Sweden)

    K. Kamal

    1992-10-01

    Full Text Available A fibre-reinforced plastic (FRP box is an important class of structural component employed as the bending, torsion, or bending-torsion load bearing member in the modern light- weight structures. This paper presents various steps involved in the design of such a box beginning with preliminary analysis and optimization to the final sizing. The box made up of carbon fibre composite is a typical numerical example of such FRP construction. Numerical results obtained from the static stress analysis, the panel buckling analysis and the structural optimization as used for this sizing exercise, are presented. It is believed that the complete procedure of analysis using finite element method and then sizing of any FRP box in a comprehensive way, is reported for the first time.

  9. Fusion welded fabrication of unshielded steel glove boxes

    International Nuclear Information System (INIS)

    This Specification deals with the manufacture, testing, inspection and delivery of fabricated glove boxes, including such internal and/or external fittings as are shown on the relevant drawings. (author)

  10. Fusion welded fabrication of unshielded steel glove boxes

    International Nuclear Information System (INIS)

    This part of the Specification together with Part 1 covers the manufacture, testing, inspection and delivery of stainless steel glove boxes including such fittings internally and externally as shown on relevant drawings. (author)

  11. 49 CFR 178.516 - Standards for fiberboard boxes.

    Science.gov (United States)

    2010-10-01

    ... wooden frame or be entirely of wood or other suitable material. Reinforcements of wooden battens or other... resistant adhesive must be used. (5) Boxes must be designed so as to provide a snug fit to the contents....

  12. Necropsy Report - Eaastern Pipistrelle Box Culvert I-55 Grenada, MS

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Necropsy report of a eastern pipisttrelle tricolored bat found dead in a box culvert along I55, near Grenada, MS provides no indication of whitenose syndrome.

  13. Black-Box Policy Search with Probabilistic Programs

    OpenAIRE

    van de Meent, Jan-Willem; Tolpin, David; Paige, Brooks; Wood, Frank

    2015-01-01

    In this work, we explore how probabilistic programs can be used to represent policies in sequential decision problems. In this formulation, a probabilistic program is a black-box stochastic simulator for both the problem domain and the agent. We relate classic policy gradient techniques to recently introduced black-box variational methods which generalize to probabilistic program inference. We present case studies in the Canadian traveler problem, Rock Sample, and a benchmark for optimal diag...

  14. Maximal unitarity for the four-mass double box

    OpenAIRE

    Johansson, Henrik; Kosower, David A.; Larsen, Kasper J.

    2014-01-01

    We extend the maximal-unitarity formalism at two loops to double-box integrals with four massive external legs. These are relevant for higher-point processes, as well as for heavy vector rescattering, VV -> VV. In this formalism, the two-loop amplitude is expanded over a basis of integrals. We obtain formulas for the coefficients of the double-box integrals, expressing them as products of tree-level amplitudes integrated over specific complex multidimensional contours. The contours are subjec...

  15. SOME RECURRENCE FORMULAS FOR BOX SPLINES AND CONE SPLINES

    Institute of Scientific and Technical Information of China (English)

    Patrick J. Van Fleet

    2004-01-01

    A degree elevation formula for multivariate simplex splines was given by Micchelli[6] and extended to hold for multivariate Dirichlet splines in [8]. We report similar formulae for multivariate cone splines and box splines. To this end, we utilize a relation due to Dahmen and Micchelli[4] that connects box splines and cone splines and a degree reduction formula given by Cohen, Lyche, and Riesenfeld in [2].

  16. SOME RECURRENCE FORMULAS FOR BOX SPLINES AND CONE SPLINES

    Institute of Scientific and Technical Information of China (English)

    Patrick J. Van Fleet

    2002-01-01

    A degree elevation formula for multivariate simplex splines was given by Micchelli [6] and extended to hold for multivariate Dirichlet splines in [8]. We report similar formulae for multivariate cone splines and box_splines. To this end, we utilize a relation due to Dahmen and Micchelli [4] that connects box splines and cone splines and a degree reduction formula given by Cohen, Lyche, and Riesenfeld in [2].

  17. Coupling polariton quantum boxes in sub-wavelength grating microcavities

    International Nuclear Information System (INIS)

    We report the construction of decoupled, coupled, and quasi-one dimensional polariton systems from zero dimensional polariton quantum boxes using microcavities with sub-wavelength gratings as the top mirror. By designing the tethering patterns around the suspended sub-wavelength gratings, we control the coupling between individual quantum boxes through different optical potentials. Energy levels and real-space or momentum space distributions of the confined modes were measured, which agreed well with simulations

  18. Safety evaluation for packaging (onsite) depleted uranium waste boxes

    International Nuclear Information System (INIS)

    This safety evaluation for packaging (SEP) allows the one-time shipment of ten metal boxes and one wooden box containing depleted uranium material from the Fast Flux Test Facility to the burial grounds in the 200 West Area for disposal. This SEP provides the analyses and operational controls necessary to demonstrate that the shipment will be safe for the onsite worker and the public

  19. Reliability Based Optimum Design of a Gear Box

    Directory of Open Access Journals (Sweden)

    D.Madhusekhar

    2014-10-01

    Full Text Available The gear box represents an important mechanical sub system. In machine tools, the propose of a gear box is to provide a series of useful output speeds so that the machining operation can be carried out at its most optimum operating conditions high spindle speeds with low feed rate for roughing operations. An important aspect in the design of machine tool transmission is to keep the cost and volume of the gear box to a minimum. The probabilistic approach to design has been considered to be more rational compared to the conventional design approach based on the factor of safety. The existence of uncertainties in either engineering simulations or manufacturing processes calls for a reliability-based design optimization (RBDO model for robust and cost-effective designs. In the present work a three shaft four speed gear box is designed using reliability principles. For the specified reliability of the system (Gear box, component reliability (Gear pair is calculated by considering the system as a series system. Design is considered to be safe and adequate if the probability of failure of gear box is less than or equal to a specified quantity in each of the two failure modes. A FORTRAN program has been developed to calculate the mean values of face widths of gears for the minimum mass of gear box. By changing the probability of failure of system variations in the face widths are studied. The reliability based optimum design results are compared with those obtained by deterministic optimum design. The minimum mass of the gear box is increase as the specified values of the reliability is increased.

  20. PTPRT regulates the interaction of Syntaxin-binding protein 1 with Syntaxin 1 through dephosphorylation of specific tyrosine residue

    International Nuclear Information System (INIS)

    Highlights: •PTPRT is a brain-specific, expressed, protein tyrosine phosphatase. •PTPRT regulated the interaction of Syntaxin-binding protein 1 with Syntaxin 1. •PTPRT dephosphorylated the specific tyrosine residue of Syntaxin-binding protein 1. •Dephosphorylation of Syntaxin-binding protein 1 enhanced the interaction with Syntaxin 1. •PTPRT appears to regulate the fusion of synaptic vesicle through dephosphorylation. -- Abstract: PTPRT (protein tyrosine phosphatase receptor T), a brain-specific tyrosine phosphatase, has been found to regulate synaptic formation and development of hippocampal neurons, but its regulation mechanism is not yet fully understood. Here, Syntaxin-binding protein 1, a key component of synaptic vesicle fusion machinery, was identified as a possible interaction partner and an endogenous substrate of PTPRT. PTPRT interacted with Syntaxin-binding protein 1 in rat synaptosome, and co-localized with Syntaxin-binding protein 1 in cultured hippocampal neurons. PTPRT dephosphorylated tyrosine 145 located around the linker between domain 1 and 2 of Syntaxin-binding protein 1. Syntaxin-binding protein 1 directly binds to Syntaxin 1, a t-SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein, and plays a role as catalysts of SNARE complex formation. Syntaxin-binding protein 1 mutant mimicking non-phosphorylation (Y145F) enhanced the interaction with Syntaxin 1 compared to wild type, and therefore, dephosphorylation of Syntaxin-binding protein 1 appeared to be important for SNARE-complex formation. In conclusion, PTPRT could regulate the interaction of Syntaxin-binding protein 1 with Syntaxin 1, and as a result, the synaptic vesicle fusion appeared to be controlled through dephosphorylation of Syntaxin-binding protein 1

  1. Measure Guideline: Optimizing the Configuration of Flexible Duct Junction Boxes

    Energy Technology Data Exchange (ETDEWEB)

    Beach, R. [IBACOS, Inc., Pittsburgh, PA (United States); Burdick, A. [IBACOS, Inc., Pittsburgh, PA (United States)

    2014-03-01

    This measure guideline offers additional recommendations to heating, ventilation, and air conditioning (HVAC) system designers for optimizing flexible duct, constant-volume HVAC systems using junction boxes within Air Conditioning Contractors of America (ACCA) Manual D guidance. IBACOS used computational fluid dynamics software to explore and develop guidance to better control the airflow effects of factors that may impact pressure losses within junction boxes among various design configurations. These recommendations can help to ensure that a system aligns more closely with the design and the occupants' comfort expectations. Specifically, the recommendations described herein show how to configure a rectangular box with four outlets, a triangular box with three outlets, metal wyes with two outlets, and multiple configurations for more than four outlets. Designers of HVAC systems, contractors who are fabricating junction boxes on site, and anyone using the ACCA Manual D process for sizing duct runs will find this measure guideline invaluable for more accurately minimizing pressure losses when using junction boxes with flexible ducts.

  2. Closure of an analytical chemistry glove box in alpha laboratory

    International Nuclear Information System (INIS)

    The works with plutonium are performed in gloves box, operated below atmospheric pressure, to protect the experimenters from this alpha-active material. After 12 years of continual processes, it was necessary the decommissioning of the chemistry glove box in our alpha-laboratory. A great deal of our attention was devoted to the working techniques because of extreme care needed to avoid activity release. The decommissioning includes the following main operations: a) Planning and documentation for the regulatory authority. b) Internal decontamination with surface cleaning and chelating agents. c) Measurement of the remainder internal radioactivity. d) Sealing of the glove ports and nozzles. e) Disconnection of the glove box from the exhaust duct. f) Design and construction of a container for the glove box. g) Transportation of the glove box from alpha-laboratory, to a transitory storage until its final disposal. The above mentioned operations are described in this paper including too: data of personal doses during the operations, characteristics and volumes of radioactive wastes and a description of the instrument used for the measurement of inside glove box activity. (Author)

  3. Unconventional Bearing Capacity Analysis and Optimization of Multicell Box Girders

    Directory of Open Access Journals (Sweden)

    Jovan Tepic

    2014-01-01

    Full Text Available This study deals with unconventional bearing capacity analysis and the procedure of optimizing a two-cell box girder. The generalized model which enables the local stress-strain analysis of multicell girders was developed based on the principle of cross-sectional decomposition. The applied methodology is verified using the experimental data (Djelosevic et al., 2012 for traditionally formed box girders. The qualitative and quantitative evaluation of results obtained for the two-cell box girder is realized based on comparative analysis using the finite element method (FEM and the ANSYS v12 software. The deflection function obtained by analytical and numerical methods was found consistent provided that the maximum deviation does not exceed 4%. Multicell box girders are rationally designed support structures characterized by much lower susceptibility of their cross-sectional elements to buckling and higher specific capacity than traditionally formed box girders. The developed local stress model is applied for optimizing the cross section of a two-cell box carrier. The author points to the advantages of implementing the model of local stresses in the optimization process and concludes that the technological reserve of bearing capacity amounts to 20% at the same girder weight and constant load conditions.

  4. Principal Investigator-in-a-Box

    Science.gov (United States)

    Young, Laurence R.

    1999-01-01

    Human performance in orbit is currently limited by several factors beyond the intrinsic awkwardness of motor control in weightlessness. Cognitive functioning can be affected by such factors as cumulative sleep loss, stress and the psychological effects of long-duration small-group isolation. When an astronaut operates a scientific experiment, the performance decrement associated with such factors can lead to lost or poor quality data and even the total loss of a scientific objective, at great cost to the sponsors and to the dismay of the Principal Investigator. In long-duration flights, as anticipated on the International Space Station and on any planetary exploration, the experimental model is further complicated by long delays between training and experiment, and the large number of experiments each crew member must perform. Although no documented studies have been published on the subject, astronauts report that an unusually large number of simple errors are made in space. Whether a result of the effects of microgravity, accumulated fatigue, stress or other factors, this pattern of increased error supports the need for a computerized decision-making aid for astronauts performing experiments. Artificial intelligence and expert systems might serve as powerful tools for assisting experiments in space. Those conducting space experiments typically need assistance exactly when the planned checklist does not apply. Expert systems, which use bits of human knowledge and human methods to respond appropriately to unusual situations, have a flexibility that is highly desirable in circumstances where an invariably predictable course of action/response does not exist. Frequently the human expert on the ground is unavailable, lacking the latest information, or not consulted by the astronaut conducting the experiment. In response to these issues, we have developed "Principal Investigator-in-a-Box," or [PI], to capture the reasoning process of the real expert, the Principal

  5. Bigenomic transcriptional regulation of all thirteen cytochrome c oxidase subunit genes by specificity protein 1

    OpenAIRE

    Dhar, Shilpa S.; Johar, Kaid; Wong-Riley, Margaret T. T.

    2013-01-01

    Cytochrome c oxidase (COX) is one of only four known bigenomic proteins, with three mitochondria-encoded subunits and 10 nucleus-encoded ones derived from nine different chromosomes. The mechanism of regulating this multi-subunit, bigenomic enzyme is not fully understood. We hypothesize that specificity protein 1 (Sp1) functionally regulates the 10 nucleus-encoded COX subunit genes directly and the three mitochondrial COX subunit genes indirectly by regulating mitochondrial transcription fact...

  6. Specificity Protein 1 Expression Contributes to Bcl-w-Induced Aggressiveness in Glioblastoma Multiforme

    OpenAIRE

    Lee, Woo Sang; Kwon, Junhye; Yun, Dong Ho; Lee, Young Nam; Woo, Eun Young; Park, Myung-Jin; Lee, Jae-Seon; Han, Young-Hoon; Bae, In Hwa

    2014-01-01

    We already had reported that Bcl-w promotes invasion or migration in gastric cancer cells and glioblastoma multiforme (GBM) by activating matrix metalloproteinase-2 (MMP-2) via specificity protein 1 (Sp1) or β-cateinin, respectively. High expression of Bcl-w also has been reported in GBM which is the most common malignant brain tumor and exhibits aggressive and invasive behavior. These reports propose that Bcl-w-induced signaling is strongly associated with aggressive characteristic of GBM. W...

  7. Regulation of Latent Membrane Protein 1 Signaling through Interaction with Cytoskeletal Proteins

    OpenAIRE

    Holthusen, Kirsten; Talaty, Pooja; Everly, David N.

    2015-01-01

    Latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) induces constitutive signaling in EBV-infected cells to ensure the survival of the latently infected cells. LMP1 is localized to lipid raft domains to induce signaling. In the present study, a genome-wide screen based on bimolecular fluorescence complementation (BiFC) was performed to identify LMP1-binding proteins. Several actin cytoskeleton-associated proteins were identified in the screen. Overexpression of these proteins affecte...

  8. Role of macrophage inflammatory protein-1alpha in T-cell-mediated immunity to viral infection

    DEFF Research Database (Denmark)

    Madsen, Andreas N; Nansen, Anneline; Christensen, Jan P; Thomsen, Allan R

    2003-01-01

    The immune response to lymphocytic choriomeningitis virus in mice lacking macrophage inflammatory protein-1alpha (MIP-1alpha) was evaluated. Generation of virus-specific effector T cells is unimpaired in MIP-1alpha-deficient mice. Furthermore, MIP-1alpha is not required for T-cell-mediated virus...... control or virus-induced T-cell-dependent inflammation. Thus, MIP-1alpha is not mandatory for T-cell-mediated antiviral immunity....

  9. Immunocytochemical localization of microtubule-associated protein 1 in rat cerebellum using monoclonal antibodies

    OpenAIRE

    1984-01-01

    Immunohistochemical staining with monoclonal antibodies showed that microtubule-associated protein 1 (MAP1) has a restricted cellular distribution in the rat cerebellum. Anti-MAP1 staining was found only in neurons, where it was much stronger in dendrites than in axons. There were striking variations in the apparent concentration of MAP1 in different classes of neurons. Purkinje cells were the most strongly labeled, while granule cell neurons gave a faint, threshold-level reaction with the an...

  10. Exendin-4 Improves Cardiac Function in Mice Overexpressing Monocyte Chemoattractant Protein-1 in Cardiomyocytes

    OpenAIRE

    Younce, Craig W; Niu, Jianli; Ayala, Jennifer; Burmeister, Melissa A.; Smith, Layton H.; Kolattukudy, Pappachan; Julio E Ayala

    2014-01-01

    The incretin hormone glucagon-like peptide-1 (Glp1) is cardioprotective in models of ischemia-reperfusion injury, myocardial infarction and gluco/lipotoxicity. Inflammation is a factor in these models, yet it is unknown whether Glp1 receptor (Glp1r) agonists are protective against cardiac inflammation. We tested the hypothesis that the Glp1r agonist Exendin-4 (Ex4) is cardioprotective in mice with cardiac-specific monocyte chemoattractant protein-1 overexpression. These MHC-MCP1 mice exhibit ...

  11. The application of Toll like receptors for cancer therapy

    Directory of Open Access Journals (Sweden)

    Eui Young So, Toru Ouchi

    2010-01-01

    Full Text Available Toll-like receptor (TLR proteins play key roles in immune responses against infection. Using TLR proteins, host can recognize the conserved molecular structures found in pathogens called pathogen-associated molecular patterns (PAMPs. At the same time, some TLRs are able to detect specific host molecules, such as high-mobility group box protein 1 (HMGB1 and heat shock proteins (hsp, and lead to inflammatory responses. Thus, it has been suggested that TLRs are involved in the development of many pathogenic conditions. Recent advances in TLR-related research not only provide us with scientific information, but also show the therapeutic potential against diseases, such as autoimmune disease and cancer. In this mini review, we demonstrate how TLRs pathways could be involved in cancer development and their therapeutic application, and discuss recent patentable subjects, in particular, that are targeting this unique pathway.

  12. Danger Signals Activating the Immune Response after Trauma

    Directory of Open Access Journals (Sweden)

    Stefanie Hirsiger

    2012-01-01

    Full Text Available Sterile injury can cause a systemic inflammatory response syndrome (SIRS that resembles the host response during sepsis. The inflammatory response following trauma comprises various systems of the human body which are cross-linked with each other within a highly complex network of inflammation. Endogenous danger signals (danger-associated molecular patterns; DAMPs; alarmins as well as exogenous pathogen-associated molecular patterns (PAMPs play a crucial role in the initiation of the immune response. With popularization of the “danger theory,” numerous DAMPs and PAMPs and their corresponding pathogen-recognition receptors have been identified. In this paper, we highlight the role of the DAMPs high-mobility group box protein 1 (HMGB1, interleukin-1α (IL-1α, and interleukin-33 (IL-33 as unique dual-function mediators as well as mitochondrial danger signals released upon cellular trauma and necrosis.

  13. A novel method to design S-box based on chaotic map and genetic algorithm

    Science.gov (United States)

    Wang, Yong; Wong, Kwok-Wo; Li, Changbing; Li, Yang

    2012-01-01

    The substitution box (S-box) is an important component in block encryption algorithms. In this Letter, the problem of constructing S-box is transformed to a Traveling Salesman Problem and a method for designing S-box based on chaos and genetic algorithm is proposed. Since the proposed method makes full use of the traits of chaotic map and evolution process, stronger S-box is obtained. The results of performance test show that the presented S-box has good cryptographic properties, which justify that the proposed algorithm is effective in generating strong S-boxes.

  14. A novel method to design S-box based on chaotic map and genetic algorithm

    International Nuclear Information System (INIS)

    The substitution box (S-box) is an important component in block encryption algorithms. In this Letter, the problem of constructing S-box is transformed to a Traveling Salesman Problem and a method for designing S-box based on chaos and genetic algorithm is proposed. Since the proposed method makes full use of the traits of chaotic map and evolution process, stronger S-box is obtained. The results of performance test show that the presented S-box has good cryptographic properties, which justify that the proposed algorithm is effective in generating strong S-boxes. -- Highlights: ► The problem of constructing S-box is transformed to a Traveling Salesman Problem. ► We present a new method for designing S-box based on chaos and genetic algorithm. ► The proposed algorithm is effective in generating strong S-boxes.

  15. Speciifc effects of c-Jun NH2-terminal kinase-interacting protein 1 in neuronal axons

    Institute of Scientific and Technical Information of China (English)

    Shu Tang; Qiang Wen; Xiao-jian Zhang; Quan-cheng Kan

    2016-01-01

    c-Jun NH2-terminal kinase (JNK)-interacting protein 3 plays an important role in brain-derived neurotrophic factor/tropomyosin-related kinase B (TrkB) anterograde axonal transport. It remains unclear whether JNK-interacting protein 1 mediates similar effects, or whether JNK-interacting protein 1 affects the regulation of TrkB anterograde axonal transport. In this study, we isolated rat embryonic hippocampus and cultured hippocampal neuronsin vitro. Coimmunoprecipitation results demonstrated that JNK-interacting protein 1 formed TrkB com-plexesin vitro andin vivo. Immunocytochemistry results showed that when JNK-interacting protein 1 was highly expressed, the distribution of TrkB gradually increased in axon terminals. However, the distribution of TrkB reduced in axon terminals after knocking out JNK-interact-ing protein 1. In addition, there were differences in distribution of TrkB after JNK-interacting protein 1 was knocked out compared with not. However, knockout of JNK-interacting protein 1 did not affect the distribution of TrkB in dendrites. These ifndings conifrm that JNK-inter-acting protein 1 can interact with TrkB in neuronal cells, and can regulate the transport of TrkB in axons, but not in dendrites.

  16. Implications of Big Box Retail Location on Regional Profits, Consumer Utility, and Land Rents

    OpenAIRE

    Stater, Mark; Visser, Michael S.

    2008-01-01

    This paper uses a monocentric city model to examine the effects of big box retailing on local retail prices, land values and utility. Relative to small local retailers, the big box offers a price discount that increases in its marginal cost advantage. Big box entry reduces local retail prices and profits, but provides an increase in household utility that depends positively on the distance between the big box location and the CBD. However, big box locations are unstable with imperfectly compe...

  17. Boxing participation by children and adolescents: A joint statement with the American Academy of Pediatrics

    OpenAIRE

    Purcell, Laura K; LeBlanc, Claire MA

    2012-01-01

    Thousands of boys and girls younger than 19 years of age participate in boxing in North America. Although boxing provides benefits for participants, including exercise, self-discipline and self-confidence, the sport of boxing encourages and rewards deliberate blows to the head and face. Participants in boxing are at risk of head, face and neck injuries, including chronic and even fatal neurological injuries. Concussions are one of the most common injuries occurring in boxing. Because of the r...

  18. Minimal components of the RNA polymerase II transcription apparatus determine the consensus TATA box

    OpenAIRE

    Bjornsdottir, Gudrun; Lawrence C Myers

    2008-01-01

    In Saccharomyces cerevisiae, multiple approaches have arrived at a consensus TATA box sequence of TATA(T/A)A(A/T)(A/G). TATA-binding protein (TBP) affinity alone does not determine TATA box function. To discover how a minimal set of factors required for basal and activated transcription contributed to the sequence requirements for a functional TATA box, we performed transcription reactions using highly purified proteins and CYC1 promoter TATA box mutants. The TATA box consensus sequence is a ...

  19. Differential expression of two MADS box genes in wild-type and mutant petunia flowers.

    Science.gov (United States)

    Angenent, G C; Busscher, M; Franken, J; Mol, J N; van Tunen, A J

    1992-08-01

    We isolated and characterized two flower-specific genes from petunia. The protein products of these genes, designated floral binding protein 1 (FBP1) and 2 (FBP2), are putative transcription factors with the MADS box DNA binding domain. RNA gel blot analysis showed that the fbp1 gene is exclusively expressed in petals and stamen of petunia flowers. In contrast, the FBP1 protein was only detectable in petals and not in stamens, suggesting post-transcriptional regulation of the fbp1 gene in these tissues. The fbp2 gene is expressed in petals, stamen, carpels, and at a very low level in sepals but not in vegetative tissues. We analyzed the spatial expression of these fbp genes in floral organs of two homeotic flower mutants. In the blind mutant, whose flower limbs are transformed into antheroid structures on top of normal tubes, identical expression levels of both genes were observed in the antheroid structures as in normal anthers. In the homeotic mutant green petals, the petals are replaced by sepaloid organs in which the expression of fbp1 is strongly reduced but not completely abolished. Our results suggest a regulation of the fbp1 gene expression by the green petals (gp) gene. Expression of the fbp2 gene was not affected in the green petals mutant. In contrast to the proposed models describing floral morphogenesis, our data indicated that homeotic genes can be functional in one whorl only. PMID:1356537

  20. Identification and characterization of a nuclear localization signal of TRIM28 that overlaps with the HP1 box

    Energy Technology Data Exchange (ETDEWEB)

    Moriyama, Tetsuji; Sangel, Percival [Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085 (Japan); Yamaguchi, Hiroki [School of Medicine, Osaka University, Osaka 565-0871 (Japan); Obuse, Chikashi [Graduate School of Life Science, Hokkaido University, Sapporo 001-0021 (Japan); Miyamoto, Yoichi [Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085 (Japan); Oka, Masahiro, E-mail: moka@nibiohn.go.jp [Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085 (Japan); Laboratory of Biomedical Innovation, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871 (Japan); Yoneda, Yoshihiro, E-mail: y-yoneda@nibiohn.go.jp [National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085 (Japan); Laboratory of Biomedical Innovation, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871 (Japan)

    2015-07-03

    Tripartite motif-containing 28 (TRIM28) is a transcription regulator, which forms a repressor complex containing heterochromatin protein 1 (HP1). Here, we report identification of a nuclear localization signal (NLS) within the 462-494 amino acid region of TRIM28 that overlaps with its HP1 binding site, HP1 box. GST-pulldown experiments revealed the interaction of the arginine-rich TRIM28 NLS with various importin α subtypes (α1, α2 and α4). In vitro transport assay demonstrated that nuclear localization of GFP-TRIM28 NLS is mediated by importin αs, in conjunction with importin β1 and Ran. Further, we demonstrated that HP1 and importin αs compete for binding to TRIM28. Together, our findings suggest that importin α has an essential role in the nuclear delivery and preferential HP1 interaction of TRIM28. - Highlights: • TRIM28 contains an NLS within the 462-494 amino acid region. • The nuclear import of TRIM28 is mediated by importin α/importin β1. • TRIM28 NLS overlaps with HP1 Box. • HP1 and importin α compete for binding to TRIM28.

  1. Identification and characterization of a nuclear localization signal of TRIM28 that overlaps with the HP1 box

    International Nuclear Information System (INIS)

    Tripartite motif-containing 28 (TRIM28) is a transcription regulator, which forms a repressor complex containing heterochromatin protein 1 (HP1). Here, we report identification of a nuclear localization signal (NLS) within the 462-494 amino acid region of TRIM28 that overlaps with its HP1 binding site, HP1 box. GST-pulldown experiments revealed the interaction of the arginine-rich TRIM28 NLS with various importin α subtypes (α1, α2 and α4). In vitro transport assay demonstrated that nuclear localization of GFP-TRIM28 NLS is mediated by importin αs, in conjunction with importin β1 and Ran. Further, we demonstrated that HP1 and importin αs compete for binding to TRIM28. Together, our findings suggest that importin α has an essential role in the nuclear delivery and preferential HP1 interaction of TRIM28. - Highlights: • TRIM28 contains an NLS within the 462-494 amino acid region. • The nuclear import of TRIM28 is mediated by importin α/importin β1. • TRIM28 NLS overlaps with HP1 Box. • HP1 and importin α compete for binding to TRIM28

  2. Computational Fluid Dynamics Analysis of Flexible Duct Junction Box Design

    Energy Technology Data Exchange (ETDEWEB)

    Beach, Robert [IBACOS, Inc., Pittsburgh, PA (United States); Prahl, Duncan [IBACOS, Inc., Pittsburgh, PA (United States); Lange, Rich [Applied Science Consultants, LLC, Pittsburgh, PA (United States)

    2013-12-01

    IBACOS explored the relationships between pressure and physical configurations of flexible duct junction boxes by using computational fluid dynamics (CFD) simulations to predict individual box parameters and total system pressure, thereby ensuring improved HVAC performance. Current Air Conditioning Contractors of America (ACCA) guidance (Group 11, Appendix 3, ACCA Manual D, Rutkowski 2009) allows for unconstrained variation in the number of takeoffs, box sizes, and takeoff locations. The only variables currently used in selecting an equivalent length (EL) are velocity of air in the duct and friction rate, given the first takeoff is located at least twice its diameter away from the inlet. This condition does not account for other factors impacting pressure loss across these types of fittings. For each simulation, the IBACOS team converted pressure loss within a box to an EL to compare variation in ACCA Manual D guidance to the simulated variation. IBACOS chose cases to represent flows reasonably correlating to flows typically encountered in the field and analyzed differences in total pressure due to increases in number and location of takeoffs, box dimensions, and velocity of air, and whether an entrance fitting is included. The team also calculated additional balancing losses for all cases due to discrepancies between intended outlet flows and natural flow splits created by the fitting. In certain asymmetrical cases, the balancing losses were significantly higher than symmetrical cases where the natural splits were close to the targets. Thus, IBACOS has shown additional design constraints that can ensure better system performance.

  3. Integrated Box Interrogation System (IBIS) Preliminary Design Study

    Energy Technology Data Exchange (ETDEWEB)

    DR. Stephen Croft; Mr. David Martancik; Dr. Brian Young; Dr. Patrick MJ Chard; Dr. Robert J Estop; Sheila Melton; Gaetano J. Arnone

    2003-01-13

    Canberra Industries has won the tendered solicitation, INEEL/EST-99-00121 for boxed waste Nondestructive Assay Development and Demonstration. Canberra will provide the Integrated Box Interrogation System (IBIS) which is a suite of assay instrumentation and a data reduction system that addresses the measurement needs for Boxed Wastes identified in the solicitation and facilitates the associated experimental program and demonstration of system capability. The IBIS system will consist of the next generation CWAM system, i.e. CWAM II, which is a Scanning Passive/Active Neutron interrogation system which we will call a Box Segmented Neutron Scanner (BSNS), combined with a physically separate Box Segmented Gamma-ray Scanning (BSGS) system. These systems are based on existing hardware designs but will be tailored to the large sample size and enhanced to allow the program to evaluate the following measurement criteria:Characterization and correction for matrix heterogeneity Characterization of non-uniform radio-nuclide and isotopic compositions Assay of high density matrices (both high-Z and high moderator contents)Correction for radioactive material physical form - such as self shielding or multiplication effects due to large accumulations of radioactive materials.Calibration with a minimal set of reference standards and representative matrices.THis document summarizes the conceptual design parameters of the IBIS and indicates areas key to the success of the project where development is to be centered. The work presented here is a collaborative effort between scientific staff within Canberra and within the NIS-6 group at LANL.

  4. Integrated Box Interrogation System (IBIS) Preliminary Design Study

    International Nuclear Information System (INIS)

    Canberra Industries has won the tendered solicitation, INEEL/EST-99-00121 for boxed waste Nondestructive Assay Development and Demonstration. Canberra will provide the Integrated Box Interrogation System (IBIS) which is a suite of assay instrumentation and a data reduction system that addresses the measurement needs for Boxed Wastes identified in the solicitation and facilitates the associated experimental program and demonstration of system capability. The IBIS system will consist of the next generation CWAM system, i.e. CWAM II, which is a Scanning Passive/Active Neutron interrogation system which we will call a Box Segmented Neutron Scanner (BSNS), combined with a physically separate Box Segmented Gamma-ray Scanning (BSGS) system. These systems are based on existing hardware designs but will be tailored to the large sample size and enhanced to allow the program to evaluate the following measurement criteria:Characterization and correction for matrix heterogeneity Characterization of non-uniform radio-nuclide and isotopic compositions Assay of high density matrices (both high-Z and high moderator contents)Correction for radioactive material physical form - such as self shielding or multiplication effects due to large accumulations of radioactive materials.Calibration with a minimal set of reference standards and representative matrices.THis document summarizes the conceptual design parameters of the IBIS and indicates areas key to the success of the project where development is to be centered. The work presented here is a collaborative effort between scientific staff within Canberra and within the NIS-6 group at LANL

  5. Inferring 3D Articulated Models for Box Packaging Robot

    CERN Document Server

    Yang, Heran; Cong, Matthew; Saxena, Ashutosh

    2011-01-01

    Given a point cloud, we consider inferring kinematic models of 3D articulated objects such as boxes for the purpose of manipulating them. While previous work has shown how to extract a planar kinematic model (often represented as a linear chain), such planar models do not apply to 3D objects that are composed of segments often linked to the other segments in cyclic configurations. We present an approach for building a model that captures the relation between the input point cloud features and the object segment as well as the relation between the neighboring object segments. We use a conditional random field that allows us to model the dependencies between different segments of the object. We test our approach on inferring the kinematic structure from partial and noisy point cloud data for a wide variety of boxes including cake boxes, pizza boxes, and cardboard cartons of several sizes. The inferred structure enables our robot to successfully close these boxes by manipulating the flaps.

  6. Stress and noises of steel box girders in Sutong Bridge

    Institute of Scientific and Technical Information of China (English)

    Xue Tao; Chen Zhijian; Dong Xuewu

    2008-01-01

    Sutong Bridge is a cable-stayed bridge with a main span of 1 088 m.370 high-precision stress monitoring measured data show that in the process of hoisting the steel box girders,the stress of the main girders is in the fluctuant and complex state and many meteorological factors,such as sunshine radiation,temperature and wind,have important influence on the change of stress of the steel box girders.According to the real-time weather data,the stress data after the process of wavelet denoising from representative measuring points in different weather conditions is picked to estab-lish the stress response brought by meteorological factors with Layered Separation method,thereby basically eliminating the influence of meteorological factors on the stress of main girders,so that accurate and reliable stress data can be got for steel box girders adjustment and cable-tensioned construction control.

  7. Thinking outside the box: fluctuations and finite size effects

    International Nuclear Information System (INIS)

    The isothermal compressibility of an interacting or non-interacting system may be extracted from the fluctuations of the number of particles in a well-chosen control volume. Finite size effects are prevalent and should be accounted for to obtain a meaningful, thermodynamic compressibility. In the traditional computational setup, where a given simulation box is replicated with periodic boundary conditions, we study particle number fluctuations outside the box (i.e. when the control volume exceeds the box itself), which bear relevant thermodynamic information. We also investigate the related problem of extracting the compressibility from the structure factor in the small wave-vector limit (k → 0). The calculation should be restricted to the discrete set of wave-vectors k that are compatible with the periodicity of the system, and we assess the consequences of considering other k values, a widespread error among beginners. (paper)

  8. Thinking outside the box: fluctuations and finite size effects

    Science.gov (United States)

    Villamaina, Dario; Trizac, Emmanuel

    2014-05-01

    The isothermal compressibility of an interacting or non-interacting system may be extracted from the fluctuations of the number of particles in a well-chosen control volume. Finite size effects are prevalent and should be accounted for to obtain a meaningful, thermodynamic compressibility. In the traditional computational setup, where a given simulation box is replicated with periodic boundary conditions, we study particle number fluctuations outside the box (i.e. when the control volume exceeds the box itself), which bear relevant thermodynamic information. We also investigate the related problem of extracting the compressibility from the structure factor in the small wave-vector limit (k → 0). The calculation should be restricted to the discrete set of wave-vectors k that are compatible with the periodicity of the system, and we assess the consequences of considering other k values, a widespread error among beginners.

  9. Qualification of box HEPA filters for nuclear applications

    International Nuclear Information System (INIS)

    We have successfully completed qualification tests on high efficiency particulate air (HEPA) filters that are encapsulated within a box and manufactured by American Air Filters. The qualification tests are required by the American Society of Mechanical Engineers Standard ASME N509 and the U.S. Military Standard MIL-F-51068 for HEPA filters to be used in nuclear applications. The qualification tests specify minimum filter efficiencies following exposure to heated air, overpressure, and rough handling. Prior to this study, no box HEPA filters from any manufacturer had been qualified despite their wide-spread use in Department of Energy (DOE) facilities. Box HEPA filters are not addressed in any of the existing HEPA standards and only briefly discussed in the Nuclear Air Cleaning Handbook

  10. Mice lacking multidrug resistance protein 1a show altered dopaminergic responses to methylenedioxymethamphetamine (MDMA) in striatum

    OpenAIRE

    Scheidweiler, Karl B.; Ladenheim, Bruce; Cadet, Jean Lud; Huestis, Marilyn A.

    2009-01-01

    Multidrug resistance protein 1a (MDR1a) potentiated methylenedioxymethamphetamine (MDMA)-induced decreases of dopamine (DA) and dopamine transport protein in mouse brain one week after MDMA administration. In the present study, we examined if mdr1a wild-type (mdr1a +/+) and knock-out (mdr1a −/−) mice differentially handle the acute effects of MDMA on the nigrostriatal DA system 0–24 h following a single drug injection. 3-way ANOVA revealed significant 2-way interactions of strain X time (F5,1...

  11. GPCR kinase 2 interacting protein 1 (GIT1) regulates osteoclast function and bone mass

    OpenAIRE

    Menon, Prashanthi; Yin, Guoyong; Smolock, Elaine M.; Zuscik, Michael J.; Yan, Chen; Berk, Bradford C.

    2010-01-01

    G-protein coupled receptor (GPCR) kinase 2 interacting protein-1 (GIT1) is a scaffold protein expressed in various cell types including neurons, endothelial and vascular smooth muscle cells. The GIT1 knockout (KO) mouse has a pulmonary phenotype due to impaired endothelial function. Because GIT1 is tyrosine phosphorylated by Src kinase, we anticipated that GIT1 KO should have a bone phenotype similar to Src KO. Microcomputed tomography of the long bones revealed that GIT1 KO mice have a 2.3-f...

  12. Impaired spine formation and learning in GPCR kinase interacting protein-1 (GIT1) knockout mice

    OpenAIRE

    Menon, Prashanthi; Deane, Rashid; Sagare, Abhay; Lane, Steven M.; Zarcone, Troy J; O’Dell, Michael R.; Yan, Chen; Zlokovic, Berislav V.; Berk, Bradford C.

    2010-01-01

    The G-protein coupled receptor (GPCR)-kinase interacting proteins 1 and 2 (GIT1 and GIT2) are scaffold proteins with ADP-ribosylating factor GTPase activity. GIT1 and GIT2 control numerous cellular functions and are highly expressed in neurons, endothelial cells and vascular smooth muscle cells (VSMC). GIT1 promotes dendritic spine formation, growth and motility in cultured neurons, but its role in brain in vivo is unknown. By using global GIT1 knockout mice (GIT1 KO), we show that deletion o...

  13. Insights from the crystal structure of the sixth BRCT domain of topoisomerase IIβ binding protein 1

    OpenAIRE

    Leung, Charles Chung Yun; Kellogg, Elizabeth; Kuhnert, Anja; Hänel, Frank; Baker, David; Glover, J N Mark

    2009-01-01

    Topoisomerase IIβ binding protein 1 (TopBP1) is a major player in the DNA damage response and interacts with a number of protein partners via its eight BRCA1 carboxy-terminal (BRCT) domains. In particular, the sixth BRCT domain of TopBP1 has been implicated in binding to the phosphorylated transcription factor, E2F1, and poly(ADP-ribose) polymerase 1 (PARP-1), where the latter interaction is responsible for the poly(ADP-ribosyl)ation of TopBP1. To gain a better understanding of the nature of ...

  14. Monocyte chemoattractant protein-1 plays a key role in type 1 diabetes

    Institute of Scientific and Technical Information of China (English)

    Dong Li; Guoliang Liu

    2005-01-01

    Type 1 diabetes is an autoimmune disease resulting from the selective destruction of β cells in the pancreatic islets.In both human and rodent models of type 1 diabetes, the clinical disease is preceded by a progressive mononuclear cell invasion of the pancreatic islets (insulitis). In the early stage of insulitis, the major components are monocyte/macrophages, and the recruitment of mononuclear cells is a critical step in the pathogenesis of the type 1 diabetes. Studies have revealed that Monocyte chemoattractant protein-1(MCP-1)specifically recruits monocytes/macrophages into pancreas and plays an important role in the development of insulitis and diabetes.

  15. Inactivation of fatty acid transport protein 1 prevents fat-induced insulin resistance in skeletal muscle

    OpenAIRE

    Jason K Kim; Gimeno, Ruth E.; Higashimori, Takamasa; Kim, Hyo-Jeong; Choi, Hyejeong; Punreddy, Sandhya; Mozell, Robin L.; TAN, GUO; Stricker-Krongrad, Alain; Hirsch, David J.; Fillmore, Jonathan J.; Liu, Zhen-Xiang; Dong, Jianying; Cline, Gary; Stahl, Andreas

    2004-01-01

    Insulin resistance in skeletal muscle plays a major role in the development of type 2 diabetes and may be causally associated with increases in intramuscular fatty acid metabolites. Fatty acid transport protein 1 (FATP1) is an acyl-CoA synthetase highly expressed in skeletal muscle and modulates fatty acid uptake and metabolism by converting fatty acids into fatty acyl-CoA. To investigate the role of FATP1 in glucose homeostasis and in the pathogenesis of insulin resistance, we examined the e...

  16. PARAMETRIC STUDY OF SKEW ANGLE ON BOX GIRDER BRIDGE DECK

    OpenAIRE

    Shrikant D. Bobade *, Dr. Valsson Varghese

    2016-01-01

    Box girder bridge deck, is the most common type of bridges in world and India, it consists of several Slab or girders. The span in the direction of the roadway and connected across their tops and bottoms by a thin continuous structural stab, the longitudinal box girders can be made of steel or concrete. The Simple supported single span concrete bridge deck is presented in present study. Skewed bridges are suitable in highway design when the geometry of straight bridges is not possible. The sk...

  17. Fermi hypernetted chain calculations in a periodic box

    International Nuclear Information System (INIS)

    The Fermi hypernetted chain theory is reformulated to perform calculations with a finite number of fermions in a periodic box. The proposed method is expected to be useful to estimate the finite size effects in Quantum Monte Carlo simulations. Moreover, it can deal with anisotropic correlations as well as with different shaped boxes. Results are given for the neutron matter Bethe homework Hamiltonian and for nuclear matter with spin-isospin dependent central interactions. It is found that finite size effects come from both the kinetic and the potential energy expectation values

  18. Host-Guest Interactions in ExBox4+

    CERN Document Server

    Das, Ranjita

    2014-01-01

    The host-guest interaction between benzene or azine with the newly synthesized ExBox4+ complex is studied with the help of DFT. The solvent phase interaction energy is found to decrease with gradual substitution of methine group of guest benzene ring with N atom in the resultant azine@ExBox4+ complex. The nature of bonding interaction is studied with the help of newly developed NCI plot program package along with energy decomposition analysis (EDA) and charge decomposition analysis (CDA). The interaction is mostly pi-type van der Waals interaction.

  19. Boxed skew plane partition and integrable phase model

    International Nuclear Information System (INIS)

    We study the relation between the boxed skew plane partition and the integrable phase model. We introduce a generalization of a scalar product of the phase model and calculate it in two ways: the first one in terms of the skew Schur functions, and the other one by use of the commutation relations of operators. In both cases, a generalized scalar product is expressed as a determinant. We show that a special choice of the spectral parameters of a generalized scalar product gives the generating function of the boxed skew plane partition

  20. Principal investigator in a box: Version 1.2 documentation

    Science.gov (United States)

    Adolph, Jurine; Bhatnagar, Rajiv; Colombano, Silvano P.; Compton, Michael; Frainer, Richard; Groleau, Nicolas; Holden, Kritina; Lai, Sen-Hao; Lam, Chih-Chao; Manahan, Meera

    1990-01-01

    Principal Investigator (PI) in a box is a computer system designed to help optimize the scientific results of experiments that are performed in space. The system will assist the astronaut experimenters in the collection and analysis of experimental data, recognition and pursuit of 'interesting' results, optimal use of the time allocated to the experiment, and troubleshooting of the experiment apparatus. This document discusses the problems that motivate development of 'PI-in-a-box', and presents a high- level system overview and a detailed description of each of the modules that comprise the current version of the system.

  1. Box jellyfish use terrestrial visual cues for navigation

    DEFF Research Database (Denmark)

    Garm, Anders; Oskarsson, Magnus; Nilsson, Dan-Eric

    2011-01-01

    Box jellyfish have an impressive set of 24 eyes of four different types, including eyes structurally similar to those of vertebrates and cephalopods [1, 2]. However, the known visual responses are restricted to simple phototaxis, shadow responses, and object avoidance responses [3-8], and it has...... been a puzzle why they need such a complex set of eyes. Here we report that medusae of the box jellyfish Tripedalia cystophora are capable of visually guided navigation in mangrove swamps using terrestrial structures seen through the water surface. They detect the mangrove canopy by an eye type that is...

  2. AN ALGORITHM FOR AUTOMATICALLY GENERATING BLACK-BOX TEST CASES

    Institute of Scientific and Technical Information of China (English)

    Xu Baowen; Nie Changhai; Shi Qunfeng; Lu Hong

    2003-01-01

    Selection of test cases plays a key role in improving testing efficiency. Black-box testing is an important way of testing, and its validity lies on the selection of test cases in some sense. A reasonable and effective method about the selection and generation of test cases is urgently needed. This letter first introduces some usualmethods on black-box test case generation,then proposes a new algorithm based on interface parameters and discusses its properties, finally shows the effectiveness of the algorithm.

  3. AN ALGORITHM FOR AUTOMATICALLY GENERATING BLACK-BOX TEST CASES

    Institute of Scientific and Technical Information of China (English)

    XuBaowen; NieChanghai; 等

    2003-01-01

    Selection of test cases plays a key role in improving testing efficiency.Black-box testing is an important way of testing,and is validity lies on the secection of test cases in some sense.A reasonable and effective method about the selection and generation of test cascs is urgently needed.This letter first introduces some usual methods on black-box test case generation,then proposes a new glgorithm based on interface parameters and discusses its properties,finally shows the effectiveness of the algorithm.

  4. Ancestry and diversity of the HMG box superfamily

    OpenAIRE

    Laudet, V; Stehelin, D.; Clevers, J.C.

    1993-01-01

    The HMG box is a novel type of DNA-binding domain found in a diverse group of proteins. The HMG box superfamily comprises a.o. the High Mobility Group proteins HMG1 and HMG2, the nucleolar transcription factor UBF, the lymphoid transcription factors TCF-1 and LEF-1, the fungal mating-type genes mat-Mc and MATA1, and the mammalian sex-determining gene SRY. The superfamily dates back to at least 1,000 million years ago, as its members appear in animals, plants and yeast. Alignment of all known ...

  5. Security of the AES with a Secret S-Box

    DEFF Research Database (Denmark)

    Tiessen, Tyge; Knudsen, Lars Ramkilde; Kölbl, Stefan;

    2015-01-01

    How does the security of the AES change when the S-box is replaced by a secret S-box, about which the adversary has no knowledge? Would it be safe to reduce the number of encryption rounds? In this paper, we demonstrate attacks based on integral cryptanalysis which allow to recover both the secret...... interesting aspect of our attack is that it works both as chosen plaintext and as chosen ciphertext attack. Surprisingly, the chosen ciphertext variant has a significantly lower time complexity in the attacks on four and five round, compared to the respective chosen plaintext attacks....

  6. Gray-box modelling approach for description of storage tunnel

    DEFF Research Database (Denmark)

    Harremoës, Poul; Carstensen, Jacob

    1999-01-01

    The dynamics of a storage tunnel is examined using a model based on on-line measured data and a combination of simple deterministic and black-box stochastic elements. This approach, called gray-box modeling, is a new promising methodology for giving an on-line state description of sewer systems...... inertia of the water in the overflow structures. The capacity of a pump draining the storage tunnel is estimated for two different rain events, revealing that the pump was malfunctioning during the first rain event. The proposed modeling approach can be used in automated online surveillance and control...

  7. Tests of CMS Hadron Forward Calorimeter Upgrade Readout Box Prototype

    CERN Document Server

    Chatrchyan, Sergey; Sirunyan, Albert; Tumasyan, Armen; Mossolov, Vladimir; Shumeiko, Nikolai; Cornelis, Tom; Ochesanu, Silvia; Roland, Benoit Florent; Staykova, Zlatka; Van Haevermaet, Hans; Van Mechelen, Pierre; Van Spilbeeck, Alex; Alves, Gilvan Augusto; Martins, Thiago Dos Reis; Pol, Maria Elena; Vaz Da Silva Filho, Mario; Alda Junior, Walter Luiz; Carvalho, Wagner De Paula; Chinellato, Jose Augusto; De Oliveira Martins, Carley Pedro; Figueiredo, Diego Matos; Tonelli Manganote, Edmilson Jose; Molina Insfran, Jorge Andres; Mundim, Luiz; Nogima, Helio; Prado Da Silva, Wanda Lucia; Santoro, Alberto; Rosa Lopes Zachi, Alessandro; Finger, Miroslav; Finger, Michael; Tsamalaidze, Zviad; Borras, Kerstin; Gunnellini, Paolo; Jung, Hannes; Knutsson, Albert Hans; Lutz, Benjamin; Ribeiro Cipriano, Pedro Miguel; Sen, Niladri; Baus, Colin; Katkov, Igor; Ulrich, Ralf Matthias; Wohrmann, H; Panagiotou, Apostolos; Bencze, Gyorgy; Horvath, D; Bala, Suman; Gupta, Ruchi; Jindal, M; Lal, Manjit Kaur; Nishu, Nishu; Saini, Lovedeep Kaur; Banerjee, Sunanda; Bhattacharya, S; Gomber, Bhawna; Jain, Shilpi; Khurana, Raman; Sharan, Manoj Kumar; Aziz, Tariq; Maity, Manas; Majumder, Gobinda; Mazumdar, Kajari; Mohanty, Gagan Bihari; Katta, Sudhakar; Banerjee, Sudeshna; Dugad, Shashikant Raichand; Etesami, Seyed Mohsen; Fahim, Ali; Jafari, Abideh; Paktinat Mehdiabadi, Saeid; Zeinali, Maryam; Penzo, Aldo; Afanasyev, A; Bunin, Pavel; Ershov, Yuri; Fedoseev, Oleg; Gavrilenko, Mikhail; Golutvin, Igor; Gorbunov, Ilya; Konoplynikov, V; Malakhov, Alexander; Moisenz, Petr; Smirnov, Vitaly; Volodko, Anton; Zarubin, Anatoly; Andreev, Yuri; Dermenev, Alexander; Krasnikov, Nikolay; Pashenkov, Anatoli; Tlisov, Danila; Toropin, A; Epshteyn, Vladimir; Erofeeva, Maria; Gavrilov, Vladimir; Kosov, Mikhail Vladimirovich; Kudinov, Ilya; Lychkovskaya, Natalia; Popov, V; Safronov, Grigory; Semenov, Sergey; Stolin, Viatcheslav; Vlassov, Evgueni; Zhokin, Alexander; Belyaev, A; Boos, Eduard; Dubinin, Mikhail; Dudko, Lev; Ershov, Alexander; Gribushin, Andrey; Klyukhin, Vyacheslav; Kodolova, Olga; Korotkikh, Vladimir; Lokhtin, Igor; Markina, Anastasia; Obraztsov, Stepan; Perfilov, Maxim; Petrushanko, Sergey; Popov, Andrey; Savrin, Victor; Snigirev, Alexander; Vardanyan, Irina; Andreev, V; Azarkin, Maksim; Dremin, Igor; Kirakosyan, Martin; Leonidov, Andrey; Mesyats, Gennady; Vinogradov, Alexey; Bayshev, Igor; Bityukov, Sergey; Grishin, Viatcheslav; Kryshkin, Victor; Petrov, V; Ryutin, Roman; Sobol, Andrey; Turchanovich, Leonid; Troshin, Sergey; Uzunyan, Andrey; Volkov, Alexey; Santanastasio, Francesco; Adiguzel, Aytul; Bakirci, Numan Mustafa; Cerci, Salim; Dozen, Candan; Dumanoglu, Isa; Eskut, Eda; Girgis, Semiray; G�kbulut, Gul; Gurpinar, Emine; Hos, Ilknur; Kangal, Evrim Ersin; Karapinar, Guler; Kayis Topaksu, Aysel; Onengut, Gulsen; Ozdemir, Kadri; Ozturk, Sertac; Polatoz, Ayse; Sogut, Kenan; Sunar Cerci, Deniz; Tali, Bayram; Topakli, Huseyin; Vergili, Latife Nukhet; Vergili, Mehmet; Aliyev, Takhmasib; Deniz, Muhammed; Guler, Ali Murat; Ozpineci, Altug; Serin, Meltem; Sever, Ramazan; Zeyrek, Mehmet; Deliomeroglu, Mehmet; Gulmez, Erhan; Isildak, Bora; Kaya, Mithat; Kaya, Ozlem; Ozkorucuklu, Suat; Sonmez, Nasuf; Cankocak, Kerem; Levchuk, Leonid; Hatakeyama, Kenichi; Liu, H; Scarborough, Tara Ann; Rumerio, Paolo; Heister, Arno; Hill, C; Lawson, Philip Daniel; Lazic, Dragoslav; Rohlf, James; St. John, Jason; Sulak, Lawrence; Gennadiy, G; Laird, Edward; Landsberg, Greg; Narain, Meenakshi; Sinthuprasith, Tutanon; Tsang, Ka Vang; Long, Owen Rosser; Nguyen, Harold; Paramesvaran, Sudarshan; Sturdy, Jared; Stuart, David; To, Wing; West, Christopher Alan; Apresyan, Artur; Chen, Y; Mott, Alexander Robert; Spiropulu, Maria; Winn, David; Abdoulline, Salavat; Anderson, J; Chlebana, Frank; Freeman, James; Green, Daniel; Hanlon, J; Hirschauer, James Francis; Joshi, Umeshwar; Kunori, Shuichi; Musienko, Yuri; Sharma, Seema; Spalding, William Jeffrey; Tkaczyk, Slawomir; Vidal, Richard; Whitmore, Juliana; Wu, W; Gaultney, Vanessa; Linn, Stephan; Markowitz, Pete Edward; Martinez, German Ruben; Gleyzer, Sergei; Hagopian, Sharon Lee; Hagopian, Vasken; Jenkins, Charles Merrill; Baarmand, Marc M; Dorney, Brian L; Vodopiyanov, Igor; Akgun, Ugur; Albayrak, Elif Asli; Bilki, Burak; Clarida, Warren James; Duru, Firdevs; Merlo, Jean-Pierre; Mermerkaya, Hamit; Mestvirishvili, Alexi; Moeller, Anthony Richard; Nachtman, Jane; Newsom, Charles Ray; Norbeck, John Edwin; Olson, Jonathan Edward; Onel, Yasar; Ozok, Ferhat; Sen, Sercan; Schmidt, Ianos; Tiras, Emrah; Yetkin, Taylan; Yi, Kai; Kenny, Raymond Patrick; Murray, Michael Joseph; Wood, Jeffrey Scott; Baden, Andrew; Calvert, Brian Michael; Eno, Sarah Catherine; Gomez, Jaime Arturo; Grassi, Tullio; Hadley, Nicholas John; Kellogg, Richard; Kolberg, Ted; Lu, Y; Marionneau, Matthieu; Mignerey, Alice Louise Cox; Peterman, Alison Marie; Skuja, Andris; Temple, Jeffrey; Tonjes, Marguerite Belt; Kao, Shih-Chuan; Klapoetke, Kevin Humphrey; Mans, Jeremiah Michael; Pastika, Nathaniel Joseph; Kroeger, Robert; Rahmat, Rahmat; Sanders, David; Cremaldi, Lucien Marcus; Jain, S; Anastassov, Anton; Velasco, Mayda Marie; Won, Steven; Heering, Adriaan; Karmgard, Daniel; Pearson, Tessa Jae; Ruchti, Randal; Berry, Edmund A; Halyo, Valerie; Hebda, Philip; Hunt, Adam Paul; Lujan, Paul Joseph; Marlow, Daniel; Medvedeva, Tatiana; Saka, Halil; Tully, Christopher; Zuranski, Andrzej Maciej; Barnes, Virgil Everett; Laasanen, Alvin; Bodek, Arie; Chung, Yeon Sei; de Barbaro, Pawel Jan; Eshaq, Yossof; Garcia-bellido, Aran Angel; Goldenzweig, Pablo David; Han, Ji Yeon; Harel, Amnon; Miner, Daniel Carl; Vishnevskiy, Dmitry; Zielinski, Marek; Bhatti, Anwar; Ciesielski, Robert Adam; Flanagan, Will Hogan; Kamon, Teruki; Montalvo, Roy Joaquin; Sakuma, Tai; Akchurin, Nural; Damgov, Jordan; Dudero, Phillip Russell; Kovitanggoon, Kittikul; Lee, Sung Won; Libeiro, Terence; Volobouev, Igor; Gurrola, Alfredo; Milstene, Caroline

    2012-01-01

    A readout box prototype for CMS Hadron Forward calorimeter upgrade is built and tested in CERN H2 beamline. The prototype is designed to enable simultaneous tests of different readout options for the four anode upgrade PMTs, new front-end electronics design and new cabling. The response of the PMTs with different readout options is uniform and the background response is minimal. Multi-channel readout options further enhance the background elimination. Passing all the electronics, mechanical and physics tests, the readout box proves to be capable of providing the forward hadron calorimeter operations requirements in the upgrade era.

  8. The oxygen evolving enhancer protein 1 (OEE) of photosystem II in green algae exhibits thioredoxin activity.

    Science.gov (United States)

    Heide, Heinrich; Kalisz, Henryk M; Follmann, Hartmut

    2004-02-01

    A thioredoxin-like chloroplast protein of the fructosebisphosphatase-stimulating f-type, but with an unusually high molecular mass of 28 kDa has previously been identified and purified to homogeneity in a fractionation scheme for resolution of the acid- and heat-stable, regular-size (12kDa) thioredoxins of the unicellular green algae, Scenedesmus obliquus. An apparently analogous protein of 26 kDa was described in a cyanobacterium, Anabaena sp., but no such large thioredoxin species f exists in the thioredoxin profiles of higher plants. The structure of the 28 kDa protein, which had been envisaged to represent a precursor, or fusion product of the two more specialized, common chloroplast thioredoxins f and m has now been determined by amino acid sequencing. Although it exhibits virtually all the properties and enzyme-modulating activities of a thioredoxin proper this algal protein, surprisingly, does not belong to the thioredoxin family of small redox proteins but is identical with OEE (oxygen evolving enhancer) protein 1, an auxiliary component of the photosystem II manganese cluster. Extracts of Chlorella vulgaris and Chlamydomonas reinhardtii also contain heat-stable protein fractions of 23-26 kDa capable of specifically stimulating chloroplast fructosebisphosphatase in vitro. In contrast, OEE protein 1 from spinach is not able to modulate FbPase or NADP malate dehydrogenase from spinach chloroplasts. A dual function of the OEE protein in algal photosynthesis is envisaged. PMID:15022827

  9. Epilepsy, Behavioral Abnormalities, and Physiological Comorbidities in Syntaxin-Binding Protein 1 (STXBP1 Mutant Zebrafish.

    Directory of Open Access Journals (Sweden)

    Brian P Grone

    Full Text Available Mutations in the synaptic machinery gene syntaxin-binding protein 1, STXBP1 (also known as MUNC18-1, are linked to childhood epilepsies and other neurodevelopmental disorders. Zebrafish STXBP1 homologs (stxbp1a and stxbp1b have highly conserved sequence and are prominently expressed in the larval zebrafish brain. To understand the functions of stxbp1a and stxbp1b, we generated loss-of-function mutations using CRISPR/Cas9 gene editing and studied brain electrical activity, behavior, development, heart physiology, metabolism, and survival in larval zebrafish. Homozygous stxbp1a mutants exhibited a profound lack of movement, low electrical brain activity, low heart rate, decreased glucose and mitochondrial metabolism, and early fatality compared to controls. On the other hand, homozygous stxbp1b mutants had spontaneous electrographic seizures, and reduced locomotor activity response to a movement-inducing "dark-flash" visual stimulus, despite showing normal metabolism, heart rate, survival, and baseline locomotor activity. Our findings in these newly generated mutant lines of zebrafish suggest that zebrafish recapitulate clinical phenotypes associated with human syntaxin-binding protein 1 mutations.

  10. Isolation and characterization of peptidoglycan recognition protein 1 from antler base of sika deer (Cervus nippon).

    Science.gov (United States)

    Jiang, Wei; Yin, Yongguang; Zhou, Yajun; He, Guidan; Qi, Yue

    2014-03-01

    Peptidoglycan recognition proteins (PGRPs) are secreted innate immunity pattern recognition molecules. In this study, a new peptidoglycan recognition protein 1 named cnPGRP1 was isolated from an antler base of sika deer Cervus nippon. The antler base antimicrobial proteins (AAP) were subjected to consecutive chromatographic methods connected to Sephadex G-25 gel filtration column (CM) anion-exchange column, and RP-HPLC. The molecular weight of cnPGRP1 was 17.2 kDa under SDS-PAGE, and peptide mass fingerprint analysis by MALDI-TOF-MS as peptidoglycan recognition protein 1 matched to Dasypus novemcinctus. The matched amino acids sequences were RLYEIIQKWPHYRA. Both Gram-positive and Gram-negative bacteria can be killed by cnPGRP1 in the 50-250 μg/mL range through in vitro. Furthermore, cnPGRP1 has been found to bind Gram-positive bacteria, Gram-negative bacteria, and even fungus. PMID:24360898

  11. Spatiotemporal patterns of the Huntingtin-interacting protein 1-related gene in the mouse head.

    Science.gov (United States)

    Masuda, Tomoyuki; Sakuma, Chie; Ueno, Takayuki; Yamada, Yuriko; Ohmomo, Hideki; Ueda, Shuichi; Yamagishi, Toshiyuki; Yaginuma, Hiroyuki

    2013-12-01

    Huntingtin-interacting protein 1-related (Hip1r) was originally identified due to its homology to Huntingtin-interacting protein 1, which contributes to the development of Huntington's disease (HD). We studied the expression of the mouse Hip1r (mHip1r) gene in the mouse head by in situ hybridization. In early embryogenesis at embryonic day (E) 13, mHip1r expression was especially prominent in the olfactory epithelium, cerebral cortex layer 1, cortical plate, and dentate gyrus. During later development from E15 to E17, strong expression of mHip1r transcripts continued to be observed in the olfactory epithelium, cortical plate, and dentate gyrus. Furthermore, not only the subplate and subventricular zone of the cortex, but also secretory glands, such as the nasal gland and the submandibular gland, were mHip1r-positive. Other positive tissues included the retinal ganglion cells, vomeronasal organ, trigeminal ganglion, and the developing molar tooth. In the adult mouse brain, similar expression patterns were observed in the cerebral cortex layers and other brain regions except the cerebellum. Additionally, by using an antibody against mHip1r, we confirmed these expression patterns at the protein level. Specific expression of mHip1r in the embryonic brain and secretory glands suggests a possible role for Hip1r in normal development and in the pathology of HD. PMID:24712472

  12. Nuclear Multidrug-Resistance Related Protein 1 Contributes to Multidrug-Resistance of Mucoepidermoid Carcinoma Mainly via Regulating Multidrug-Resistance Protein 1: A Human Mucoepidermoid Carcinoma Cells Model and Spearman's Rank Correlation Analysis

    OpenAIRE

    Bolei Cai; Ye Miao; Yuan Liu; Xiaofang Xu; Sumin Guan; Junzheng Wu; Yanpu Liu

    2013-01-01

    BACKGROUND: Multidrug resistance-related protein 1 (MRP1/ABCC1) and multidrug resistance protein 1 (MDR1/P-glycoprotein/ABCB1) are both membrane-bound drug transporters. In contrast to MDR1, MRP1 also transports glutathione (GSH) and drugs conjugated to GSH. Due to its extraordinary transport properties, MRP1/ABCC1 contributes to several physiological functions and pathophysiological incidents. We previously found that nuclear translocation of MRP1 contributes to multidrug-resistance (MDR) of...

  13. Motivating crowding theory - opening the black box of intrinsic motivation

    DEFF Research Database (Denmark)

    Jacobsen, Christian Bøtcher

    2010-01-01

    . Studies have found support for the motivation crowding claim, but have neglected intrinsic motivation. This study opens the black box of intrinsic motivation and finds a meaningful distinction between task motivation and public service motivation. Among 2,772 physiotherapists in the Danish public sector...

  14. The Popcorn Box Activity and Reasoning about Optimization

    Science.gov (United States)

    Whiteley, Walter J.; Mamolo, Ami

    2012-01-01

    A well-known optimization problem is the Popcorn Box investigation, which involves a movie theater snack container. The problem has been tailored for classroom investigations by the Ontario Association for Mathematics Education. The exploration was designed for students in grades 9 through 12. A common strategy proposed for algebra students is to…

  15. A Grey Box Model for the Hydraulics in a Creek

    DEFF Research Database (Denmark)

    Jonsdottir, Harpa; Jacobsen, Judith L.; Madsen, Henrik

    1998-01-01

    The Saint-Venant equation of mass balance is used to derive a stochastics lumped model, describing the dynamics of a cross-sectional area in a river. The unknown parameters of the model are estimated by combining the physical equation with a set of data, a method known as grey box modelling. The ...

  16. Approach to a correct function of stuffing boxes

    International Nuclear Information System (INIS)

    Stuff boxes are often used to tighten the gaps between valve stems and the housing. The stuffing box packing material is compressed axially to achieve a radial stress value, which is necessary for tightness. Tightness is achieved, if the sealing materials are seated properly and if a sufficient stress value is acting in radial direction during all states of operation. High prestress values are necessary for tightening purposes, lower values are better for the function of the valve. As the seating and the prestressing force is applied axially (using the bolts of a gland), gasket factors must be known, that characterize the deformation behavior and the transmission (relation between radial/axial stress). Furthermore, gasket factors, that characterize the tightening behavior, are necessary. Such gasket factors give the relation between radial stress and leakage of the packing materials. A friction coefficient -- this parameter determines the function of the valve (together with the radial stress) -- is another important gasket factor. Additionally the relaxation of the stuffing box packing material between the assembly and the operating state must be known. In the paper definitions for the most important gasket factors of stuffing box materials are provided. Test procedures and test rigs for the determination of the gasket factors are discussed. Gasket factors, which have been measured with these newly developed test rigs, are related to experiences with real applications. Finally a method for a controlled prestressing of gland packings is described

  17. BMOBench: Black-Box Multi-Objective Optimization Benchmarking Platform

    OpenAIRE

    Al-Dujaili, Abdullah; Suresh, S.

    2016-01-01

    This document briefly describes the Black-Box Multi-Objective Optimization Benchmarking (BMOBench) platform. It presents the test problems, evaluation procedure, and experimental setup. To this end, the BMOBench is demonstrated by comparing recent multi-objective solvers from the literature, namely SMS-EMOA, DMS, and MO-SOO.

  18. How Users Search the Library from a Single Search Box

    Science.gov (United States)

    Lown, Cory; Sierra, Tito; Boyer, Josh

    2013-01-01

    Academic libraries are turning increasingly to unified search solutions to simplify search and discovery of library resources. Unfortunately, very little research has been published on library user search behavior in single search box environments. This study examines how users search a large public university library using a prominent, single…

  19. 30 CFR 18.42 - Explosion-proof distribution boxes.

    Science.gov (United States)

    2010-07-01

    ... to a distribution box. The current-carrying capacity of the specified connector shall be compatible... permanently marked to indicate its current-carrying capacity and each receptacle shall be such that it will..., EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES...

  20. Workplace statistical literacy for teachers: interpreting box plots

    Science.gov (United States)

    Pierce, Robyn; Chick, Helen

    2013-06-01

    As a consequence of the increased use of data in workplace environments, there is a need to understand the demands that are placed on users to make sense of such data. In education, teachers are being increasingly expected to interpret and apply complex data about student and school performance, and, yet it is not clear that they always have the appropriate knowledge and experience to interpret the graphs, tables and other data that they receive. This study examined the statistical literacy demands placed on teachers, with a particular focus on box plot representations. Although box plots summarise the data in a way that makes visual comparisons possible across sets of data, this study showed that teachers do not always have the necessary fluency with the representation to describe correctly how the data are distributed in the representation. In particular, a significant number perceived the size of the regions of the box plot to be depicting frequencies rather than density, and there were misconceptions associated with outlying data that were not displayed on the plot. As well, teachers' perceptions of box plots were found to relate to three themes: attitudes, perceived value and misconceptions.

  1. MADS-box gene evolution-structure and transcription patterns

    DEFF Research Database (Denmark)

    Johansen, Bo; Pedersen, Louise B; Skipper, Martin;

    2002-01-01

    This study presents a phylogenetic analysis of 198 MADS-box genes based on 420 parsimony-informative characters. The analysis includes only MIKC genes; therefore several genes from gymnosperms and pteridophytes are excluded. The strict consensus tree identifies all major monophyletic groups known...

  2. Features for Exploiting Black-Box Optimization Problem Structure

    DEFF Research Database (Denmark)

    Tierney, Kevin; Malitsky, Yuri; Abell, Tinus

    2013-01-01

    Black-box optimization (BBO) problems arise in numerous scientic and engineering applications and are characterized by compu- tationally intensive objective functions, which severely limit the number of evaluations that can be performed. We present a robust set of features that analyze the tness...

  3. Fitting boxes to Manhattan scenes using linear integer programming

    KAUST Repository

    Li, Minglei

    2016-02-19

    We propose an approach for automatic generation of building models by assembling a set of boxes using a Manhattan-world assumption. The method first aligns the point cloud with a per-building local coordinate system, and then fits axis-aligned planes to the point cloud through an iterative regularization process. The refined planes partition the space of the data into a series of compact cubic cells (candidate boxes) spanning the entire 3D space of the input data. We then choose to approximate the target building by the assembly of a subset of these candidate boxes using a binary linear programming formulation. The objective function is designed to maximize the point cloud coverage and the compactness of the final model. Finally, all selected boxes are merged into a lightweight polygonal mesh model, which is suitable for interactive visualization of large scale urban scenes. Experimental results and a comparison with state-of-the-art methods demonstrate the effectiveness of the proposed framework.

  4. A 23 GHz survey of GRB error boxes

    CERN Document Server

    Hewitt, J N; Barthelmy, S D; Baumgartner, W H; Cline, T L; Corey, B E; Fishman, G J; Gehrels, N; Hurley, K C; Kouveliotou, C; Meegan, C A; Moore, C B; Rutledge, R E; Trotter, C S

    1996-01-01

    The Haystack 37-meter telescope was used in a pilot project in May 1995 to observe GRB error boxes at 23~GHz. Seven BATSE error boxes and two IPN arcs were scanned by driving the beam of the telescope rapidly across their area. For the BATSE error boxes, the radio observations took place two to eighteen days after the BATSE detection and several boxes were observed more than once. Total power data were recorded continuously as the telescope was driven at a rate of 0.2~degrees/second, yielding Nyquist sampling of the beam with an integration time of 50~milliseconds, corresponding to a theoretical rms sensitivity of 0.5~Jy. Under conditions of good weather, this sensitivity was achieved. In a preliminary analysis of the data we detect only two sources, 3C273 and 0552+398, both catalogued sources that are known to be variable at 23~GHz. Neither had a flux density that was unusally high or low at the time of our observations.

  5. Optimal Black-Box Secret Sharing over Arbitrary Abelian Groups

    DEFF Research Database (Denmark)

    Cramer, Ronald; Fehr, Serge

    A black-box secret sharing scheme for the threshold access structure T t,n is one which works over any finite Abelian group G. Briefly, such a scheme differs from an ordinary linear secret sharing scheme (over, say, a given finite field) in that distribution matrix and reconstruction vectors are ...

  6. Energy Savings Assessment for Digital-to-Analog Converter Boxes

    Energy Technology Data Exchange (ETDEWEB)

    Cheung, Hoi Ying Iris; Meier, Alan; Brown, Richard

    2011-01-18

    The Digital Television (DTV) Converter Box Coupon Program was administered by the U.S. government to subsidize purchases of digital-to-analog converter boxes, with up to two $40 coupons for each eligible household. In order to qualify as Coupon Eligible Converter Boxes (CECBs), these devices had to meet a number of minimum performance specifications, including energy efficiency standards. The Energy Star Program also established voluntary energy efficiency specifications that are more stringent than the CECB requirements. In this study, we measured the power and energy consumptions for a sample of 12 CECBs (including 6 Energy Star labeled models) in-use in homes and estimated aggregate energy savings produced by the energy efficiency policies. Based on the 35 million coupons redeemed through the end of the program, our analysis indicates that between 2500 and 3700 GWh per year are saved as a result of the energy efficiency policies implemented on digital-to-analog converter boxes. The energy savings generated are equivalent to the annual electricity use of 280,000 average US homes.

  7. Developing Box Plots While Navigating the Maze of Data Representations

    Science.gov (United States)

    Duncan, Bruce; Fitzallen, Noleine

    2013-01-01

    The learning sequence described in this article was developed to provide students with a demonstration of the development of box plots from authentic data as an illustration of the advantages gained from using multiple forms of data representation. The sequence follows an authentic process that starts with a problem to which data representations…

  8. Optimizing PHB and Protease Production by Box Behnken Design

    Directory of Open Access Journals (Sweden)

    Amro Abd al fattah Amara

    2013-04-01

    Full Text Available Mixed culture is more suitable to adapt more flexible fermentation process and produce different product simultaneously. In this study a mixed Bacillus culture was investigated for their ability to produce the bioplastic "Polyhydroxybutyrate" and both of the mesophilic and the thermophilic proteases in one flask. Box-Behnken experimental design was used. The produced amount of PHB has been increased significantly. Meanwhile there is a competition between PHB and proteases. The maximum produced amount of PHB using Box-Behnken design was 2.82 g/l/48 h with protease activity equal to 41.9 Units/ml/48 h for thermophilic proteases and 99.65 Units/ml/48 h for mesophilic proteases. Excel solver was used for extra-optimization for the optimum conditions obtained from Box-Behnken experiments and its model. The maximum PHB obtained after using Excel solver was 2.88 g/l/48 h. The maximum mesophilic and thermophilic activities obtained at the same PHB production conditions were 175.68 and 243.38 Units/ml respectively. The model accuracy as obtained from Excel solver was 118.8%, which prove the power of the experimental design in optimizing such complicated process. The strategies used in this study are recommended for the production of PHB and different proteases simultaneously using Bacillus mixed culture. ABSTRAK: Kultur campuran adalah lebih sesuai bagi proses penapaian yang fleksibel dan ia boleh menghasilkan produk yang berbeza secara serentak. Dalam kajian ini keupayaan  menghasilkan "Polyhydroxybutyrate" bioplastik serta mesofilik dan termofilik protease dalam satu flask oleh  kultur Bacillus campuran telah disiasat. Eksperimen rekabentuk Box-Behnken telah digunakan. Jumlah PHB yang dikeluarkan meningkat dengan ketara dan terdapat persaingan antara PHB dan protease. Jumlah keluaran PHB maksima menggunakan rekabentuk Box-Behnken adalah 2.82 g/l/48 jam dengan aktiviti protease sama dengan 41.9 Unit/ml/48 jam untuk protease termofilik dan 99.65 Unit

  9. Regulated Inositol‐Requiring Protein 1‐Dependent Decay as a Mechanism of Corin RNA and Protein Deficiency in Advanced Human Systolic Heart Failure

    Science.gov (United States)

    Lee, Rebecca; Xu, Bin; Rame, J. Eduardo; Felkin, Leanne E.; Barton, Paul; Dries, Daniel L.

    2014-01-01

    Background The compensatory actions of the endogenous natriuretic peptide system require adequate processing of natriuretic peptide pro‐hormones into biologically active, carboxyl‐terminal fragments. Natriuretic peptide pro‐peptide processing is accomplished by corin, a transmembrane serine protease expressed by cardiomyocytes. Brain natriuretic peptide (BNP) processing is inadequate in advanced heart failure and is independently associated with adverse outcomes; however, the molecular mechanisms causing impaired BNP processing are not understood. We hypothesized that the development of endoplasmic reticulum stress in cardiomyocytes in advanced heart failure triggers inositol‐requiring protein 1 (IRE1)‐dependent corin mRNA decay, which would favor a molecular substrate favoring impaired natriuretic peptide pro‐peptide processing. Methods and Results Two independent samples of hearts obtained from patients with advanced heart failure at transplant demonstrated that corin RNA was reduced as Atrial natriuretic peptide (ANP)/BNP RNA increased. Increases in spliced X‐box protein 1, a marker for IRE1‐endoribonuclease activity, were associated with decreased corin RNA. Moreover, ≈50% of the hearts demonstrated significant reductions in corin RNA and protein as compared to the nonfailing control sample. In vitro experiments demonstrated that induction of endoplasmic reticulum stress in cultured cardiomyocytes with thapsigargin activated IRE1's endoribonuclease activity and time‐dependent reductions in corin mRNA. In HL‐1 cells, overexpression of IRE1 activated IRE1 endoribonuclease activity and caused corin mRNA decay, whereas IRE1‐RNA interference with shRNA attenuated corin mRNA decay after induction of endoplasmic reticulum stress with thapsigargin. Pre‐treatment of cells with Actinomycin D to inhibit transcription did not alter the magnitude or time course of thapsigargin‐induced corin mRNA decline, supporting the hypothesis that this was

  10. Borrelia burgdorferi Regulates Expression of Complement Regulator-Acquiring Surface Protein 1 during the Mammal-Tick Infection Cycle

    OpenAIRE

    von Lackum, Kate; Miller, Jennifer C.; Bykowski, Tomasz; Riley, Sean P; Woodman, Michael E.; Brade, Volker; Kraiczy, Peter; Stevenson, Brian; Wallich, Reinhard

    2005-01-01

    During the natural mammal-tick infection cycle, the Lyme disease spirochete Borrelia burgdorferi comes into contact with components of the alternative complement pathway. B. burgdorferi, like many other human pathogens, has evolved the immune evasion strategy of binding two host-derived fluid-phase regulators of complement, factor H and factor H-like protein 1 (FHL-1). The borrelial complement regulator-acquiring surface protein 1 (CRASP-1) is a surface-exposed lipoprotein that binds both fac...

  11. High-level expression and characterization of a glycosylated human cementum protein 1 with lectin activity.

    Science.gov (United States)

    Romo-Arévalo, Enrique; Arzate, Higinio; Montoya-Ayala, Gonzalo; Rodríguez-Romero, Adela

    2016-01-01

    This work aims to contribute to the knowledge of human cementum protein 1 (CEMP1), its conformational characteristics and influence during the biomineralization process. The results revealed that hrCEMP1 expressed in Pichia pastoris is a 2.4% glycosylated, thermostable protein which possesses a molecular mass of 28 770 Da. The circular dichroism spectrum indicated a secondary structure content of 28.6% of alpha-helix, 9.9% of beta-sheet and 61.5% of random-coil forms. Biological activity assays demonstrated that hrCEMP1 nucleates and regulates hydroxyapatite crystal growth. Hereby, it is demonstrated for the first time that CEMP1 has a (C-type) lectin-like activity and specifically recognizes mannopyranoside. The information produced by this biochemical and structural characterization may contribute to understand more fully the biological functions of CEMP1. PMID:26763148

  12. Involvement of fractalkine and macrophage inflammatory protein-1 alpha in moderate-severe depression

    Directory of Open Access Journals (Sweden)

    Rosaria Alba Merendino

    2004-01-01

    Full Text Available MODERATE-severe depression (MSD is linked to overexpression of proinflammatory cytokines and chemokines. Fractalkine (FKN and macrophage inflammatory protein-1 alpha (MIP-1α are, respectively, members of CX3C and C-C chemokines, and both are involved in recruiting and activating mononuclear phagocytes in the central nervous system. We analysed the presence of FKN and MIP-1α in sera of untreated MSD patients and healthy donors. High FKN levels were observed in all MSD patients as compared with values only detectable in 26% of healthy donors. MIP-1α was measurable in 20% of patients, while no healthy donors showed detectable chemokine levels. In conclusion, we describe a previously unknown involvement of FKN in the pathogenesis of MSD, suggesting that FKN may represent a target for a specific immune therapy of this disease.

  13. Homocysteine induces production of monocyte chemoattractant protein-1 and interleukin-8 in cultured human whole blood

    Institute of Scientific and Technical Information of China (English)

    Xiao-kun ZENG; Daniel G REMICK; Xian WANG

    2004-01-01

    AIM: To investigate whether increased plasma L-homocysteine (Hcy) level could promote monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in cultured whole blood. METHODS: Human whole blood or different type of peripheral blood cells from health volunteers were incubated with Hcy and/or the inhibitors. MCP- 1 and IL-8 level were measured by ELISA assay. RESULTS: Hcy 10-1000 μmol/L induced production of MCP-1 and IL-8 in cultured human whole blood (P<0.05). The major cellular source of these chemokines comed from monocytes.Meanwhile,Hcy also promoted the upregulation of MPO level even at the 10 μmol/L in the cultured whole blood.secretion in cultured human whole blood, especially in monocytes via oxidative stress mechanism.

  14. Arabidopsis dynamin-related protein 1A polymers bind, but do not tubulate, liposomes

    International Nuclear Information System (INIS)

    The Arabidopsis dynamin-related protein 1A (AtDRP1A) is involved in endocytosis and cell plate maturation in Arabidopsis. Unlike dynamin, AtDRP1A does not have any recognized membrane binding or protein-protein interaction domains. We report that GTPase active AtDRP1A purified from Escherichia coli as a fusion to maltose binding protein forms homopolymers visible by negative staining electron microscopy. These polymers interact with protein-free liposomes whose lipid composition mimics that of the inner leaflet of the Arabidopsis plasma membrane, suggesting that lipid-binding may play a role in AtDRP1A function. However, AtDRP1A polymers do not appear to assemble and disassemble in a dynamic fashion and do not have the ability to tubulate liposomes in vitro, suggesting that additional factors or modifications are necessary for AtDRP1A's in vivo function.

  15. Human Cementum Protein 1 induces expression of bone and cementum proteins by human gingival fibroblasts

    International Nuclear Information System (INIS)

    We recently presented evidence showing that a human cementoblastoma-derived protein, named Cementum Protein 1 (CEMP1) may play a role as a local regulator of cementoblast differentiation and cementum-matrix mineralization. This protein was shown to be expressed by cementoblasts and progenitor cells localized in the periodontal ligament. In this study we demonstrate that transfection of CEMP1 into human gingival fibroblasts (HGF) induces mineralization and expression of bone and cementum-matrix proteins. The transfected HGF cells had higher alkaline phosphatase activity and proliferation rate and they expressed genes for alkaline phosphatase, bone sialoprotein, osteocalcin, osteopontin, the transcription factor Runx2/Cbfa1, and cementum attachment protein (CAP). They also produced biological-type hydroxyapatite. These findings indicate that the CEMP1 might participate in differentiation and mineralization of nonosteogenic cells, and that it might have a potential function in cementum and bone formation

  16. Dynamin-Related Protein 1 Translocates from the Cytosol to Mitochondria during UV-Induced Apoptosis

    International Nuclear Information System (INIS)

    Mitochondria are dynamic structures that frequently divide and fuse with one another to form interconnecting network. This network disintegrates into punctiform organelles during apoptosis. However, the mechanisms involved in these processes are still not well characterized. In this study, we investigate the role of dynamin-related protein 1 (Drp1), a large GTPase that mediates outer mitochondrial membrane fission, in mitochondrial dynamics in response to UV irradiation in human lung adenocarcinoma cells (ASTC-α-1) and HeLa cells. Using time-lapse fluorescent imaging, we find that Drp1 primarily distributes in cytosol under physiological conditions. After UV treatment, Drp1 translocates from cytosol to mitochondria, indicating the enhancement of Drp1 mitochondrial accumulation. Our results suggest that Drp1 is involved in the regulation of transition from an interconnecting network to a punctiform mitochondrial phenotype during UV-induced apoptosis.

  17. Surveillance of artemether-lumefantrine associated Plasmodium falciparum multidrug resistance protein-1 gene polymorphisms in Tanzania

    DEFF Research Database (Denmark)

    Kavishe, Reginald A; Paulo, Petro; Kaaya, Robert D;

    2014-01-01

    recommended first-line drug in treatment of uncomplicated malaria. This study surveyed the distribution of the Plasmodium falciparum multidrug resistance protein-1 single nucleotide polymorphisms (SNPs) associated with increased parasite tolerance to ALu, in Tanzania. METHODS: A total of 687 Plasmodium......BACKGROUND: Resistance to anti-malarials is a major public health problem worldwide. After deployment of artemisinin-based combination therapy (ACT) there have been reports of reduced sensitivity to ACT by malarial parasites in South-East Asia. In Tanzania, artemether-lumefantrine (ALu) is the...... in all regions, ranging from 17% - 26%. CONCLUSION: This is the first country-wide survey on Pfmdr1 mutations associated with ACT resistance. Distribution of individual Pfmdr1 mutations at codons 86, 184 and 1246 varies throughout Tanzanian regions. There is a general homogeneity in distribution of...

  18. Uncoupling protein 1 (UCP1 of brown adipocyte, the only uncoupler: historical perspective

    Directory of Open Access Journals (Sweden)

    Daniel eRicquier

    2011-12-01

    Full Text Available Uncoupling protein 1 - UCP1, is a unique mitochondrial membranous protein devoted to adaptive thermogenesis, a specialized function operated by the highly specialized oxidative brown adipocytes. Whereas the family of mitochondrial metabolite carriers comprises ~40 members including UCP1, the UCP1 is specifically identified by its ability to translocate protons through the inner membrane of brown adipocyte mitochondria. Doing that, UCP1 uncouples respiration from ATP synthesis and therefore provokes energy dissipation of oxidative energy as heat while, in parallel it markedly stimulates respiration and activates fatty acid oxidation. UCP1 homologues were identified but they are biochemically and physiologically different from UCP1. Thirty five years after its identification, UCP1 still appears as a fascinating component, and the recent renewal of the interest in human brown adipose tissue makes UCP1 as a potential target for strategies of treatment of metabolic disorders.

  19. X-ray repair cross complementing protein 1 in base excision repair

    DEFF Research Database (Denmark)

    Hanssen-Bauer, Audun; Solvang-Garten, Karin; Akbari, Mansour;

    2012-01-01

    X-ray Repair Cross Complementing protein 1 (XRCC1) acts as a scaffolding protein in the converging base excision repair (BER) and single strand break repair (SSBR) pathways. XRCC1 also interacts with itself and rapidly accumulates at sites of DNA damage. XRCC1 can thus mediate the assembly of large...... multiprotein DNA repair complexes as well as facilitate the recruitment of DNA repair proteins to sites of DNA damage. Moreover, XRCC1 is present in constitutive DNA repair complexes, some of which associate with the replication machinery. Because of the critical role of XRCC1 in DNA repair, its common...... variants Arg194Trp, Arg280His and Arg399Gln have been extensively studied. However, the prevalence of these variants varies strongly in different populations, and their functional influence on DNA repair and disease remains elusive. Here we present the current knowledge about the role of XRCC1 and its...

  20. Expression of the lysosomal-associated membrane protein-1 (LAMP-1) in astrocytomas

    DEFF Research Database (Denmark)

    Jensen, Stine S; Aaberg-Jessen, Charlotte; Christensen, Karina G;

    2013-01-01

    Targeting of lysosomes is a novel therapeutic anti-cancer strategy for killing the otherwise apoptosis-resistant cancer cells. Such strategies are urgently needed for treatment of brain tumors, especially the glioblastoma, which is the most frequent and most malignant type. The aim of the present...... study was to investigate the presence of lysosomes in astrocytic brain tumors focussing also on the therapy resistant tumor stem cells. Expression of the lysosomal marker LAMP-1 (lysosomal-associated membrane protein-1) was investigated by immunohistochemistry in 112 formalin fixed paraffin embedded...... individual tumor grades. LAMP-1/GFAP showed pronounced co-expression and LAMP-1/CD133 was co-expressed as well suggesting that tumor cells including the proposed tumor stem cells contain lysosomes. The results suggest that high amounts of lysosomes are present in glioblastomas and in the proposed tumor stem...

  1. Serum concentration and interaction properties of MBL/ficolin associated protein-1

    DEFF Research Database (Denmark)

    Skjoedt, Mikkel-Ole; Hummelshoj, Tina; Palarasah, Yaseelan;

    2011-01-01

    Recently, a novel protein named MBL/ficolin associated protein-1 (MAP-1) derived from the MASP1 gene through differential splicing was identified. In the present study, we established biochemical characteristics, determined the serum level and assessed the interactions between the lectin complement...... pathway (LCP) recognition molecules and MAP-1. We expressed recombinant MAP-1 in CHO DG44 cells, developed a quantitative ELISA assay based on a MAP-1 specific monoclonal capture antibody and measured the serum levels in 100 Danish blood donors. In addition we assessed the association properties between...... without the signal peptide. We found that serum MAP-1 was very stable when subjected to repeated freeze and thaw cycles. The mean serum concentration of MAP-1 was found to be 240ng/ml (range: 115-466ng/ml). MAP-1 was predominantly found in complex with Ficolin-3 and to a lesser degree with Ficolin-2...

  2. Molecular modeling of the human multidrug resistance protein 1 (MRP1/ABCC1)

    International Nuclear Information System (INIS)

    Multidrug resistance protein 1 (MRP1/ABCC1) is a 190 kDa member of the ATP-binding cassette (ABC) superfamily of transmembrane transporters that is clinically relevant for its ability to confer multidrug resistance by actively effluxing anticancer drugs. Knowledge of the atomic structure of MRP1 is needed to elucidate its transport mechanism, but only low resolution structural data are currently available. Consequently, comparative modeling has been used to generate models of human MRP1 based on the crystal structure of the ABC transporter Sav1866 from Staphylococcus aureus. In these Sav1866-based models, the arrangement of transmembrane helices differs strikingly from earlier models of MRP1 based on the structure of the bacterial lipid transporter MsbA, both with respect to packing of the twelve helices and their interactions with the nucleotide binding domains. The functional importance of Tyr324 in transmembrane helix 6 predicted to project into the substrate translocation pathway was investigated

  3. Progesterone-Dependent Induction of Phospholipase C-Related Catalytically Inactive Protein 1 (PRIP-1) in Decidualizing Human Endometrial Stromal Cells.

    Science.gov (United States)

    Muter, Joanne; Brighton, Paul J; Lucas, Emma S; Lacey, Lauren; Shmygol, Anatoly; Quenby, Siobhan; Blanks, Andrew M; Brosens, Jan J

    2016-07-01

    Decidualization denotes the transformation of endometrial stromal cells into specialized decidual cells. In pregnancy, decidual cells form a protective matrix around the implanting embryo, enabling coordinated trophoblast invasion and formation of a functional placenta. Continuous progesterone (P4) signaling renders decidual cells resistant to various environmental stressors, whereas withdrawal inevitably triggers tissue breakdown and menstruation or miscarriage. Here, we show that PLCL1, coding phospholipase C (PLC)-related catalytically inactive protein 1 (PRIP-1), is highly induced in response to P4 signaling in decidualizing human endometrial stromal cells (HESCs). Knockdown experiments in undifferentiated HESCs revealed that PRIP-1 maintains basal phosphoinositide 3-kinase/Protein kinase B activity, which in turn prevents illicit nuclear translocation of the transcription factor forkhead box protein O1 and induction of the apoptotic activator BIM. By contrast, loss of this scaffold protein did not compromise survival of decidual cells. PRIP-1 knockdown did also not interfere with the responsiveness of HESCs to deciduogenic cues, although the overall expression of differentiation markers, such as PRL, IGFBP1, and WNT4, was blunted. Finally, we show that PRIP-1 in decidual cells uncouples PLC activation from intracellular Ca(2+) release by attenuating inositol 1,4,5-trisphosphate signaling. In summary, PRIP-1 is a multifaceted P4-inducible scaffold protein that gates the activity of major signal transduction pathways in the endometrium. It prevents apoptosis of proliferating stromal cells and contributes to the relative autonomy of decidual cells by silencing PLC signaling downstream of Gq protein-coupled receptors. PMID:27167772

  4. Technology Solutions Case Study: New Insights for Improving the Designs of Flexible Duct Junction Boxes

    Energy Technology Data Exchange (ETDEWEB)

    None

    2014-01-01

    In this project, IBACOS explored the relationships between pressure and physical configurations of flexible duct junction boxes by using computational fluid dynamics simulations to predict individual box parameters and total system pressure, thereby ensuring improved HVAC performance.

  5. Enhancing Advanced Encryption Standard S-Box Generation Based on Round Key

    Directory of Open Access Journals (Sweden)

    Julia Juremi

    2015-05-01

    Full Text Available This paper presents a new AES-like design for key- dependent AES using S-box rotation. The algorithm involves key expansion algorithm together with S-box rotation and this property can be used to make the S-box key-dependent, hence providing a better security to the block cipher. Fixed S-box allows attackers to study S- box and find weak points while by using key-dependent S-Box approach, it makes it harder for attacker to do any offline analysis of an attack of one particular set of S- boxes. The cipher structure resembles the original AES, only the S-box is made key-dependent without changing the value. This new design is tested using the NIST Statistical Test and will be further cryptanalyzed with algebraic attack in order to permit its subversion or evasion.

  6. 77 FR 38705 - Draft Specification for Airport Light Bases, Transformer Housings, Junction Boxes, and...

    Science.gov (United States)

    2012-06-28

    ... Federal Aviation Administration Draft Specification for Airport Light Bases, Transformer Housings... comment on the Draft ``Specification for Airport Light Bases, Transformer Housings, Junction Boxes, and... recommendations for airport light bases, transformer housings, junction boxes and accessories. The FAA has...

  7. Specific Genomic Fingerprints of Phosphate Solubilizing Pseudomonas Strains Generated by Box Elements

    OpenAIRE

    Mohammad Bagher Javadi Nobandegani; Halimi Mohd Saud; Wong Mui Yun

    2014-01-01

    Primers corresponding to conserved bacterial repetitive of BOX elements were used to show that BOX-DNA sequences are widely distributed in phosphate solubilizing Pseudomonas strains. Phosphate solubilizing Pseudomonas was isolated from oil palm fields (tropical soil) in Malaysia. BOX elements were used to generate genomic fingerprints of a variety of Pseudomonas isolates to identify strains that were not distinguishable by other classification methods. BOX-PCR, that derived genomic fingerprin...

  8. Comparison of Laparoscopy Training Using the Box Trainer Versus the Virtual Trainer

    OpenAIRE

    Mohammadi, Yousef; Lerner, Michelle A.; Sethi, Amanjot S.; Sundaram, Chandru P.

    2010-01-01

    Background and Objectives: To evaluate whether training on a virtual reality laparoscopic simulator improves the performance on a laparoscopic box trainer. Methods: Twenty-six subjects were trained using a box trainer, and 17 participants were trained using a virtual simulator. Participants in the experimental group completed 1 session of 5 exercises on the box trainer, 4 sessions on the virtual simulator, and a final session on the box trainer. Participants in the control group completed 6 s...

  9. Experimental Research and Numerical Simulation of Wing Boxes under Pure Bending Load

    OpenAIRE

    Peiyan Wang; Shile Yao; Xinmei Wang; Zhufeng Yue

    2014-01-01

    Two full-scale wing boxes with different types of butt joints were investigated under pure bending load, and numerical methods, including global analysis and detailed analysis, were proposed to determine the reasons for failure of the wing boxes. Wing boxes were tested under bending loads applied by a multichannel force control system. The experimental results showed that the region of the butt joint was the weakest location of the wing boxes, and the damage loads were far less than the desig...

  10. Frequency distribution of TATA Box and extension sequences on human promoters

    OpenAIRE

    2006-01-01

    Background TATA box is one of the most important transcription factor binding sites. But the exact sequences of TATA box are still not very clear. Results In this study, we conduct a dedicated analysis on the frequency distribution of TATA Box and its extension sequences on human promoters. Sixteen TATA elements derived from the TATA Box motif, TATAWAWN, are classified into three distribution patterns: peak, bottom-peak, and bottom. Fourteen TATA extension sequences are predicted to be the ne...

  11. The progesterone receptor can regulate transcription in the absence of a functional TATA box element

    OpenAIRE

    Thomson, A A; Ham, J.; Bakker, O.; Parker, M G

    1990-01-01

    We have investigated the importance of the TATA box element in the induction of transcription by the progesterone receptor. Transcription was analyzed from promoters containing a steroid response element upstream of a wild-type or mutated TATA box. Mutation of the TATA box resulted in a loss of correctly initiated transcripts and abolished binding of TATA factor to the TATA box in vitro but did not inhibit transcriptional activation by the progesterone receptor. Thus we conclude that the rece...

  12. The Role of Protein Electrostatics in Facilitating the Catalysis of DEAD-box Proteins

    OpenAIRE

    Frenz, Christopher M.

    2008-01-01

    Protein electrostatic states have been demonstrated to play crucial roles in catalysis, ligand binding, protein stability, and in the modulation of allosteric effects. Electrostatic states are demonstrated to appear conserved among DEAD-box motifs and evidence is presented that the structural changes that occur to DEAD box proteins upon ligand binding alter the DEAD-box motif electrostatics in a way the facilitates the catalytic role of the DEAD-box glutatmate.

  13. 49 CFR 230.63 - Smoke box, steam pipes and pressure parts.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Smoke box, steam pipes and pressure parts. 230.63... Appurtenances Steam Pipes § 230.63 Smoke box, steam pipes and pressure parts. The smoke box, steam pipes and pressure parts shall be inspected at each annual inspection, or any other time that conditions warrant....

  14. 77 FR 29740 - Self-Regulatory Organizations; BOX Options Exchange LLC; Notice of Filing and Immediate...

    Science.gov (United States)

    2012-05-18

    ... requires greater expenditure of human and technical resources than regulating non- customer trading... Transactions (transactions executed on the BOX Book). The account types on BOX are Public Customer..., Inc. Liquidity Fees and Credits for Non-Auction Transactions Orders that add liquidity to the BOX...

  15. Entanglement and decoherence of a micromechanical resonator via coupling to a Cooper box

    OpenAIRE

    Armour, A. D.; Blencowe, M. P.; Schwab, K. C.

    2001-01-01

    We analyse the quantum dynamics of a micromechanical resonator capacitively coupled to a Cooper box. With appropriate quantum state control of the Cooper box, the resonator can be driven into a superposition of spatially separated states. The Cooper box can also be used to probe the environmentally-induced decoherence of the resonator superposition state.

  16. Justification procedure of hydrogen safety of RU BN compartments as exemplified by steam generator box

    International Nuclear Information System (INIS)

    Basic proposals on completing calculational procedures of sodium cooled reactors hydrogen safety justification, particularly steam generator (SG) box, are presented. It is pointed out that hydrogen appearance in SG box is possible only in accidents with multiple failures. The data presented shows that hydrogen safety and explosion-proofness of fast reactor facility SG box are provided without any special complex and expensive means

  17. A white-box model of S-shaped and double S-shaped single-species population growth

    OpenAIRE

    Kalmykov, Lev V.; Vyacheslav L. Kalmykov

    2015-01-01

    Complex systems may be mechanistically modelled by white-box modeling with using logical deterministic individual-based cellular automata. Mathematical models of complex systems are of three types: black-box (phenomenological), white-box (mechanistic, based on the first principles) and grey-box (mixtures of phenomenological and mechanistic models). Most basic ecological models are of black-box type, including Malthusian, Verhulst, Lotka–Volterra models. In black-box models, the individual-bas...

  18. Box products in nilpotent normal form theory: The factoring method

    Science.gov (United States)

    Murdock, James

    2016-01-01

    Let N be a nilpotent matrix and consider vector fields x ˙ = Nx + v (x) in normal form. Then v is equivariant under the flow eN*t for the inner product normal form or eMt for the sl2 normal form. These vector equivariants can be found by finding the scalar invariants for the Jordan blocks in N* or M; taking the box product of these to obtain the invariants for N* or M itself; and then boosting the invariants to equivariants by another box product. These methods, developed by Murdock and Sanders in 2007, are here given a self-contained exposition with new foundations and new algorithms yielding improved (simpler) Stanley decompositions for the invariants and equivariants. Ideas used include transvectants (from classical invariant theory), Stanley decompositions (from commutative algebra), and integer cones (from integer programming). This approach can be extended to covariants of sl2k for k > 1, known as SLOCC in quantum computing.

  19. Observational semantics of the Prolog Resolution Box Model

    CERN Document Server

    Deransart, Pierre; Ferrand, Gérard

    2007-01-01

    This paper specifies an observational semantics and gives an original presentation of the Byrd box model. The approach accounts for the semantics of Prolog tracers independently of a particular Prolog implementation. Prolog traces are, in general, considered as rather obscure and difficult to use. The proposed formal presentation of its trace constitutes a simple and pedagogical approach for teaching Prolog or for implementing Prolog tracers. It is a form of declarative specification for the tracers. The trace model introduced here is only one example to illustrate general problems relating to tracers and observing processes. Observing processes know, from observed processes, only their traces. The issue is then to be able to reconstitute, by the sole analysis of the trace, part of the behaviour of the observed process, and if possible, without any loss of information. As a matter of fact, our approach highlights qualities of the Prolog resolution box model which made its success, but also its insufficiencies...

  20. Permanent sealing: Valve stuffing boxes in nuclear power stations

    International Nuclear Information System (INIS)

    Water in nuclear powerstations contains up to 2000 ppm of boric acid. If a valve leaks, the boric acid crystallises out around the stuffing box and the packing is destroyed. Replacement is very problematical, particularly because of radiation, takes a long time and is very expensive (possible shutdown). Electricite de France has therefore developed stuffing boxes made of expanding graphite. Before E.d.F. uses a seal permanently in a nuclear powerstation, intensive tests are carried out such as the investigation of dynamic sealing for boric acid solutions at 200 bar and 3000C (JAPET experimental plant), corrosion tests (6 months life test a 3000C and 90 bar) and test of deformation characteristics under pressure and pressure transients. ''Lattygraf E1'', a packing made of expanding graphite, was selected as the best product. The construction and operation are discussed. (DOMA)

  1. Competitive markets, collective action, and the Big Box Retailer problem

    Directory of Open Access Journals (Sweden)

    Brent D. Beal

    2012-11-01

    Full Text Available I use a stylized scenario—the Big Box retailer Problem—to demonstrate that the presence of behavioural interdependence in economic markets may result in deficient outcomes that are both stable and supported by ongoing participant behaviour. I present a theoretical discussion of social dilemmas and use the Big Box retailer Problem to illustrate that these characteristics—stability and ongoing support—cannot be reliably employed as indicators of outcome efficiency. Equally important is the conclusion that upfront costs and the ongoing necessity of monitoring and encouraging contributory behaviour are not reliable indicators of the relative inefficiency of outcomes associated with collective action. Questions are raised regarding the ethical responsibilities of business educators and the implications of social dilemmas for corporate social responsibility research.

  2. Free box^k Scalar Conformal Field Theory

    CERN Document Server

    Brust, Christopher

    2016-01-01

    We consider the generalizations of the free U(N) and O(N) scalar conformal field theories to actions with higher powers of the Laplacian, box^k, in general dimension d. We study the spectra, Verma modules, anomalies and OPE of these theories. We argue that in certain d and k, the spectrum contains zero norm operators which are both primary and descendant, as well as extension operators which are neither primary nor descendant. In addition, we argue that in even dimensions d <= 2k, there are well-defined operator algebras which are related to the box^k theories and are novel in that they have a finite number of single-trace states.

  3. Application of glove box robotics to hazardous waste management

    International Nuclear Information System (INIS)

    Lawrence Livermore Laboratory (LLNL) is developing a semi-automated system for handling, characterizing, processing, sorting, and repackaging hazardous wastes containing tritium. The system combines an IBM developed gantry robot with a special glove box enclosure designed to protect the operators and minimize the potential release of tritium to the atmosphere. All hazardous waste handling and processing will be performed remotely using the robot in a telerobotic mode for one-of-a-kind functions and in an autonomous mode for repetitive type operations. The system will initially be used in conjunction with a portable gas system designed to capture any gaseous phase tritium released into the glove box. This paper presents the objectives of this program, provides background related to LLNL's robotics and waste handling program, describes the major system components, outlines system operation, and discusses current status and plans

  4. Pressure regulation in the dry-boxes. Argon purification

    International Nuclear Information System (INIS)

    Each dry-box is equipped with an autonomous installation for circulation and purification of argon and for pressure regulation. This installation consists essentially of a ballast tank, a compressor and two valves electromagnetically controlled by a contact manometer. The compressor and the valves are enclosed in the tank to form a system as compact as possible. The argon is purified by passing it over a furnace filled with titanium-zirconium turnings brought to about 800 deg. C, branching off the main system. With this set-up as well as the automatic maintenance of a constant depression in the box, a quality of argon is obtained whose oxygen contact is undetectable by the manganous hydroxide method. (author)

  5. Study of plutonium fire extinction in glove-boxes

    International Nuclear Information System (INIS)

    The report concerns attempts to extinguish fire in uranium - chosen as a basis for comparison - and in plutonium, these being contained in glove boxes. The extinguishing powders TEC and MG 10 were tried and compared. The operator used in plastic bags. The metal was dealt with respectively in the form of billets, compact chips and finally thin shavings. In each case fire control was without difficulty. One must allow a certain time for cooling. The powder MG 10 showed very good results. Moreover, the trials proved that densely packed shavings are a very real security factor. The interior lay-out of the glove boxes ought, in order to facilitate further manipulations, be such as to render extinction as easy as possible should the need arise. (authors)

  6. The role of secondary electron collection in box IEMP coupling

    International Nuclear Information System (INIS)

    Analytical models have been developed to estimate the secondary electron current collected at a biased land during box IEMP. The simple models are intended for the use of systems designers who must estimate the threat to active electronics during box IEMP and who may not have access to the large computer codes which simulate SGEMP. Separate theories apply to the nonself-consistent regime (when the collected charge does not greatly perturb the cavity fields) and the spacecharge-limited regime (when the secondary electrons screen the potential near the land). Analytical calculations for simple test cases compare well with selfconsistent SGEMP computer simulations and with data from past experiments at an MBS facility. Underprediction of the response at biases above +100 V suggests that an undetermined physical mechanism becomes important at high biases

  7. Application Analysis of Ad Lamp-box Controller

    Institute of Scientific and Technical Information of China (English)

    FANG Yuan; LU Bin

    2014-01-01

    The ad lamp-box controller is designed in consideration that ordinary urban ad lights usually remain lit through the night and a specially assigned staff needs to be on duty to control their switches. It can be automatically controlled with a photo resistance testing the day and night as well as a CD4060 chip controlling the length of time interval between switching the ad lamp-boxes on and off. In this way, both energy and labor can be saved with the controller. It is matching with the target of“constructing a conservation-minded society”in our country and deserves to be promoted in market with its practical signifi-cance.

  8. Safeguards Approaches for Black Box Processes or Facilities

    Energy Technology Data Exchange (ETDEWEB)

    Diaz-Marcano, Helly; Gitau, Ernest TN; Hockert, John; Miller, Erin; Wylie, Joann

    2013-09-25

    The objective of this study is to determine whether a safeguards approach can be developed for “black box” processes or facilities. These are facilities where a State or operator may limit IAEA access to specific processes or portions of a facility; in other cases, the IAEA may be prohibited access to the entire facility. The determination of whether a black box process or facility is safeguardable is dependent upon the details of the process type, design, and layout; the specific limitations on inspector access; and the restrictions placed upon the design information that can be provided to the IAEA. This analysis identified the necessary conditions for safeguardability of black box processes and facilities.

  9. Gas box control system for Tandem Mirror Experiment-Upgrade

    International Nuclear Information System (INIS)

    The Tandem Mirror Experiment-Upgrade (TMX-U) uses several methods to feed gas (usually deuterium) at different energies into the plasma region of the machine. One is an arrangement of eight high-speed piezo-electric valves mounted on special manifolds (gas box) that feed cold gas directly to the plasma. This paper describes the electronic valve control and data acquisition portions of the gas box, which are controlled by a desk-top computer. Various flow profiles have been developed and stored in the control computer for ready access by the operator. The system uses two modes of operation, one that exercises and characterizes the valves and one that operates the valves with the rest of the experiment. Both the valve control signals and the pressure transducers data are recorded on the diagnostics computer so that they are available for experiment analysis

  10. Gray-Box Modeling of a Pneumatic Servo-Valve

    OpenAIRE

    Mojtaba Aghamirsalim; Hosein Farahmandzad; Farhad Toorani

    2010-01-01

    This paper presents the evaluation as well as the combined analytical andexperimental identification (gray box identification) of a servo-valve torque motor as thedirectional valve applied in a pneumatic actuator. Based on analytical modelling, a simplelinear parametric model with transfer function and block diagram is developed. Next, thestatic and dynamic characteristics of the torque motor are obtained from experimentalobservations. The characteristics confirm the desired linear behaviour ...

  11. Stiffened flanges used in steel box girder bridges

    OpenAIRE

    Ferreira, Pedro; Virtuoso, Francisco

    2015-01-01

    This paper presents a design method for stiffened flanges used in steel box girder bridges based on a set of design curves that take into account all relevant parameters regarding the ultimate strength of stiffened flanges, including the real boundary conditions for the inplane displacements at the edges. These design curves were developed and calibrated based on the results obtained with nonlinear analysis using the semi-analytical and finite element methods and they were vali...

  12. Black-Box Algorithms for Sampling from Continuous Distributions

    OpenAIRE

    Hörmann, Wolfgang; Leydold, Josef

    2006-01-01

    For generating non-uniform random variates, black-box algorithms are powerful tools that allow drawing samples from large classes of distributions. We give an overview of the design principles of such methods and show that they have advantages compared to specialized algorithms even for standard distributions, e.g., the marginal generation times are fast and depend mainly on the chosen method and not on the distribution. Moreover these methods are suitable for specialized tasks like sampling ...

  13. Evaluation of multi-box diagrams in six dimensions

    International Nuclear Information System (INIS)

    We present a simple method which simplifies the evaluation of the on-shell multiple box diagrams reducing them to triangle type ones. For the L-loop diagram one gets the expression in terms of Feynman parameters with 2L-fold integration. As examples we consider the 2 and 3 loops cases, the numerical integration up to six loops is also presented. The method is valid in six dimensions where neither UV not IR divergences appear

  14. A NEW PRINCIPAL PIVOTING SCHEME FOR BOX LINEAR COMPLEMENTARITY PROBLEMS

    Institute of Scientific and Technical Information of China (English)

    WANGZHEMIN

    1997-01-01

    Judice and Pires developed in recent years principal pivoting methods for the solving ofthe so-called box linear complementarity problems (BLCPs) where the constraint matrices are restrictedly supposed to be of P-matrices. This paper aims at presenting a new principal pivoting scheme for BLCPs where the constraint matrices are loosely supposed to be row sufficient. This scheme can be applied to the solving of convex quadratic programs subject to linear constraints and arbitrary upper and lower bound constraints on variables.

  15. Fermionic Casimir energy in a three-dimensional box

    International Nuclear Information System (INIS)

    In this paper we calculate the Casimir energy for a massless fermionic field confined inside a three-dimensional rectangular box. We use the MIT bag model boundary condition for the confinement. We use the direct mode summation method along with the Abel-Plana summation formula to compute the Casimir energy, without any use of regularization or analytic continuation techniques. We obtain a negative Casimir energy, as opposed to the previously reported result for the interior of a three-dimensional sphere.

  16. Chinese boxes: "Typhoon" and Conrad's history of the Chinese

    OpenAIRE

    Kerr, D.

    2009-01-01

    This essay examines the novel "Typhoon," by Joseph Conrad, as a story about Chinamen coolies and seamen onboard a steamer transporting Chinese laborers. It argues that the Chinese boxes of the coolies represent several versions of the history of the Chinese and that the coolies are also representatives of a civilization with ideas and institutions, a law and order of nature. It also describes the images of Chinese life and their association to sociality, cooperation, nourishment, simplicity, ...

  17. Salmonella in pig lairage and in stunning box

    OpenAIRE

    Karabasil Neđeljko; Dimitrijević Mirjana; Pavlićević Nataša; Teodorović Vlado; Lončina Jasna; Nedeljković-Trailović Jelena; Baltić Milan Ž.

    2012-01-01

    Salmonella is one of the most important zoonotic pathogens and the consumption of pork meat is a major source of human infection. The aim of this study was to investigate the presence of Salmonella on different surfaces in the pig lairage and stunning box as potential sources of cross contamination of animals and carcasses. Sampling was conducted in two abattoirs (slaughterhouse A and slaughterhouse B). Samples were taken from slaughterhouse A in two instan...

  18. Numerical cubature from Archimedes' hat-box theorem

    OpenAIRE

    Kuperberg, Greg

    2004-01-01

    Archimedes' hat-box theorem states that uniform measure on a sphere projects to uniform measure on an interval. This fact can be used to derive Simpson's rule. We present various constructions of, and lower bounds for, numerical cubature formulas using moment maps as a generalization of Archimedes' theorem. We realize some well-known cubature formulas on simplices as projections of spherical designs. We combine cubature formulas on simplices and tori to make new formulas on spheres. In partic...

  19. ArduiPod Box: a low-cost and open-source Skinner box using an iPod Touch and an Arduino microcontroller.

    Science.gov (United States)

    Pineño, Oskar

    2014-03-01

    This article introduces the ArduiPod Box, an open-source device built using two main components (i.e., an iPod Touch and an Arduino microcontroller), developed as a low-cost alternative to the standard operant conditioning chamber, or "Skinner box." Because of its affordability, the ArduiPod Box provides an opportunity for educational institutions with small budgets seeking to set up animal laboratories for research and instructional purposes. A pilot experiment is also presented, which shows that the ArduiPod Box, in spite of its extraordinary simplicity, can be effectively used to study animal learning and behavior. PMID:23813238

  20. Wind Turbine Box - energy fluxes around a characteristic wind turbine

    Science.gov (United States)

    Calaf, Marc; Cortina, Gerard; Sharma, Varun

    2015-11-01

    This research project presents a new tool, so called ``Wind Turbine Box'', that allows for the direct comparison between the flow around a single wind turbine and the flow around a characteristic wind turbine immersed within a large wind farm. The Wind Turbine Box consists of a limited control volume defined around each wind turbine that is timely co-aligned with each corresponding turbine's yaw-angle. Hence it is possible to extract flow statistics around each wind turbine, regardless of whether the turbine is fully isolated or it is plunged within a large wind farm. The Wind Turbine Box tool has been used to compute the energy fluxes around a characteristic wind turbine of a large wind farm to better understand the wake replenishment processes throughout a complete diurnal cycle. The effective loading of the wind farm has been gradually increased, ranging from quasi-isolated wind turbines to a highly packed wind farm. For this purpose, several Large Eddy Simulations have been run, forced with a constant geostrophic wind and a time varying surface temperature extracted from a selected period of the CASES-99 field experiment. Results illustrate the differences in the flow dynamics as it evolves around a characteristic wind turbine within a large wind farm and its asymptotic transition to the fully developed wind turbine array boundary layer.