Clinical Value of High Mobility Group Box 1 and the Receptor for Advanced Glycation End-products in Head and Neck Cancer: A Systematic Review

Directory of Open Access Journals (Sweden)

Nguyen, Austin

2016-04-01

Full Text Available Introduction High mobility group box 1 is a versatile protein involved in gene transcription, extracellular signaling, and response to inflammation. Extracellularly, high mobility group box 1 binds to several receptors, notably the receptor for advanced glycation end-products. Expression of high mobility group box 1 and the receptor for advanced glycation end-products has been described in many cancers. Objectives To systematically review the available literature using PubMed and Web of Science to evaluate the clinical value of high mobility group box 1 and the receptor for advanced glycation end-products in head and neck squamous cell carcinomas. Data synthesis A total of eleven studies were included in this review. High mobility group box 1 overexpression is associated with poor prognosis and many clinical and pathological characteristics of head and neck squamous cell carcinomas patients. Additionally, the receptor for advanced glycation end-products demonstrates potential value as a clinical indicator of tumor angiogenesis and advanced staging. In diagnosis, high mobility group box 1 demonstrates low sensitivity. Conclusion High mobility group box 1 and the receptor for advanced glycation end-products are associated with clinical and pathological characteristics of head and neck squamous cell carcinomas. Further investigation of the prognostic and diagnostic value of these molecules is warranted.

A Group Action Method for Construction of Strong Substitution Box

Science.gov (United States)

Jamal, Sajjad Shaukat; Shah, Tariq; Attaullah, Atta

2017-06-01

In this paper, the method to develop cryptographically strong substitution box is presented which can be used in multimedia security and data hiding techniques. The algorithm of construction depends on the action of a projective general linear group over the set of units of the finite commutative ring. The strength of substitution box and ability to create confusion is assessed with different available analyses. Moreover, the ability of resistance against malicious attacks is also evaluated. The substitution box is examined by bit independent criterion, strict avalanche criterion, nonlinearity test, linear approximation probability test and differential approximation probability test. This substitution box is equated with well-recognized substitution boxes such as AES, Gray, APA, S8, prime of residue, Xyi and Skipjack. The comparison shows encouraging results about the strength of the proposed box. The majority logic criterion is also calculated to analyze the strength and its practical implementation.

Direct modulation of T-box riboswitch-controlled transcription by protein synthesis inhibitors.

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Stamatopoulou, Vassiliki; Apostolidi, Maria; Li, Shuang; Lamprinou, Katerina; Papakyriakou, Athanasios; Zhang, Jinwei; Stathopoulos, Constantinos

2017-09-29

Recently, it was discovered that exposure to mainstream antibiotics activate numerous bacterial riboregulators that control antibiotic resistance genes including metabolite-binding riboswitches and other transcription attenuators. However, the effects of commonly used antibiotics, many of which exhibit RNA-binding properties, on the widespread T-box riboswitches, remain unknown. In Staphylococcus aureus, a species-specific glyS T-box controls the supply of glycine for both ribosomal translation and cell wall synthesis, making it a promising target for next-generation antimicrobials. Here, we report that specific protein synthesis inhibitors could either significantly increase T-box-mediated transcription antitermination, while other compounds could suppress it, both in vitro and in vivo. In-line probing of the full-length T-box combined with molecular modelling and docking analyses suggest that the antibiotics that promote transcription antitermination stabilize the T-box:tRNA complex through binding specific positions on stem I and the Staphylococcal-specific stem Sa. By contrast, the antibiotics that attenuate T-box transcription bind to other positions on stem I and do not interact with stem Sa. Taken together, our results reveal that the transcription of essential genes controlled by T-box riboswitches can be directly modulated by commonly used protein synthesis inhibitors. These findings accentuate the regulatory complexities of bacterial response to antimicrobials that involve multiple riboregulators. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Optimal Black-Box Secret Sharing over Arbitrary Abelian Groups

DEFF Research Database (Denmark)

Cramer, Ronald; Fehr, Serge

2002-01-01

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 defined over ℤ and are designed independently of the group G from which the secret and the shares are sampled. This means that perfect completeness and perfect privacy are guaranteed regardless of which group G is chosen. We define the black-box secret sharing problem as the problem of devising......, for an arbitrary given T t,n , a scheme with minimal expansion factor, i.e., where the length of the full vector of shares divided by the number of players n is minimal. Such schemes are relevant for instance in the context of distributed cryptosystems based on groups with secret or hard to compute group order...

Classification of EA1-box proteins and new insights into their role during reproduction in grasses.

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Uebler, Susanne; Márton, Mihaela L; Dresselhaus, Thomas

2015-12-01

EA1-box protein classification. Success in reproduction and vegetative development in flowering plants strongly depends on precise cell-to-cell signaling events mediated by secreted peptides.A small peptide family named as EA1-like (EAL) has been first described 10 years ago and includes EA1 involved in pollen tubes attraction by the female gametophyte and EAL1-regulating germ cell identity in maize. EALs consist of an N-terminal endoplasmic reticulum-targeting motif, the highly conserved EA1-box and a short C-terminal alanine-rich domain. Whereas EAL peptides are exclusively found in the Gramineae, the EA1-box is widely distributed throughout the plant kingdom. Based on in silico analysis and subcellular localization studies, we report here a new classification of EA1-box proteins in flowering plants. They can be distinguished into three protein classes: the already defined EAL proteins, the EAG (EA1-box glycine-rich) proteins and the EAC (EA1-box containing)proteins. While fusion proteins of EAL and EAC classes locate to the secretory pathway, EAGs are cytoplasmic and locate also to the nucleus. Moreover, we further show that the third EAL protein of Zea mays, EAL2, appears to be also involved in processes related to late embryogenic development as its peptide level increases after formation of leaf primordia. Immunohistochemical studies indicate its presence in the scutellar parenchyma and around the vasculature, where it is secreted to the extracellular space. In conclusion, the members of the maize EAL family possess very diverse functions during reproduction and it will now be exciting to elucidate the functions of EAGs and EACs in plants.

Vagal modulation of high mobility group box-1 protein mediates electroacupuncture-induced cardioprotection in ischemia-reperfusion injury.

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Zhang, Juan; Yong, Yue; Li, Xing; Hu, Yu; Wang, Jian; Wang, Yong-qiang; Song, Wei; Chen, Wen-ting; Xie, Jian; Chen, Xue-mei; Lv, Xin; Hou, Li-li; Wang, Ke; Zhou, Jia; Wang, Xiang-rui; Song, Jian-gang

2015-10-26

Excessive release of high mobility group box-1 (HMGB1) protein from ischemic cardiomyocytes activates inflammatory cascades and enhances myocardial injury after reperfusion. Here we report evidence that electroacupuncture of mice at Neiguan acupoints can inhibit the up-regulation of cardiac HMGB1 following myocardial ischemia and attenuate the associated inflammatory responses and myocardial injury during reperfusion. These benefits of electroacupuncture were partially reversed by administering recombinant HMGB1 to the mice, and further potentiated by administering anti-HMGB1 antibody. Electroacupuncture-induced inhibition of HMGB1 release was markedly reduced by unilateral vagotomy or administration of nicotinic receptor antagonist, but not by chemical sympathectomy. The cholinesterase inhibitor neostigmine mimicked the effects of electroacupuncture on HMGB1 release and myocardial ischemia reperfusion injury. Culture experiments with isolated neonatal cardiomyocytes showed that acetylcholine, but not noradrenaline, inhibited hypoxia-induced release of HMGB1 via a α7nAchR-dependent pathway. These results suggest that electroacupuncture acts via the vagal nerve and its nicotinic receptor-mediated signaling to inhibit HMGB1 release from ischemic cardiomyocytes. This helps attenuate pro-inflammatory responses and myocardial injury during reperfusion.

[Effects of exogenous high mobility group protein box 1 on angiogenesis in ischemic zone of early scald wounds of rats].

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Dai, L; Guo, X; Huang, H J; Liao, X M; Luo, X Q; Li, D; Zhou, H; Gao, X C; Tan, M Y

2018-04-20

Objective: To observe effects of exogenous high mobility group protein box 1 (HMGB1) on angiogenesis in ischemic zone of early scald wounds of rats. Methods: Thirty-six Sprague-Dawley rats were divided into HMGB1 group and simple scald (SS) group according to the random number table, with 18 rats in each group. Comb-like copper mould was placed on the back of rats for 20 s after being immersed in 100 ℃ hot water for 3 to 5 min to make three ischemic zones of wound. Immediately after scald, rats in HMGB1 group were subcutaneously injected with 0.4 μg HMGB1 and 0.1 mL phosphate buffer solution (PBS), and rats in SS group were subcutaneously injected with 0.1 mL PBS from boarders of ischemic zone of scald wound. At post scald hour (PSH) 24, 48, and 72, 6 rats in each group were collected. Protein expressions of vascular endothelial growth factor (VEGF) in ischemic zone of wound at PSH 24, 48, and 72 and protein expressions of CD31 in ischemic zone of wound at PSH 48 and 72 were detected by immunohistochemistry. The number of microvessel in CD31 immunohistochemical sections of ischemic zone of wound at PSH 48 and 72 was calculated after observing by the microscope. The mRNA expressions of VEGF and CD31 in ischemic zone of wound were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction at PSH 24, 48, and 72. Data were processed with analysis of variance of factorial design, t test, and Bonferroni correction. Results: (1) At PSH 24, 48, and 72, protein expressions of VEGF in ischemic zone of wound of rats in HMGB1 group were significantly higher than those of rats in SS group ( t =7.496, 4.437, 5.402, P zone of wound of rats in HMGB1 group were 0.038 8±0.007 9 and 0.057 7±0.001 2 respectively, significantly higher than 0.013 4±0.004 9 and 0.030 3±0.004 0 of rats in SS group ( t =10.257, 15.055, P zone of wound of rats in HMGB1 group was obviously more than that of rats in SS group ( t =3.536, 4.000, P zone of wound of

21 CFR 864.9185 - Blood grouping view box.

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2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Blood grouping view box. 864.9185 Section 864.9185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Products Used In Establishments That Manufacture Blood...

F-BOX proteins in cancer cachexia and muscle wasting: Emerging regulators and therapeutic opportunities.

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Sukari, Ammar; Muqbil, Irfana; Mohammad, Ramzi M; Philip, Philip A; Azmi, Asfar S

2016-02-01

Cancer cachexia is a debilitating metabolic syndrome accounting for fatigue, an impairment of normal activities, loss of muscle mass associated with body weight loss eventually leading to death in majority of patients with advanced disease. Cachexia patients undergoing skeletal muscle atrophy show consistent activation of the SCF ubiquitin ligase (F-BOX) family member Atrogin-1 (also known as MAFBx/FBXO32) alongside the activation of the muscle ring finger protein1 (MuRF1). Other lesser known F-BOX family members are also emerging as key players supporting muscle wasting pathways. Recent work highlights a spectrum of different cancer signaling mechanisms impacting F-BOX family members that feed forward muscle atrophy related genes during cachexia. These novel players provide unique opportunities to block cachexia induced skeletal muscle atrophy by therapeutically targeting the SCF protein ligases. Conversely, strategies that induce the production of proteins may be helpful to counter the effects of these F-BOX proteins. Through this review, we bring forward some novel targets that promote atrogin-1 signaling in cachexia and muscle wasting and highlight newer therapeutic opportunities that can help in the better management of patients with this devastating and fatal disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

Protective effect of Sestrin2 on apoptosis of dendritic cells induced by high mobility group box-1 protein

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Li-xue WANG

2018-04-01

Full Text Available Objective To investigate the potential role of Sestrin2 (SESN2 in regulating the apoptosis of dendritic cells (DCs induced by high mobility group box-1 protein (HMGB1. Methods DCs (the murine DC cell line DC2.4 were cultured with or without HMGB1 stimulation (cultured with 10ng/ml HMGB1 for 8, 24 and 48 hours, or cultured with HMGB1 for 48 hours at different concentrations of 1, 10 and 100ng/ml, respectively, n=4. The protein level of SESN2, cleaved-caspase-3 and Bcl-2 were analyzed with Western blotting. Localization of SESN2 in cells was observed under confocal laser microscope (LSCM. Cell apoptosis was analyzed with flow cytometry. In addition, DC2.4 cells were transfected with lentivirus containing SESN2 LV-RNA, SESN2 siRNA sequence expressing plasmids or blank vector (NC, NS, n=4. These cells were then stimulated with HMGB1 (100ng/ml for 48 hours, and the apoptosis was accessed as mentioned above. Results Compared with the control group, the expression of SESN2 was obviously up-regulated after HMGB1 (10ng/ml stimulation for 24 and 48 hours (P<0.05. In a dose-dependent response, the expression of SESN2 was markedly enhanced in treatment with 1, 10, 100ng/ml HMGB1 for 48 hours (P<0.05. Compared with the control group (7.35%±1.33%, the percentage of apoptosis was significantly increased with 10, 100ng/ml HMGB1 for 48 hours [(17.02%±4.85%, 17.48%±4.04%, respectively, P<0.05 or P<0.01]. After transfection, compared with blank vector group, the apoptosis of SESN2 siRNA group obviously elevated [(65.96%±2.50% vs. (50.01%±2.07%, P<0.05], and cleaved-caspase-3 expression significantly increased while Bcl-2 expression obviously decreased. In SESN2 LV-RNA group, the apoptosis significantly decreased [(35.57%±1.69% vs. (49.04%±4.87%, P<0.05], and cleaved-caspase-3 expression decreased and Bcl-2 expression obviously increased compared with blank vector group (P<0.05. Conclusion SESN2 has a protective effect against HMGB1 induced apoptosis of DC2

Cyclin B1 Destruction Box-Mediated Protein Instability: The Enhanced Sensitivity of Fluorescent-Protein-Based Reporter Gene System

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Chao-Hsun Yang

2013-01-01

Full Text Available The periodic expression and destruction of several cyclins are the most important steps for the exact regulation of cell cycle. Cyclins are degraded by the ubiquitin-proteasome system during cell cycle. Besides, a short sequence near the N-terminal of cyclin B called the destruction box (D-box; CDB is also required. Fluorescent-protein-based reporter gene system is insensitive to analysis because of the overly stable fluorescent proteins. Therefore, in this study, we use human CDB fused with both enhanced green fluorescent protein (EGFP at C-terminus and red fluorescent protein (RFP, DsRed at N-terminus in the transfected human melanoma cells to examine the effects of CDB on different fluorescent proteins. Our results indicated that CDB-fused fluorescent protein can be used to examine the slight gene regulations in the reporter gene system and have the potential to be the system for screening of functional compounds in the future.

[Changing laws of serum high mobility group box 1 protein in septic rats and the intervention effect of xuebijing].

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Zhao, Shi-bing; He, Xian-di; Wang, Hua-xue; Zheng, Sheng-yong; Deng, Xi-ming; Duan, Li-bin

2014-06-01

To investigate the changing laws of serum high mobility group box 1 protein (HMGB1) in septic rats and intervention effect of Xuebijing on it. Lipopolysaccharide (LPS) (5 mg/kg BW) was intravenously injected into the tail vein of healthy male Wistar rats to prepare the sepsis rat model. In Experiment 1: 50 Wistar rats were randomly divided into three groups, i.e., the normal group (A, n=10); the LPS model group (B, n=10), the LPS +Xuebijing treatment group (C, n=30). Rats in the C group were further divided into three subgroups, i.e., 2 h before LPS injection (group C1), 2 h after LPS injection (group C2), and 8 h after LPS injection (group C3), 10 in each group. Blood samples were collected from the caudal vein to detect serum HMGB1 levels by Western blot at 4, 12, 24, 48, and 72 h after LPS injection. Experiment 2: 30 Wistar rats were equally divided into the LPS model group (D) and the LPS + Xuebijing treatment group (E), 15 in each group. They were treated as rats in the B group and the C1 group respectively. Five rats were sacrificed at 12, 24, and 48 h after LPS injection in the two groups. Blood as well as the tissue samples were harvested to measure such indices as ALT, AST, Cr, and BUN, as well as pathological changes of liver, lung, and kidney. (1) Compared with the A group, serum HMGB1 levels were higher at various time points in the B group (P decrement in the C3 group was less than that in the C1 and C2 groups (P multiple organ dysfunction. Xuebijing could reduce the serum levels of HMGB1, improve biochemical parameters, and attenuate severe inflammatory response of liver, lung, and kidney tissues in septic rats. Besides, the earlier use, the better effect obtained.

F-box-like domain in the polerovirus protein P0 is required for silencing suppressor function

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Pazhouhandeh, Maghsoud; Dieterle, Monika; Marrocco, Katia; Lechner, Esther; Berry, Bassam; Brault, Véronique; Hemmer, Odile; Kretsch, Thomas; Richards, Kenneth E.; Genschik, Pascal; Ziegler-Graff, Véronique

2006-01-01

Plants employ small RNA-mediated posttranscriptional gene silencing as a virus defense mechanism. In response, plant viruses encode proteins that can suppress RNA silencing, but the mode of action of most such proteins is poorly understood. Here, we show that the silencing suppressor protein P0 of two Arabidopsis-infecting poleroviruses interacts by means of a conserved minimal F-box motif with Arabidopsis thaliana orthologs of S-phase kinase-related protein 1 (SKP1), a component of the SCF family of ubiquitin E3 ligases. Point mutations in the F-box-like motif abolished the P0–SKP1 ortholog interaction, diminished virus pathogenicity, and inhibited the silencing suppressor activity of P0. Knockdown of expression of a SKP1 ortholog in Nicotiana benthamiana rendered the plants resistant to polerovirus infection. Together, the results support a model in which P0 acts as an F-box protein that targets an essential component of the host posttranscriptional gene silencing machinery. PMID:16446454

Bioactive L acidissima protein hydrolysates using Box-Behnken design.

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Sonawane, Sachin K; Arya, Shalini S

2017-07-01

This study examines the extraction and hydrolysis of proteins using single factor and Box-Behnken Design (BBD). From single factor tests, optimised extraction parameters were 1% alkali concentration, 40 °C temperature, 60 min time, and 1:20 solid to alkali ratio. Under these conditions; 924.31 mg/g of total protein was obtained from Limonia acidissima (L acidissima). The maximum degree of hydrolysis was 39.82% at pH 2, enzyme to substrate ratio 2.5% (w/w), and hydrolysis time was 42.41 min using BBD design. L acidissima seed protein hydrolysate showed 32.94% DPPH and 88.18% of ABTS activity at concentration of 100 µg/ml and 1 mg/ml, respectively. Reducing power of 0.16 and metal chelating activity of 87.39% was obtained from 5 mg/ml protein hydrolysates. This implied that L acidissima seed protein hydrolysate could be utilised in protein rich product or as protein supplements.

Real-time Kinetics of High-mobility Group Box 1 (HMGB1) Oxidation in Extracellular Fluids Studied by in Situ Protein NMR Spectroscopy*

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Zandarashvili, Levani; Sahu, Debashish; Lee, Kwanbok; Lee, Yong Sun; Singh, Pomila; Rajarathnam, Krishna; Iwahara, Junji

2013-01-01

Some extracellular proteins are initially secreted in reduced forms via a non-canonical pathway bypassing the endoplasmic reticulum and become oxidized in the extracellular space. One such protein is HMGB1 (high-mobility group box 1). Extracellular HMGB1 has different redox states that play distinct roles in inflammation. Using a unique NMR-based approach, we have investigated the kinetics of HMGB1 oxidation and the half-lives of all-thiol and disulfide HMGB1 species in serum, saliva, and cell culture medium. In this approach, salt-free lyophilized 15N-labeled all-thiol HMGB1 was dissolved in actual extracellular fluids, and the oxidation and clearance kinetics were monitored in situ by recording a series of heteronuclear 1H-15N correlation spectra. We found that the half-life depends significantly on the extracellular environment. For example, the half-life of all-thiol HMGB1 ranged from ∼17 min (in human serum and saliva) to 3 h (in prostate cancer cell culture medium). Furthermore, the binding of ligands (glycyrrhizin and heparin) to HMGB1 significantly modulated the oxidation kinetics. Thus, the balance between the roles of all-thiol and disulfide HMGB1 proteins depends significantly on the extracellular environment and can also be artificially modulated by ligands. This is important because extracellular HMGB1 has been suggested as a therapeutic target for inflammatory diseases and cancer. Our work demonstrates that the in situ protein NMR approach is powerful for investigating the behavior of proteins in actual extracellular fluids containing an enormous number of different molecules. PMID:23447529

The F-box Protein FBXO44 Mediates BRCA1 Ubiquitination and Degradation*

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Lu, Yunzhe; Li, Jiezhi; Cheng, Dongmei; Parameswaran, Balaji; Zhang, Shaohua; Jiang, Zefei; Yew, P. Renee; Peng, Junmin; Ye, Qinong; Hu, Yanfen

2012-01-01

BRCA1 mutations account for a significant proportion of familial breast and ovarian cancers. In addition, reduced BRCA1 protein is associated with sporadic cancer cases in these tissues. At the cellular level, BRCA1 plays a critical role in multiple cellular functions such as DNA repair and cell cycle checkpoint control. Its protein level is regulated in a cell cycle-dependent manner. However, regulation of BRCA1 protein stability is not fully understood. Our earlier study showed that the amino terminus of BRCA1 harbors a degron sequence that is sufficient and necessary for conferring BRCA1 degradation. In the current study, we used mass spectrometry to identify Skp1 that regulates BRCA1 protein stability. Small interfering RNA screening that targets all human F-box proteins uncovered FBXO44 as an important protein that influences BRCA1 protein level. The Skp1-Cul1-F-box-protein44 (SCFFBXO44) complex ubiquitinates full-length BRCA1 in vitro. Furthermore, the N terminus of BRCA1 mediates the interaction between BRCA1 and FBXO44. Overexpression of SCFFBXO44 reduces BRCA1 protein level. Taken together, our work strongly suggests that SCFFBXO44 is an E3 ubiquitin ligase responsible for BRCA1 degradation. In addition, FBXO44 expression pattern in breast carcinomas suggests that SCFFBXO44-mediated BRCA1 degradation might contribute to sporadic breast tumor development. PMID:23086937

A proteomic screen reveals the mitochondrial outer membrane protein Mdm34p as an essential target of the F-box protein Mdm30p.

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Ota, Kazuhisa; Kito, Keiji; Okada, Satoshi; Ito, Takashi

2008-10-01

Ubiquitination plays various critical roles in eukaryotic cellular regulation and is mediated by a cascade of enzymes including ubiquitin protein ligase (E3). The Skp1-Cullin-F-box protein complex comprises the largest E3 family, in each member of which a unique F-box protein binds its targets to define substrate specificity. Although genome sequencing uncovers a growing number of F-box proteins, most of them have remained as "orphans" because of the difficulties in identification of their substrates. To address this issue, we tested a quantitative proteomic approach by combining the stable isotope labeling by amino acids in cell culture (SILAC), parallel affinity purification (PAP) that we had developed for efficient enrichment of ubiquitinated proteins, and mass spectrometry (MS). We applied this SILAC-PAP-MS approach to compare ubiquitinated proteins between yeast cells with and without over-expressed Mdm30p, an F-box protein implicated in mitochondrial morphology. Consequently, we identified the mitochondrial outer membrane protein Mdm34p as a target of Mdm30p. Furthermore, we found that mitochondrial defects induced by deletion of MDM30 are not only recapitulated by a mutant Mdm34p defective in interaction with Mdm30p but alleviated by ubiquitination-mimicking forms of Mdm34p. These results indicate that Mdm34p is a physiologically important target of Mdm30p.

Identification of the self-incompatibility locus F-box protein-containing complex in Petunia inflata.

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Li, Shu; Sun, Penglin; Williams, Justin Stephen; Kao, Teh-hui

2014-03-01

The polymorphic S-locus regulating self-incompatibility (SI) in Petunia contains the S-RNase gene and a number of S-locus F-box (SLF) genes. While penetrating the style through the stigma, a pollen tube takes up all S-RNases, but only self S-RNase inhibits pollen tube growth. Recent evidence suggests that SLFs produced by pollen collectively interact with and detoxify non-self S-RNases, but none can interact with self S-RNase. An SLF may be the F-box protein component of an SCF complex (containing Cullin1, Skp1 and Rbx1), which mediates ubiquitination of protein substrates for degradation by the 26S proteasome. However, the precise nature of the complex is unknown. We used pollen extracts of a transgenic plant over-expressing GFP-fused S2-SLF1 (SLF1 of S 2-haplotype) for co-immunoprecipitation (Co-IP) followed by mass spectrometry (MS). We identified PiCUL1-P (a pollen-specific Cullin1), PiSSK1 (a pollen-specific Skp1-like protein) and PiRBX1 (an Rbx1). To validate the results, we raised transgenic plants over-expressing PiSSK1:FLAG:GFP and used pollen extracts for Co-IP-MS. The results confirmed the presence of PiCUL1-P and PiRBX1 in the complex and identified two different SLFs as the F-box protein component. Thus, all but Rbx1 of the complex may have evolved in SI, and all SLFs may be the F-box component of similar complexes.

A novel F-box protein CaF-box is involved in responses to plant hormones and abiotic stress in pepper (Capsicum annuum L.).

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Chen, Rugang; Guo, Weili; Yin, Yanxu; Gong, Zhen-Hui

2014-02-10

The F-box protein family is characterized by an F-box motif that has been shown to play an important role in regulating various developmental processes and stress responses. In this study, a novel F-box-containing gene was isolated from leaves of pepper cultivar P70 (Capsicum annuum L.) and designated CaF-box. The full-length cDNA is 2088 bp and contains an open reading frame of 1914 bp encoding a putative polypeptide of 638 amino acids with a mass of 67.8 kDa. CaF-box was expressed predominantly in stems and seeds, and the transcript was markedly upregulated in response to cold stress, abscisic acid (ABA) and salicylic acid (SA) treatment, and downregulated under osmotic and heavy metal stress. CaF-box expression was dramatically affected by salt stress, and was rapidly increased for the first hour, then sharply decreased thereafter. In order to further assess the role of CaF-box in the defense response to abiotic stress, a loss-of-function experiment in pepper plants was performed using a virus-induced gene silencing (VIGS) technique. Measurement of thiobarbituric acid reactive substances (TBARS) and electrolyte leakage revealed stronger lipid peroxidation and cell death in the CaF-box-silenced plants than in control plants, suggesting CaF-box plays an important role in regulating the defense response to abiotic stress resistance in pepper plants.

The DEAD-Box Protein CYT-19 Uses Arginine Residues in Its C-Tail To Tether RNA Substrates.

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Busa, Veronica F; Rector, Maxwell J; Russell, Rick

2017-07-18

DEAD-box proteins are nonprocessive RNA helicases that play diverse roles in cellular processes. The Neurospora crassa DEAD-box protein CYT-19 promotes mitochondrial group I intron splicing and functions as a general RNA chaperone. CYT-19 includes a disordered, arginine-rich "C-tail" that binds RNA, positioning the helicase core to capture and unwind nearby RNA helices. Here we probed the C-tail further by varying the number and positions of arginines within it. We found that removing sets of as few as four of the 11 arginines reduced RNA unwinding activity (k cat /K M ) to a degree equivalent to that seen upon removal of the C-tail, suggesting that a minimum or "threshold" number of arginines is required. In addition, a mutant with 16 arginines displayed RNA unwinding activity greater than that of wild-type CYT-19. The C-tail modifications impacted unwinding only of RNA helices within constructs that included an adjacent helix or structured RNA element that would allow C-tail binding, indicating that the helicase core remained active in the mutants. In addition, changes in RNA unwinding efficiency of the mutants were mirrored by changes in functional RNA affinity, as determined from the RNA concentration dependence of ATPase activity, suggesting that the C-tail functions primarily to increase RNA affinity. Interestingly, the salt concentration dependence of RNA unwinding activity is unaffected by C-tail composition, suggesting that the C-tail uses primarily hydrogen bonding, not electrostatic interactions, to bind double-stranded RNA. Our results provide insights into how an unstructured C-tail contributes to DEAD-box protein activity and suggest parallels with other families of RNA- and DNA-binding proteins.

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

International Nuclear Information System (INIS)

Lee, Hanna; Park, Minhee; Shin, Nara; Kim, Gamin; Kim, Yun Gi; Shin, Jeon-Soo; Kim, Hoguen

2012-01-01

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.

The F-box protein FBXO44 mediates BRCA1 ubiquitination and degradation.

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Lu, Yunzhe; Li, Jiezhi; Cheng, Dongmei; Parameswaran, Balaji; Zhang, Shaohua; Jiang, Zefei; Yew, P Renee; Peng, Junmin; Ye, Qinong; Hu, Yanfen

2012-11-30

BRCA1 mutations account for a significant proportion of familial breast and ovarian cancers. In addition, reduced BRCA1 protein is associated with sporadic cancer cases in these tissues. At the cellular level, BRCA1 plays a critical role in multiple cellular functions such as DNA repair and cell cycle checkpoint control. Its protein level is regulated in a cell cycle-dependent manner. However, regulation of BRCA1 protein stability is not fully understood. Our earlier study showed that the amino terminus of BRCA1 harbors a degron sequence that is sufficient and necessary for conferring BRCA1 degradation. In the current study, we used mass spectrometry to identify Skp1 that regulates BRCA1 protein stability. Small interfering RNA screening that targets all human F-box proteins uncovered FBXO44 as an important protein that influences BRCA1 protein level. The Skp1-Cul1-F-box-protein44 (SCF(FBXO44)) complex ubiquitinates full-length BRCA1 in vitro. Furthermore, the N terminus of BRCA1 mediates the interaction between BRCA1 and FBXO44. Overexpression of SCF(FBXO44) reduces BRCA1 protein level. Taken together, our work strongly suggests that SCF(FBXO44) is an E3 ubiquitin ligase responsible for BRCA1 degradation. In addition, FBXO44 expression pattern in breast carcinomas suggests that SCF(FBXO44)-mediated BRCA1 degradation might contribute to sporadic breast tumor development.

Identification and characterization of the direct interaction between methotrexate (MTX and high-mobility group box 1 (HMGB1 protein.

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Yuki Kuroiwa

Full Text Available BACKGROUND: Methotrexate (MTX is an agent used in chemotherapy of tumors and autoimmune disease including rheumatoid arthritis (RA. In addition, MTX has some anti-inflammatory activity. Although dihydrofolate reductase (DHFR is a well-known target for the anti-tumor effect of MTX, the mode of action for the anti-inflammatory activity of MTX is not fully understood. METHODOLOGY/RESULT: Here, we performed a screening of MTX-binding proteins using T7 phage display with a synthetic biotinylated MTX derivative. We then characterized the interactions using surface plasmon resonance (SPR analysis and electrophoretic mobility shift assay (EMSA. Using a T7 phage display screen, we identified T7 phages that displayed part of high-mobility group box 1 (HMGB1 protein (K86-V175. Binding affinities as well as likely binding sites were characterized using genetically engineered truncated versions of HMGB1 protein (Al G1-K87, Bj: F88-K181, indicating that MTX binds to HMGB1 via two independent sites with a dissociation constants (KD of 0.50±0.03 µM for Al and 0.24 ± 0.01 µM for Bj. Although MTX did not inhibit the binding of HMGB1 to DNA via these domains, HMGB1/RAGE association was impeded in the presence of MTX. These data suggested that binding of MTX to part of the RAGE-binding region (K149-V175 in HMGB1 might be significant for the anti-inflammatory effect of MTX. Indeed, in murine macrophage-like cells (RAW 264.7, TNF-α release and mitogenic activity elicited by specific RAGE stimulation with a truncated monomeric HMGB1 were inhibited in the presence of MTX. CONCLUSIONS/SIGNIFICANCE: These data demonstrate that HMGB1 is a direct binding protein of MTX. Moreover, binding of MTX to RAGE-binding region in HMGB1 inhibited the HMGB1/RAGE interaction at the molecular and cellular levels. These data might explain the molecular basis underlying the mechanism of action for the anti-inflammatory effect of MTX.

A MADS box protein interacts with a mating-type protein and is required for fruiting body development in the homothallic ascomycete Sordaria macrospora.

Science.gov (United States)

Nolting, Nicole; Pöggeler, Stefanie

2006-07-01

MADS box transcription factors control diverse developmental processes in plants, metazoans, and fungi. To analyze the involvement of MADS box proteins in fruiting body development of filamentous ascomycetes, we isolated the mcm1 gene from the homothallic ascomycete Sordaria macrospora, which encodes a putative homologue of the Saccharomyces cerevisiae MADS box protein Mcm1p. Deletion of the S. macrospora mcm1 gene resulted in reduced biomass, increased hyphal branching, and reduced hyphal compartment length during vegetative growth. Furthermore, the S. macrospora Deltamcm1 strain was unable to produce fruiting bodies or ascospores during sexual development. A yeast two-hybrid analysis in conjugation with in vitro analyses demonstrated that the S. macrospora MCM1 protein can interact with the putative transcription factor SMTA-1, encoded by the S. macrospora mating-type locus. These results suggest that the S. macrospora MCM1 protein is involved in the transcriptional regulation of mating-type-specific genes as well as in fruiting body development.

An algorithm for the construction of substitution box for block ciphers based on projective general linear group

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Anas Altaleb

2017-03-01

Full Text Available The aim of this work is to synthesize 8*8 substitution boxes (S-boxes for block ciphers. The confusion creating potential of an S-box depends on its construction technique. In the first step, we have applied the algebraic action of the projective general linear group PGL(2,GF(28 on Galois field GF(28. In step 2 we have used the permutations of the symmetric group S256 to construct new kind of S-boxes. To explain the proposed extension scheme, we have given an example and constructed one new S-box. The strength of the extended S-box is computed, and an insight is given to calculate the confusion-creating potency. To analyze the security of the S-box some popular algebraic and statistical attacks are performed as well. The proposed S-box has been analyzed by bit independent criterion, linear approximation probability test, non-linearity test, strict avalanche criterion, differential approximation probability test, and majority logic criterion. A comparison of the proposed S-box with existing S-boxes shows that the analyses of the extended S-box are comparatively better.

Molecular cloning and characterization of an F-box family gene CarF-box1 from chickpea (Cicer arietinum L.).

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Jia, Yuying; Gu, Hanyan; Wang, Xiansheng; Chen, Quanjia; Shi, Shubing; Zhang, Jusong; Ma, Lin; Zhang, Hua; Ma, Hao

2012-03-01

F-box protein family has been found to play important roles in plant development and abiotic stress responses via the ubiquitin pathway. In this study, an F-box gene CarF-box1 (for Cicer arietinum F-box gene 1, Genbank accession no. GU247510) was isolated based on a cDNA library constructed with chickpea seedling leaves treated by polyethylene glycol. CarF-box1 encoded a putative protein with 345 amino acids and contained no intron within genomic DNA sequence. CarF-box1 is a KFB-type F-box protein, having a conserved F-box domain in the N-terminus and a Kelch repeat domain in the C-terminus. CarF-box1 was localized in the nucleus. CarF-box1 exhibited organ-specific expression and showed different expression patterns during seed development and germination processes, especially strongly expressed in the blooming flowers. In the leaves, CarF-box1 could be significantly induced by drought stress and slightly induced by IAA treatment, while in the roots, CarF-box1 could be strongly induced by drought, salinity and methyl jasmonate stresses. Our results suggest that CarF-box1 encodes an F-box protein and may be involved in various plant developmental processes and abiotic stress responses.

The effect of box shape on the dynamic properties of proteins simulated under periodic boundary conditions

NARCIS (Netherlands)

Wassenaar, T.A.; Mark, A.E.

The effect of the box shape on the dynamic behavior of proteins simulated under periodic boundary conditions is evaluated. In particular, the influence of simulation boxes defined by the near-densest lattice packing (NDLP) in conjunction with rotational constraints is compared to that of standard

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

Energy Technology Data Exchange (ETDEWEB)

Lee, Hanna; Park, Minhee; Shin, Nara; Kim, Gamin [Department of Pathology, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul (Korea, Republic of); Kim, Yun Gi [Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744 (Korea, Republic of); Shin, Jeon-Soo [Department of Microbiology, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul (Korea, Republic of); Kim, Hoguen, E-mail: hkyonsei@yuhs.ac [Department of Pathology, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul (Korea, Republic of)

2012-07-27

Highlights: Black-Right-Pointing-Pointer Specific enzyme for HMGB1 phosphorylation and its secretion is proposed. Black-Right-Pointing-Pointer Inhibition of PKC-{zeta} leads to significant reduction of the secreted HMGB1. Black-Right-Pointing-Pointer Phosphorylation of specific site of HMGB1 redirects its secretion in cancer cells. Black-Right-Pointing-Pointer Activation of PKC-{zeta} 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-{zeta}, {lambda}, and {iota}) and cytoplasmic HMGB1 were observed in HCT116 cells. We further identified the most critical PKC isotype that regulates HMGB1 secretion is PKC-{zeta} 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-{zeta} in colon cancer tissues. Our findings suggest that PKC-{zeta} 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.

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

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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.

Olympic boxing is associated with elevated levels of the neuronal protein tau in plasma.

Science.gov (United States)

Neselius, Sanna; Zetterberg, Henrik; Blennow, Kaj; Randall, Jeffrey; Wilson, David; Marcusson, Jan; Brisby, Helena

2013-01-01

The aim of this study was to investigate if olympic (amateur) boxing is associated with elevation of brain injury biomarkers in peripheral blood compared to controls. Thirty olympic boxers competing in at least 47 bouts were compared to 25 controls. Blood was collected from the controls at one occasion and from the boxers within 1-6 days after a bout and after a rest period of at least 14 days. Tau concentration in plasma was determined using a novel single molecule ELISA assay and S-100B, glial fibrillary acidic protein, brain-derived neurotrophic factor and amyloid β 1-42 were determined using standard immunoassays. None of the boxers had been knocked-out during the bout. Plasma-tau was significantly increased in the boxers after a bout compared to controls (mean ± SD, 2.46 ± 5.10 vs. 0.79 ± 0.961 ng L(-1), p = 0.038). The other brain injury markers did not differ between the groups. Plasma-tau decreased significantly in the boxers after a resting period compared to after a bout (p = 0.030). Olympic boxing is associated with elevation of tau in plasma. The repetitive minimal head injury in boxing may lead to axonal injuries that can be diagnosed with a blood test.

Protein arginine methyltransferase 1 regulates herpes simplex virus replication through ICP27 RGG-box methylation

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Yu, Jungeun; Shin, Bongjin; Park, Eui-Soon; Yang, Sujeong; Choi, Seunga [Department of Microbiology, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of); BK21 Bio Brain Center, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of); Kang, Misun [Department of Microbiology, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of); Rho, Jaerang, E-mail: jrrho@cnu.ac.kr [Department of Microbiology, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of); BK21 Bio Brain Center, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of); GRAST, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of)

2010-01-01

Protein arginine methylation is involved in viral infection and replication through the modulation of diverse cellular processes including RNA metabolism, cytokine signaling, and subcellular localization. It has been suggested previously that the protein arginine methylation of the RGG-box of ICP27 is required for herpes simplex virus type-1 (HSV-1) viral replication and gene expression in vivo. However, a cellular mediator for this process has not yet been identified. In our current study, we show that the protein arginine methyltransferase 1 (PRMT1) is a cellular mediator of the arginine methylation of ICP27 RGG-box. We generated arginine substitution mutants in this domain and examined which arginine residues are required for methylation by PRMT1. R138, R148 and R150 were found to be the major sites of this methylation but additional arginine residues serving as minor methylation sites are still required to sustain the fully methylated form of ICP27 RGG. We also demonstrate that the nuclear foci-like structure formation, SRPK interactions, and RNA-binding activity of ICP27 are modulated by the arginine methylation of the ICP27 RGG-box. Furthermore, HSV-1 replication is inhibited by hypomethylation of this domain resulting from the use of general PRMT inhibitors or arginine mutations. Our data thus suggest that the PRMT1 plays a key role as a cellular regulator of HSV-1 replication through ICP27 RGG-box methylation.

In silico studies on structure-function of DNA GCC- box binding domain of brassica napus DREB1 protein

International Nuclear Information System (INIS)

Qamarunnisa, S.; Hussain, M.

2012-01-01

DREB1 is a transcriptional factor, which selectively binds with the promoters of the genes involved in stress response in the plants. Homology of DREB protein and its binding element have been detected in the genome of many plants. However, only a few reports exist that discusses the binding properties of this protein with the gene (s) promoter. In the present study, we have undertaken studies exploring the structure-function relationship of Brassica napus DREB1. Multiple sequence alignment, protein homology modeling and intermolecular docking of GCC-box binding domain (GBD) of the said protein was carried out using atomic coordinates of GBD from Arabdiopsis thaliana and GCC-box containing DNA respectively. Similarities and/or identities in multiple, sequence alignment, particularly at the functionally important amino acids, strongly suggested the binding specificity of B. napus DREB1 to GCC-box. Similarly, despite 56% sequence homology, tertiary structures of both template and modeled protein were found to be extremely similar as indicated by root mean square deviation of 0.34 A. More similarities were established between GBD of both A. thaliana and B. napus DREB1 by conducting protein docking with the DNA containing GCC-box. It appears that both proteins interact through their beta-sheet with the major DNA groove including both nitrogen bases and phosphate and sugar moieties. Additionally, in most cases the interacting residues were also found to be identical. Briefly, this study attempts to elucidate the molecular basis of DREB1 interaction with its target sequence in the promoter. (author)

Neurochemical aftermath of amateur boxing.

Science.gov (United States)

Zetterberg, Henrik; Hietala, M Albert; Jonsson, Michael; Andreasen, Niels; Styrud, Ewa; Karlsson, Ingvar; Edman, Ake; Popa, Cornel; Rasulzada, Abdullah; Wahlund, Lars-Olof; Mehta, Pankaj D; Rosengren, Lars; Blennow, Kaj; Wallin, Anders

2006-09-01

Little solid information is available on the possible risks for neuronal injury in amateur boxing. To determine whether amateur boxing and severity of hits are associated with elevated levels of biochemical markers for neuronal injury in cerebrospinal fluid. Longitudinal study. Referral center specializing in evaluation of neurodegenerative disorders. Fourteen amateur boxers (11 men and 3 women) and 10 healthy male nonathletic control subjects. The boxers underwent lumbar puncture 7 to 10 days and 3 months after a bout. The control subjects underwent LP once. Neurofilament light protein, total tau, glial fibrillary acidic protein, phosphorylated tau, and beta-amyloid protein 1-40 (Abeta([1-40])) and 1-42 (Abeta([1-42])) concentrations in cerebrospinal fluid were measured. Increased levels after a bout compared with after 3 months of rest from boxing were found for 2 markers for neuronal and axonal injury, neurofilament light protein (mean +/- SD, 845 +/- 1140 ng/L vs 208 +/- 108 ng/L; P = .008) and total tau (mean +/- SD, 449 +/- 176 ng/L vs 306 +/- 78 ng/L; P = .006), and for the astroglial injury marker glial fibrillary acidic protein (mean +/- SD, 541 +/- 199 ng/L vs 405 +/- 138 ng/L; P = .003). The increase was significantly higher among boxers who had received many hits (>15) or high-impact hits to the head compared with boxers who reported few hits. In the boxers, concentrations of neurofilament light protein and glial fibrillary acidic protein, but not total tau, were significantly elevated after a bout compared with the nonathletic control subjects. With the exception of neurofilament light protein, there were no significant differences between boxers after 3 months of rest from boxing and the nonathletic control subjects. Amateur boxing is associated with acute neuronal and astroglial injury. If verified in longitudinal studies with extensive follow-up regarding the clinical outcome, analyses of cerebrospinal fluid may provide a scientific basis for

High mobility group box 1 levels are not associated with subclinical carotid atherosclerosis in patients with granulomatosis with polyangiitis but are reduced by glucocorticoids and statins

NARCIS (Netherlands)

Silva de Souza, Alexandre; De Leeuw, Karina; Westra, Johanna; Smit, Andries J.; Van Der Graaf, Anne Marijn; Nienhuis, Hans L.A.; Bijzet, Johan; Limburg, Pieter C.; Stegeman, Coen A.; Bijl, Marc; Kallenberg, Cees G.M.

2012-01-01

Background/Purpose: High mobility group box 1 (HMGB1) is a non-histone DNA binding protein that is passively released by dying cells or actively secreted by immunocompetent cells and the receptor for advanced glycation end-products (RAGE) is one of its receptors. Higher levels of HMGB1 have been

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

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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.

The role of high mobility group box 1 (HMGB-1) in the diabetic retinopathy inflammation and apoptosis.

Science.gov (United States)

Yu, Yao; Yang, Lu; Lv, Jinlei; Huang, Xu; Yi, Jinglin; Pei, Chonggang; Shao, Yi

2015-01-01

Diabetic Retinopathy (DR) is one of the most common complications of the late phase diabetes, and also a common cause of blindness. High mobility group box 1 (HMGB-1) is considered to be an inflammatory mediator in the late phase that promotes inflammation and neovascularization in diabetes. Therefore, this paper discussed the role of HMGB-1 in diabetic retinopathy inflammation and neovascularization. 96 adult SD rats were randomly divided into control and diabetes group. The diabetic rat model was established by intraperitoneal injection of streptomycin (0.1 mol/L). Western blot was applied to determine HMGB-1 and its receptor RAGE and TLR2 protein expression in the serum. TUNEL was used to detect retinal apoptosis. Immunofluorescence was performed to test HMGB1 protein expression in retina. HBGM-1 and RAGE expression in diabetic rat retina was significantly higher than the control (P detection showed that diabetic rat retinal cells presented obviously higher apoptosis rate (P diabetic rat retinal cells (P diabetic retinopathy by binding with RAGE receptor to accelerate rat retinal cells apoptosis.

Roles of F-box proteins in human digestive system tumors (Review).

Science.gov (United States)

Gong, Jian; Lv, Liang; Huo, Jirong

2014-12-01

F-box proteins (FBPs), the substrate-recognition subunit of E3 ubiquitin (Ub) ligase, are the important components of Ub proteasome system (UPS). FBPs are involved in multiple cellular processes through ubiquitylation and subsequent degradation of their target proteins. Many studies have described the roles of FBPs in human cancers. Digestive system tumors account for a large proportion of all the tumors, and their mortality is very high. This review summarizes for the first time the roles of FBPs in digestive system tumorige-nesis and tumor progression, aiming at finding new routes for the rational design of targeted anticancer therapies in digestive system tumors.

F-box protein FBXL2 targets cyclin D2 for ubiquitination and degradation to inhibit leukemic cell proliferation

Science.gov (United States)

Chen, Bill B.; Glasser, Jennifer R.; Coon, Tiffany A.; Zou, Chunbin; Miller, Hannah L.; Fenton, Moon; McDyer, John F.; Boyiadzis, Michael

2012-01-01

Hematologic maligancies exhibit a growth advantage by up-regulation of components within the molecular apparatus involved in cell-cycle progression. The SCF (Skip-Cullin1-F-box protein) E3 ligase family provides homeostatic feedback control of cell division by mediating ubiquitination and degradation of cell-cycle proteins. By screening several previously undescribed E3 ligase components, we describe the behavior of a relatively new SCF subunit, termed FBXL2, that ubiquitinates and destabilizes cyclin D2 protein leading to G0 phase arrest and apoptosis in leukemic and B-lymphoblastoid cell lines. FBXL2 expression was strongly suppressed, and yet cyclin D2 protein levels were robustly expressed in acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) patient samples. Depletion of endogenous FBXL2 stabilized cyclin D2 levels, whereas ectopically expressed FBXL2 decreased cyclin D2 lifespan. FBXL2 did not bind a phosphodegron within its substrate, which is typical of other F-box proteins, but uniquely targeted a calmodulin-binding signature within cyclin D2 to facilitate its polyubiquitination. Calmodulin competes with the F-box protein for access to this motif where it bound and protected cyclin D2 from FBXL2. Calmodulin reversed FBXL2-induced G0 phase arrest and attenuated FBXL2-induced apoptosis of lymphoblastoid cells. These results suggest an antiproliferative effect of SCFFBXL2 in lymphoproliferative malignancies. PMID:22323446

Wheat F-Box Protein Gene TaFBA1 Is Involved in Plant Tolerance to Heat Stress

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Qinxue Li

2018-04-01

Full Text Available Adverse environmental conditions, including high temperature, often affect the growth and production of crops worldwide. F-box protein, a core component of the Skp1-Cullin-F-box (SCF E3 ligase complex, plays an important role in abiotic stress responses. A previously cloned gene from wheat, TaFBA1, encodes a homologous F-box protein. A Yeast two-Hybrid (Y2H assay showed that TaFBA1 interacted with other SCF proteins. We found that the expression of TaFBA1 could be induced by heat stress (45°C. Overexpression of TaFBA1 enhanced heat stress tolerance in transgenic tobacco, because growth inhibition was reduced and photosynthesis increased as compared with those in the wild type (WT plants. Furthermore, the accumulation of H2O2, O2-, and carbonyl protein decreased and cell damage was alleviated in transgenic plants under heat stress, which resulted in less oxidative damage. However, the transgenic plants contained more enzymatic antioxidants after heat stress, which might be related to the regulation of some antioxidant gene expressions. The qRT-PCR analysis showed that the overexpression of TaFBA1 upregulated the expression of genes involved in reactive oxygen species (ROS scavenging, proline biosynthesis, and abiotic stress responses. We identified the interaction of TaFBA1 with Triticum aestivum stress responsive protein 1 (TaASRP1 by Y2H assay and bimolecular fluorescence complementation (BiFC assay. The results suggested that TaFBA1 may improve enzymatic antioxidant levels and regulate gene expression by interacting with other proteins, such as TaASRP1, which leads to the enhanced heat stress tolerance seen in the transgenic plants.

A new set of ESTs from chickpea (Cicer arietinum L. embryo reveals two novel F-box genes, CarF-box_PP2 and CarF-box_LysM, with potential roles in seed development.

Directory of Open Access Journals (Sweden)

Shefali Gupta

Full Text Available Considering the economic importance of chickpea (C. arietinum L. seeds, it is important to understand the mechanisms underlying seed development for which a cDNA library was constructed from 6 day old chickpea embryos. A total of 8,186 ESTs were obtained from which 4,048 high quality ESTs were assembled into 1,480 unigenes that majorly encoded genes involved in various metabolic and regulatory pathways. Of these, 95 ESTs were found to be involved in ubiquitination related protein degradation pathways and 12 ESTs coded specifically for putative F-box proteins. Differential transcript accumulation of these putative F-box genes was observed in chickpea tissues as evidenced by quantitative real-time PCR. Further, to explore the role of F-box proteins in chickpea seed development, two F-box genes were selected for molecular characterization. These were named as CarF-box_PP2 and CarF-box_LysM depending on their C-terminal domains, PP2 and LysM, respectively. Their highly conserved structures led us to predict their target substrates. Subcellular localization experiment revealed that CarF-box_PP2 was localized in the cytoplasm and CarF-box_LysM was localized in the nucleus. We demonstrated their physical interactions with SKP1 protein, which validated that they function as F-box proteins in the formation of SCF complexes. Sequence analysis of their promoter regions revealed certain seed specific cis-acting elements that may be regulating their preferential transcript accumulation in the seed. Overall, the study helped in expanding the EST database of chickpea, which was further used to identify two novel F-box genes having a potential role in seed development.

A new set of ESTs from chickpea (Cicer arietinum L.) embryo reveals two novel F-box genes, CarF-box_PP2 and CarF-box_LysM, with potential roles in seed development.

Science.gov (United States)

Gupta, Shefali; Garg, Vanika; Bhatia, Sabhyata

2015-01-01

Considering the economic importance of chickpea (C. arietinum L.) seeds, it is important to understand the mechanisms underlying seed development for which a cDNA library was constructed from 6 day old chickpea embryos. A total of 8,186 ESTs were obtained from which 4,048 high quality ESTs were assembled into 1,480 unigenes that majorly encoded genes involved in various metabolic and regulatory pathways. Of these, 95 ESTs were found to be involved in ubiquitination related protein degradation pathways and 12 ESTs coded specifically for putative F-box proteins. Differential transcript accumulation of these putative F-box genes was observed in chickpea tissues as evidenced by quantitative real-time PCR. Further, to explore the role of F-box proteins in chickpea seed development, two F-box genes were selected for molecular characterization. These were named as CarF-box_PP2 and CarF-box_LysM depending on their C-terminal domains, PP2 and LysM, respectively. Their highly conserved structures led us to predict their target substrates. Subcellular localization experiment revealed that CarF-box_PP2 was localized in the cytoplasm and CarF-box_LysM was localized in the nucleus. We demonstrated their physical interactions with SKP1 protein, which validated that they function as F-box proteins in the formation of SCF complexes. Sequence analysis of their promoter regions revealed certain seed specific cis-acting elements that may be regulating their preferential transcript accumulation in the seed. Overall, the study helped in expanding the EST database of chickpea, which was further used to identify two novel F-box genes having a potential role in seed development.

NSs Virulence Factor of Rift Valley Fever Virus Engages the F-Box Proteins FBXW11 and β-TRCP1 To Degrade the Antiviral Protein Kinase PKR.

Science.gov (United States)

Kainulainen, Markus; Lau, Simone; Samuel, Charles E; Hornung, Veit; Weber, Friedemann

2016-07-01

Rift Valley fever virus (RVFV, family Bunyaviridae, genus Phlebovirus) is a relevant pathogen of both humans and livestock in Africa. The nonstructural protein NSs is a major virulence factor known to suppress the type I interferon (IFN) response by inhibiting host cell transcription and by proteasomal degradation of a major antiviral IFN effector, the translation-inhibiting protein kinase PKR. Here, we identified components of the modular SCF (Skp1, Cul1, F-box protein)-type E3 ubiquitin ligases as mediators of PKR destruction by NSs. Small interfering RNAs (siRNAs) against the conserved SCF subunit Skp1 protected PKR from NSs-mediated degradation. Consequently, RVFV replication was severely reduced in Skp1-depleted cells when PKR was present. SCF complexes have a variable F-box protein subunit that determines substrate specificity for ubiquitination. We performed an siRNA screen for all (about 70) human F-box proteins and found FBXW11 to be involved in PKR degradation. The partial stabilization of PKR by FBXW11 depletion upregulated PKR autophosphorylation and phosphorylation of the PKR substrate eIF2α and caused a shutoff of host cell protein synthesis in RVFV-infected cells. To maximally protect PKR from the action of NSs, knockdown of structurally and functionally related FBXW1 (also known as β-TRCP1), in addition to FBXW11 deletion, was necessary. Consequently, NSs was found to interact with both FBXW11 and β-TRCP1. Thus, NSs eliminates the antiviral kinase PKR by recruitment of SCF-type E3 ubiquitin ligases containing FBXW11 and β-TRCP1 as substrate recognition subunits. This antagonism of PKR by NSs is essential for efficient RVFV replication in mammalian cells. Rift Valley fever virus is a pathogen of humans and animals that has the potential to spread from Africa and the Arabian Peninsula to other regions. A major virulence mechanism is the proteasomal degradation of the antiviral kinase PKR by the viral protein NSs. Here, we demonstrate that NSs

Insights into the quality of DnaA boxes and their cooperativity

DEFF Research Database (Denmark)

Hansen, Flemming G.; Christensen, Bjarke Bak; Nielsen, Christina Bang

2006-01-01

Plasmids carrying the mioC promoter region with its two DnaA boxes are as efficient in titration of DnaA protein as plasmids carrying a replicationinactivated oriC region with its five DnaA boxes. The two DnaA boxes upstream of the mioC promoter were mutated in various ways to study the cooperati......Plasmids carrying the mioC promoter region with its two DnaA boxes are as efficient in titration of DnaA protein as plasmids carrying a replicationinactivated oriC region with its five DnaA boxes. The two DnaA boxes upstream of the mioC promoter were mutated in various ways to study...... the cooperativity between the DnaA boxes, and to study in vivo the in vitrodefined 9mer DnaA box consensus sequence TTA/TTNCACA). The quality and cooperativity of the DnaA oxes were determined in two complementary ways: as titration of DnaA protein leading to derepression of the dnaA promoter, and as repression...... of the mioC promoter caused by the DnaA protein binding to the DnaA boxes. Titration of DnaA protein correlated with repression of the mioC promoter. The level of titration and repression with the normal promoter-proximal box (TTTTCCACA) depends strongly on the presence and the quality of a DnaA box...

Serum levels of high mobility group box 1 protein and its association with quality of life and psychological and functional status in patients with fibromyalgia.

Science.gov (United States)

Oktayoglu, Pelin; Tahtasiz, Mehmet; Bozkurt, Mehtap; Em, Serda; Ucar, Demet; Yazmalar, Levent; Mete, Nuriye; Nas, Kemal; Gezer, Orhan

2013-08-01

High mobility group box 1 protein (HMGB1) is a proinflammatory cytokine. Previous studies have suggested that HMGB1 can play an important role in the pathogenesis of many rheumatic diseases. The purpose of this study was to investigate the serum levels of HMGB1 in patients with fibromyalgia (FM) and its association with quality of life and psychological and functional status in these patients. Twenty-nine patients who met the 1990 American College of Rheumatology (ACR) criteria for the classification of FM and 29 healthy controls (HC) were included in the present study. Serum samples were collected from both the patients and the HC, and HMGB1 levels were measured by enzyme-linked immunosorbent assay (ELISA). The Fibromyalgia Impact Questionnaire (FIQ) was used to assess the disease severity and functional status in patients with FM. Furthermore, the Nottingham Health Profile was used to assess quality of life in all subjects, as well as the Hospital Anxiety and Depression Scale (HADS) to assess depression and anxiety. The serum levels of HMGB1 protein were positively correlated with the FIQ scores in patients with FM (P = 0.002). Mean serum levels of HMGB1 were higher in patients with FM than in HC but this difference was not statistically significant. HMGB1 protein might be a good laboratory-sourced candidate for the assessment of functional status and disease severity in patients with FM. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

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

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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.

Neogambogic acid prevents silica-induced fibrosis via inhibition of high-mobility group box 1 and MCP-1-induced protein 1

Energy Technology Data Exchange (ETDEWEB)

Zhang, Wei [Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096 (China); Department of Respiration, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Zhang, Mei, E-mail: meizhang1717@163.com [Department of Respiration, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Wang, Zhongjiang [Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Cheng, Yusi; Liu, Haijun [Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Zhou, Zewei [Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Han, Bing [Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Chen, Baoan [Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Yao, Honghong, E-mail: yaohh@seu.edu.cn [Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096 (China); Chao, Jie, E-mail: chaojie@seu.edu.cn [Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096 (China); Department of Respiration, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China)

2016-10-15

Background: Silicosis is a systemic disease caused by inhaling silicon dioxide (SiO{sub 2}); early stages are characterized by alveolar inflammation, and later stages are characterized by progressive lung fibrosis. Mounting evidence indicates that high-mobility group box 1 (HMGB1) is involved in pulmonary fibrosis. Whether neogambogic acid (NGA) inhibits macrophage and fibroblast activation induced by SiO{sub 2} by targeting HMGB1 remains unclear. Methods and results: Experiments using cultured mouse macrophages (RAW264.7 cells) demonstrated that SiO{sub 2} treatment induces the expression of HMGB1 in a time- and dose-dependent manner via mitogen-activated protein kinases (MAPKs) and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway; in turn, this expression causes macrophage apoptosis and fibroblast activation. Pretreating macrophages with NGA inhibited the HMGB1 expression induced by SiO{sub 2} and attenuated both macrophage apoptosis and fibroblast activation. Moreover, NGA directly inhibited MCP-1-induced protein 1 (MCPIP1) expression, as well as markers of fibroblast activation and migration induced by SiO{sub 2}. Furthermore, the effects of NGA on macrophages and fibroblasts were confirmed in vivo by exposing mice to SiO{sub 2}. Conclusion: NGA can prevent SiO{sub 2}-induced macrophage activation and apoptosis via HMGB1 inhibition and SiO{sub 2}-induced fibrosis via the MCPIP1 pathway. Targeting HMGB1 and MCPIP1 with NGA could provide insights into the potential development of a therapeutic approach for alleviating the inflammation and fibrosis induced by SiO{sub 2}. - Highlights: • The SiO{sub 2} induced HMGB1 in alveolar macrophage and MCPIP1 in fibroblast. • NGA rescued the SiO{sub 2}-induced apoptosis of alveolar macrophages via HMGB1 signaling. • NGA inhibited the fibroblast activation induced by SiO{sub 2} via MCPIP1 signaling. • NGA might represent a potential therapeutic approach for silicosis.

Cyclin-like F-box protein plays a role in growth and development of the three model species Medicago truncatula, Lotus japonicus, and Arabidopsis thaliana

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Boycheva I

2015-08-01

Full Text Available Irina Boycheva,1 Valya Vassileva,2 Miglena Revalska,1 Grigor Zehirov,2 Anelia Iantcheva1 1Department of Functional Genetics Legumes, 2AgroBioInstitute, Department of Plant Stress Molecular Biology, Institute of Plant Physiology and Genetics, Sofia, Bulgaria Abstract: In eukaryotes, F-box proteins are one of the main components of the SCF complex that belongs to the family of ubiquitin E3 ligases, which catalyze protein ubiquitination and maintain the balance between protein synthesis and degradation. In the present study, we clarified the role and function of the gene encoding cyclin-like F-box protein from Medicago truncatula using transgenic plants of the model species M. truncatula, Lotus japonicas, and Arabidopsis thaliana generated by Agrobacterium-mediated transformation. Morphological and transcriptional analyses combined with flow cytometry and histochemistry demonstrated the participation of this protein in many aspects of plant growth and development, including processes of indirect somatic embryogenesis and symbiotic nodulation. The cyclin-like F-box gene showed expression in all plant organs and tissues comprised of actively dividing cells. The observed variations in root and hypocotyl growth, leaf and silique development, ploidy levels, and leaf parameters in the obtained transgenic lines demonstrated the effects of this gene on organ development. Furthermore, knockdown of cyclin-like F-box led to accumulation of higher levels of the G2/M transition-specific gene cyclin B1:1 (CYCB1:1, suggesting its possible role in cell cycle control. Together, the collected data suggest a similar role of the cyclin-like F-box protein in the three model species, providing evidence for the functional conservation of the studied gene. Keywords: cyclin-like F-box, model legumes, Arabidopsis thaliana, plant growth, plant development, cell cycle

Spliced X-box binding protein 1 couples the unfolded protein response to hexosamine biosynthetic pathway.

Science.gov (United States)

Wang, Zhao V; Deng, Yingfeng; Gao, Ningguo; Pedrozo, Zully; Li, Dan L; Morales, Cyndi R; Criollo, Alfredo; Luo, Xiang; Tan, Wei; Jiang, Nan; Lehrman, Mark A; Rothermel, Beverly A; Lee, Ann-Hwee; Lavandero, Sergio; Mammen, Pradeep P A; Ferdous, Anwarul; Gillette, Thomas G; Scherer, Philipp E; Hill, Joseph A

2014-03-13

The hexosamine biosynthetic pathway (HBP) generates uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) for glycan synthesis and O-linked GlcNAc (O-GlcNAc) protein modifications. Despite the established role of the HBP in metabolism and multiple diseases, regulation of the HBP remains largely undefined. Here, we show that spliced X-box binding protein 1 (Xbp1s), the most conserved signal transducer of the unfolded protein response (UPR), is a direct transcriptional activator of the HBP. We demonstrate that the UPR triggers HBP activation via Xbp1s-dependent transcription of genes coding for key, rate-limiting enzymes. We further establish that this previously unrecognized UPR-HBP axis is triggered in a variety of stress conditions. Finally, we demonstrate a physiologic role for the UPR-HBP axis by showing that acute stimulation of Xbp1s in heart by ischemia/reperfusion confers robust cardioprotection in part through induction of the HBP. Collectively, these studies reveal that Xbp1s couples the UPR to the HBP to protect cells under stress. Copyright © 2014 Elsevier Inc. All rights reserved.

F-box protein interactions with the hallmark pathways in cancer.

Science.gov (United States)

Randle, Suzanne J; Laman, Heike

2016-02-01

F-box proteins (FBP) are the substrate specifying subunit of Skp1-Cul1-FBP (SCF)-type E3 ubiquitin ligases and are responsible for directing the ubiquitination of numerous proteins essential for cellular function. Due to their ability to regulate the expression and activity of oncogenes and tumour suppressor genes, FBPs themselves play important roles in cancer development and progression. In this review, we provide a comprehensive overview of FBPs and their targets in relation to their interaction with the hallmarks of cancer cell biology, including the regulation of proliferation, epigenetics, migration and invasion, metabolism, angiogenesis, cell death and DNA damage responses. Each cancer hallmark is revealed to have multiple FBPs which converge on common signalling hubs or response pathways. We also highlight the complex regulatory interplay between SCF-type ligases and other ubiquitin ligases. We suggest six highly interconnected FBPs affecting multiple cancer hallmarks, which may prove sensible candidates for therapeutic intervention. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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 (Peggs laid there. Second, each of the hen groups was moved to another pen allocated at random, and where...

A bifunctional archaeal protein that is a component of 30S ribosomal subunits and interacts with C/D box small RNAs

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Andrea Ciammaruconi

2008-01-01

Full Text Available We have identified a novel archaeal protein that apparently plays two distinct roles in ribosome metabolism. It is a polypeptide of about 18 kDa (termed Rbp18 that binds free cytosolic C/D box sRNAs in vivo and in vitro and behaves as a structural ribosomal protein, specifically a component of the 30S ribosomal subunit. As Rbp18 is selectively present in Crenarcheota and highly thermophilic Euryarchaeota, we propose that it serves to protect C/D box sRNAs from degradation and perhaps to stabilize thermophilic 30S subunits.

Structure and biochemical function of a prototypical Arabidopsis U-box domain

DEFF Research Database (Denmark)

Andersen, Pernille; Kragelund, Birthe B; Olsen, Addie N

2004-01-01

U-box proteins, as well as other proteins involved in regulated protein degradation, are apparently over-represented in Arabidopsis compared with other model eukaryotes. The Arabidopsis protein AtPUB14 contains a typical U-box domain followed by an Armadillo repeat region, a domain organization t...

SCF Ubiquitin Ligase F-box Protein Fbx15 Controls Nuclear Co-repressor Localization, Stress Response and Virulence of the Human Pathogen Aspergillus fumigatus.

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Bastian Jöhnk

2016-09-01

Full Text Available F-box proteins share the F-box domain to connect substrates of E3 SCF ubiquitin RING ligases through the adaptor Skp1/A to Cul1/A scaffolds. F-box protein Fbx15 is part of the general stress response of the human pathogenic mold Aspergillus fumigatus. Oxidative stress induces a transient peak of fbx15 expression, resulting in 3x elevated Fbx15 protein levels. During non-stress conditions Fbx15 is phosphorylated and F-box mediated interaction with SkpA preferentially happens in smaller subpopulations in the cytoplasm. The F-box of Fbx15 is required for an appropriate oxidative stress response, which results in rapid dephosphorylation of Fbx15 and a shift of the cellular interaction with SkpA to the nucleus. Fbx15 binds SsnF/Ssn6 as part of the RcoA/Tup1-SsnF/Ssn6 co-repressor and is required for its correct nuclear localization. Dephosphorylated Fbx15 prevents SsnF/Ssn6 nuclear localization and results in the derepression of gliotoxin gene expression. fbx15 deletion mutants are unable to infect immunocompromised mice in a model for invasive aspergillosis. Fbx15 has a novel dual molecular function by controlling transcriptional repression and being part of SCF E3 ubiquitin ligases, which is essential for stress response, gliotoxin production and virulence in the opportunistic human pathogen A. fumigatus.

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.

The F-box protein Fbp1 functions in the invasive growth and cell wall integrity mitogen-activated protein kinase (MAPK) pathways in Fusarium oxysporum.

Science.gov (United States)

Miguel-Rojas, Cristina; Hera, Concepcion

2016-01-01

F-box proteins determine substrate specificity of the ubiquitin-proteasome system. Previous work has demonstrated that the F-box protein Fbp1, a component of the SCF(Fbp1) E3 ligase complex, is essential for invasive growth and virulence of the fungal plant pathogen Fusarium oxysporum. Here, we show that, in addition to invasive growth, Fbp1 also contributes to vegetative hyphal fusion and fungal adhesion to tomato roots. All of these functions have been shown previously to require the mitogen-activated protein kinase (MAPK) Fmk1. We found that Fbp1 is required for full phosphorylation of Fmk1, indicating that Fbp1 regulates virulence and invasive growth via the Fmk1 pathway. Moreover, the Δfbp1 mutant is hypersensitive to sodium dodecylsulfate (SDS) and calcofluor white (CFW) and shows reduced phosphorylation levels of the cell wall integrity MAPK Mpk1 after SDS treatment. Collectively, these results suggest that Fbp1 contributes to both the invasive growth and cell wall integrity MAPK pathways of F. oxysporum. © 2015 BSPP AND JOHN WILEY & SONS LTD.

PIP degron proteins, substrates of CRL4Cdt2, and not PIP boxes, interfere with DNA polymerase η and κ focus formation on UV damage

OpenAIRE

Tsanov, Nikolay; Kermi, Chames; Coulombe, Philippe; Van der Laan, Siem; Hodroj, Dana; Maiorano, Domenico

2014-01-01

Proliferating cell nuclear antigen (PCNA) is a well-known scaffold for many DNA replication and repair proteins, but how the switch between partners is regulated is currently unclear. Interaction with PCNA occurs via a domain known as a PCNA-Interacting Protein motif (PIP box). More recently, an additional specialized PIP box has been described, the « PIP degron », that targets PCNA-interacting proteins for proteasomal degradation via the E3 ubiquitin ligase CRL4Cdt2. Here we provide evidence...

Beyond ubiquitination: the atypical functions of Fbxo7 and other F-box proteins.

Science.gov (United States)

Nelson, David E; Randle, Suzanne J; Laman, Heike

2013-10-09

F-box proteins (FBPs) are substrate-recruiting subunits of Skp1-cullin1-FBP (SCF)-type E3 ubiquitin ligases. To date, 69 FBPs have been identified in humans, but ubiquitinated substrates have only been identified for a few, with the majority of FBPs remaining 'orphans'. In recent years, a growing body of work has identified non-canonical, SCF-independent roles for about 12% of the human FBPs. These atypical FBPs affect processes as diverse as transcription, cell cycle regulation, mitochondrial dynamics and intracellular trafficking. Here, we provide a general review of FBPs, with a particular emphasis on these expanded functions. We review Fbxo7 as an exemplar of this special group as it has well-defined roles in both SCF and non-SCF complexes. We review its function as a cell cycle regulator, via its ability to stabilize p27 protein and Cdk6 complexes, and as a proteasome regulator, owing to its high affinity binding to PI31. We also highlight recent advances in our understanding of Fbxo7 function in Parkinson's disease, where it functions in the regulation of mitophagy with PINK1 and Parkin. We postulate that a few extraordinary FBPs act as platforms that seamlessly segue their canonical and non-canonical functions to integrate different cellular pathways and link their regulation.

The role of high mobility group box 1(HMGB1)in the pathogenesis of kidney diseases

Institute of Scientific and Technical Information of China (English)

Qingjie Chen; Xiaofeng Guan; Xiaocong Zuo; Jianglin Wang; Wenjun Yin

2016-01-01

High mobility group box 1(HMGB1) is a nuclear protein that can bind to DNA and act as a co-factor for gene transcription. When released into extracellular fluid, it plays a proinflammatory role by acting as a damage-associated molecular pattern molecule(DAMP)(also known as an alarmin) to initiate innate immune responses by activating multiple cell surface receptors such as the receptor for advanced glycation end-products(RAGE) and toll-like receptors(TLRs), TLR2, TLR4 or TLR9. This proinflammatory role is now considered to be important in the pathogenesis of a wide range of kidney diseases whether they result from hemodynamic changes, renal tubular epithelial cell apoptosis, kidney tissue fibrosis or inflammation. This review summarizes our current understanding of the role of HMGB1 in kidney diseases and how the HMGB1-mediated signaling pathway may constitute a new strategy for the treatment of kidney diseases.

Evidence for multiple major histocompatibility class II X-box binding proteins.

OpenAIRE

Celada, A; Maki, R

1989-01-01

The X box is a loosely conserved DNA sequence that is located upstream of all major histocompatibility class II genes and is one of the cis-acting regulatory elements. Despite the similarity between all X-box sequences, each promoter-proximal X box in the mouse appears to bind a separate nuclear factor.

Sequence-specific high mobility group box factors recognize 10-12-base pair minor groove motifs

DEFF Research Database (Denmark)

van Beest, M; Dooijes, D; van De Wetering, M

2000-01-01

Sequence-specific high mobility group (HMG) box factors bind and bend DNA via interactions in the minor groove. Three-dimensional NMR analyses have provided the structural basis for this interaction. The cognate HMG domain DNA motif is generally believed to span 6-8 bases. However, alignment...

A photo-responsive F-box protein FOF2 regulates floral initiation by promoting FLC expression in Arabidopsis.

Science.gov (United States)

He, Reqing; Li, Xinmei; Zhong, Ming; Yan, Jindong; Ji, Ronghuan; Li, Xu; Wang, Qin; Wu, Dan; Sun, Mengsi; Tang, Dongying; Lin, Jianzhong; Li, Hongyu; Liu, Bin; Liu, Hongtao; Liu, Xuanming; Zhao, Xiaoying; Lin, Chentao

2017-09-01

Floral initiation is regulated by various genetic pathways in response to light, temperature, hormones and developmental status; however, the molecular mechanisms underlying the interactions between different genetic pathways are not fully understood. Here, we show that the photoresponsive gene FOF2 (F-box of flowering 2) negatively regulates flowering. FOF2 encodes a putative F-box protein that interacts specifically with ASK14, and its overexpression results in later flowering under both long-day and short-day photoperiods. Conversely, transgenic plants expressing the F-box domain deletion mutant of FOF2 (FOF2ΔF), or double loss of function mutant of FOF2 and FOL1 (FOF2-LIKE 1) present early flowering phenotypes. The late flowering phenotype of the FOF2 overexpression lines is suppressed by the flc-3 loss-of-function mutation. Furthermore, FOF2 mRNA expression is regulated by autonomous pathway gene FCA, and the repressive effect of FOF2 in flowering can be overcome by vernalization. Interestingly, FOF2 expression is regulated by light. The protein level of FOF2 accumulates in response to light, whereas it is degraded under dark conditions via the 26S proteasome pathway. Our findings suggest a possible mechanistic link between light conditions and the autonomous floral promotion pathway in Arabidopsis. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Poxviral Ankyrin Proteins

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Michael H. Herbert

2015-02-01

Full Text Available Multiple repeats of the ankyrin motif (ANK are ubiquitous throughout the kingdoms of life but are absent from most viruses. The main exception to this is the poxvirus family, and specifically the chordopoxviruses, with ANK repeat proteins present in all but three species from separate genera. The poxviral ANK repeat proteins belong to distinct orthologue groups spread over different species, and align well with the phylogeny of their genera. This distribution throughout the chordopoxviruses indicates these proteins were present in an ancestral vertebrate poxvirus, and have since undergone numerous duplication events. Most poxviral ANK repeat proteins contain an unusual topology of multiple ANK motifs starting at the N-terminus with a C-terminal poxviral homologue of the cellular F-box enabling interaction with the cellular SCF ubiquitin ligase complex. The subtle variations between ANK repeat proteins of individual poxviruses suggest an array of different substrates may be bound by these protein-protein interaction domains and, via the F-box, potentially directed to cellular ubiquitination pathways and possible degradation. Known interaction partners of several of these proteins indicate that the NF-κB coordinated anti-viral response is a key target, whilst some poxviral ANK repeat domains also have an F-box independent affect on viral host-range.

The DEAD-box protein MEL-46 is required in the germ line of the nematode Caenorhabditis elegans.

Science.gov (United States)

Minasaki, Ryuji; Puoti, Alessandro; Streit, Adrian

2009-06-17

In the hermaphrodite of the nematode Caenorhabditis elegans, the first germ cells differentiate as sperm. Later the germ line switches to the production of oocytes. This process requires the activity of a genetic regulatory network that includes among others the fem, fog and mog genes. The function of some of these genes is germline specific while others also act in somatic tissues. DEAD box proteins have been shown to be involved in the control of gene expression at different steps such as transcription and pre-mRNA processing. We show that the Caenorhabditis elegans gene mel-46 (maternal effect lethal) encodes a DEAD box protein that is related to the mammalian DDX20/Gemin3/DP103 genes. mel-46 is expressed throughout development and mutations in mel-46 display defects at multiple developmental stages. Here we focus on the role of mel-46 in the hermaphrodite germ line. mel-46(yt5) mutant hermaphrodites are partially penetrant sterile and fully penetrant maternal effect lethal. The germ line of mutants shows variable defects in oogenesis. Further, mel-46(yt5) suppresses the complete feminization caused by mutations in fog-2 and fem-3, two genes that are at the top and the center, respectively, of the genetic germline sex determining cascade, but not fog-1 that is at the bottom of this cascade. The C. elegans gene mel-46 encodes a DEAD box protein that is required maternally for early embryogenesis and zygotically for postembryonic development. In the germ line, it is required for proper oogenesis. Although it interacts genetically with genes of the germline sex determination machinery its primary function appears to be in oocyte differentiation rather than sex determination.

Extracellular high-mobility group box 1 mediates pressure overload-induced cardiac hypertrophy and heart failure.

Science.gov (United States)

Zhang, Lei; Liu, Ming; Jiang, Hong; Yu, Ying; Yu, Peng; Tong, Rui; Wu, Jian; Zhang, Shuning; Yao, Kang; Zou, Yunzeng; Ge, Junbo

2016-03-01

Inflammation plays a key role in pressure overload-induced cardiac hypertrophy and heart failure, but the mechanisms have not been fully elucidated. High-mobility group box 1 (HMGB1), which is increased in myocardium under pressure overload, may be involved in pressure overload-induced cardiac injury. The objectives of this study are to determine the role of HMGB1 in cardiac hypertrophy and cardiac dysfunction under pressure overload. Pressure overload was imposed on the heart of male wild-type mice by transverse aortic constriction (TAC), while recombinant HMGB1, HMGB1 box A (a competitive antagonist of HMGB1) or PBS was injected into the LV wall. Moreover, cardiac myocytes were cultured and given sustained mechanical stress. Transthoracic echocardiography was performed after the operation and sections for histological analyses were generated from paraffin-embedded hearts. Relevant proteins and genes were detected. Cardiac HMGB1 expression was increased after TAC, which was accompanied by its translocation from nucleus to both cytoplasm and intercellular space. Exogenous HMGB1 aggravated TAC-induced cardiac hypertrophy and cardiac dysfunction, as demonstrated by echocardiographic analyses, histological analyses and foetal cardiac genes detection. Nevertheless, the aforementioned pathological change induced by TAC could partially be reversed by HMGB1 inhibition. Consistent with the in vivo observations, mechanical stress evoked the release and synthesis of HMGB1 in cultured cardiac myocytes. This study indicates that the activated and up-regulated HMGB1 in myocardium, which might partially be derived from cardiac myocytes under pressure overload, may be of crucial importance in pressure overload-induced cardiac hypertrophy and cardiac dysfunction. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Microclimate boxes for panel paintings

DEFF Research Database (Denmark)

Wadum, Jørgen

1998-01-01

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...... buffer material to stabilize the internal RH, a more recent box containing no added buffer material, and, in recent times, boxes with an altered gas content. Another concern is the appearance (aesthetics) of the box....

75 FR 71642 - Group E Post Office Box Service

Science.gov (United States)

2010-11-24

...: PART 111--[AMENDED] 1. The authority citation for 39 CFR part 111 continues to read as follows... box units, apartment style receptacles, mailrooms, or clusters of roadside receptacles. 3. Locations...

The involvement of wheat F-box protein gene TaFBA1 in the oxidative stress tolerance of plants.

Directory of Open Access Journals (Sweden)

Shu-Mei Zhou

Full Text Available As one of the largest gene families, F-box domain proteins have been found to play important roles in abiotic stress responses via the ubiquitin pathway. TaFBA1 encodes a homologous F-box protein contained in E3 ubiquitin ligases. In our previous study, we found that the overexpression of TaFBA1 enhanced drought tolerance in transgenic plants. To investigate the mechanisms involved, in this study, we investigated the tolerance of the transgenic plants to oxidative stress. Methyl viologen was used to induce oxidative stress conditions. Real-time PCR and western blot analysis revealed that TaFBA1 expression was up-regulated by oxidative stress treatments. Under oxidative stress conditions, the transgenic tobacco plants showed a higher germination rate, higher root length and less growth inhibition than wild type (WT. The enhanced oxidative stress tolerance of the transgenic plants was also indicated by lower reactive oxygen species (ROS accumulation, malondialdehyde (MDA content and cell membrane damage under oxidative stress compared with WT. Higher activities of antioxidant enzymes, including superoxide dismutase (SOD, catalase (CAT, ascorbate peroxidase (APX and peroxidase (POD, were observed in the transgenic plants than those in WT, which may be related to the upregulated expression of some antioxidant genes via the overexpression of TaFBA1. In others, some stress responsive elements were found in the promoter region of TaFBA1, and TaFBA1 was located in the nucleus, cytoplasm and plasma membrane. These results suggest that TaFBA1 plays an important role in the oxidative stress tolerance of plants. This is important for understanding the functions of F-box proteins in plants' tolerance to multiple stress conditions.

High mobility group box1 (HMGB1) in relation to cutaneous inflammation in systemic lupus erythematosus (SLE)

NARCIS (Netherlands)

Abdulahad, D.A.; Westra, J.; Reefman, E.; Zuidersma, E.; Bijzet, J.; Limburg, P.C.; Kallenberg, C.G.M.; Bijl, M.

2013-01-01

Photosensitivity is characteristic of systemic lupus erythematosus (SLE). Upon ultraviolet B (UVB) exposure, patients develop inflammatory skin lesions in the vicinity of sunburn cells (SBCs). High mobility group box 1 (HMGB1) is released from apoptotic and activated cells and exerts inflammatory

Structure of the SPRY domain of the human RNA helicase DDX1, a putative interaction platform within a DEAD-box protein

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Kellner, Julian N.; Meinhart, Anton, E-mail: anton.meinhart@mpimf-heidelberg.mpg.de [Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg (Germany)

2015-08-25

The structure of the SPRY domain of the human RNA helicase DDX1 was determined at 2.0 Å resolution. The SPRY domain provides a putative protein–protein interaction platform within DDX1 that differs from other SPRY domains in its structure and conserved regions. The human RNA helicase DDX1 in the DEAD-box family plays an important role in RNA processing and has been associated with HIV-1 replication and tumour progression. Whereas previously described DEAD-box proteins have a structurally conserved core, DDX1 shows a unique structural feature: a large SPRY-domain insertion in its RecA-like consensus fold. SPRY domains are known to function as protein–protein interaction platforms. Here, the crystal structure of the SPRY domain of human DDX1 (hDSPRY) is reported at 2.0 Å resolution. The structure reveals two layers of concave, antiparallel β-sheets that stack onto each other and a third β-sheet beneath the β-sandwich. A comparison with SPRY-domain structures from other eukaryotic proteins showed that the general β-sandwich fold is conserved; however, differences were detected in the loop regions, which were identified in other SPRY domains to be essential for interaction with cognate partners. In contrast, in hDSPRY these loop regions are not strictly conserved across species. Interestingly, though, a conserved patch of positive surface charge is found that may replace the connecting loops as a protein–protein interaction surface. The data presented here comprise the first structural information on DDX1 and provide insights into the unique domain architecture of this DEAD-box protein. By providing the structure of a putative interaction domain of DDX1, this work will serve as a basis for further studies of the interaction network within the hetero-oligomeric complexes of DDX1 and of its recruitment to the HIV-1 Rev protein as a viral replication factor.

Overexpression of high mobility group box 1 contributes to progressive clinicopathological features and poor prognosis of human bladder urothelial carcinoma

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Huang CK

2018-04-01

Full Text Available Changkun Huang,* Zhichao Huang,* Xiaokun Zhao, Yinhuai Wang, Hongqing Zhao, Zhaohui Zhong, Lang Wang Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China *These authors contributed equally to this work Background: High mobility group box 1 (HMGB1, a versatile protein with intranuclear and extracellular functions, plays an important role in a variety of human cancers. However, the clinical/prognostic significance of HMGB1 expression in human bladder urothelial carcinoma (BUC remains unclear. The aim of this study was to investigate the HMGB1 expression in human BUC with regard to its clinical and prognostic significance.Patients and methods: HMGB1 mRNA and protein expressions in tumor and paired normal bladder tissues were detected in 20 BUC cases by quantitative real-time polymerase chain reaction (qRT-PCR and Western blot. HMGB1 protein expression in 165 primary BUC tissues was evaluated by immunohistochemistry (IHC, and its correlations with clinicopathological characteristics and prognosis were also analyzed. Student’s t-test, χ2 test, Kaplan–Meier plots, and Cox proportional hazard regression model were performed to analyze the data. Results: By using qRT-PCR and Western blot, the upregulated expression of HMGB1 mRNA and protein was detected in BUC, compared with paired normal tissue (P<0.05. By using IHC, high HMGB1 expression was examined in 84 of 165 (51.0% BUC cases. High HMGB1 expression was significantly correlated with poorer differentiation and higher T and N classification (all P<0.05. Univariate analysis showed that high HMGB1 expression was significantly associated with a shortened patients’ overall survival (OS and disease-free survival (DFS; both P<0.001. In different subgroups of BUC patients, HMGB1 expression was a prognostic factor in patients with different histological grades or T classification (all P<0.05, pN− (both P<0.001 for OS and DFS, and

Activation of Plant Innate Immunity by Extracellular High Mobility Group Box 3 and Its Inhibition by Salicylic Acid.

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Hyong Woo Choi

2016-03-01

Full Text Available Damage-associated molecular pattern molecules (DAMPs signal the presence of tissue damage to induce immune responses in plants and animals. Here, we report that High Mobility Group Box 3 (HMGB3 is a novel plant DAMP. Extracellular HMGB3, through receptor-like kinases BAK1 and BKK1, induced hallmark innate immune responses, including i MAPK activation, ii defense-related gene expression, iii callose deposition, and iv enhanced resistance to Botrytis cinerea. Infection by necrotrophic B. cinerea released HMGB3 into the extracellular space (apoplast. Silencing HMGBs enhanced susceptibility to B. cinerea, while HMGB3 injection into apoplast restored resistance. Like its human counterpart, HMGB3 binds salicylic acid (SA, which results in inhibition of its DAMP activity. An SA-binding site mutant of HMGB3 retained its DAMP activity, which was no longer inhibited by SA, consistent with its reduced SA-binding activity. These results provide cross-kingdom evidence that HMGB proteins function as DAMPs and that SA is their conserved inhibitor.

Cell differentiation by interaction of two HMG-box proteins: Mat1-Mc activates M cell-specific genes in S.pombe by recruiting the ubiquitous transcription factor Ste11 to weak binding sites

DEFF Research Database (Denmark)

Kjaerulff, S; Dooijes, D; Clevers, H

1997-01-01

The Schizosaccharomyces pombe mfm1 gene is expressed in an M cell-specific fashion. This regulation requires two HMG-box proteins: the ubiquitous Ste11 transcription factor and the M cell-controlling protein Mat1-Mc. Here we report that the mfm1 promoter contains a single, weak Stell-binding site...... where we could not detect Mat1-Mc in the resulting protein-DNA complex. When we changed a single base in the mfm1 TR-box, such that it resembled those boxes found in ubiquitously expressed genes, Ste11 binding was enhanced, and in vivo the mfm1 gene also became expressed in P cells where Mat1-Mc...

Comparative structural analysis of human DEAD-box RNA helicases.

Science.gov (United States)

Schütz, Patrick; Karlberg, Tobias; van den Berg, Susanne; Collins, Ruairi; Lehtiö, Lari; Högbom, Martin; Holmberg-Schiavone, Lovisa; Tempel, Wolfram; Park, Hee-Won; Hammarström, Martin; Moche, Martin; Thorsell, Ann-Gerd; Schüler, Herwig

2010-09-30

DEAD-box RNA helicases play various, often critical, roles in all processes where RNAs are involved. Members of this family of proteins are linked to human disease, including cancer and viral infections. DEAD-box proteins contain two conserved domains that both contribute to RNA and ATP binding. Despite recent advances the molecular details of how these enzymes convert chemical energy into RNA remodeling is unknown. We present crystal structures of the isolated DEAD-domains of human DDX2A/eIF4A1, DDX2B/eIF4A2, DDX5, DDX10/DBP4, DDX18/myc-regulated DEAD-box protein, DDX20, DDX47, DDX52/ROK1, and DDX53/CAGE, and of the helicase domains of DDX25 and DDX41. Together with prior knowledge this enables a family-wide comparative structural analysis. We propose a general mechanism for opening of the RNA binding site. This analysis also provides insights into the diversity of DExD/H- proteins, with implications for understanding the functions of individual family members.

Comparative structural analysis of human DEAD-box RNA helicases.

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Patrick Schütz

2010-09-01

Full Text Available DEAD-box RNA helicases play various, often critical, roles in all processes where RNAs are involved. Members of this family of proteins are linked to human disease, including cancer and viral infections. DEAD-box proteins contain two conserved domains that both contribute to RNA and ATP binding. Despite recent advances the molecular details of how these enzymes convert chemical energy into RNA remodeling is unknown. We present crystal structures of the isolated DEAD-domains of human DDX2A/eIF4A1, DDX2B/eIF4A2, DDX5, DDX10/DBP4, DDX18/myc-regulated DEAD-box protein, DDX20, DDX47, DDX52/ROK1, and DDX53/CAGE, and of the helicase domains of DDX25 and DDX41. Together with prior knowledge this enables a family-wide comparative structural analysis. We propose a general mechanism for opening of the RNA binding site. This analysis also provides insights into the diversity of DExD/H- proteins, with implications for understanding the functions of individual family members.

PIP degron proteins, substrates of CRL4Cdt2, and not PIP boxes, interfere with DNA polymerase η and κ focus formation on UV damage.

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Tsanov, Nikolay; Kermi, Chames; Coulombe, Philippe; Van der Laan, Siem; Hodroj, Dana; Maiorano, Domenico

2014-04-01

Proliferating cell nuclear antigen (PCNA) is a well-known scaffold for many DNA replication and repair proteins, but how the switch between partners is regulated is currently unclear. Interaction with PCNA occurs via a domain known as a PCNA-Interacting Protein motif (PIP box). More recently, an additional specialized PIP box has been described, the « PIP degron », that targets PCNA-interacting proteins for proteasomal degradation via the E3 ubiquitin ligase CRL4(Cdt2). Here we provide evidence that CRL4(Cdt2)-dependent degradation of PIP degron proteins plays a role in the switch of PCNA partners during the DNA damage response by facilitating accumulation of translesion synthesis DNA polymerases into nuclear foci. We show that expression of a nondegradable PIP degron (Cdt1) impairs both Pol η and Pol κ focus formation on ultraviolet irradiation and reduces cell viability, while canonical PIP box-containing proteins have no effect. Furthermore, we identify PIP degron-containing peptides from several substrates of CRL4(Cdt2) as efficient inhibitors of Pol η foci formation. By site-directed mutagenesis we show that inhibition depends on a conserved threonine residue that confers high affinity for PCNA-binding. Altogether these findings reveal an important regulative role for the CRL4(Cdt2) pathway in the switch of PCNA partners on DNA damage.

A STE12 homologue of the homothallic ascomycete Sordaria macrospora interacts with the MADS box protein MCM1 and is required for ascosporogenesis.

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Nolting, Nicole; Pöggeler, Stefanie

2006-11-01

The MADS box protein MCM1 controls diverse developmental processes and is essential for fruiting body formation in the homothallic ascomycete Sordaria macrospora. MADS box proteins derive their regulatory specificity from a wide range of different protein interactions. We have recently shown that the S. macrospora MCM1 is able to interact with the alpha-domain mating-type protein SMTA-1. To further evaluate the functional roles of MCM1, we used the yeast two-hybrid approach to identify MCM1-interacting proteins. From this screen, we isolated a protein with a putative N-terminal homeodomain and C-terminal C2/H2-Zn2+ finger domains. The protein is a member of the highly conserved fungal STE12 transcription factor family of proteins and was therefore termed STE12. Furthermore, we demonstrate by means of two-hybrid and far western analysis that in addition to MCM1, the S. macrospora STE12 protein is able to interact with the mating-type protein SMTA-1. Unlike the situation in the closely related heterothallic ascomycete Neurospora crassa, deletion (Delta) of the ste12 gene in S. macrospora neither affects vegetative growth nor fruiting body formation. However, ascus and ascospore development are highly impaired by the Deltaste12 mutation. Our data provide another example of the functional divergence within the fungal STE12 transcription factor family.

First results from the BOXING (Birmingham-OCIW XMM and IMACS Nearby Groups) project.

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Miles, T. A.; Raychaudhury, S.; Mulchaey, J. S.

2004-12-01

We present the first results from the BOXING (Birmingham-OCIW XMM and IMACS Nearby Groups) project, a collaboration between the Observatories of the Carnegie Institute of Washington (OCIW) and the University of Birmingham U.K. to study a sample of 25 galaxy groups (z ˜ 0.06) by means of optical photometry and spectroscopy (du Pont 2.5m; IMACS/Magellan) combined with x-ray observations (XMM). The combination of x-ray with optical data allows us to study the nature of the relationship between the properties of the groups and the galaxies that they contain. In this preliminary study, we present optical luminosity functions, which shows bimodal behavior in the poorer systems, interpreted as result of rapid merging. We also examine the dependence of galaxy morphology on local environment. Once spectroscopic observations are completed, we will be able to study velocity dispersions, star formation and nuclear activity in individual galaxies.

Extensive Mutagenesis of the Conserved Box E Motif in Duck Hepatitis B Virus P Protein Reveals Multiple Functions in Replication and a Common Structure with the Primer Grip in HIV-1 Reverse Transcriptase

OpenAIRE

Wang, Yong-Xiang; Luo, Cheng; Zhao, Dan; Beck, Jürgen; Nassal, Michael

2012-01-01

Hepadnaviruses, including the pathogenic hepatitis B virus (HBV), replicate their small DNA genomes through protein-primed reverse transcription, mediated by the terminal protein (TP) domain in their P proteins and an RNA stem-loop, ϵ, on the pregenomic RNA (pgRNA). No direct structural data are available for P proteins, but their reverse transcriptase (RT) domains contain motifs that are conserved in all RTs (box A to box G), implying a similar architecture; however, experimental support for...

Genome-wide analysis of the SBP-box gene family in Chinese cabbage (Brassica rapa subsp. pekinensis).

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Tan, Hua-Wei; Song, Xiao-Ming; Duan, Wei-Ke; Wang, Yan; Hou, Xi-Lin

2015-11-01

The SQUAMOSA PROMOTER BINDING PROTEIN (SBP)-box gene family contains highly conserved plant-specific transcription factors that play an important role in plant development, especially in flowering. Chinese cabbage (Brassica rapa subsp. pekinensis) is a leafy vegetable grown worldwide and is used as a model crop for research in genome duplication. The present study aimed to characterize the SBP-box transcription factor genes in Chinese cabbage. Twenty-nine SBP-box genes were identified in the Chinese cabbage genome and classified into six groups. We identified 23 orthologous and 5 co-orthologous SBP-box gene pairs between Chinese cabbage and Arabidopsis. An interaction network among these genes was constructed. Sixteen SBP-box genes were expressed more abundantly in flowers than in other tissues, suggesting their involvement in flowering. We show that the MiR156/157 family members may regulate the coding regions or 3'-UTR regions of Chinese cabbage SBP-box genes. As SBP-box genes were found to potentially participate in some plant development pathways, quantitative real-time PCR analysis was performed and showed that Chinese cabbage SBP-box genes were also sensitive to the exogenous hormones methyl jasmonic acid and salicylic acid. The SBP-box genes have undergone gene duplication and loss, evolving a more refined regulation for diverse stimulation in plant tissues. Our comprehensive genome-wide analysis provides insights into the SBP-box gene family of Chinese cabbage.

F-box only protein 2 (Fbxo2) regulates amyloid precursor protein levels and processing.

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Atkin, Graham; Hunt, Jack; Minakawa, Eiko; Sharkey, Lisa; Tipper, Nathan; Tennant, William; Paulson, Henry L

2014-03-07

The amyloid precursor protein (APP) is an integral membrane glycoprotein whose cleavage products, particularly amyloid-β, accumulate in Alzheimer disease (AD). APP is present at synapses and is thought to play a role in both the formation and plasticity of these critical neuronal structures. Despite the central role suggested for APP in AD pathogenesis, the mechanisms regulating APP in neurons and its processing into cleavage products remain incompletely understood. F-box only protein 2 (Fbxo2), a neuron-enriched ubiquitin ligase substrate adaptor that preferentially binds high-mannose glycans on glycoproteins, was previously implicated in APP processing by facilitating the degradation of the APP-cleaving β-secretase, β-site APP-cleaving enzyme. Here, we sought to determine whether Fbxo2 plays a similar role for other glycoproteins in the amyloid processing pathway. We present in vitro and in vivo evidence that APP is itself a substrate for Fbxo2. APP levels were decreased in the presence of Fbxo2 in non-neuronal cells, and increased in both cultured hippocampal neurons and brain tissue from Fbxo2 knock-out mice. The processing of APP into its cleavage products was also increased in hippocampi and cultured hippocampal neurons lacking Fbxo2. In hippocampal slices, this increase in cleavage products was accompanied by a significant reduction in APP at the cell surface. Taken together, these results suggest that Fbxo2 regulates APP levels and processing in the brain and may play a role in modulating AD pathogenesis.

The Role of Y-Box Binding Protein 1 in Kidney Injury: Friend or Foe?

Science.gov (United States)

Ke, Ben; Fan, Chuqiao; Tu, Weiping; Fang, Xiangdong

2018-01-01

Y-box-binding protein 1 (YB-1) is a multifunctional protein involved in various cellular processes via the transcriptional and translational regulation of target gene expression. YB-1 promotes acute or chronic kidney injury through multiple molecular pathways; however, accumulating evidence suggests that significantly increased YB-1 levels are of great importance in renoprotection. In addition, YB-1 may contribute to obesity-related kidney disease by promoting adipogenesis. Thus, the role of YB-1 in kidney injury is complicated, and no comprehensive review is currently available. In this review, we summarise recent progress in our understanding of the function of YB-1 in kidney injury and provide an overview of the dual role of YB-1 in kidney disease. Moreover, we propose that YB-1 is a potential therapeutic target to restrict kidney disease. © 2018 The Author(s). Published by S. Karger AG, Basel.

High-Mobility Group Box 1 Mediates Fibroblast Activity via RAGE-MAPK and NF-κB Signaling in Keloid Scar Formation

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Jihee Kim

2017-12-01

Full Text Available Emerging studies have revealed the involvement of high-mobility group box 1 (HMGB1 in systemic fibrotic diseases, yet its role in the cutaneous scarring process has not yet been investigated. We hypothesized that HMGB1 may promote fibroblast activity to cause abnormal cutaneous scarring. In vitro wound healing assay with normal and keloid fibroblasts demonstrated that HMGB1 administration promoted the migration of both fibroblasts with increased speed and a greater traveling distance. Treatment of the HMGB1 inhibitor glycyrrhizic acid (GA showed an opposing effect on both activities. To analyze the downstream mechanism, the protein levels of extracellular signal-regulated kinase (ERK 1/2, protein kinase B (AKT, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB were measured by western blot analysis. HMGB1 increased the expression levels of ERK1/2, AKT, and NF-κB compared to the control, which was suppressed by GA. HMGB1 promoted both normal and keloid fibroblasts migration to a degree equivalent to that achieved with TGF-β. We concluded that HMGB1 activates fibroblasts via the receptor for advanced glycation end product (RAGE—mitogen-activated protein kinases (MAPK and NF-κB interaction signaling pathways. Further knowledge of the relationship of HMGB1 with skin fibrosis may lead to a promising clinical approach to manage abnormal scarring.

High-Mobility Group Box 1 Mediates Fibroblast Activity via RAGE-MAPK and NF-κB Signaling in Keloid Scar Formation.

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Kim, Jihee; Park, Jong-Chul; Lee, Mi Hee; Yang, Chae Eun; Lee, Ju Hee; Lee, Won Jai

2017-12-28

Emerging studies have revealed the involvement of high-mobility group box 1 (HMGB1) in systemic fibrotic diseases, yet its role in the cutaneous scarring process has not yet been investigated. We hypothesized that HMGB1 may promote fibroblast activity to cause abnormal cutaneous scarring. In vitro wound healing assay with normal and keloid fibroblasts demonstrated that HMGB1 administration promoted the migration of both fibroblasts with increased speed and a greater traveling distance. Treatment of the HMGB1 inhibitor glycyrrhizic acid (GA) showed an opposing effect on both activities. To analyze the downstream mechanism, the protein levels of extracellular signal-regulated kinase (ERK) 1/2, protein kinase B (AKT), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were measured by western blot analysis. HMGB1 increased the expression levels of ERK1/2, AKT, and NF-κB compared to the control, which was suppressed by GA. HMGB1 promoted both normal and keloid fibroblasts migration to a degree equivalent to that achieved with TGF-β. We concluded that HMGB1 activates fibroblasts via the receptor for advanced glycation end product (RAGE)-mitogen-activated protein kinases (MAPK) and NF-κB interaction signaling pathways. Further knowledge of the relationship of HMGB1 with skin fibrosis may lead to a promising clinical approach to manage abnormal scarring.

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

International Nuclear Information System (INIS)

Zhang, Xufang; Jiang, Hongwei; Gong, Qimei; Fan, Chen; Huang, Yihua; Ling, Junqi

2014-01-01

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

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.

A human Polycomb isoform lacking the Pc box does not participate to PRC1 complexes but forms protein assemblies and represses transcription.

Science.gov (United States)

Völkel, Pamela; Le Faou, Perrine; Vandamme, Julien; Pira, Dorcas; Angrand, Pierre-Olivier

2012-05-01

Polycomb repression controls the expression of hundreds of genes involved in development and is mediated by essentially two classes of chromatin-associated protein complexes. The Polycomb repressive complex 2 (PRC2) trimethylates histone H3 at lysine 27, an epigenetic mark that serves as a docking site for the PRC1 protein complex. Drosophila core PRC1 is composed of four subunits: Polycomb (Pc), Posterior sex combs (Psc), Polyhomeotic (Ph) and Sex combs extra (Sce). Each of these proteins has multiple orthologs in vertebrates, thus generating an enormous scope for potential combinatorial diversity. In particular, mammalian genomes encode five Pc family members: CBX2, CBX4, CBX6, CBX7 and CBX8. To complicate matters further, distinct isoforms might arise from single genes. Here, we address the functional role of the two human CBX2 isoforms. Owing to different polyadenylation sites and alternative splicing events, the human CBX2 locus produces two transcripts: a 5-exon transcript that encodes the 532-amino acid CBX2-1 isoform that contains the conserved chromodomain and Pc box and a 4-exon transcript encoding a shorter isoform, CBX2-2, lacking the Pc box but still possessing a chromodomain. Using biochemical approaches and a novel in vivo imaging assay, we show that the short CBX2-2 isoform lacking the Pc box, does not participate in PRC1 protein complexes, but self-associates in vivo and forms complexes of high molecular weight. Furthermore, the CBX2 short isoform is still able to repress transcription, suggesting that Polycomb repression might occur in the absence of PRC1 formation.

Cdc20 mediates D-box-dependent degradation of Sp100

International Nuclear Information System (INIS)

Wang, Ran; Li, Ke-min; Zhou, Cai-hong; Xue, Jing-lun; Ji, Chao-neng; Chen, Jin-zhong

2011-01-01

Highlights: ► Cdc20 is a co-activator of APC/C complex. ► Cdc20 recruits Sp100 and mediates its degradation. ► The D-box of Sp100 is required for Cdc20-mediated degradation. ► Sp100 expresses consistently at both the mRNA and protein levels in cell cycle. -- Abstract: Cdc20 is a co-activator of the anaphase-promoting complex/cyclosome (APC/C complex), which recruits substrates at particular phases of the cell cycle and mediates their degradation. Sp100 is a PML-NB scaffold protein, which localizes to nuclear particles during interphase and disperses from them during mitosis, participates in viral resistance, transcriptional regulation, and apoptosis. However, its metabolism during the cell cycle has not yet been fully characterized. We found a putative D-box in Sp100 using the Eukaryotic Linear Motif (ELM) predictor database. The putative D-box of Sp100 was verified by mutational analysis. Overexpression of Cdc20 resulted in decreased levels of both endogenous Sp100 protein and overexpressed Sp100 mRNA in HEK 293 cells. Only an overexpressed D-box deletion mutant of Sp100 accumulated in HEK293 cells that also overexpressed Cdc20. Cdc20 knockdown by cdc20 specific siRNA resulted in increased Sp100 protein levels in cells. Furthermore, we discovered that the Cdc20 mediated degradation of Sp100 is diminished by the proteasome inhibitor MG132, which suggests that the ubiquitination pathway is involved in this process. However, unlike the other Cdc20 substrates, which display oscillating protein levels, the level of Sp100 protein remains constant throughout the cell cycle. Additionally, both overexpression and knockdown of endogenous Sp100 had no effect on the cell cycle. Our results suggested that sp100 is a novel substrate of Cdc20 and it is degraded by the ubiquitination pathway. The intact D-box of Sp100 was necessary for this process. These findings expand our knowledge of both Sp100 and Cdc20 as well as their role in ubiquitination.

Laparoscopic virtual reality simulator and box trainer in gynecology.

Science.gov (United States)

Akdemir, Ali; Sendağ, Fatih; Oztekin, Mehmet K

2014-05-01

To investigate whether a virtual reality simulator (LapSim) and traditional box trainer are effective tools for the acquisition of basic laparoscopic skills, and whether the LapSim is superior to the box trainer in surgical education. In a study at Ege University School of Medicine, Izmir, Turkey, between September 2008 and March 2013, 40 first- and second-year residents were randomized to train via the LapSim or box trainer for 4 weeks, and 20 senior residents were allocated to a control group. All 3 groups performed laparoscopic bilateral tubal ligation. Video records of each operation were assessed via the general rating scale of the Objective Structured Assessment of Laparoscopic Salpingectomy and by operation time in seconds. Compared with the control group, the LapSim and box trainer groups performed significantly better in total score (Peducation. Training with a virtual reality simulator or box trainer should be considered before actual laparoscopic procedures are carried out. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Ocular complications of boxing

Science.gov (United States)

Bianco, M; Vaiano, A; Colella, F; Coccimiglio, F; Moscetti, M; Palmieri, V; Focosi, F; Zeppilli, P; Vinger, P

2005-01-01

Objectives: To investigate the prevalence of ocular injuries in a large population of boxers over a period of 16 years, in particular, the most severe lesions that may be vision threatening. Methods: Clinical records of the medical archive of the Italian Boxing Federation were analysed. A total of 1032 boxers were examined from February 1982 to October 1998. A complete ophthalmological history was available for 956, who formed the study population (a total of 10 697 examinations). The following data were collected: age when started boxing; duration of competitive boxing career (from the date of the first bout); weight category; a thorough ocular history. The following investigations were carried out: measurement of visual acuity and visual fields, anterior segment inspection, applanation tonometry, gonioscopy, and examination of ocular fundus. Eighty age matched healthy subjects, who had never boxed, formed the control group. Results: Of the 956 boxers examined, 428 were amateur (44.8%) and 528 professional (55.2%). The median age at first examination was 23.1 (4.3) years (range 15–36). The prevalence of conjunctival, corneal, lenticular, vitreal, ocular papilla, and retinal alterations in the study population was 40.9% compared with 3.1% in the control group (p⩽0.0001). The prevalence of serious ocular findings (angle, lens, macula, and peripheral retina alterations) was 5.6% in boxers and 3.1% in controls (NS). Conclusions: Boxing does not result in a higher prevalence of severe ocular lesions than in the general population. However, the prevalence of milder lesions (in particular with regard to the conjunctiva and cornea) is noteworthy, justifying the need for adequate ophthalmological surveillance. PMID:15665199

Full trans-activation mediated by the immediate-early protein of equine herpesvirus 1 requires a consensus TATA box, but not its cognate binding sequence.

Science.gov (United States)

Kim, Seong K; Shakya, Akhalesh K; O'Callaghan, Dennis J

2016-01-04

The immediate-early protein (IEP) of equine herpesvirus 1 (EHV-1) has extensive homology to the IEP of alphaherpesviruses and possesses domains essential for trans-activation, including an acidic trans-activation domain (TAD) and binding domains for DNA, TFIIB, and TBP. Our data showed that the IEP directly interacted with transcription factor TFIIA, which is known to stabilize the binding of TBP and TFIID to the TATA box of core promoters. When the TATA box of the EICP0 promoter was mutated to a nonfunctional TATA box, IEP-mediated trans-activation was reduced from 22-fold to 7-fold. The IEP trans-activated the viral promoters in a TATA motif-dependent manner. Our previous data showed that the IEP is able to repress its own promoter when the IEP-binding sequence (IEBS) is located within 26-bp from the TATA box. When the IEBS was located at 100 bp upstream of the TATA box, IEP-mediated trans-activation was very similar to that of the minimal IE(nt -89 to +73) promoter lacking the IEBS. As the distance from the IEBS to the TATA box decreased, IEP-mediated trans-activation progressively decreased, indicating that the IEBS located within 100 bp from the TATA box sequence functions as a distance-dependent repressive element. These results indicated that IEP-mediated full trans-activation requires a consensus TATA box of core promoters, but not its binding to the cognate sequence (IEBS). Copyright © 2015 Elsevier B.V. All rights reserved.

Full trans–activation mediated by the immediate–early protein of equine herpesvirus 1 requires a consensus TATA box, but not its cognate binding sequence

Science.gov (United States)

Kim, Seong K.; Shakya, Akhalesh K.; O'Callaghan, Dennis J.

2015-01-01

The immediate-early protein (IEP) of equine herpesvirus 1 (EHV-1) has extensive homology to the IEP of alphaherpesviruses and possesses domains essential for trans-activation, including an acidic trans-activation domain (TAD) and binding domains for DNA, TFIIB, and TBP. Our data showed that the IEP directly interacted with transcription factor TFIIA, which is known to stabilize the binding of TBP and TFIID to the TATA box of core promoters. When the TATA box of the EICP0 promoter was mutated to a nonfunctional TATA box, IEP-mediated trans-activation was reduced from 22-fold to 7-fold. The IEP trans-activated the viral promoters in a TATA motif-dependent manner. Our previous data showed that the IEP is able to repress its own promoter when the IEP-binding sequence (IEBS) is located within 26-bp from the TATA box. When the IEBS was located at 100 bp upstream of the TATA box, IEP-mediated trans-activation was very similar to that of the minimal IE(nt −89 to +73) promoter lacking the IEBS. As the distance from the IEBS to the TATA box decreased, IEP-mediated trans-activation progressively decreased, indicating that the IEBS located within 100 bp from the TATA box sequence functions as a distance-dependent repressive element. These results indicated that IEP-mediated full trans-activation requires a consensus TATA box of core promoters, but not its binding to the cognate sequence (IEBS). PMID:26541315

Assaying Auxin Receptor Activity Using SPR Assays with F-Box Proteins and Aux/IAA Degrons.

Science.gov (United States)

Quareshy, Mussa; Uzunova, Veselina; Prusinska, Justyna M; Napier, Richard M

2017-01-01

The identification of TIR1 as an auxin receptor combined with advanced biophysical instrumentation has led to the development of real-time activity assays for auxins. Traditionally, molecules have been assessed for auxinic activity using bioassays, and agrochemical compound discovery continues to be based on "spray and pray" technologies. Here, we describe the methodology behind an SPR-based assay that uses TIR1 and related F-box proteins with surface plasmon resonance spectrometry for rapid compound screening. In addition, methods for collecting kinetic binding data and data processing are given so that they may support programs for rational design of novel auxin ligands.

A human Polycomb isoform lacking the Pc box does not participate to PRC1 complexes but forms protein assemblies and represses transcription

DEFF Research Database (Denmark)

Völkel, Pamela; Le Faou, Perrine; Vandamme, Julien

2012-01-01

site for the PRC1 protein complex. Drosophila core PRC1 is composed of four subunits: Polycomb (Pc), Posterior sex combs (Psc), Polyhomeotic (Ph) and Sex combs extra (Sce). Each of these proteins has multiple orthologs in vertebrates, thus generating an enormous scope for potential combinatorial...... diversity. In particular, mammalian genomes encode five Pc family members: CBX2, CBX4, CBX6, CBX7 and CBX8. To complicate matters further, distinct isoforms might arise from single genes. Here, we address the functional role of the two human CBX2 isoforms. Owing to different polyadenylation sites...... and alternative splicing events, the human CBX2 locus produces two transcripts: a 5-exon transcript that encodes the 532-amino acid CBX2-1 isoform that contains the conserved chromodomain and Pc box and a 4-exon transcript encoding a shorter isoform, CBX2-2, lacking the Pc box but still possessing a chromodomain...

Therapeutic potential of an anti-high mobility group box-1 monoclonal antibody in epilepsy.

Science.gov (United States)

Zhao, Junli; Wang, Yi; Xu, Cenglin; Liu, Keyue; Wang, Ying; Chen, Liying; Wu, Xiaohua; Gao, Feng; Guo, Yi; Zhu, Junming; Wang, Shuang; Nishibori, Masahiro; Chen, Zhong

2017-08-01

Brain inflammation is a major factor in epilepsy, and the high mobility group box-1 (HMGB1) protein is known to contribute significantly to the generation of seizures. Here, we investigated the therapeutic potential of an anti-HMGB1 monoclonal antibody (mAb) in epilepsy. anti-HMGB1 mAb attenuated both acute seizure models (maximal electroshock seizure, pentylenetetrazole-induced and kindling-induced), and chronic epilepsy model (kainic acid-induced) in a dose-dependent manner. Meanwhile, the anti-HMGB1 mAb also attenuated seizure activities of human brain slices obtained from surgical resection from drug-resistant epilepsy patients. The mAb showed an anti-seizure effect with a long-term manner and appeared to be minimal side effects at even very high dose (no disrupted physical EEG rhythm and no impaired basic physical functions, such as body growth rate and thermoregulation). This anti-seizure effect of mAb results from its inhibition of translocated HMGB1 from nuclei following seizures, and the anti-seizure effect was absent in toll-like receptor 4 knockout (TLR4 -/- ) mice. Interestingly, the anti-HMGB1 mAb also showed a disease-modifying anti-epileptogenetic effect on epileptogenesis after status epileptics, which is indicated by reducing seizure frequency and improving the impaired cognitive function. These results indicate that the anti-HMGB1 mAb should be viewed as a very promising approach for the development of novel therapies to treat refractory epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

Genome-wide identification and expression analysis of the B-box gene family in the Apple (Malus domestica Borkh.) genome.

Science.gov (United States)

Liu, Xin; Li, Rong; Dai, Yaqing; Chen, Xuesen; Wang, Xiaoyun

2018-04-01

The B-box proteins (BBXs) are a family of zinc finger proteins containing one/two B-box domain(s). Compared with intensive studies of animal BBXs, investigations of the plant BBX family are limited, though some specific plant BBXs have been demonstrated to act as transcription factors in the regulation of flowering and photomorphogenesis. In this study, using a global search of the apple (Malus domestica Borkh.) genome, a total of 64 members of BBX (MdBBX) were identified. All the MdBBXs were divided into five groups based on the phylogenetic relationship, numbers of B-boxes contained and whether there was with an additional CCT domain. According to the characteristics of organ-specific expression, MdBBXs were divided into three groups based on the microarray information. An analysis of cis-acting elements showed that elements related to the stress response were prevalent in the promoter sequences of most MdBBXs. Twelve MdBBX members from different groups were randomly selected and exposed to abiotic stresses. Their expressions were up-regulated to some extent in the roots and leaves. Six among 12 MdBBXs were sensitive to osmotic pressure, salt, cold stress and exogenous abscisic acid treatment, with their expressions enhanced more than 20-fold. Our results suggested that MdBBXs may take part in response to abiotic stress.

Involvement of high mobility group box 1 in the development and maintenance of chemotherapy-induced peripheral neuropathy in rats

International Nuclear Information System (INIS)

Nishida, Takeshi; Tsubota, Maho; Kawaishi, Yudai; Yamanishi, Hiroki; Kamitani, Natsuki; Sekiguchi, Fumiko; Ishikura, Hiroyasu; Liu, Keyue; Nishibori, Masahiro; Kawabata, Atsufumi

2016-01-01

Given that high mobility group box 1 (HMGB1), a nuclear protein, once released to the extracellular space, promotes nociception, we asked if inactivation of HMGB1 prevents or reverses chemotherapy-induced painful neuropathy in rats and also examined possible involvement of Toll-like receptor 4 (TLR4) and the receptor for advanced glycation endproduct (RAGE), known as targets for HMGB1. Painful neuropathy was produced by repeated i.p. administration of paclitaxel or vincristine in rats. Nociceptive threshold was determined by the paw pressure method and/or von Frey test in the hindpaw. Tissue protein levels were determined by immunoblotting. Repeated i.p. administration of the anti-HMGB1-neutralizing antibody or recombinant human soluble thrombomodulin (rhsTM), known to inactivate HMGB1, prevented the development of hyperalgesia and/or allodynia induced by paclitaxel or vincristine in rats. A single i.p. or intraplantar (i.pl.) administration of the antibody or rhsTM reversed the chemotherapy-induced neuropathy. A single i.pl. administration of a TLR4 antagonist or low molecular weight heparin, known to inhibit RAGE, attenuated the hyperalgesia caused by i.pl. HMGB1 and also the chemotherapy-induced painful neuropathy. Paclitaxel or vincristine treatment significantly decreased protein levels of HMGB1 in the dorsal root ganglia, but not sciatic nerves. HMGB1 thus participates in both development and maintenance of chemotherapy-induced painful neuropathy, in part through RAGE and TLR4. HMGB1 inactivation is considered useful to prevent and treat the chemotherapy-induced painful neuropathy.

Boxing-acute complications and late sequelae: from concussion to dementia.

Science.gov (United States)

Förstl, Hans; Haass, Christian; Hemmer, Bernhard; Meyer, Bernhard; Halle, Martin

2010-11-01

Boxing has received increased public attention and acceptance in recent years. However, this development has not been accompanied by a critical discussion of the early and late health complications. We selectively review recent studies on the acute, subacute, and chronic neuropsychiatric consequences of boxing. Cerebral concussions ("knock-outs") are the most relevant acute consequence of boxing. The number of reported cases of death in the ring seems to have mildly decreased. Subacute neuropsychological deficits appear to last longer than subjective symptoms. The associated molecular changes demonstrate neuronal and glial injury correlated with the number and severity of blows to the head (altered total tau, beta-amyloid, neurofilament light protein, glial fibrillary acidic protein, and neuron-specific enolase). The risk of a punch-drunk syndrome (boxer's dementia, dementia pugilistica) as a late effect of chronic traumatic brain injury is associated with the duration of a boxer's career and with his earlier stamina. There are similarities (e.g. increased risk with ApoE4-polymorphism, beta-amyloid pathology) and differences (more tau pathology in boxers) compared with Alzheimer's disease. Protective gear has led to a remarkable reduction of risks in amateur boxing. Similar measures can also be used in professional boxing, but may decrease the thrill, which does appeal to many supporters.

Characterization of differential ripening pattern in association with ethylene biosynthesis in the fruits of five naturally occurring banana cultivars and detection of a GCC-box-specific DNA-binding protein.

Science.gov (United States)

Choudhury, Swarup Roy; Roy, Sujit; Saha, Progya Paramita; Singh, Sanjay Kumar; Sengupta, Dibyendu N

2008-07-01

MA-ACS1 and MA-ACO1 are the two major ripening genes in banana and play crucial role in the regulation of ethylene production during ripening. Here, we report a comparative ripening pattern in five different naturally occurring banana cultivars namely Cavendish (AAA), Rasthali (AAB), Kanthali (AB), Poovan (AAB) and Monthan (ABB), which have distinct genome composition. We found a distinct variation in the climacteric ethylene production and in-vivo ACC oxidase activity level during the ripening stages in the five cultivars. We identified the cDNAs for MA-ACS1 and MA-ACO1 from the five cultivars and studied the transcript accumulation patterns of the two genes, which correlated well with the differential timing in the expression of these two genes during ripening. The GCC-box is one of the ethylene-responsive elements (EREs) found in the promoters of many ethylene-inducible genes. We have identified a GCC-box motif (putative ERE) in the promoters of MA-ACS1 and MA-ACO1 in banana cultivars. DNA-protein interaction studies revealed the presence of a GCC-box-specific DNA-binding activity in the fruit nuclear extract and such DNA-binding activity was enhanced following ethylene treatment. South-Western blotting revealed a 25-kDa nuclear protein that binds specifically to GCC-box DNA in the climacteric banana fruit. Together, these results indicate the probable involvement of the GCC-box motif as the cis-acting ERE in the regulation of MA-ACS1 and MA-ACO1 during ripening in banana fruits via binding of specific ERE-binding protein.

Necrotic enlargement of cone photoreceptor cells and the release of high-mobility group box-1 in retinitis pigmentosa

Science.gov (United States)

Murakami, Y; Ikeda, Y; Nakatake, S; Tachibana, T; Fujiwara, K; Yoshida, N; Notomi, S; Nakao, S; Hisatomi, T; Miller, J W; Vavvas, DG; Sonoda, KH; Ishibashi, T

2015-01-01

Retinitis pigmentosa (RP) refers to a group of inherited retinal degenerations resulting form rod and cone photoreceptor cell death. The rod cell death due to deleterious genetic mutations has been shown to occur mainly through apoptosis, whereas the mechanisms and features of the secondary cone cell death have not been fully elucidated. Our previous study showed that the cone cell death in rd10 mice, an animal model of RP, involves necrotic features and is partly mediated by the receptor interacting protein kinase. However, the relevancy of necrotic cone cell death in human RP patients remains unknown. In the present study, we showed that dying cone cells in rd10 mice exhibited cellular enlargement, along with necrotic changes such as cellular swelling and mitochondrial rupture. In human eyes, live imaging of cone cells by adaptive optics scanning laser ophthalmoscopy revealed significantly increased percentages of enlarged cone cells in the RP patients compared with the control subjects. The vitreous of the RP patients contained significantly higher levels of high-mobility group box-1, which is released extracellularly associated with necrotic cell death. These findings suggest that necrotic enlargement of cone cells is involved in the process of cone degeneration, and that necrosis may be a novel target to prevent or delay the loss of cone-mediated central vision in RP. PMID:27551484

Fibrillarin and Nop56 interact before being co-assembled in box C/D snoRNPs

International Nuclear Information System (INIS)

Lechertier, Tanguy; Grob, Alice; Hernandez-Verdun, Daniele; Roussel, Pascal

2009-01-01

Small nucleolar RNAs play crucial roles in ribosome biogenesis. They guide folding, site-specific nucleotide modifications and participate in cleavage of precursor ribosomal RNAs. To better understand how the biogenesis of the box C/D small nucleolar RNPs (snoRNPs) occur in a cellular context, we used a new approach based on the possibility of relocalizing a given nuclear complex by adding an affinity tag for B23 to one component of this complex. We selectively delocalized each core box C/D protein, namely 15.5kD, Nop56, Nop58 and fibrillarin, and analyzed the effect of such changes on other components of the box C/D snoRNPs. We show that modifying the localization and the mobility of core box C/D proteins impairs their association with box C/D snoRNPs. In addition, we demonstrate that fibrillarin and Nop56 directly interact in vivo. This interaction, indispensable for the association of both proteins with the box C/D snoRNPs, does not involve the glycine- and arginine-rich domain or the RNA-binding domain but the alpha-helix domain of fibrillarin. In addition, no RNA seems required to maintain fibrillarin-Nop56 interaction

Cdc20 mediates D-box-dependent degradation of Sp100

Energy Technology Data Exchange (ETDEWEB)

Wang, Ran; Li, Ke-min; Zhou, Cai-hong; Xue, Jing-lun [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai (China); Ji, Chao-neng, E-mail: Chnji@fudan.edu.cn [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai (China); Chen, Jin-zhong, E-mail: kingbellchen@fudan.edu.cn [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai (China)

2011-12-02

Highlights: Black-Right-Pointing-Pointer Cdc20 is a co-activator of APC/C complex. Black-Right-Pointing-Pointer Cdc20 recruits Sp100 and mediates its degradation. Black-Right-Pointing-Pointer The D-box of Sp100 is required for Cdc20-mediated degradation. Black-Right-Pointing-Pointer Sp100 expresses consistently at both the mRNA and protein levels in cell cycle. -- Abstract: Cdc20 is a co-activator of the anaphase-promoting complex/cyclosome (APC/C complex), which recruits substrates at particular phases of the cell cycle and mediates their degradation. Sp100 is a PML-NB scaffold protein, which localizes to nuclear particles during interphase and disperses from them during mitosis, participates in viral resistance, transcriptional regulation, and apoptosis. However, its metabolism during the cell cycle has not yet been fully characterized. We found a putative D-box in Sp100 using the Eukaryotic Linear Motif (ELM) predictor database. The putative D-box of Sp100 was verified by mutational analysis. Overexpression of Cdc20 resulted in decreased levels of both endogenous Sp100 protein and overexpressed Sp100 mRNA in HEK 293 cells. Only an overexpressed D-box deletion mutant of Sp100 accumulated in HEK293 cells that also overexpressed Cdc20. Cdc20 knockdown by cdc20 specific siRNA resulted in increased Sp100 protein levels in cells. Furthermore, we discovered that the Cdc20 mediated degradation of Sp100 is diminished by the proteasome inhibitor MG132, which suggests that the ubiquitination pathway is involved in this process. However, unlike the other Cdc20 substrates, which display oscillating protein levels, the level of Sp100 protein remains constant throughout the cell cycle. Additionally, both overexpression and knockdown of endogenous Sp100 had no effect on the cell cycle. Our results suggested that sp100 is a novel substrate of Cdc20 and it is degraded by the ubiquitination pathway. The intact D-box of Sp100 was necessary for this process. These findings expand

Boxing injuries presenting to U.S. emergency departments, 1990-2008.

Science.gov (United States)

Potter, Matthew R; Snyder, Ashley J; Smith, Gary A

2011-04-01

Boxing injuries can have serious consequences. To examine the epidemiology of boxing injuries in the U.S. with attention to head injuries and children. National estimates of boxing injuries were calculated using data from the National Electronic Injury Surveillance System. Injury rates per 1000 participants for the year 2003 were calculated using boxing participation data. Data analysis was conducted in 2009-2010. An estimated 165,602 individuals (95% CI=134891, 196313) sustained boxing injuries that resulted in a visit to a U.S. hospital emergency department from 1990 through 2008. An average of 8716 (95% CI=7078, 10354) injuries occurred annually, and there was a statistically significant increase in the annual number of injuries during the 19-year study period (slope=610, pboxing injuries. The percentage of injuries that were concussions/closed head injuries in the group aged 12-17 years (8.9%) was similar to that in the group aged 18-24 years (8.1%) and the group aged 25-34 years (8.5%). These findings, based on a nationally representative sample, indicate that injuries related to boxing are increasing in number. Increased efforts are needed to prevent boxing injuries. Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Differential stability of TATA box binding proteins from archaea with different optimal growth temperatures

Science.gov (United States)

Kopitz, Annette; Soppa, Jörg; Krejtschi, Carsten; Hauser, Karin

2009-09-01

The TATA box binding protein (TBP) is involved in promoter recognition, the first step of transcription initiation. TBP is universally conserved and essential in archaea and eukaryotes. In archaea, TBPs have to be stable and to function in species that cover an extremely wide range of optimal growth temperatures (OGTs), from below 0 °C to more than 100 °C. Thus, the archaeal TBP family is ideally suited to study the evolutionary adaptation of proteins to an extremely wide range of temperatures. We characterized the thermostability of one mesophilic and one thermophilic TBP by infrared spectroscopy. Transition temperatures ( Tms) of thermal unfolding have been determined using TBPs from Methanosarcina mazei (OGT 37 °C) and from Methanothermobacter thermautotrophicus (OGT 65 °C). Furthermore, the influence of protein and salt concentration on thermostability has been characterized. Together with previous studies, our results reveal that the Tms of archaeal TBPs are closely correlated with the OGTs of the respective species. Noteworthy, this is also true for the TBP from M. mazei representing the first characterized TBP from a mesophilic archaeon. In contrast, the only characterized eukaryotic TBP of the mesophilic plant Arabidopsis thaliana has a Tm more than 40 °C above the OGT.

Molecular dissection of the APC/C inhibitor Rca1 shows a novel F-box-dependent function.

Science.gov (United States)

Zielke, Norman; Querings, Silvia; Grosskortenhaus, Ruth; Reis, Tânia; Sprenger, Frank

2006-12-01

Rca1 (regulator of Cyclin A)/Emi (early mitotic inhibitor) proteins are essential inhibitors of the anaphase-promoting complex/cyclosome (APC/C). In Drosophila, Rca1 is required during G2 to prevent premature cyclin degradation by the Fizzy-related (Fzr)-dependent APC/C activity. Here, we present a structure and function analysis of Rca1 showing that a carboxy-terminal fragment is sufficient for APC/C inhibition. Rca1/Emi proteins contain a conserved F-box and interact with components of the Skp-Cullin-F-box (SCF) complex. So far, no function has been ascribed to this domain. We find that the F-box of Rca1 is dispensable for APC/C-Fzr inhibition during G2. Nevertheless, we show that Rca1 has an additional function at the G1-S transition, which requires the F-box. Overexpression of Rca1 accelerates the G1-S transition in an F-box-dependent manner. Conversely, S-phase entry is delayed in cells in which endogenous Rca1 is replaced by a transgene lacking the F-box. We propose that Rca1 acts as an F-box protein in an as yet uncharacterized SCF complex, which promotes S-phase entry.

Crystal structure of the UBR-box from UBR6/FBXO11 reveals domain swapping mediated by zinc binding.

Science.gov (United States)

Muñoz-Escobar, Juliana; Kozlov, Guennadi; Gehring, Kalle

2017-10-01

The UBR-box is a 70-residue zinc finger domain present in the UBR family of E3 ubiquitin ligases that directly binds N-terminal degradation signals in substrate proteins. UBR6, also called FBXO11, is an UBR-box containing E3 ubiquitin ligase that does not bind N-terminal signals. Here, we present the crystal structure of the UBR-box domain from human UBR6. The dimeric crystal structure reveals a unique form of domain swapping mediated by zinc coordination, where three independent protein chains come together to regenerate the topology of the monomeric UBR-box fold. Analysis of the structure suggests that the absence of N-terminal residue binding arises from the lack of an amino acid binding pocket. © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

BC-Box Motif-Mediated Neuronal Differentiation of Somatic Stem Cells

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Hiroshi Kanno

2018-02-01

Full Text Available Von Hippel-Lindau tumor suppressor protein (pVHL functions to induce neuronal differentiation of neural stem/progenitor cells (NSCs and skin-derived precursors (SKPs. Here we identified a neuronal differentiation domain (NDD in pVHL. Neuronal differentiation of SKPs was induced by intracellular delivery of a peptide composed of the amino-acid sequences encoded by the NDD. Neuronal differentiation mediated by the NDD was caused by the binding between it and elongin C followed by Janus kinase-2 (JAK2 ubiquitination of JAK2 and inhibition of the JAK2/the signal transducer and activator of transcription-3(STAT3 pathway. The NDD in pVHL contained the BC-box motif ((A,P,S,TLXXX (A,C XXX(A,I,L,V corresponding to the binding site of elongin C. Therefore, we proposed that other BC-box proteins might also contain an NDD; and subsequently also identified in them an NDD containing the amino-acid sequence encoded by the BC-box motif in BC-box proteins. Furthermore, we showed that different NDD peptide-delivered cells differentiated into different kinds of neuron-like cells. That is, dopaminergic neuron-like cells, cholinergic neuron-like cells, GABAnergic neuron-like cells or rhodopsin-positive neuron-like cells were induced by different NDD peptides. These novel findings might contribute to the development of a new method for promoting neuronal differentiation and shed further light on the mechanism of neuronal differentiation of somatic stem cells.

Polycomb group protein-mediated repression of transcription

DEFF Research Database (Denmark)

Morey, Lluís; Helin, Kristian

2010-01-01

The polycomb group (PcG) proteins are essential for the normal development of multicellular organisms. They form multi-protein complexes that work as transcriptional repressors of several thousand genes controlling differentiation pathways during development. How the PcG proteins work as transcri......The polycomb group (PcG) proteins are essential for the normal development of multicellular organisms. They form multi-protein complexes that work as transcriptional repressors of several thousand genes controlling differentiation pathways during development. How the PcG proteins work...... as transcriptional repressors is incompletely understood, but involves post-translational modifications of histones by two major PcG protein complexes: polycomb repressive complex 1 and polycomb repressive complex 2....

Crystallization and preliminary X-ray diffraction analysis of the C-terminal domain of the human spliceosomal DExD/H-box protein hPrp22

International Nuclear Information System (INIS)

Kudlinzki, Denis; Nagel, Christian; Ficner, Ralf

2009-01-01

The cloning, purification and crystallization of the C-terminal domain of human hPrp22 are reported. This communication also contains data for the preliminary X-ray diffraction analysis. The Homo sapiens DExD/H-box protein hPrp22 is a crucial component of the eukaryotic pre-mRNA splicing machinery. Within the splicing cycle, it is involved in the ligation of exons and generation of the lariat and it additionally catalyzes the release of mature mRNA from the spliceosomal U5 snRNP. The yeast homologue of this protein, yPrp22, shows ATP-dependent RNA-helicase activity and is capable of unwinding RNA/RNA duplex molecules. A truncated construct coding for residues 950–1183 of human Prp22, comprising the structurally and functionally uncharacterized C-terminal domain, was cloned into an Escherichia coli expression vector. The protein was subsequently overproduced, purified and crystallized. The crystals obtained diffracted to 2.1 Å resolution, belonged to the tetragonal space group P4 1 2 1 2 or P4 3 2 1 2, with unit-cell parameters a = b = 78.2, c = 88.4 Å, and contained one molecule in the asymmetric unit

Identification of novel putative-binding proteins for cellular prion protein and a specific interaction with the STIP1 homology and U-Box-containing protein 1

Science.gov (United States)

Gimenez, Ana Paula Lappas; Richter, Larissa Morato Luciani; Atherino, Mariana Campos; Beirão, Breno Castello Branco; Fávaro, Celso; Costa, Michele Dietrich Moura; Zanata, Silvio Marques; Malnic, Bettina; Mercadante, Adriana Frohlich

2015-01-01

ABSTRACT Prion diseases involve the conversion of the endogenous cellular prion protein, PrPC, into a misfolded infectious isoform, PrPSc. Several functions have been attributed to PrPC, and its role has also been investigated in the olfactory system. PrPC is expressed in both the olfactory bulb (OB) and olfactory epithelium (OE) and the nasal cavity is an important route of transmission of diseases caused by prions. Moreover, Prnp−/− mice showed impaired behavior in olfactory tests. Given the high PrPC expression in OE and its putative role in olfaction, we screened a mouse OE cDNA library to identify novel PrPC-binding partners. Ten different putative PrPC ligands were identified, which were involved in functions such as cellular proliferation and apoptosis, cytoskeleton and vesicle transport, ubiquitination of proteins, stress response, and other physiological processes. In vitro binding assays confirmed the interaction of PrPC with STIP1 homology and U-Box containing protein 1 (Stub1) and are reported here for the first time. Stub1 is a co-chaperone with ubiquitin E3-ligase activity, which is associated with neurodegenerative diseases characterized by protein misfolding and aggregation. Physiological and pathological implications of PrPC-Stub1 interaction are under investigation. The PrPC-binding proteins identified here are not exclusive to the OE, suggesting that these interactions may occur in other tissues and play general biological roles. These data corroborate the proposal that PrPC is part of a multiprotein complex that modulates several cellular functions and provide a platform for further studies on the physiological and pathological roles of prion protein. PMID:26237451

The Polerovirus F box protein P0 targets ARGONAUTE1 to suppress RNA silencing.

Science.gov (United States)

Bortolamiol, Diane; Pazhouhandeh, Maghsoud; Marrocco, Katia; Genschik, Pascal; Ziegler-Graff, Véronique

2007-09-18

Plants employ post-transcriptional gene silencing (PTGS) as an antiviral defense response. In this mechanism, viral-derived small RNAs are incorporated into the RNA-induced silencing complex (RISC) to guide degradation of the corresponding viral RNAs. ARGONAUTE1 (AGO1) is a key component of RISC: it carries the RNA slicer activity. As a counter-defense, viruses have evolved various proteins that suppress PTGS. Recently, we showed that the Polerovirus P0 protein carries an F box motif required to form an SCF-like complex, which is also essential for P0's silencing suppressor function. Here, we investigate the molecular mechanism by which P0 impairs PTGS. First we show that P0's expression does not affect the biogenesis of primary siRNAs in an inverted repeat-PTGS assay, but it does affect their activity. Moreover, P0's expression in transformed Arabidopsis plants leads to various developmental abnormalities reminiscent of mutants affected in miRNA pathways, which is accompanied by enhanced levels of several miRNA-target transcripts, suggesting that P0 acts at the level of RISC. Interestingly, ectopic expression of P0 triggered AGO1 protein decay in planta. Finally, we provide evidence that P0 physically interacts with AGO1. Based on these results, we propose that P0 hijacks the host SCF machinery to modulate gene silencing by destabilizing AGO1.

Interaction of a non-histone chromatin protein (high-mobility group protein 2) with DNA

International Nuclear Information System (INIS)

Goodwin, G.H.; Shooter, K.V.; Johns, E.W.

1975-01-01

The interaction with DNA of the calf thymus chromatin non-histone protein termed the high-mobility group protein 2 has been studied by sedimentation analysis in the ultracentrifuge and by measuring the binding of the 125 I-labelled protein to DNA. The results have been compared with those obtained previously by us [Eur. J. Biochem. (1974) 47, 263-270] for the interaction of high-mobility group protein 1 with DNA. Although the binding parameters are similar for these two proteins, high-mobility group protein 2 differs from high-mobility group protein 1 in that the former appears to change the shape of the DNA to a more compact form. The molecular weight of high-mobility group protein 2 has been determined by equilibrium sedimentation and a mean value of 26,000 was obtained. A low level of nuclease activity detected in one preparation of high-mobility group protein 2 has been investigated. (orig.) [de

Virtual Box

DEFF Research Database (Denmark)

Davis, Hilary; Skov, Mikael B.; Stougaard, Malthe

2007-01-01

. This paper reports on the design, implementation and initial evaluation of Virtual Box. Virtual Box attempts to create a physical and engaging context in order to support reciprocal interactions with expressive content. An implemented version of Virtual Box is evaluated in a location-aware environment...

Timing of APC/C substrate degradation is determined by fzy/fzr specificity of destruction boxes

OpenAIRE

Zur, Amit; Brandeis, Michael

2002-01-01

The anaphase promoting complex/cyclosome (APC/C), activated by fzy and fzr, degrades cell cycle proteins that carry RXXL or KEN destruction boxes (d-boxes). APC/C substrates regulate sequential events and must be degraded in the correct order during mitosis and G1. We studied how d-boxes determine APC/Cfzy/APC/Cfzr specificity and degradation timing. Cyclin B1 has an RXXL box and is degraded by both APC/Cfzy and APC/Cfzr; fzy has a KEN box and is degraded by APC/Cfzr only. We characterized th...

Functional conservation and divergence of four ginger AP1/AGL9 MADS-box genes revealed by analysis of their expression and protein-protein interaction, and ectopic expression of AhFUL gene in Arabidopsis.

Directory of Open Access Journals (Sweden)

Xiumei Li

Full Text Available Alpinia genus are known generally as ginger-lilies for showy flowers in the ginger family, Zingiberaceae, and their floral morphology diverges from typical monocotyledon flowers. However, little is known about the functions of ginger MADS-box genes in floral identity. In this study, four AP1/AGL9 MADS-box genes were cloned from Alpinia hainanensis, and protein-protein interactions (PPIs and roles of the four genes in floral homeotic conversion and in floral evolution are surveyed for the first time. AhFUL is clustered to the AP1 lineage, AhSEP4 and AhSEP3b to the SEP lineage, and AhAGL6-like to the AGL6 lineage. The four genes showed conserved and divergent expression patterns, and their encoded proteins were localized in the nucleus. Seven combinations of PPI (AhFUL-AhSEP4, AhFUL-AhAGL6-like, AhFUL-AhSEP3b, AhSEP4-AhAGL6-like, AhSEP4-AhSEP3b, AhAGL6-like-AhSEP3b, and AhSEP3b-AhSEP3b were detected, and the PPI patterns in the AP1/AGL9 lineage revealed that five of the 10 possible combinations are conserved and three are variable, while conclusions cannot yet be made regarding the other two. Ectopic expression of AhFUL in Arabidopsis thaliana led to early flowering and floral organ homeotic conversion to sepal-like or leaf-like. Therefore, we conclude that the four A. hainanensis AP1/AGL9 genes show functional conservation and divergence in the floral identity from other MADS-box genes.

Apple F-box Protein MdMAX2 Regulates Plant Photomorphogenesis and Stress Response

Directory of Open Access Journals (Sweden)

Jian-Ping An

2016-11-01

Full Text Available MAX2 (MORE AXILLARY GROWTH2 is involved in diverse physiological processes, including photomorphogenesis, the abiotic stress response, as well as karrikin and strigolactone signaling-mediated shoot branching. In this study, MdMAX2, an F-box protein that is a homolog of Arabidopsis MAX2, was identified and characterized. Overexpression of MdMAX2 in apple calli enhanced the accumulation of anthocyanin. Ectopic expression of MdMAX2 in Arabidopsis exhibited photomorphogenesis phenotypes, including increased anthocyanin content and decreased hypocotyl length. Further study indicated that MdMAX2 might promote plant photomorphogenesis by affecting the auxin signaling as well as other plant hormones. Transcripts of MdMAX2 were noticeably up-regulated in response to NaCl and Mannitol treatments. Moreover, compared with the wild type, the MdMAX2-overexpressing apple calli and Arabidopsis exhibited increased tolerance to salt and drought stresses. Taken together, these results suggest that MdMAX2 plays a positive regulatory role in plant photomorphogenesis and stress response.

Cell-Free DNA, High-Mobility Group Box-1, and Procalcitonin Concentrations in Dogs With Gastric Dilatation–Volvulus Syndrome

OpenAIRE

Roberta Troia; Massimo Giunti; Stefano Calipa; Robert Goggs

2018-01-01

Canine gastric dilatation–volvulus (GDV) is a life-threatening disease characterized by extensive tissue ischemia, tissue hypoperfusion, and systemic inflammation. Biomarkers that better reflect the severity of gastric necrosis and systemic inflammation would aid clinicians in the management of these patients. This study aimed to investigate the prognostic significance of cell-free DNA (cfDNA), high-mobility group box-1 (HMGB1), and procalcitonin (PCT) in dogs with GDV. Concentrations of cfDN...

Genomic Organization, Phylogenetic Comparison and Differential Expression of the SBP-Box Family Genes in Grape

Science.gov (United States)

Hou, Hongmin; Li, Jun; Gao, Min; Singer, Stacy D.; Wang, Hao; Mao, Linyong; Fei, Zhangjun; Wang, Xiping

2013-01-01

Background The SBP-box gene family is specific to plants and encodes a class of zinc finger-containing transcription factors with a broad range of functions. Although SBP-box genes have been identified in numerous plants including green algae, moss, silver birch, snapdragon, Arabidopsis, rice and maize, there is little information concerning SBP-box genes, or the corresponding miR156/157, function in grapevine. Methodology/Principal Findings Eighteen SBP-box gene family members were identified in Vitis vinifera, twelve of which bore sequences that were complementary to miRNA156/157. Phylogenetic reconstruction demonstrated that plant SBP-domain proteins could be classified into seven subgroups, with the V. vinifera SBP-domain proteins being more closely related to SBP-domain proteins from dicotyledonous angiosperms than those from monocotyledonous angiosperms. In addition, synteny analysis between grape and Arabidopsis demonstrated that homologs of several grape SBP genes were found in corresponding syntenic blocks of Arabidopsis. Expression analysis of the grape SBP-box genes in various organs and at different stages of fruit development in V. quinquangularis ‘Shang-24’ revealed distinct spatiotemporal patterns. While the majority of the grape SBP-box genes lacking a miR156/157 target site were expressed ubiquitously and constitutively, most genes bearing a miR156/157 target site exhibited distinct expression patterns, possibly due to the inhibitory role of the microRNA. Furthermore, microarray data mining and quantitative real-time RT-PCR analysis identified several grape SBP-box genes that are potentially involved in the defense against biotic and abiotic stresses. Conclusion The results presented here provide a further understanding of SBP-box gene function in plants, and yields additional insights into the mechanism of stress management in grape, which may have important implications for the future success of this crop. PMID:23527172

High-mobility group box 1 and the receptor for advanced glycation end products contribute to lung injury during Staphylococcus aureus pneumonia

NARCIS (Netherlands)

Achouiti, Ahmed; van der Meer, Anne Jan; Florquin, Sandrine; Yang, Huan; Tracey, Kevin J.; van 't Veer, Cornelis; de Vos, Alex F.; van der Poll, Tom

2013-01-01

Staphylococcus (S.) aureus has emerged as an important cause of necrotizing pneumonia. Lung injury during S. aureus pneumonia may be enhanced by local release of damage associated molecular patterns such as high-mobility group box 1 (HMGB1). In the current study we sought to determine the functional

Beneficial Effects of Ethyl Pyruvate through Inhibiting High-Mobility Group Box 1 Expression and TLR4/NF-κB Pathway after Traumatic Brain Injury in the Rat

Directory of Open Access Journals (Sweden)

Xingfen Su

2011-01-01

Full Text Available Ethyl pyruvate (EP has demonstrated neuroprotective effects against acute brain injury through its anti-inflammatory action. The nuclear protein high-mobility group box 1 (HMGB1 can activate inflammatory pathways when released from dying cells. This study was designed to investigate the protective effects of EP against secondary brain injury in rats after Traumatic Brain Injury (TBI. Adult male rats were randomly divided into three groups: (1 Sham + vehicle group, (2 TBI + vehicle group, and (3 TBI + EP group (n=30 per group. Right parietal cortical contusion was made by using a weight-dropping TBI method. In TBI + EP group, EP was administered intraperitoneally at a dosage of 75 mg/kg at 5 min, 1 and 6 h after TBI. Brain samples were harvested at 24 h after TBI. We found that EP treatment markedly inhibited the expressions of HMGB1 and TLR4, NF-κB DNA binding activity and inflammatory mediators, such as IL-1β, TNF-α and IL-6. Also, EP treatment significantly ameliorated beam walking performance, brain edema, and cortical apoptotic cell death. These results suggest that the protective effects of EP may be mediated by the reduction of HMGB1/TLR4/NF-κB-mediated inflammatory response in the injured rat brain.

Pollen S-locus F-box proteins of Petunia involved in S-RNase-based self-incompatibility are themselves subject to ubiquitin-mediated degradation.

Science.gov (United States)

Sun, Penglin; Li, Shu; Lu, Dihong; Williams, Justin S; Kao, Teh-Hui

2015-07-01

Many flowering plants show self-incompatibility, an intra-specific reproductive barrier by which pistils reject self-pollen to prevent inbreeding and accept non-self pollen to promote out-crossing. In Petunia, the polymorphic S-locus determines self/non-self recognition. The locus contains a gene encoding an S-RNase, which controls pistil specificity, and multiple S-locus F-box (SLF) genes that collectively control pollen specificity. Each SLF is a component of an SCF (Skp1/Cullin/F-box) complex that is responsible for mediating degradation of non-self S-RNase(s), with which the SLF interacts, via the ubiquitin-26S proteasome pathway. A complete set of SLFs is required to detoxify all non-self S-RNases to allow cross-compatible pollination. Here, we show that SLF1 of Petunia inflata is itself subject to degradation via the ubiquitin-26S proteasome pathway, and identify an 18 amino acid sequence in the C-terminal region of S2 -SLF1 (SLF1 of S2 haplotype) that contains a degradation motif. Seven of the 18 amino acids are conserved among all 17 SLF proteins of S2 haplotype and S3 haplotype involved in pollen specificity, suggesting that all SLF proteins are probably subject to similar degradation. Deleting the 18 amino acid sequence from S2 -SLF1 stabilized the protein but abolished its function in self-incompatibility, suggesting that dynamic cycling of SLF proteins is an integral part of their function in self-incompatibility. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

46 CFR 111.81-1 - Outlet boxes and junction boxes; general.

Science.gov (United States)

2010-10-01

... fixture, wiring device, or similar item, including each separately installed connection and junction box... used. (d) As appropriate, each outlet-box or junction-box installation must meet the following...

BOX-PCR-based identification of bacterial species belonging to Pseudomonas syringae: P. viridiflava group

Directory of Open Access Journals (Sweden)

Abi S.A. Marques

2008-01-01

Full Text Available The phenotypic characteristics and genetic fingerprints of a collection of 120 bacterial strains, belonging to Pseudomonas syringae sensu lato group, P. viridiflava and reference bacteria were evaluated, with the aim of species identification. The numerical analysis of 119 nutritional characteristics did not show patterns that would help with identification. Regarding the genetic fingerprinting, the results of the present study supported the observation that BOX-PCR seems to be able to identify bacterial strains at species level. After numerical analyses of the bar-codes, all pathovars belonging to each one of the nine described genomospecies were clustered together at a distance of 0.72, and could be separated at genomic species level. Two P. syringae strains of unknown pathovars (CFBP 3650 and CFBP 3662 and the three P. syringae pv. actinidiae strains were grouped in two extra clusters and might eventually constitute two new species. This genomic species clustering was particularly evident for genomospecies 4, which gathered P. syringae pvs. atropurpurea, coronafaciens, garçae, oryzae, porri, striafaciens, and zizaniae at a noticeably low distance.

Msx1 and Msx2 are functional interacting partners of T-box factors in the regulation of Connexin43.

Science.gov (United States)

Boogerd, Kees-Jan; Wong, L Y Elaine; Christoffels, Vincent M; Klarenbeek, Meinke; Ruijter, Jan M; Moorman, Antoon F M; Barnett, Phil

2008-06-01

T-box factors Tbx2 and Tbx3 play key roles in the development of the cardiac conduction system, atrioventricular canal, and outflow tract of the heart. They regulate the gap-junction-encoding gene Connexin43 (Cx43) and other genes critical for heart development and function. Discovering protein partners of Tbx2 and Tbx3 will shed light on the mechanisms by which these factors regulate these gene programs. Employing an yeast 2-hybrid screen and subsequent in vitro pull-down experiments we demonstrate that muscle segment homeobox genes Msx1 and Msx2 are able to bind the cardiac T-box proteins Tbx2, Tbx3, and Tbx5. This interaction, as that of the related Nkx2.5 protein, is supported by the T-box and homeodomain alone. Overlapping spatiotemporal expression patterns of Msx1 and Msx2 together with the T-box genes during cardiac development in mouse and chicken underscore the biological significance of this interaction. We demonstrate that Msx proteins together with Tbx2 and Tbx3 suppress Cx43 promoter activity and down regulate Cx43 gene activity in a rat heart-derived cell line. Using chromatin immunoprecipitation analysis we demonstrate that Msx1 can bind the Cx43 promoter at a conserved binding site located in close proximity to a previously defined T-box binding site, and that the activity of Msx proteins on this promoter appears dependent in the presence of Tbx3. Msx1 and Msx2 can function in concert with the T-box proteins to suppress Cx43 and other working myocardial genes.

The F box protein Fbx6 regulates Chk1 stability and cellular sensitivity to replication stress.

Science.gov (United States)

Zhang, You-Wei; Brognard, John; Coughlin, Chris; You, Zhongsheng; Dolled-Filhart, Marisa; Aslanian, Aaron; Manning, Gerard; Abraham, Robert T; Hunter, Tony

2009-08-28

ATR and Chk1 are two key protein kinases in the replication checkpoint. Activation of ATR-Chk1 has been extensively investigated, but checkpoint termination and replication fork restart are less well understood. Here, we report that DNA damage not only activates Chk1, but also exposes a degron-like region at the carboxyl terminus of Chk1 to an Fbx6-containing SCF (Skp1-Cul1-F box) E3 ligase, which mediates the ubiquitination and degradation of Chk1 and, in turn, terminates the checkpoint. The protein levels of Chk1 and Fbx6 showed an inverse correlation in both cultured cancer cells and in human breast tumor tissues. Further, we show that low levels of Fbx6 and consequent impairment of replication stress-induced Chk1 degradation are associated with cancer cell resistance to the chemotherapeutic agent, camptothecin. We propose that Fbx6-dependent Chk1 degradation contributes to S phase checkpoint termination and that a defect in this mechanism might increase tumor cell resistance to certain anticancer drugs.

Structural basis for substrate placement by an archaeal box C/D ribonucleoprotein particle.

Science.gov (United States)

Xue, Song; Wang, Ruiying; Yang, Fangping; Terns, Rebecca M; Terns, Michael P; Zhang, Xinxin; Maxwell, E Stuart; Li, Hong

2010-09-24

Box C/D small nucleolar and Cajal body ribonucleoprotein particles (sno/scaRNPs) direct site-specific 2'-O-methylation of ribosomal and spliceosomal RNAs and are critical for gene expression. Here we report crystal structures of an archaeal box C/D RNP containing three core proteins (fibrillarin, Nop56/58, and L7Ae) and a half-mer box C/D guide RNA paired with a substrate RNA. The structure reveals a guide-substrate RNA duplex orientation imposed by a composite protein surface and the conserved GAEK motif of Nop56/58. Molecular modeling supports a dual C/D RNP structure that closely mimics that recently visualized by electron microscopy. The substrate-bound dual RNP model predicts an asymmetric protein distribution between the RNP that binds and methylates the substrate RNA. The predicted asymmetric nature of the holoenzyme is consistent with previous biochemical data on RNP assembly and provides a simple solution for accommodating base-pairing between the C/D guide RNA and large ribosomal and spliceosomal substrate RNAs. Copyright © 2010 Elsevier Inc. All rights reserved.

Association of high mobility group BOX-1 and receptor for advanced glycation endproducts with clinicopathological features of haematological malignancies: a systematic review

Directory of Open Access Journals (Sweden)

Austin H. Nguyen

2017-01-01

Full Text Available High-mobility group box 1 (HMGB1 is a versatile protein with nuclear and extracellular functions. In the extracellular milieu, HMGB1 binds to several receptors, notably the receptor for advanced glycation end-products (RAGE. The expressions of HMGB1 and RAGE have been described in a variety of cancers. However, the clinical values of HMGB1 and RAGE in haematological malignancies have yet to be evaluated. A systematic search through PubMed and the Web of Science for articles discussing the role of HMGB1 and RAGE in haematological malignancies produced 15 articles. Overexpression of HMGB1 was reported to be associated with malignancy and, in certain studies, poor prognosis and tumour aggressiveness. Only one included study investigated the clinical value of RAGE, in which no significant difference was found between expression of RAGE in CLL neoplastic cells and nonmalignant controls. The discussed associations of HMGB1 and RAGE with clinicopathological characteristics of patients with haematological malignancies warrants further investigation into the prognostic and diagnostic value of both of these molecules.

Channel box

International Nuclear Information System (INIS)

Tanabe, Akira.

1993-01-01

In a channel box of a BWR type reactor, protruding pads are disposed in axial position on the lateral side of a channel box opposing to a control rod and facing the outer side portion of the control rod in a reactor core loaded state. In the initial loading stage of fuel assemblies, channel fasteners and spacer pads are abutted against each other in the upper portion between the channel boxes sandwiching the control rod therebetween. Further, in the lower portion, a gap as a channel for the movement of the control rod is ensured by the support of fuel support metals. If the channel box is bent toward the control rod along with reactor operation, the pads are abutted against each other to always ensure the gap through which the control rod can move easily. Further, when the pads are brought into contact with each other, the bending deformation of the channel box is corrected by urging to each other. Thus, the control rod can always be moved smoothly to attain reactor safety operation. (N.H.)

Effect of heterogeneity of nest boxes on occurrence of gregarious nesting in laying hens

DEFF Research Database (Denmark)

Clausen, Tina; Riber, Anja Brinch

2012-01-01

Gregarious nesting, where hens select already occupied nest boxes even when other nest boxes are unoccupied, is an unwanted behaviour in laying hens that may reduce animal welfare and pose a financial cost to the producer. It has been suggested that gregarious nesting is caused by the difficulties...... nesting was higher in experimental groups compared to control groups (P right were higher compared to nest boxes positioned...

Vegetarian Choices in the Protein Foods Group

Science.gov (United States)

... foods selected are adequate. Protein sources from the Protein Foods Group for vegetarians include eggs (for ovo-vegetarians), beans and peas, nuts, nut butters, and soy products (tofu, tempeh, ...

Ankyrin repeat and SOCS box containing protein 4 (Asb-4 colocalizes with insulin receptor substrate 4 (IRS4 in the hypothalamic neurons and mediates IRS4 degradation

Directory of Open Access Journals (Sweden)

Xia Zefeng

2011-09-01

Full Text Available Abstract Background The arcuate nucleus of the hypothalamus regulates food intake. Ankyrin repeat and SOCS box containing protein 4 (Asb-4 is expressed in neuropeptide Y and proopiomelanocortin (POMC neurons in the arcuate nucleus, target neurons in the regulation of food intake and metabolism by insulin and leptin. However, the target protein(s of Asb-4 in these neurons remains unknown. Insulin receptor substrate 4 (IRS4 is an adaptor molecule involved in the signal transduction by both insulin and leptin. In the present study we examined the colocalization and interaction of Asb-4 with IRS4 and the involvement of Asb-4 in insulin signaling. Results In situ hybridization showed that the expression pattern of Asb-4 was consistent with that of IRS4 in the rat brain. Double in situ hybridization showed that IRS4 colocalized with Asb-4, and both Asb-4 and IRS4 mRNA were expressed in proopiomelanocortin (POMC and neuropeptide Y (NPY neurons within the arcuate nucleus of the hypothalamus. In HEK293 cells co-transfected with Myc-tagged Asb-4 and Flag-tagged IRS4, Asb-4 co-immunoprecipitated with IRS4; In these cells endogenous IRS4 also co-immunoprecipitated with transfected Myc-Asb-4; Furthermore, Asb-4 co-immunoprecipitated with IRS4 in rat hypothalamic extracts. In HEK293 cells over expression of Asb-4 decreased IRS4 protein levels and deletion of the SOCS box abolished this effect. Asb-4 increased the ubiquitination of IRS4; Deletion of SOCS box abolished this effect. Expression of Asb-4 decreased both basal and insulin-stimulated phosphorylation of AKT at Thr308. Conclusions These data demonstrated that Asb-4 co-localizes and interacts with IRS4 in hypothalamic neurons. The interaction of Asb-4 with IRS4 in cell lines mediates the degradation of IRS4 and decreases insulin signaling.

Meal box schemes a convenient way to avoid convenience food? Uses and understandings of meal box schemes among Danish consumers.

Science.gov (United States)

Hertz, Frej Daniel; Halkier, Bente

2017-07-01

The term convenience food is subject to diversification, lack of clarity and moral ambiguity. In this paper we address these issues and critically discuss convenience food by using empirical findings from a Danish study that deals with practitioners' uses of meal box schemes. The methodological design consists of thirteen individual interviews, four focus groups and some observations of cooking practices. We combine the empirical findings with a particular definition of convenience food by Brunner et al. (2010) and selected practice theoretical concepts. This particular combination enables us to categorize meal box schemes as a new form of convenience food called convenient food. In addition, results suggest that meal box schemes reduce leftovers from dinner. Meal boxes also influence dinner related activities such as planning ahead in time and grocery shopping, which require less physical and mental effort. Copyright © 2017 Elsevier Ltd. All rights reserved.

Acute subdural hematoma because of boxing.

Science.gov (United States)

Kushi, Hidehiko; Saito, Takeshi; Sakagami, Yuichiro; Ohtsuki, Jyoji; Tanjoh, Katsuhisa

2009-02-01

To identify factors determining the clinical characteristics and prognosis of acute subdural hematoma (ASDH) arising from boxing injuries by comparing with ASDH due to any nonboxing cause. Two groups were selected for this study: 10 patients with ASDH because of boxing injuries and 26 patients with nonboxer ASDH. All of the patients underwent neurologic examination by neurosurgeons. Primary resuscitation and stabilization as well as operative therapy were performed to all patients according to the European Brain Injury Consortium Guidelines. Two groups were compared in terms of age, the Glasgow Coma Scale at admission, neurologic findings, craniogram and brain computed tomography scan findings, operative findings, and prognosis. As potential prognostic indicators for boxers, the time interval until surgery, the Glasgow Outcome Scale, hematoma thickness, midline shift, and the site of bleeding were analyzed. The characteristics of patients because of boxing injuries are that patients were younger, had lucid interval, and had no cerebral contusion or contralateral brain injury. There was no significant difference in initial Glasgow Coma Scale, hematoma thickness, midline shift, and their prognosis. The most peculiar clinical presentation of boxers' ASDH was that all bleedings were limited from "bridging veins" or "cortical veins." The prognosis of boxers was most closely correlated with the site of bleeding (r2 = 0.81; p = 0.0001) and the midline shift (r2 = 0.67; p = 0.007). Our study shows that ASDH because of boxing is characterized by bleeding from bridging or cortical veins, and that the site of bleeding is a significant determinant of their prognosis.

An apple B-box protein, MdCOL11, is involved in UV-B- and temperature-induced anthocyanin biosynthesis.

Science.gov (United States)

Bai, Songling; Saito, Takanori; Honda, Chikako; Hatsuyama, Yoshimichi; Ito, Akiko; Moriguchi, Takaya

2014-11-01

Our studies showed that an apple B-box protein, MdCOL11, the homolog of AtBBX22, is involved in UV-B- and temperature-induced anthocyanin biosynthesis in apple peel. Anthocyanin is responsible for the red pigmentation in apple peel and a R2R3 MYB gene, MdMYBA/1/10, a homolog of MdMYBA, controls its accumulation. Arabidopsis PAP1 is under the control of a series of upstream factors involved in light signal transduction and photomorphogenesis, such as ELONGATED HYPOCOTYL 5 (HY5) and B-box family (BBX) proteins. In this study, we identified and characterized the homolog of Arabidopsis BBX22 in apple, designated as MdCOL11. Overexpression of MdCOL11 in Arabidopsis enhanced the accumulation of anthocyanin. In apples, MdCOL11 was differentially expressed in all tissues, with the highest expression in petals and the lowest expression in the xylem. Transcripts of MdCOL11 noticeably accumulated at the ripening stage, concomitant with increases in the expressions of anthocyanin biosynthesis-related genes. In an in vitro treatment experiment, MdCOL11 was upregulated in an ultra-violet (UV)-B- and temperature-dependent manner, together with the inductions of anthocyanin biosynthesis-related genes and anthocyanin accumulation in apple peel. Furthermore, a dual-luciferase assay indicated that (1) MdCOL11 regulated the expression of MdMYBA and (2) MdCOL11 was a target of MdHY5. Taken together, our results suggest that MdCOL11 is involved in MdHY5-mediated signal transduction and regulates anthocyanin accumulation in apple peel, which sheds new light on anthocyanin accumulation in apples.

Evaluation of cyclooxygenase protein expression in traumatized versus normal tissues from eastern box turtles (Terrapene carolina carolina).

Science.gov (United States)

Royal, Lillian W; Lascelles, B Duncan X; Lewbart, Gregory A; Correa, Maria T; Jones, Samuel L

2012-06-01

This pilot study was designed to determine whether cyclooxygenase (COX)-1, COX-2, or both are expressed in normal turtle tissues and whether level of expression changes when tissue becomes inflamed. Five eastern box turtles, Terrapene carolina carolina, that either died or were euthanatized due to disease or injuries were used for this work. Tissues were obtained from the five turtles. Western blot analysis was used to evaluate tissues for COX-1 and COX-2 proteins. Densiometric analysis was used to compare Western blot bands within each turtle. COX-1 and COX-2 were found in the liver, kidney, grossly normal muscle, and grossly traumatized (inflamed) muscle of all study turtles. In all cases, COX-1 and COX-2 proteins were increased in traumatized muscle over grossly normal nontraumatized muscle. The highest levels of COX-1 and COX-2 proteins were found in kidney and liver. There was no statistical difference between the amount of COX-1 protein in liver and kidney, but traumatized muscle compared with grossly normal muscle had significantly greater COX-1 but not COX 2 protein concentrations. There was no statistical difference between the amount of COX-2 protein in liver and kidney. Traumatized muscle expressed nonstatistically significant greater amounts of COX-2 compared with grossly normal muscle. COX-1 and COX-2 proteins are expressed in turtle tissues, and both isoforms are upregulated during inflammation of muscle tissue. Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) that block both COX isoforms might be more efficacious than COX-2-selective drugs. This work suggests that NSAIDs should be evaluated for potential liver and kidney toxicity in turtles.

The Roles of T-Box Genes in Vertebrate Limb Development.

Science.gov (United States)

Sheeba, C J; Logan, M P O

2017-01-01

Members of the T-box gene family have diverse roles during embryogenesis and many play critical roles in the developing limb. This is exemplified by the fact that, in humans, mutations in T-box genes are associated with several congenital syndromes that include limb defects as part of their characteristic spectrum of abnormalities. T-box genes encode for evolutionary conserved transcription factors that include both transcriptional activators and repressors. The hallmark of T-box gene members is the presence of the eponymous DNA-binding T-box domain. There are 17 mammalian T-box genes, which based on the sequence homology of the T-box domain, are grouped into five subfamilies, namely, T, Tbx1, Tbx2, Tbx6, and Tbr1. At least nine T-box genes are expressed during limb development with distinct and dynamic expression patterns. All four members of Tbx2 subfamily (Tbx2, Tbx3, Tbx4, Tbx5) and three members of Tbx1 (Tbx1, Tbx15, Tbx18), Brachyury (T) and Eomes (Tbr2) are expressed in the developing limb. © 2017 Elsevier Inc. All rights reserved.

Effects of a sitting boxing program on upper limb function, balance, gait, and quality of life in stroke patients.

Science.gov (United States)

Park, Junhyuck; Gong, Jihwan; Yim, Jongeun

2017-01-01

Boxing training including traditional stretching, muscular strength training, and duration training would be considered to be effective for improved functional stretching, dynamic balance, walking speed, and quality of life. We aimed to investigate upper limb function, balance, gait, and quality of life in stroke patients before and after a sitting boxing program. Twenty-six participants were randomly allocated to a boxing group (n = 13) and control group (n = 13) after the upper limb function, balance, gait, and quality of Life were recorded. The boxing group underwent a sitting boxing program (3 times/week) as well as conventional physical therapy (3 times/week) for 6 weeks. The control group only underwent conventional physical therapy (3 times/week) for 6 weeks. The Manual Functional Test (MFT), non-affected hand grip, Berg Balance Scale (BBS), velocity moment with eye opened, 10-m Walk Test (10 MWT), and Stroke-Specific Quality of Life questionnaire (SS-QOL) were significantly improved in the boxing group (p boxing group compared to the control group (p boxing program group had positive effects on upper extremity function, balance, gait, and quality of life in stroke patients.

Air tight electrical box

Energy Technology Data Exchange (ETDEWEB)

Pringle, C.G.

1990-08-14

An air-impervious electrical box to facilitate air sealing a house comprises an integral, rigid box body having a continuous flange, integral with the body, circumscribing and outwardly extending from the sides of the body. This flange is rearwardly positioned behind the front edges of the sides of the body a predetermined distance so that the electrical box may be secured to framing by nailing through the flange. Drywall is then secured to the frame on top of and adjecent to the flange. Such box eliminates the necessity for solid backing and minimizes passage of air through the box and space between the drywall and the box.

The F-box Protein KIB1 Mediates Brassinosteroid-Induced Inactivation and Degradation of GSK3-like Kinases in Arabidopsis.

Science.gov (United States)

Zhu, Jia-Ying; Li, Yuyao; Cao, Dong-Mei; Yang, Hongjuan; Oh, Eunkyoo; Bi, Yang; Zhu, Shengwei; Wang, Zhi-Yong

2017-06-01

The glycogen synthase kinase-3 (GSK3) family kinases are central cellular regulators highly conserved in all eukaryotes. In Arabidopsis, the GSK3-like kinase BIN2 phosphorylates a range of proteins to control broad developmental processes, and BIN2 is degraded through unknown mechanism upon receptor kinase-mediated brassinosteroid (BR) signaling. Here we identify KIB1 as an F-box E3 ubiquitin ligase that promotes the degradation of BIN2 while blocking its substrate access. Loss-of-function mutations of KIB1 and its homologs abolished BR-induced BIN2 degradation and caused severe BR-insensitive phenotypes. KIB1 directly interacted with BIN2 in a BR-dependent manner and promoted BIN2 ubiquitination in vitro. Expression of an F-box-truncated KIB1 caused BIN2 accumulation but dephosphorylation of its substrate BZR1 and activation of BR responses because KIB1 blocked BIN2 binding to BZR1. Our study demonstrates that KIB1 plays an essential role in BR signaling by inhibiting BIN2 through dual mechanisms of blocking substrate access and promoting degradation. Copyright © 2017 Elsevier Inc. All rights reserved.

The architecture of metal coordination groups in proteins.

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Harding, Marjorie M

2004-05-01

A set of tables is presented and a survey given of the architecture of metal coordination groups in a representative set of protein structures from the Protein Data Bank [Bernstein et al. (1977), J. Mol. Biol. 112, 535-542; Berman et al. (2000), Nucleic Acids Res. 28, 235-242]. The structures have been determined to a resolution of 2.5 A or better; the metals considered are Ca, Mg, Mn, Fe, Cu, Zn, Na and K, with particular emphasis on Ca and Zn and the exclusion of haem groups and Fe/S clusters; the proteins are a representative set in which none has more than 30% sequence identity with any other. In them the metal is coordinated by several donor groups from different amino-acid residues in the protein chain and often also by water or other small molecules. The tables, for approximately 600 metal coordination groups, include information on the conformations of the protein chain in the region around the metal and reliability indicators. They illustrate the wide variety of coordination numbers, chelate-loop sizes and other properties and the different characteristics of different metals. They show that glycine has a particular significance in the position adjacent to a donor residue, especially in Ca coordination groups. They also show that metal coordination does not appear to lead to significant distortions of the torsion angles phi, psi from their normally allowed values. Very few metal coordination groups occur more than once in the representative set and when they do they are usually related in fold and function; they have similar but not necessarily identical conformations. However, individual chelate loops, for example Zn(-C-X-X'-C-), in which both cysteines are coordinated to Zn through S, and X and X' are any amino acids, are repeated frequently in many different and unrelated proteins. Not all chelate loops with the same composition have the same conformation, but for smaller loops there are usually one or two strongly preferred and well defined

In vivo mapping of the functional regions of the DEAD-box helicase Vasa

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Mehrnoush Dehghani

2015-03-01

Full Text Available The maternally expressed Drosophila melanogaster DEAD-box helicase Vasa (Vas is necessary for many cellular and developmental processes, including specification of primordial germ cells (pole cells, posterior patterning of the embryo, piRNA-mediated repression of transposon-encoded mRNAs, translational activation of gurken (grk mRNA, and completion of oogenesis itself. Vas protein accumulates in the perinuclear nuage in nurse cells soon after their specification, and then at stage 10 Vas translocates to the posterior pole plasm of the oocyte. We produced a series of transgenic constructs encoding eGFP-Vas proteins carrying mutations affecting different regions of the protein, and analyzed in vivo which Vas functions each could support. We identified novel domains in the N- and C-terminal regions of the protein that are essential for localization, transposon repression, posterior patterning, and pole cell specification. One such functional region, the most C-terminal seven amino acids, is specific to Vas orthologues and is thus critical to distinguishing Vas from other closely related DEAD-box helicases. Surprisingly, we also found that many eGFP-Vas proteins carrying mutations that would be expected to abrogate DEAD-box helicase function localized to the nuage and posterior pole, and retained the capacity to support oogenesis, although they did not function in embryonic patterning, pole cell specification, grk activation, or transposon repression. We conclude from these experiments that Vas, a multifunctional protein, uses different domains and different molecular associations to carry out its various cellular and developmental roles.

Protein Interaction Screening for the Ankyrin Repeats and Suppressor of Cytokine Signaling (SOCS) Box (ASB) Family Identify Asb11 as a Novel Endoplasmic Reticulum Resident Ubiquitin Ligase

DEFF Research Database (Denmark)

Andresen, Christina Aaen; Smedegaard, Stine; Sylvestersen, Kathrine Beck

2014-01-01

The Ankyrin and SOCS (Suppressor of Cytokine Signaling) box (ASB) family of proteins function as the substrate recognition subunit in a subset of Elongin-Cullin-SOCS (ECS) E3 ubiquitin ligases. Despite counting with 18 members in humans, the identity of the physiological targets of the Asb protei...

CASAS: A Smart Home in a Box.

Science.gov (United States)

Cook, Diane J; Crandall, Aaron S; Thomas, Brian L; Krishnan, Narayanan C

2013-07-01

While the potential benefits of smart home technology are widely recognized, a lightweight design is needed for the benefits to be realized at a large scale. We introduce the CASAS "smart home in a box", a lightweight smart home design that is easy to install and provides smart home capabilities out of the box with no customization or training. We discuss types of data analysis that have been performed by the CASAS group and can be pursued in the future by using this approach to designing and implementing smart home technologies.

Novel functions of prototype foamy virus Gag glycine- arginine-rich boxes in reverse transcription and particle morphogenesis.

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Müllers, Erik; Uhlig, Tobias; Stirnnagel, Kristin; Fiebig, Uwe; Zentgraf, Hanswalter; Lindemann, Dirk

2011-02-01

Prototype foamy virus (PFV) Gag lacks the characteristic orthoretroviral Cys-His motifs that are essential for various steps of the orthoretroviral replication cycle, such as RNA packaging, reverse transcription, infectivity, integration, and viral assembly. Instead, it contains three glycine-arginine-rich boxes (GR boxes) in its C terminus that putatively represent a functional equivalent. We used a four-plasmid replication-deficient PFV vector system, with uncoupled RNA genome packaging and structural protein translation, to analyze the effects of deletion and various substitution mutations within each GR box on particle release, particle-associated protein composition, RNA packaging, DNA content, infectivity, particle morphology, and intracellular localization. The degree of viral particle release by all mutants was similar to that of the wild type. Only minimal effects on Pol encapsidation, exogenous reverse transcriptase (RT) activity, and genomic viral RNA packaging were observed. In contrast, particle-associated DNA content and infectivity were drastically reduced for all deletion mutants and were undetectable for all alanine substitution mutants. Furthermore, GR box I mutants had significant changes in particle morphology, and GR box II mutants lacked the typical nuclear localization pattern of PFV Gag. Finally, it could be shown that GR boxes I and III, but not GR box II, can functionally complement each other. It therefore appears that, similar to the orthoretroviral Cys-His motifs, the PFV Gag GR boxes are important for RNA encapsidation, genome reverse transcription, and virion infectivity as well as for particle morphogenesis.

Transcriptional regulation by Polycomb group proteins

DEFF Research Database (Denmark)

Di Croce, Luciano; Helin, Kristian

2013-01-01

Polycomb group (PcG) proteins are epigenetic regulators of transcription that have key roles in stem-cell identity, differentiation and disease. Mechanistically, they function within multiprotein complexes, called Polycomb repressive complexes (PRCs), which modify histones (and other proteins......) and silence target genes. The dynamics of PRC1 and PRC2 components has been the focus of recent research. Here we discuss our current knowledge of the PRC complexes, how they are targeted to chromatin and how the high diversity of the PcG proteins allows these complexes to influence cell identity....

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

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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.

Up-regulation of TLR2 and TLR4 in high mobility group Box1-stimulated macrophages in pulpitis patients

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Mahmoudi, Javad; Sabermarouf, Babak; Baradaran, Behzad; Sadat-Hatamnezhad, Leila; Shotorbani, Siamak Sandoghchian

2017-01-01

Objective(s): High Mobility Group Box1 (HMGB1) is a nonhistone, DNA-binding protein that serves a crucial role in regulating gene transcription and is involved in a variety of proinflammatory, extracellular activities. The aim of this study was to explore whether HMGB1 stimulation can up-regulate the expression of Toll-like Receptor 2 (TLR2) and Toll-like Receptor 4 (TLR4) on macrophages from pulpitis and to clarify the subsequent events involving Th17 cells and Th17 cell-associated cytokine changes. Materials and Methods: Having prepared dental pulp tissues of pulpitis and healthy controls, macrophage were isolated and cultured. Macrophages were thereafter stimulated by HMGB1 time course. RT-QPCR, flowcytometer, immunofluorescence, Western blotting, and ELISA techniques were used in the present research. Results: Our results showed that the expression of TLR2 and TLR4 on macrophages stimulated with HMGB1 increased in pulpitis compared with controls (macrophages without HMGB1 stimulation) with a statistical significance (Ppulpitis increased, and NF-kB, the downstream target of TLR2 and TLR4, also showed a marked elevation after macrophages’ stimulation by HMGB1. Conclusion: The evidence from the present study suggests that the enhanced TLR2 and TLR4 pathways and Th17 cell polarization may be due to HMGB1 stimulation in pulpitis. PMID:28293399

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

-infected patients and all infected patients, the area under the curve for HMGB1 was 0.59 (P white blood cell count, neutrophils, C-reactive protein, interleukin-6, procalcitonin, and lipopolysaccharide-binding protein (P

The F-box protein Cdc4/Fbxw7 is a novel regulator of neural crest development in Xenopus laevis

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Hartley Rebecca S

2010-01-01

Full Text Available Abstract Background The neural crest is a unique population of cells that arise in the vertebrate ectoderm at the neural plate border after which they migrate extensively throughout the embryo, giving rise to a wide range of derivatives. A number of proteins involved in neural crest development have dynamic expression patterns, and it is becoming clear that ubiquitin-mediated protein degradation is partly responsible for this. Results Here we demonstrate a novel role for the F-box protein Cdc4/Fbxw7 in neural crest development. Two isoforms of Xenopus laevis Cdc4 were identified, and designated xCdc4α and xCdc4β. These are highly conserved with vertebrate Cdc4 orthologs, and the Xenopus proteins are functionally equivalent in terms of their ability to degrade Cyclin E, an established vertebrate Cdc4 target. Blocking xCdc4 function specifically inhibited neural crest development at an early stage, prior to expression of c-Myc, Snail2 and Snail. Conclusions We demonstrate that Cdc4, an ubiquitin E3 ligase subunit previously identified as targeting primarily cell cycle regulators for proteolysis, has additional roles in control of formation of the neural crest. Hence, we identify Cdc4 as a protein with separable but complementary functions in control of cell proliferation and differentiation.

Forkhead box transcription factors in embryonic heart development and congenital heart disease.

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Zhu, Hong

2016-01-01

Embryonic heart development is a very complicated process regulated precisely by a network composed of many genes and signaling pathways in time and space. Forkhead box (Fox, FOX) proteins are a family of transcription factors characterized by the presence of an evolutionary conserved "forkhead"or "winged-helix" DNA-binding domain and able to organize temporal and spatial gene expression during development. They are involved in a wide variety of cellular processes, such as cell cycle progression, proliferation, differentiation, migration, metabolism and DNA damage response. An abundance of studies in model organisms and systems has established that Foxa2, Foxc1/c2, Foxh1 and Foxm1, Foxos and Foxps are important components of the signaling pathways that instruct cardiogenesis and embryonic heart development, playing paramount roles in heart development. The previous studies also have demonstrated that mutations in some of the forkhead box genes and the aberrant expression of forkhead box gene are heavily implicated in the congenital heart disease (CHD) of humans. This review primarily focuses on the current understanding of heart development regulated by forkhead box transcription factors and molecular genetic mechanisms by which forkhead box factors modulate heart development during embryogenesis and organogenesis. This review also summarizes human CHD related mutations in forkhead box genes as well as the abnormal expression of forkhead box gene, and discusses additional possible regulatory mechanisms of the forkhead box genes during embryonic heart development that warrant further investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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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.

Medical and Safety Reforms in Boxing

Science.gov (United States)

Jordan, Barry D.

1988-01-01

The continued existence of boxing as an accepted sport in civilized society has been long debated. The position of the American Medical Association (AMA) has evolved from promoting increased safety and medical reform to recommending total abolition of both amateur and professional boxing. In response to the AMA opposition to boxing, the boxing community has attempted to increase the safeguards in amateur and professional boxing. The United States of America Amateur Boxing Federation, which is the national regulatory agency for all amateur boxing in the United States, has taken several actions to prevent the occurrence of acute brain injury and is currently conducting epidemiologic studies to assess the long-term neuropsychologic consequences of amateur boxing. In professional boxing, state regulatory agencies such as the New York State Athletic Commission have introduced several medical interventions to prevent and reduce neurologic injury. The lack of a national regulatory agency to govern professional boxing has stimulated the formation of the Association of Boxing Commissions and potential legislation for the federal regulation of professional boxing by a federally chartered organization called the United States Boxing Commission. The AMA's opposition to boxing and the medical and safety reforms implemented by the proponents of boxing are discussed. PMID:3385788

Glove box

International Nuclear Information System (INIS)

Morita, Atsushi

1990-01-01

Wire rope earthquake proof supports having sufficient vibration transmitting and attenuating property are disposed between a fixed floor and the bottom of a glove box in order to improve earthquake proofness of the glove box. The vertical weight of the glove box is supported by support legs slidable on the surface of the fixed floor. The wire rope earthquake-proof supports when undergoing a load, cause stretching and rolling against the external force such as earthquakes, and provide flexible spring support and cause a great damping due to friction with strands. Further, the vertical weight is always supported by the support legs and, when a horizontal weight is applied, the glove box slides on the fixed floor freely with slidable members. In this way, stress concentration generated at joint portions of columns and beams can be moderated greatly and earthquake proofness can be improved. Further, quality control and maintenance for the device is almost unnecessary owing to excellent fatigue-resistant characteristics of the wire rope earthquake proof supports. (N.H.)

The rice F-box protein KISS ME DEADLY2 functions as a negative regulator of cytokinin signalling.

Science.gov (United States)

Kim, Hyo Jung; Kieber, Joseph J; Schaller, G Eric

2013-01-01

Cytokinins are plant hormones that play critical roles in growth and development. We recently determined that the transcriptional response to cytokinin of Arabidopsis is modulated by the KISS ME DEADLY (KMD) family of F-box proteins. Here we demonstrate a conserved function for a member of the rice KMD family. Ectopic overexpression of OsKMD2 in Arabidopsis results in decreased cytokinin sensitivity based on a hypocotyl growth response assay, the decrease in sensitivity correlating with a decrease in the levels of the transcriptional regulator AtARR12. Furthermore, OsKMD2 directly interacts with AtARR12 based on yeast two-hybrid and co-immunoprecipitation assays. These results indicate that both monocots and dicots employ a similar KMD-dependent mechanism to regulate the transcriptional response to cytokinin.

Bento Boxes

Science.gov (United States)

Hasio, Cindy

2010-01-01

Bento boxes are common objects in Japanese culture, designed to hold enough lunch for one person. They have individual compartments and sometimes multiple tiers for rice, vegetables, and other side dishes. They are made of materials ranging from wood, cloth, aluminum, or plastic. In general, the greater the number of foods, the better the box is…

Genome-wide identification and characterization of the SBP-box gene family in Petunia.

Science.gov (United States)

Zhou, Qin; Zhang, Sisi; Chen, Feng; Liu, Baojun; Wu, Lan; Li, Fei; Zhang, Jiaqi; Bao, Manzhu; Liu, Guofeng

2018-03-12

SQUAMOSA PROMOTER BINDING PROTEIN (SBP)-box genes encode a family of plant-specific transcription factors (TFs) that play important roles in many growth and development processes including phase transition, leaf initiation, shoot and inflorescence branching, fruit development and ripening etc. The SBP-box gene family has been identified and characterized in many species, but has not been well studied in Petunia, an important ornamental genus. We identified 21 putative SPL genes of Petunia axillaris and P. inflata from the reference genome of P. axillaris N and P. inflata S6, respectively, which were supported by the transcriptome data. For further confirmation, all the 21 genes were also cloned from P. hybrida line W115 (Mitchel diploid). Phylogenetic analysis based on the highly conserved SBP domains arranged PhSPLs in eight groups, analogous to those from Arabidopsis and tomato. Furthermore, the Petunia SPL genes had similar exon-intron structure and the deduced proteins contained very similar conserved motifs within the same subgroup. Out of 21 PhSPL genes, fourteen were predicted to be potential targets of PhmiR156/157, and the putative miR156/157 response elements (MREs) were located in the coding region of group IV, V, VII and VIII genes, but in the 3'-UTR regions of group VI genes. SPL genes were also identified from another two wild Petunia species, P. integrifolia and P. exserta, based on their transcriptome databases to investigate the origin of PhSPLs. Phylogenetic analysis and multiple alignments of the coding sequences of PhSPLs and their orthologs from wild species indicated that PhSPLs were originated mainly from P. axillaris. qRT-PCR analysis demonstrated differential spatiotemperal expression patterns of PhSPL genes in petunia and many were expressed predominantly in the axillary buds and/or inflorescences. In addition, overexpression of PhSPL9a and PhSPL9b in Arabidopsis suggested that these genes play a conserved role in promoting the vegetative

Anti-high mobility group box-1 antibody therapy for traumatic brain injury.

Science.gov (United States)

Okuma, Yu; Liu, Keyue; Wake, Hidenori; Zhang, Jiyong; Maruo, Tomoko; Date, Isao; Yoshino, Tadashi; Ohtsuka, Aiji; Otani, Naoki; Tomura, Satoshi; Shima, Katsuji; Yamamoto, Yasuhiko; Yamamoto, Hiroshi; Takahashi, Hideo K; Mori, Shuji; Nishibori, Masahiro

2012-09-01

High mobility group box-1 (HMGB1) plays an important role in triggering inflammatory responses in many types of diseases. In this study, we examined the involvement of HMGB1 in traumatic brain injury (TBI) and evaluated the ability of intravenously administered neutralizing anti-HMGB1 monoclonal antibody (mAb) to attenuate brain injury. Traumatic brain injury was induced in rats or mice by fluid percussion. Anti-HMGB1 mAb or control mAb was administered intravenously after TBI. Anti-HMGB1 mAb remarkably inhibited fluid percussion-induced brain edema in rats, as detected by T2-weighted magnetic resonance imaging; this was associated with inhibition of HMGB1 translocation, protection of blood-brain barrier (BBB) integrity, suppression of inflammatory molecule expression, and improvement of motor function. In contrast, intravenous injection of recombinant HMGB1 dose-dependently produced the opposite effects. Experiments using receptor for advanced glycation end product (RAGE)(-/-) , toll-like receptor-4 (TLR4)(-/-) , and TLR2(-/-) mice suggested the involvement of RAGE as the predominant receptor for HMGB1. Anti-HMGB1 mAb may provide a novel and effective therapy for TBI by protecting against BBB disruption and reducing the inflammatory responses induced by HMGB1. Copyright © 2012 American Neurological Association.

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

International Nuclear Information System (INIS)

Tong, Wei; Wang, Wei; Huang, Jing; Ren, Ning; Wu, Sheng-Xi; Li, Yong-Qi

2010-01-01

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.

[Boxing: traumatology and prevention].

Science.gov (United States)

Cabanis, Emmanuel-Alain; Iba-Zizen, Marie-Thérèse; Perez, Georges; Senegas, Xavier; Furgoni, Julien; Pineau, Jean-Claude; Louquet, Jean-Louis; Henrion, Roger

2010-10-01

In 1986, a surgeon who, as an amateur boxer himself was concerned with boxers' health, approached a pioneering Parisian neuroimaging unit. Thus began a study in close cooperation with the French Boxing Federation, spanning 25 years. In a first series of 52 volunteer boxers (13 amateurs and 39 professionals), during which MRI gradually replaced computed tomography, ten risk factors were identified, which notably included boxing style: only one of 40 "stylists" with a good boxing technique had cortical atrophy (4.5 %), compared to 15 % of "sloggers". Changes to the French Boxing Federation rules placed the accent on medical prevention. The second series, of 247 boxers (81 amateurs and 266 professionals), showed a clear improvement, as lesions were suspected in 14 individuals, of which only 4 (1.35 %) were probably due to boxing. The third and fourth series were part of a protocol called "Brain-Boxing-Ageing", which included 76 boxers (11 having suffered KOs) and 120 MRI scans, with reproducible CT and MRI acquisitions (9 sequences with 1.5 T then 3 T, and CT). MRI anomalies secondary to boxing were found in 11 % of amateurs and 38 % of professionals (atrophy, high vascular T2 signal areas, 2 cases of post-KO subdural bleeding). CT revealed sinus damage in 13 % of the amateurs and 19 % of the professionals. The risk of acute and chronic facial and brain damage was underline, along with detailed precautionary measures (organization of bouts, role of the referee and ringside doctor, and application of French Boxing Federation rules).

[Expression of high mobility group box-1 in the lung tissue and serum of patients with pulmonary tuberculosis].

Science.gov (United States)

Yang, Xiao-min; Yang, Hua

2013-07-01

To explore the expression of high mobility group box-1 (HMGB1) in the lung tissue and serum of patients with pulmonary tuberculosis and to explore its relationship with tumor necrosis factor (TNF)-α and interleukin(IL)-1β. Sixty samples of lung tissues were obtained from patients with pulmonary tuberculosis who had underwent pneumonectomy in Department of Chest Surgery, First Affiliated Hospital of Zunyi Medical College from June 2010 to December 2011. At the same period, 40 normal lung samples were also obtained from patients with pulmonary contusion and lung cancer by surgical resections as the control group. The mRNA expressions of HMGB1 was detected by reverse transcription-polymerase chain reaction (RT-PCR), and the protein level of HMGB1 was measured by immunohistochemical staining of tissue microarrays in lung tissue. Blood samples were taken from 89 patients with active pulmonary tuberculosis (pulmonary tuberculosis group), including hematogenous disseminated pulmonary tuberculosis (type II) in 35 cases and secondary pulmonary tuberculosis (type III) in 54 cases, and 50 healthy volunteers (control group). Furthermore, the 54 patients with secondary pulmonary tuberculosis were divided into different subgroups according to cavity formation and the lung fields involved: patients without lung cavity (35 cases) vs those with lung cavity (19 cases), patients with involvement of pulmonary tuberculosis (69 ± 29) was significantly higher than that in normal lung tissue (22 ± 12) (t = 2.389, P pulmonary tuberculosis (786 ± 86) was significantly higher than that in normal lung tissue (202 ± 60) (t = 3.872, P pulmonary tuberculosis group were (5.0 ± 3.2) µg/L, (118 ± 77) ng/L and (33 ± 20) ng/L, respectively, which were significantly higher than those in the control group [(1.7 ± 1.0) µg/L, (40 ± 11) ng/L and (18 ± 12) ng/L, respectively], the respective t values being -0.928, 4.268 and 11.064, all P pulmonary tuberculosis, the serum concentration of HMGB

Genome-wide identification and analysis of the SBP-box family genes in apple (Malus × domestica Borkh.).

Science.gov (United States)

Li, Jun; Hou, Hongmin; Li, Xiaoqin; Xiang, Jiang; Yin, Xiangjing; Gao, Hua; Zheng, Yi; Bassett, Carole L; Wang, Xiping

2013-09-01

SQUAMOSA promoter binding protein (SBP)-box genes encode a family of plant-specific transcription factors and play many crucial roles in plant development. In this study, 27 SBP-box gene family members were identified in the apple (Malus × domestica Borkh.) genome, 15 of which were suggested to be putative targets of MdmiR156. Plant SBPs were classified into eight groups according to the phylogenetic analysis of SBP-domain proteins. Gene structure, gene chromosomal location and synteny analyses of MdSBP genes within the apple genome demonstrated that tandem and segmental duplications, as well as whole genome duplications, have likely contributed to the expansion and evolution of the SBP-box gene family in apple. Additionally, synteny analysis between apple and Arabidopsis indicated that several paired homologs of MdSBP and AtSPL genes were located in syntenic genomic regions. Tissue-specific expression analysis of MdSBP genes in apple demonstrated their diversified spatiotemporal expression patterns. Most MdmiR156-targeted MdSBP genes, which had relatively high transcript levels in stems, leaves, apical buds and some floral organs, exhibited a more differential expression pattern than most MdmiR156-nontargeted MdSBP genes. Finally, expression analysis of MdSBP genes in leaves upon various plant hormone treatments showed that many MdSBP genes were responsive to different plant hormones, indicating that MdSBP genes may be involved in responses to hormone signaling during stress or in apple development. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Obtention of a prosthetic group for labelling of radioiodinated proteins

International Nuclear Information System (INIS)

Santos, Josefina da S.; Colturato, Maria Tereza; Araujo, Elaine B. de

2000-01-01

Antibodies and peptides labeled with radionuclides has been extensively used in radioimmunotherapy and radioimmunodetection. The principal problem with the use of radioiodinated proteins is the in vivo dehalogenation. The use of prosthetic groups for indirect labeling of proteins with radioiodine has showed to be useful on labeling proteins with greater in vivo stability. A procedure is described for the preparation of an radioiodinated prosthetic group (N-succinimidyl 4-radioiodine-benzoate-SIB), using procedure described by Stocklin et al, with the iodination of p-bromo-benzoic acid and subsequent reaction with TSTU. Preliminary labeling results showed that the prosthetic group can be obtained in a good yield. The coupling of the SIB to the protein will be studied using human IgG as protein model. (author)

Production of radioiodinated prosthetic group for indirect protein labeling

International Nuclear Information System (INIS)

Santos, Josefina da Silva

2001-01-01

Monoclonal antibodies and their fragments and, more recently, radiolabeled peptides have been extensively studied in order to develop radiopharmaceuticals for diagnostic and therapy in Nuclear Medicine. The radioiodination of proteins can be done by a direct method, with radioiodine being incorporated in to a tyrosine residue of the protein by electrophilic substitution. The main problem in the use of radioiodinated proteins, is that they are often dehalogenated in vivo by the action of specific enzymes, probably because of the structural similarity between iodophenyl groups and thyroid hormones. Several protein radioiodination methods have been developed in order to minimize this in vivo dehalogenation using prosthetic groups for indirect labeling. In this case, the radioiodine is first incorporated in to the prosthetic group that is subsequently attached to a terminal amino group or to a ε-amino group of lysine residue. The aim of this work is to obtain a radioiodinated prosthetic group for indirect labeling of proteins. The prosthetic group selected was the N-succinimidyl-4-radioiodine benzoate (SIB), obtained by the iodination of the p-bromobenzoic acid followed by the reaction with TSTU (0-(N-succinimidyl)-N,N,N',N'-tetramethyl uronium tetrafluoroborate) The results of these studies showed that the p-radio iodobenzoic acid was obtained with a radiochemical purity greater than 92% and a labeling yield of about 65%. Some reaction parameters were studied like temperature, time and Cu Cl mass (cataliser). The SIB was quantitatively obtained from p-radio iodobenzoic acid, using basic medium and after removing the water from the reaction using an nitrogen stream. The kinetic of this reaction is very fast with complete consumption of the p-radioiodebenzoic acid after 5 minutes. The coupling of the SIB prosthetic group to the protein was studied using Human Immunoglobulin (IgG) as a protein model. In a comparative way, the same protein was used on direct labeling

High Expression of High-Mobility Group Box 1 in Menstrual Blood: Implications for Endometriosis.

Science.gov (United States)

Shimizu, Keiko; Kamada, Yasuhiko; Sakamoto, Ai; Matsuda, Miwa; Nakatsuka, Mikiya; Hiramatsu, Yuji

2017-11-01

Endometriosis is a benign gynecologic disease characterized by the presence of ectopic endometrium and associated with inflammation and immune abnormalities. However, the molecular basis for endometriosis is not well understood. To address this issue, the present study examined the expression of high-mobility group box (HMGB) 1 in menstrual blood to investigate its role in the ectopic growth of human endometriotic stromal cells (ESCs). A total of 139 patients were enrolled in this study; 84 had endometriosis and 55 were nonendometriotic gynecological patients (control). The HMGB1 levels in various fluids were measured by enzyme-linked immunosorbent assay. Expression of receptor for advanced glycation end products (RAGE) in eutopic and ectopic endometrium was assessed by immunohistochemistry, and RAGE and vascular endothelial growth factor ( VEGF) messenger RNA expression in HMGB1- and lipopolysaccharide (LPS)-treated ESCs was evaluated by real-time polymerase chain reaction. The HMGB1 concentration was higher in menstrual blood than in serum or peritoneal fluid ( P endometriosis following retrograde menstruation when complexed with other factors such as LPS by inducing inflammation and angiogenesis.

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.

Induction of fibroblast growth factor 21 does not require activation of the hepatic X-box binding protein 1 in mice

Directory of Open Access Journals (Sweden)

Shantel Olivares

2017-12-01

Full Text Available Objective: Fibroblast growth factor 21 (FGF21, a key regulator of the metabolic response to fasting, is highly induced by endoplasmic reticulum (ER stress. The X-box binding protein 1 (Xbp1 is one of several ER stress proteins that has been shown to directly activate the FGF21 promoter. We aimed to determine whether hepatic Xbp1 is required for induction of hepatic FGF21 in vivo. Methods: Mice bearing a hepatocyte-specific deletion of Xbp1 (Xbp1LKO were subjected to fasting, pharmacologic ER stress, or a ketogenic diet, all potent stimuli of Fgf21 expression. Results: Hepatocyte-specific Xbp1 knockout mice demonstrated normal induction of FGF21 in response to fasting or pharmacologic ER stress and enhanced induction of FGF21 in response to a ketogenic diet. Consistent with preserved induction of FGF21, Xbp1LKO mice exhibited normal induction of FGF21 target genes and normal ketogenesis in response to fasting or a ketogenic diet. Conclusion: Hepatic Xbp1 is not required for induction of FGF21 under physiologic or pathophysiologic conditions in vivo. Keywords: Unfolded protein response, Endoplasmic reticulum stress, Fasting, Fatty acid oxidation, Ketogenic diet

Boxing-related head injuries.

Science.gov (United States)

Jayarao, Mayur; Chin, Lawrence S; Cantu, Robert C

2010-10-01

Fatalities in boxing are most often due to traumatic brain injury that occurs in the ring. In the past 30 years, significant improvements in ringside and medical equipment, safety, and regulations have resulted in a dramatic reduction in the fatality rate. Nonetheless, the rate of boxing-related head injuries, particularly concussions, remains unknown, due in large part to its variability in clinical presentation. Furthermore, the significance of repeat concussions sustained when boxing is just now being understood. In this article, we identify the clinical manifestations, pathophysiology, and management of boxing-related head injuries, and discuss preventive strategies to reduce head injuries sustained by boxers.

Exergaming boxing versus heavy-bag boxing: are these equipotent for individuals with spinal cord injury?

Science.gov (United States)

Mat Rosly, Maziah; Mat Rosly, Hadi; Hasnan, Nazirah; Davis, Glen M; Husain, Ruby

2017-08-01

Current strategies for increased physical activity and exercise in individuals with spinal cord injury (SCI) face many challenges with regards to maintaining their continuity of participation. Barriers cited often include problems with accessing facilities, mundane, monotonous or boring exercises and expensive equipment that is often not adapted for wheelchair users. To compare the physiological responses and user preferences between conventional heavy-bag boxing against a novel form of video game boxing, known as exergaming boxing. Cross-sectional study. Exercise laboratory setting in a university medical center. Seventeen participants with SCI were recruited, of which sixteen were male and only one female. Their mean age was 35.6±10.2 years. All of them performed a 15-minute physical exercise session of exergaming and heavy-bag boxing in a sitting position. The study assessed physiological responses in terms of oxygen consumption, metabolic equivalent (MET) and energy expenditure between exergaming and heavy-bag boxing derived from open-circuit spirometry. Participants also rated their perceived exertion using Borg's category-ratio ratings of perceived exertion. Both exergaming (MET: 4.3±1.0) and heavy-bag boxing (MET: 4.4±1.0) achieved moderate exercise intensities in these participants with SCI. Paired t-test revealed no significant differences (P>0.05, Cohen's d: 0.02-0.49) in the physiological or perceived exertional responses between the two modalities of boxing. Post session user survey reported all the participants found exergaming boxing more enjoyable. Exergaming boxing, was able to produce equipotent physiological responses as conventional heavy-bag boxing. The intensity of both exercise modalities achieved recommended intensities for health and fitness benefits. Exergaming boxing have the potential to provide an enjoyable, self-competitive environment for moderate-vigorous exercise even at the comfort of their homes.

Somatotype analysis of elite boxing athletes compared with nonathletes for sports physiotherapy.

Science.gov (United States)

Noh, Ji-Woong; Kim, Ju-Hyun; Kim, Mee-Young; Lee, Jeong-Uk; Lee, Lim-Kyu; Park, Byoung-Sun; Yang, Seung-Min; Jeon, Hye-Joo; Lee, Won-Deok; Kwak, Taek-Yong; Jang, Sung-Ho; Lee, Tae-Hyun; Kim, Ju-Young; Kim, Junghwan

2014-08-01

[Purpose] The purpose of this study was to show somatotype and physical characteristic differences between elite boxing athletes and non-athletes. [Methods] The somatotypes of 23 elite boxing athletes and 23 nonathletes were measured with the Heath-Carter method. The subjects were divided into four weight divisions as follows: lightweight, light middleweight, middleweight, and heavyweight class. [Results] The endomorphic component values of the boxing athletes were lower than those of the nonathletes. However, the mesomorphic component values of the boxing athletes were higher than those of the nonathletes. There was no significant difference in the ectomorphic component between the two groups. The higher weight divisions tended to have higher values of height, weight, and BMI than the lower weight divisions. The higher weight divisions also tended to have higher values for the endomorphic and mesomorphic components and a lower value for the ectomorphic component than the lower weight divisions. The group of nonathletes consisted of eight endomorphs, four mesomorphs, six ectomorphs, and five central types. Among the boxing athletes, there were 16 mesomorphic, four ectomorphic, and two central types and one endomorphic type. Subdividing the athletes into 13 somatotypes resulted in five balanced mesomorphs, five endomorphic mesomorphs, five mesomorph-ectomorphs, three mesomorph-endomorphs, two mesomorphic ectomorphs, two central types, and one ectomorphic mesomorph type. [Conclusion] The data from this study provides in part physical characteristics of elite boxing athletes that can be used to establish a reference for systemic study of sports physiotherapy.

Phylogenetic continuum indicates "galaxies" in the protein universe: preliminary results on the natural group structures of proteins.

Science.gov (United States)

Ladunga, I

1992-04-01

The markedly nonuniform, even systematic distribution of sequences in the protein "universe" has been analyzed by methods of protein taxonomy. Mapping of the natural hierarchical system of proteins has revealed some dense cores, i.e., well-defined clusterings of proteins that seem to be natural structural groupings, possibly seeds for a future protein taxonomy. The aim was not to force proteins into more or less man-made categories by discriminant analysis, but to find structurally similar groups, possibly of common evolutionary origin. Single-valued distance measures between pairs of superfamilies from the Protein Identification Resource were defined by two chi 2-like methods on tripeptide frequencies and the variable-length subsequence identity method derived from dot-matrix comparisons. Distance matrices were processed by several methods of cluster analysis to detect phylogenetic continuum between highly divergent proteins. Only well-defined clusters characterized by relatively unique structural, intracellular environmental, organismal, and functional attribute states were selected as major protein groups, including subsets of viral and Escherichia coli proteins, hormones, inhibitors, plant, ribosomal, serum and structural proteins, amino acid synthases, and clusters dominated by certain oxidoreductases and apolar and DNA-associated enzymes. The limited repertoire of functional patterns due to small genome size, the high rate of recombination, specific features of the bacterial membranes, or of the virus cycle canalize certain proteins of viruses and Gram-negative bacteria, respectively, to organismal groups.

The Mind as Black Box: A Simulation of Theory Building in Psychology.

Science.gov (United States)

Hildebrandt, Carolyn; Oliver, Jennifer

2000-01-01

Discusses an activity that uses the metaphor "the mind is a black box," in which students work in groups to discover what is inside a sealed, black, plastic box. States that the activity enables students to understand the need for theories in psychology and to comprehend how psychologists build, test, and refine those theories. (CMK)

Invariant box-parameterization of neutrino oscillations

International Nuclear Information System (INIS)

Weiler, Thomas J.; Wagner, DJ

1998-01-01

The model-independent 'box' parameterization of neutrino oscillations is examined. The invariant boxes are the classical amplitudes of the individual oscillating terms. Being observables, the boxes are independent of the choice of parameterization of the mixing matrix. Emphasis is placed on the relations among the box parameters due to mixing-matrix unitarity, and on the reduction of the number of boxes to the minimum basis set. Using the box algebra, we show that CP-violation may be inferred from measurements of neutrino flavor mixing even when the oscillatory factors have averaged. General analyses of neutrino oscillations among n≥3 flavors can readily determine the boxes, which can then be manipulated to yield magnitudes of mixing matrix elements

A Novel Image Encryption Based on Algebraic S-box and Arnold Transform

Science.gov (United States)

Farwa, Shabieh; Muhammad, Nazeer; Shah, Tariq; Ahmad, Sohail

2017-09-01

Recent study shows that substitution box (S-box) only cannot be reliably used in image encryption techniques. We, in this paper, propose a novel and secure image encryption scheme that utilizes the combined effect of an algebraic substitution box along with the scrambling effect of the Arnold transform. The underlying algorithm involves the application of S-box, which is the most imperative source to create confusion and diffusion in the data. The speciality of the proposed algorithm lies, firstly, in the high sensitivity of our S-box to the choice of the initial conditions which makes this S-box stronger than the chaos-based S-boxes as it saves computational labour by deploying a comparatively simple and direct approach based on the algebraic structure of the multiplicative cyclic group of the Galois field. Secondly the proposed method becomes more secure by considering a combination of S-box with certain number of iterations of the Arnold transform. The strength of the S-box is examined in terms of various performance indices such as nonlinearity, strict avalanche criterion, bit independence criterion, linear and differential approximation probabilities etc. We prove through the most significant techniques used for the statistical analyses of the encrypted image that our image encryption algorithm satisfies all the necessary criteria to be usefully and reliably implemented in image encryption applications.

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.

Comprehensive Cloning of Prunus mume Dormancy Associated MADS-Box Genes and Their Response in Flower Bud Development and Dormancy

Directory of Open Access Journals (Sweden)

Kai Zhao

2018-02-01

Full Text Available Dormancy Associated MADS-box genes are SVP/MADs-box members and supposed to play crucial roles in plant dormancy of perennial species. In Prunus mume, PmDAM6 has been previously identified to induce plant dormancy. In the current study, six PmDAMs were cloned in P. mume and functionally analyzed in yeast and tobacco to detect the roles of the genes paralogous to PmDAM6. The expression patterns together with sequence similarities indicate that PmDAMs are divided into two sub-clades within SVP group. Moreover, PmDAMs are verified to take part in the development of different plant organs, specifically the flower buds, in some intricate patterns. Furthermore, the PmDAM proteins are found to have special functions by forming corresponding protein complex during the development of flower bud and induction of dormancy. In particular, when PmDAM1 dominating in flower bud in the warm months, the protein complexes are consisted of PmDAM1 itself or with PmDAM2. With the decrease temperatures in the following months, PmDAM6 was found to be highly expressed and gradually changed the complex structure to PmDAM6-protein complex due to strong binding tendencies with PmDAM1 and PmDAM3. Finally, the homodimers of PmDAM6 prevailed to induce the dormancy. The results obtained in the current study highlight the functions of PmDAMs in the tissue development and dormancy, which provide available suggestions for further explorations of protein-complex functions in association with bud growth and dormancy.

TIF1alpha: a possible link between KRAB zinc finger proteins and nuclear receptors

DEFF Research Database (Denmark)

Le Douarin, B; You, J; Nielsen, Anders Lade

1998-01-01

Ligand-induced gene activation by nuclear receptors (NRs) is thought to be mediated by transcriptional intermediary factors (TIFs), that interact with their ligand-dependent AF-2 activating domain. Included in the group of the putative AF-2 TIFs identified so far is TIF1alpha, a member of a new...... family of proteins which contains an N-terminal RBCC (RING finger-B boxes-coiled coil) motif and a C-terminal bromodomain preceded by a PHD finger. In addition to these conserved domains present in a number of transcriptional regulatory proteins, TIF1alpha was found to contain several protein......-protein interaction sites. Of these, one specifically interacts with NRs bound to their agonistic ligand and not with NR mutants that are defective in the AF-2 activity. Immediately adjacent to this 'NR box', TIF1alpha contains an interaction site for members of the chromatin organization modifier (chromo) family, HP...

Repackaging SRS Black Box TRU Waste

International Nuclear Information System (INIS)

Swale, D. J.; Stone, K.A.; Milner, T. N.

2006-01-01

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

Forkhead-box transcription factors and their role in the immune system

NARCIS (Netherlands)

Coffer, PJ; Burgering, BMT

2004-01-01

It is more than a decade since the discovery of the first forkhead-box (FOX) transcription factor in the fruit fly Drosophila melanogaster. In the intervening time, there has been an explosion in the identification and characterization of members of this family of proteins. Importantly, in the past

Invariant box parameterization of neutrino oscillations

International Nuclear Information System (INIS)

Weiler, T.J.; Wagner, D.

1998-01-01

The model-independent 'box' parameterization of neutrino oscillations is examined. The invariant boxes are the classical amplitudes of the individual oscillating terms. Being observables, the boxes are independent of the choice of parameterization of the mixing matrix. Emphasis is placed on the relations among the box parameters due to mixing matrix unitarity, and on the reduction of the number of boxes to the minimum basis set. Using the box algebra, we show that CP-violation may be inferred from measurements of neutrino flavor mixing even when the oscillatory factors have averaged. General analyses of neutrino oscillations among n≥3 flavors can readily determine the boxes, which can then be manipulated to yield magnitudes of mixing matrix elements. copyright 1998 American Institute of Physics

Surface reflectance drives nest box temperature profiles and thermal suitability for target wildlife.

Directory of Open Access Journals (Sweden)

Stephen R Griffiths

Full Text Available Thermal properties of tree hollows play a major role in survival and reproduction of hollow-dependent fauna. Artificial hollows (nest boxes are increasingly being used to supplement the loss of natural hollows; however, the factors that drive nest box thermal profiles have received surprisingly little attention. We investigated how differences in surface reflectance influenced temperature profiles of nest boxes painted three different colors (dark-green, light-green, and white: total solar reflectance 5.9%, 64.4%, and 90.3% respectively using boxes designed for three groups of mammals: insectivorous bats, marsupial gliders and brushtail possums. Across the three different box designs, dark-green (low reflectance boxes experienced the highest average and maximum daytime temperatures, had the greatest magnitude of variation in daytime temperatures within the box, and were consistently substantially warmer than light-green boxes (medium reflectance, white boxes (high reflectance, and ambient air temperatures. Results from biophysical model simulations demonstrated that variation in diurnal temperature profiles generated by painting boxes either high or low reflectance colors could have significant ecophysiological consequences for animals occupying boxes, with animals in dark-green boxes at high risk of acute heat-stress and dehydration during extreme heat events. Conversely in cold weather, our modelling indicated that there are higher cumulative energy costs for mammals, particularly smaller animals, occupying light-green boxes. Given their widespread use as a conservation tool, we suggest that before boxes are installed, consideration should be given to the effect of color on nest box temperature profiles, and the resultant thermal suitability of boxes for wildlife, particularly during extremes in weather. Managers of nest box programs should consider using several different colors and installing boxes across a range of both orientations and

Box-particle intensity filter

OpenAIRE

Schikora, Marek; Gning, Amadou; Mihaylova, Lyudmila; Cremers, Daniel; Koch, Wofgang; Streit, Roy

2012-01-01

This paper develops a novel approach for multi-target tracking, called box-particle intensity filter (box-iFilter). The approach is able to cope with unknown clutter, false alarms and estimates the unknown number of targets. Furthermore, it is capable of dealing with three sources of uncertainty: stochastic, set-theoretic and data association uncertainty. The box-iFilter reduces the number of particles significantly, which improves the runtime considerably. The low particle number enables thi...

Identification of group specific motifs in Beta-lactamase family of proteins

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Saxena Akansha

2009-12-01

Full Text Available Abstract Background Beta-lactamases are one of the most serious threats to public health. In order to combat this threat we need to study the molecular and functional diversity of these enzymes and identify signatures specific to these enzymes. These signatures will enable us to develop inhibitors and diagnostic probes specific to lactamases. The existing classification of beta-lactamases was developed nearly 30 years ago when few lactamases were available. DLact database contain more than 2000 beta-lactamase, which can be used to study the molecular diversity and to identify signatures specific to this family. Methods A set of 2020 beta-lactamase proteins available in the DLact database http://59.160.102.202/DLact were classified using graph-based clustering of Best Bi-Directional Hits. Non-redundant (> 90 percent identical protein sequences from each group were aligned using T-Coffee and annotated using information available in literature. Motifs specific to each group were predicted using PRATT program. Results The graph-based classification of beta-lactamase proteins resulted in the formation of six groups (Four major groups containing 191, 726, 774 and 73 proteins while two minor groups containing 50 and 8 proteins. Based on the information available in literature, we found that each of the four major groups correspond to the four classes proposed by Ambler. The two minor groups were novel and do not contain molecular signatures of beta-lactamase proteins reported in literature. The group-specific motifs showed high sensitivity (> 70% and very high specificity (> 90%. The motifs from three groups (corresponding to class A, C and D had a high level of conservation at DNA as well as protein level whereas the motifs from the fourth group (corresponding to class B showed conservation at only protein level. Conclusion The graph-based classification of beta-lactamase proteins corresponds with the classification proposed by Ambler, thus there is

Molecular cloning, identification, and chromosomal localization of two MADS box genes in peach (Prunus persica).

Science.gov (United States)

Zhang, Lin; Xu, Yong; Ma, Rongcai

2008-06-01

MADS box proteins play an important role in floral development. To find genes involved in the floral transition of Prunus species, cDNAs for two MADS box genes, PpMADS1 and PpMADS10, were cloned using degenerate primers and 5'- and 3'-RACE based on the sequence database of P. persica and P. dulcis. The full length of PpMADS1 cDNA is 1,071 bp containing an open reading frame (ORF) of 717 bp and coding for a polypeptide of 238 amino acid residues. The full length of PpMADS10 cDNA is 937 bp containing an ORF of 633 bp and coding for a polypeptide of 210 amino acid residues. Sequence comparison revealed that PpMADS1 and PpMADS10 were highly homologous to genes AP1 and PI in Arabidopsis, respectively. Phylogenetic analysis indicated that PpMADS1 belongs to the euAP1 clade of class A, and PpMADS10 is a member of GLO/PI clade of class B. RT-PCR analysis showed that PpMADS1 was expressed in sepal, petal, carpel, and fruit, which was slightly different from the expression pattern of AP1; PpMADS10 was expressed in petal and stamen, which shared the same expression pattern as PI. Using selective mapping strategy, PpMADS1 was assigned onto the Bin1:50 on the G1 linkage group between the markers MCO44 and TSA2, and PpMADS10 onto the Bin1:73 on the same linkage group between the markers Lap-1 and FGA8. Our results provided the basis for further dissection of the two MADS box gene function.

Identification of unique interactions between the flexible linker and the RecA-like domains of DEAD-box helicase Mss116

International Nuclear Information System (INIS)

Zhang, Yuan; Palla, Mirkó; Liao, Jung-Chi; Sun, Andrew

2013-01-01

DEAD-box RNA helicases are ATP-dependent proteins implicated in nearly all aspects of RNA metabolism. The yeast DEAD-box helicase Mss116 is unique in its functions of splicing group I and group II introns and activating mRNA translation, but the structural understanding of why it performs these unique functions remains unclear. Here we used sequence analysis and molecular dynamics simulation to identify residues in the flexible linker specific for yeast Mss116, potentially associated with its unique functions. We first identified residues that are 100% conserved in Mss116 of different species of the Saccharomycetaceae family. The amino acids of these conserved residues were then compared with the amino acids of the corresponding residue positions of other RNA helicases to identify residues that have distinct amino acids from other DEAD-box proteins. Four residues in the flexible linker, i.e. N334, E335, P336 and H339, are conserved and Mss116-specific. Molecular dynamics simulation was conducted for the wild-type Mss116 structure and mutant models to examine mutational effects of the linker on the conformational equilibrium. Relatively short MD simulation runs (within 20 ns) were enough for us to observe mutational effects, suggesting serious structural perturbations by these mutations. The mutation of E335 depletes the interactions between E335 and K95 in domain 1. The interactions between N334/P336 and N496/I497 of domain 2 are also abolished by mutation. Our results suggest that tight interactions between the Mss116-specific flexible linker and the two RecA-like domains may be mechanically required to crimp RNA for the unique RNA processes of yeast Mss116. (paper)

Identification of unique interactions between the flexible linker and the RecA-like domains of DEAD-box helicase Mss116

Science.gov (United States)

Zhang, Yuan; Palla, Mirkó; Sun, Andrew; Liao, Jung-Chi

2013-09-01

DEAD-box RNA helicases are ATP-dependent proteins implicated in nearly all aspects of RNA metabolism. The yeast DEAD-box helicase Mss116 is unique in its functions of splicing group I and group II introns and activating mRNA translation, but the structural understanding of why it performs these unique functions remains unclear. Here we used sequence analysis and molecular dynamics simulation to identify residues in the flexible linker specific for yeast Mss116, potentially associated with its unique functions. We first identified residues that are 100% conserved in Mss116 of different species of the Saccharomycetaceae family. The amino acids of these conserved residues were then compared with the amino acids of the corresponding residue positions of other RNA helicases to identify residues that have distinct amino acids from other DEAD-box proteins. Four residues in the flexible linker, i.e. N334, E335, P336 and H339, are conserved and Mss116-specific. Molecular dynamics simulation was conducted for the wild-type Mss116 structure and mutant models to examine mutational effects of the linker on the conformational equilibrium. Relatively short MD simulation runs (within 20 ns) were enough for us to observe mutational effects, suggesting serious structural perturbations by these mutations. The mutation of E335 depletes the interactions between E335 and K95 in domain 1. The interactions between N334/P336 and N496/I497 of domain 2 are also abolished by mutation. Our results suggest that tight interactions between the Mss116-specific flexible linker and the two RecA-like domains may be mechanically required to crimp RNA for the unique RNA processes of yeast Mss116.

Integrated Box Interrogation System (IBIS) Preliminary Design Study

International Nuclear Information System (INIS)

Croft, Stephen; Martancik, David; Young, Brian; Chard MJ, Patrick; Estop J, Robert; Sheila Melton; Arnone, Gaetano J.

2003-01-01

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

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.

A flexible system to capture sample vials in a storage box - the box vial scanner.

Science.gov (United States)

Nowakowski, Steven E; Kressin, Kenneth R; Deick, Steven D

2009-01-01

Tracking sample vials in a research environment is a critical task and doing so efficiently can have a large impact on productivity, especially in high volume laboratories. There are several challenges to automating the capture process, including the variety of containers used to store samples. We developed a fast and robust system to capture the location of sample vials being placed in storage that allows the laboratories the flexibility to use sample containers of varying dimensions. With a single scan, this device captures the box identifier, the vial identifier and the location of each vial within a freezer storage box. The sample vials are tracked through a barcode label affixed to the cap while the boxes are tracked by a barcode label on the side of the box. Scanning units are placed at the point of use and forward data to a sever application for processing the scanned data. Scanning units consist of an industrial barcode reader mounted in a fixture positioning the box for scanning and providing lighting during the scan. The server application transforms the scan data into a list of storage locations holding vial identifiers. The list is then transferred to the laboratory database. The box vial scanner captures the IDs and location information for an entire box of sample vials into the laboratory database in a single scan. The system accommodates a wide variety of vials sizes by inserting risers under the sample box and a variety of storage box layouts are supported via the processing algorithm on the server.

Dimension measuring method for channel box

International Nuclear Information System (INIS)

Jo, Hiroto.

1995-01-01

The device of the present invention concerns detection of a channel box for spent fuel assemblies of a BWR type reactor, which measures a cross sectional shape and dimension of the channel box to check deformation amount such as expansion. That is, a customary fuel exchanger and a dimension measuring device are used. The lower end of the channel box is measured by a distance sensor of the dimension measuring device when it is aligned with a position of the distance sensor. The channel box is lowered at the same time while detecting axial position data of the fuel exchanger. The position of the channel box in an axial direction is detected based on axial position data of the fuel exchanger. The lower end of the channel box can accurately be recognized by the detection of both of them. Subsequent deformation measurement for the channel box at accurate axial positions is enabled. In addition, since the axial position data of the fuel exchanger per se are detected, an axial profile of the channel box can be measured even if a lifting speed of the channel box is varied on every region. (I.S.)

Objectifying when to halt a boxing match: a video analysis of fatalities.

Science.gov (United States)

Miele, Vincent J; Bailes, Julian E

2007-02-01

Although numerous prestigious medical organizations have called for its abolishment, participation in the sport of boxing has reached an all-time high among both men and women, and its elimination is unlikely in the near future. Physicians should strive to increase boxing safety by improving the rules of competition, which have evolved minimally over the past two centuries. Currently, subjective criteria are used to determine whether or not a contest should be halted. Developing a standardized, objective method of determining when a contest should be halted would be a significant paradigm shift and could increase the safety of the sport's participants. This study analyzed the number and types of punches landed in a typical professional match, in bouts considered to be competitive and in those that ended in fatalities, to determine whether or not this would be a practical method of differentiating between these groups. Three groups of professional boxing matches were defined at the beginning of the study: 1) a "fatal" group, consisting of bouts that resulted in the death of a participant; 2) a "classic" group that represented competitive matches; and 3) a "control" group of 4000 professional boxing matches representing the average bout. A computer program known as Punchstat (Compubox, Inc., Manorville, NY) was used in the objective analysis of these matches via videotape playback. Several statistically significant differences were discovered between matches that resulted in fatalities and the control group. These include the number of punches landed per round, the number of power punches landed per round, and the number of power punches thrown per round by losing boxers. However, when the fatal bouts were compared with the most competitive bouts, these differences were no longer evident. Based on the data analyzed between the control and fatal-bout groups, a computerized method of counting landed blows at ringside could provide sufficient data to stop matches that

Virulence factor NSs of rift valley fever virus recruits the F-box protein FBXO3 to degrade subunit p62 of general transcription factor TFIIH.

Science.gov (United States)

Kainulainen, Markus; Habjan, Matthias; Hubel, Philipp; Busch, Laura; Lau, Simone; Colinge, Jacques; Superti-Furga, Giulio; Pichlmair, Andreas; Weber, Friedemann

2014-03-01

The nonstructural protein NSs is the main virulence factor of Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), a serious pathogen of livestock and humans in Africa. RVFV NSs blocks transcriptional upregulation of antiviral type I interferons (IFN) and destroys the general transcription factor TFIIH subunit p62 via the ubiquitin/proteasome pathway. Here, we identified a subunit of E3 ubiquitin ligases, F-box protein FBXO3, as a host cell interactor of NSs. Small interfering RNA (siRNA)-mediated depletion of FBXO3 rescued p62 protein levels in RVFV-infected cells and elevated IFN transcription by 1 order of magnitude. NSs interacts with the full-length FBXO3 protein as well as with a truncated isoform that lacks the C-terminal acidic and poly(R)-rich domains. These isoforms are present in both the nucleus and the cytoplasm. NSs exclusively removes the nuclear pool of full-length FBXO3, likely due to consumption during the degradation process. F-box proteins form the variable substrate recognition subunit of the so-called SCF ubiquitin ligases, which also contain the constant components Skp1, cullin 1 (or cullin 7), and Rbx1. siRNA knockdown of Skp1 also protected p62 from degradation, suggesting involvement in NSs action. However, knockdown of cullin 1, cullin 7, or Rbx1 could not rescue p62 degradation by NSs. Our data show that the enzymatic removal of p62 via the host cell factor FBXO3 is a major mechanism of IFN suppression by RVFV. Rift Valley fever virus is a serious emerging pathogen of animals and humans. Its main virulence factor, NSs, enables unhindered virus replication by suppressing the antiviral innate immune system. We identified the E3 ubiquitin ligase FBXO3 as a novel host cell interactor of NSs. NSs recruits FBXO3 to destroy the general host cell transcription factor TFIIH-p62, resulting in suppression of the transcriptional upregulation of innate immunity.

Track plate enclosures: Box designs affecting attractiveness to riparian mammals

Science.gov (United States)

Loukmas, J.J.; Mayack, D.T.; Richmond, M.E.

2003-01-01

We examined the efficacy of four track plate enclosure designs for monitoring the abundance of small and medium-sized mammals along 10 streams in New York State. Box size and clarity of view through the box were evaluated as factors affecting visitation. We checked track plate stations weekly from September 1999 to March 2000. Eleven mammalian species or species groups visited the track plate stations. Raccoons (Procyon lotor) (P = 0.020) and feral cats (Felis catus) (P = 0.008) visited large enclosures significantly more than small enclosures. Feral cats visited clear-view enclosures significantly more than obstructed-view enclosures (P = 0.025). Enclosure size and view did not significantly affect visitation by other species; however, a large box with a clear view was the most effective design.

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.

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

International Nuclear Information System (INIS)

Wang, Y.F.; Wu, M.; Ma, B.J.; Cai, D.A.; Yin, B.B.

2014-01-01

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

Isolation of three B-box zinc finger proteins that interact with STF1 and COP1 defines a HY5/COP1 interaction network involved in light control of development in soybean

International Nuclear Information System (INIS)

Shin, Su Young; Kim, Seong Hee; Kim, Hye Jin; Jeon, Su Jeong; Sim, Soon Ae; Ryu, Gyeong Ryul; Yoo, Cheol Min; Cheong, Yong Hwa; Hong, Jong Chan

2016-01-01

LONG HYPOCOTYL5 (HY5) and STF1 (Soybean TGACG-motif binding Factor 1) are two related bZIP transcription factors that play a positive role in photomorphogenesis and hormonal signaling. In this study, we compared full length STF1 and truncated STF1 overexpression lines and found that the C-terminal 133 amino acids (194–306) possess all the HY5-like function in Arabidopsis. The STF1-DC1 mutant (1–306), with a 20 amino acid deletion at the carboxy terminus, failed to complement the hy5 mutant phenotype, which suggests an intact C-terminus is required for STF1 function. To understand the role of the C-terminal domain in photomorphogenesis we used a yeast two-hybrid screen to isolate proteins that bind to the STF1 C-terminus. We isolated three soybean cDNAs encoding the zinc-finger proteins GmSTO, GmSTH, and GmSTH2, which interact with STF1. These proteins belong to a family of B-box zinc finger proteins that include Arabidopsis SALT TOLERANCE (STO) and STO HOMOLOG (STH) and STH2, which play a role in light-dependent development and gene expression. The C-terminal 63 amino acids of STF1, containing a leucine zipper and the two N-terminal B-boxes, contains the domain involved in interactions between STF1 and GmSTO. In addition, we identified an interaction between soybean COP1 (GmCOP1) and GmSTO and GmSTH, as well as STF1, which strongly suggests the presence of a similar regulatory circuit for light signaling in soybean as in Arabidopsis. This study shows that photomorphogenic control requires complex molecular interactions among several different classes of transcription factors such as bZIP, B-box factors, and COP1, a ubiquitin ligase. - Highlights: • STF1 interact with GmSTO, GmSTH and GmSTH2. • The bZIP transcription factor STF1 requires an intact C-terminal domain for STF1 function. • STF1 and GmSTO are nuclear proteins.

Discovery of candidate KEN-box motifs using cell cycle keyword enrichment combined with native disorder prediction and motif conservation.

Science.gov (United States)

Michael, Sushama; Travé, Gilles; Ramu, Chenna; Chica, Claudia; Gibson, Toby J

2008-02-15

KEN-box-mediated target selection is one of the mechanisms used in the proteasomal destruction of mitotic cell cycle proteins via the APC/C complex. While annotating the Eukaryotic Linear Motif resource (ELM, http://elm.eu.org/), we found that KEN motifs were significantly enriched in human protein entries with cell cycle keywords in the UniProt/Swiss-Prot database-implying that KEN-boxes might be more common than reported. Matches to short linear motifs in protein database searches are not, per se, significant. KEN-box enrichment with cell cycle Gene Ontology terms suggests that collectively these motifs are functional but does not prove that any given instance is so. Candidates were surveyed for native disorder prediction using GlobPlot and IUPred and for motif conservation in homologues. Among >25 strong new candidates, the most notable are human HIPK2, CHFR, CDC27, Dab2, Upf2, kinesin Eg5, DNA Topoisomerase 1 and yeast Cdc5 and Swi5. A similar number of weaker candidates were present. These proteins have yet to be tested for APC/C targeted destruction, providing potential new avenues of research.

Sub-grouping and sub-functionalization of the RIFIN multi-copy protein family

Directory of Open Access Journals (Sweden)

Sonnhammer Erik L

2008-01-01

Full Text Available Abstract Background Parasitic protozoans possess many multicopy gene families which have central roles in parasite survival and virulence. The number and variability of members of these gene families often make it difficult to predict possible functions of the encoded proteins. The families of extra-cellular proteins that are exposed to a host immune response have been driven via immune selection to become antigenically variant, and thereby avoid immune recognition while maintaining protein function to establish a chronic infection. Results We have combined phylogenetic and function shift analyses to study the evolution of the RIFIN proteins, which are antigenically variant and are encoded by the largest multicopy gene family in Plasmodium falciparum. We show that this family can be subdivided into two major groups that we named A- and B-RIFIN proteins. This suggested sub-grouping is supported by a recently published study that showed that, despite the presence of the Plasmodium export (PEXEL motif in all RIFIN variants, proteins from each group have different cellular localizations during the intraerythrocytic life cycle of the parasite. In the present study we show that function shift analysis, a novel technique to predict functional divergence between sub-groups of a protein family, indicates that RIFINs have undergone neo- or sub-functionalization. Conclusion These results question the general trend of clustering large antigenically variant protein groups into homogenous families. Assigning functions to protein families requires their subdivision into meaningful groups such as we have shown for the RIFIN protein family. Using phylogenetic and function shift analysis methods, we identify new directions for the investigation of this broad and complex group of proteins.

Combined effects of astragalus soup and persistent Taiji boxing on improving the immunity of elderly women.

Science.gov (United States)

Song, Qing-Hua; Xu, Rong-Mei; Zhang, Quan-Hai; Shen, Guo-Qing; Ma, Ming; Zhao, Xin-Ping; Guo, Yan-Hua; Wang, Yi

2014-01-01

To observe the combined effects of astragalus soup and persistent Taiji boxing on improving the immunity of women of advanced years. 120 elderly women lacking daily exercise were chosen as the study subjects. By using the table of random numbers, they were then divided into the control group and the experiment group, consisting of 60 each. The control group practiced Taiji boxing for 45 minutes twice a day. The experiment group did the same, and, in addition, took astragalus soup after each boxing. Indexes related to physical immunity of the two groups were observed and compared when they were first chosen, when the alternative treatment was applied three, six and twelve months later, respectively. The two groups demonstrated no significant differences in general data and research indexes when chosen (P > 0.05). Three months after the two groups were chosen and treated differently, the control group demonstrated no significant improvement while most indexes of the experiment group improved considerably (P > 0.05). After six months, the related indexes of both groups improved substantially (P soup.

A CRM domain protein functions dually in group I and group II intron splicing in land plant chloroplasts.

Science.gov (United States)

Asakura, Yukari; Barkan, Alice

2007-12-01

The CRM domain is a recently recognized RNA binding domain found in three group II intron splicing factors in chloroplasts, in a bacterial protein that associates with ribosome precursors, and in a family of uncharacterized proteins in plants. To elucidate the functional repertoire of proteins with CRM domains, we studied CFM2 (for CRM Family Member 2), which harbors four CRM domains. RNA coimmunoprecipitation assays showed that CFM2 in maize (Zea mays) chloroplasts is associated with the group I intron in pre-trnL-UAA and group II introns in the ndhA and ycf3 pre-mRNAs. T-DNA insertions in the Arabidopsis thaliana ortholog condition a defective-seed phenotype (strong allele) or chlorophyll-deficient seedlings with impaired splicing of the trnL group I intron and the ndhA, ycf3-int1, and clpP-int2 group II introns (weak alleles). CFM2 and two previously described CRM proteins are bound simultaneously to the ndhA and ycf3-int1 introns and act in a nonredundant fashion to promote their splicing. With these findings, CRM domain proteins are implicated in the activities of three classes of catalytic RNA: group I introns, group II introns, and 23S rRNA.

Heart Rate and Liking During "Kinect Boxing" Versus "Wii Boxing": The Potential for Enjoyable Vigorous Physical Activity Videogames.

Science.gov (United States)

Sanders, Gabriel J; Peacock, Corey A; Barkley, Jacob E; Gish, Brian; Brock, Scott; Volpenhein, Josh

2015-08-01

Nintendo(®) (Kyoto, Japan) "Wii™ Sports Boxing" ("Wii Boxing") and Xbox(®) (Microsoft, Redmond, WA) "Kinect(®) Sports Boxing" ("Kinect Boxing") are both boxing simulation videogames that are available for two different active videogame (AVG) systems. Although these AVGs are similar, the style of gameplay required is different (i.e., upper body only versus total body movements) and may alter physical activity intensity and one's preference for playing one game over the other. AVGs that elicit the greatest physiologic challenge and are preferred by users should be identified in an effort to enhance the efficacy of physical activity interventions and programs that include AVGs. The mean heart rate (HRmean) and peak heart rate (HRpeak) for 27 adults (22.7±4.2 years old) were recorded during four 10-minute conditions: seated rest, treadmill walking at 3 miles/hour, "Wii Boxing," and "Kinect Boxing." Upon completion of all four conditions, participants indicated which condition they preferred, and HRmean and HRpeak were calculated as a percentage of age-predicted maximum heart rate to classify physical activity intensity for the three activity conditions (treadmill, "Wii Boxing," and "Kinect Boxing"). "Kinect Boxing" significantly (P<0.001) increased percentage HRmean (64.1±1.6 percent of age-predicted maximum) and percentage HRpeak (76.5±1.9 percent) above all other conditions: Wii HRmean, 53.0±1.2 percent; Wii HRpeak, 61.8±1.5 percent; treadmill HRmean, 52.4±1.2 percent; treadmill HRpeak, 55.2±2.2 percent. Percentage HRpeak for "Kinect Boxing" was great enough to be considered a vigorous-intensity physical activity. There was no difference (P=0.55) in percentage HRmean between "Wii Boxing" and treadmill walking. Participants also preferred "Kinect Boxing" (P<0.001; n=26) to all other conditions ("Wii Boxing," n=1; treadmill n=0). "Kinect Boxing" was the most preferred and the only condition that was physiologically challenging enough to be classified as a

Beads task vs. box task: The specificity of the jumping to conclusions bias.

Science.gov (United States)

Balzan, Ryan P; Ephraums, Rachel; Delfabbro, Paul; Andreou, Christina

2017-09-01

Previous research involving the probabilistic reasoning 'beads task' has consistently demonstrated a jumping-to-conclusions (JTC) bias, where individuals with delusions make decisions based on limited evidence. However, recent studies have suggested that miscomprehension may be confounding the beads task. The current study aimed to test the conventional beads task against a conceptually simpler probabilistic reasoning "box task" METHODS: One hundred non-clinical participants completed both the beads task and the box task, and the Peters et al. Delusions Inventory (PDI) to assess for delusion-proneness. The number of 'draws to decision' was assessed for both tasks. Additionally, the total amount of on-screen evidence was manipulated for the box task, and two new box task measures were assessed (i.e., 'proportion of evidence requested' and 'deviation from optimal solution'). Despite being conceptually similar, the two tasks did not correlate, and participants requested significantly less information on the beads task relative to the box task. High-delusion-prone participants did not demonstrate hastier decisions on either task; in fact, for box task, this group was observed to be significantly more conservative than low-delusion-prone group. Neither task was incentivized; results need replication with a clinical sample. Participants, and particularly those identified as high-delusion-prone, displayed a more conservative style of responding on the novel box task, relative to the beads task. The two tasks, whilst conceptually similar, appear to be tapping different cognitive processes. The implications of these results are discussed in relation to the JTC bias and the theoretical mechanisms thought to underlie it. Copyright © 2016 Elsevier Ltd. All rights reserved.

A specific box switches the cell fate determining activity of XOTX2 and XOTX5b in the Xenopus retina

Directory of Open Access Journals (Sweden)

He Rong-Qiao

2007-06-01

Full Text Available Abstract Background Otx genes, orthologues of the Drosophila orthodenticle gene (otd, play crucial roles in vertebrate brain development. In the Xenopus eye, Xotx2 and Xotx5b promote bipolar and photoreceptor cell fates, respectively. The molecular basis of their differential action is not completely understood, though the carboxyl termini of the two proteins seem to be crucial. To define the molecular domains that make the action of these proteins so different, and to determine whether their retinal abilities are shared by Drosophila OTD, we performed an in vivo molecular dissection of their activity by transfecting retinal progenitors with several wild-type, deletion and chimeric constructs of Xotx2, Xotx5b and otd. Results We identified a small 8–10 amino acid divergent region, directly downstream of the homeodomain, that is crucial for the respective activities of XOTX2 and XOTX5b. In lipofection experiments, the exchange of this 'specificity box' completely switches the retinal activity of XOTX5b into that of XOTX2 and vice versa. Moreover, the insertion of this box into Drosophila OTD, which has no effect on retinal cell fate, endows it with the specific activity of either XOTX protein. Significantly, in cell transfection experiments, the diverse ability of XOTX2 and XOTX5b to synergize with NRL, a cofactor essential for vertebrate rod development, to transactivate the rhodopsin promoter is also switched depending on the box. We also show by GST-pull down that XOTX2 and XOTX5b differentially interact with NRL, though this property is not strictly dependent on the box. Conclusion Our data provide molecular evidence on how closely related homeodomain gene products can differentiate their functions to regulate distinct cell fates. A small 'specificity box' is both necessary and sufficient to confer on XOTX2 and XOTX5b their distinct activities in the developing frog retina and to convert the neutral orthologous OTD protein of Drosophila

Y-box protein-1/p18 fragment identifies malignancies in patients with chronic liver disease

International Nuclear Information System (INIS)

Tacke, Frank; Kanig, Nicolas; En-Nia, Abdelaziz; Kaehne, Thilo; Eberhardt, Christiane S; Shpacovitch, Victoria; Trautwein, Christian; Mertens, Peter R

2011-01-01

Immunohistochemical detection of cold shock proteins is predictive for deleterious outcome in various malignant diseases. We recently described active secretion of a family member, denoted Y-box (YB) protein-1. We tested the clinical and diagnostic value of YB-1 protein fragment p18 (YB-1/p18) detection in blood for malignant diseases. We used a novel monoclonal anti-YB-1 antibody to detect YB-1/p18 by immunoblotting in plasma samples of healthy volunteers (n = 33), patients with non-cancerous, mostly inflammatory diseases (n = 60), hepatocellular carcinoma (HCC; n = 25) and advanced solid tumors (n = 20). YB-1/p18 was then tested in 111 patients with chronic liver diseases, alongside established tumor markers and various diagnostic measures, during evaluation for potential liver transplantation. We developed a novel immunoblot to detect the 18 kD fragment of secreted YB-1 in human plasma (YB-1/p18) that contains the cold-shock domains (CSD) 1-3 of the full-length protein. YB-1/p18 was detected in 11/25 HCC and 16/20 advanced carcinomas compared to 0/33 healthy volunteers and 10/60 patients with non-cancerous diseases. In 111 patients with chronic liver disease, YB-1/p18 was detected in 20 samples. Its occurrence was not associated with advanced Child stages of liver cirrhosis or liver function. In this cohort, YB-1/p18 was not a good marker for HCC, but proved most powerful in detecting malignancies other than HCC (60% positive) with a lower rate of false-positive results compared to established tumor markers. Alpha-fetoprotein (AFP) was most sensitive in detecting HCC, but simultaneous assessment of AFP, CA19-9 and YB-1/p18 improved overall identification of HCC patients. Plasma YB-1/p18 can identify patients with malignancies, independent of acute inflammation, renal impairment or liver dysfunction. The detection of YB-1/p18 in human plasma may have potential as a tumor marker for screening of high-risk populations, e.g. before organ transplantation, and should

Boxing headguard performance in punch machine tests.

Science.gov (United States)

McIntosh, Andrew S; Patton, Declan A

2015-09-01

The paper presents a novel laboratory method for assessing boxing headguard impact performance. The method is applied to examine the effects of headguards on head impact dynamics and injury risk. A linear impactor was developed, and a range of impacts was delivered to an instrumented Hybrid III head and neck system both with and without an AIBA (Association Internationale de Boxe Amateur)-approved headguard. Impacts at selected speeds between 4.1 and 8.3 m/s were undertaken. The impactor mass was approximately 4 kg and an interface comprising a semirigid 'fist' with a glove was used. The peak contact forces were in the range 1.9-5.9 kN. Differences in head impact responses between the Top Ten AIBA-approved headguard and bare headform in the lateral and forehead tests were large and/or significant. In the 8.3 m/s fist-glove impacts, the mean peak resultant headform accelerations for bare headform tests was approximately 130 g compared with approximately 85 g in the forehead impacts. In the 6.85 m/s bare headform impacts, mean peak resultant angular head accelerations were in the range of 5200-5600 rad/s(2) and almost halved by the headguard. Linear and angular accelerations in 45° forehead and 60° jaw impacts were reduced by the headguard. The data support the opinion that current AIBA headguards can play an important role in reducing the risk of concussion and superficial injury in boxing competition and training. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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. © FASEB.

The three-box paradox revisited

International Nuclear Information System (INIS)

Ravon, Tamar; Vaidman, Lev

2007-01-01

The classical three-box paradox of Kirkpatrick (2003 J. Phys. A: Math. Gen. 36 4891) is compared to the original quantum three-box paradox of Aharonov and Vaidman (1991 J. Phys. A: Math. Gen. 24 2315). It is argued that the quantum three-box experiment is a 'quantum paradox' in the sense that it is an example of a classical task which cannot be accomplished using classical means, but can be accomplished using quantum devices. It is shown that Kirkpatrick's card game is analogous to a different game with a particle in three boxes which does not contain paradoxical features

IMPROVED, FAVORABLE FOR ENVIRONMENT POLYURETHANE COLD-BOX-PROCESS (COLD BOX «HUTTENES-ALBERTUS» .

Directory of Open Access Journals (Sweden)

A. Sergini

2005-01-01

Full Text Available The results of the laboratory and industrial investigations, the purpose of which is improvement of the classical Cold-box-process, i.e. the process of the slugs hardening in cold boxes, are presented.

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

DEFF Research Database (Denmark)

Bruni, Roberto; Corradini, Andrea; Gadducci, Fabio

2015-01-01

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 environ......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...

Decommissioning a small glove box

International Nuclear Information System (INIS)

Bond, R.D.; McSherry, K.

1985-11-01

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)

77 FR 45337 - Folding Gift Boxes From the People's Republic of China: Extension of Time Limits for Preliminary...

Science.gov (United States)

2012-07-31

... DEPARTMENT OF COMMERCE International Trade Administration [A-570-866] Folding Gift Boxes From the... (``sunset'') review of the antidumping duty (``AD'') order on certain folding gift boxes from the People's...'').\\1\\ The Folding Gift Boxes Fair Trade Coalition,\\2\\ a group of producers of the domestic like product...

[Effects of shadow boxing training on exercise endurance and quality of life of patients with chronic obstructive pulmonary disease].

Science.gov (United States)

Gu, Gang; Zhou, Yu-min; Wang, Da-li; Chen, Lian; Zhong, Nan-shan; Ran, Pi-xin

2012-04-10

To evaluate the effects of shadow boxing training on the exercise endurance and quality of life of Chinese patients with COPD (chronic obstructive pulmonary disease). From May 2010 to March 2011, a total of 70 COPD patients in stable phases were recruited from Liwan, Yuexiu and Haizhu districts of Guangzhou. There were 35 patients in the shadow boxing exercise group and 35 patients in the control group. And they were matched by gender and age. The patients in the shadow boxing group exercised for 3 months while those in the control group received the conventional out-hospital management only. Their demographic, medical history, smoking status, medicinal use, spirometric data, clinical COPD questionnaire (CCQ) scores, 6-minute walking distance and Borg scores were collected before and after trial. A total of 63 COPD patients (33 in shadow boxing group vs. 30 in control group) completed the study. There was an average dropout rate of 5.7% (2/35) in shadow boxing group and 14.3% (5/35) in control group. No differences existed between two groups in age (67 ± 8 vs 69 ± 9 yr), male proportion (84.8% vs 86.7%), body mass index (22.8 ± 2.6 vs 22.7 ± 3.0), usage proportion of medicine (42.4% vs 33.3%), duration of disease (4.0 ± 7.5 vs 5.5 ± 7.3), percentage of smokers (78.8% vs 80.0%), 6-minute walking distance (447 ± 94 vs 414 ± 100), CCQ total score (15.0 ± 9.4 vs 14.1 ± 8.8), CCQ symptom score (9.2 ± 5.6 vs 8.3 ± 5.0) and activity score (5.8 ± 4.5 vs 5.8 ± 4.4) at baseline (all P > 0.05). At the end of study, the 6-minute walking distance of patients had statistical differences between two groups (P boxing group increased by (51 ± 55) m while the control dropped by (19 ± 58) m. The total score, symptom score and activity score of clinical COPD questionnaire had statistical differences between two groups. They decreased significantly in the shadow boxing group as compared with the baseline data while there was no significant change in the control group

Using BOX-PCR to exclude a clonal outbreak of melioidosis

Directory of Open Access Journals (Sweden)

Ward Linda

2007-06-01

Full Text Available Abstract Background Although melioidosis in endemic regions is usually caused by a diverse range of Burkholderia pseudomallei strains, clonal outbreaks from contaminated potable water have been described. Furthermore B. pseudomallei is classified as a CDC Group B bioterrorism agent. Ribotyping, pulsed-field gel electrophoresis (PFGE and multilocus sequence typing (MLST have been used to identify genetically related B. pseudomallei isolates, but they are time consuming and technically challenging for many laboratories. Methods We have adapted repetitive sequence typing using a BOX A1R primer for typing B. pseudomallei and compared BOX-PCR fingerprinting results on a wide range of well-characterized B. pseudomallei isolates with MLST and PFGE performed on the same isolates. Results BOX-PCR typing compared favourably with MLST and PFGE performed on the same isolates, both discriminating between the majority of multilocus sequence types and showing relatedness between epidemiologically linked isolates from various outbreak clusters. Conclusion Our results suggest that BOX-PCR can be used to exclude a clonal outbreak of melioidosis within 10 hours of receiving the bacterial strains.

Polycomb group protein bodybuilding: working out the routines.

Science.gov (United States)

Sievers, Cem; Paro, Renato

2013-09-30

Polycomb group (PcG) proteins regulate gene expression by modifying chemical and structural properties of chromatin. Isono et al. (2013) now report in Developmental Cell a polymerization-dependent mechanism used by PcG proteins to form higher-order chromatin structures, referred to as Polycomb bodies, and demonstrate its necessity for gene silencing. Copyright © 2013 Elsevier Inc. All rights reserved.

SMART lunch box intervention to improve the food and nutrient content of children's packed lunches: UK wide cluster randomised controlled trial.

Science.gov (United States)

Evans, C E L; Greenwood, D C; Thomas, J D; Cleghorn, C L; Kitchen, M S; Cade, J E

2010-11-01

Government standards are now in place for children's school meals but not for lunches prepared at home. The aim of this trial is to improve the content of children's packed lunches. A cluster randomised controlled trial in 89 primary schools across the UK involving 1291 children, age 8-9 years at baseline. Follow-up was 12 months after baseline. A "SMART" lunch box intervention programme consisted of food boxes, bag and supporting materials. The main outcome measures were weights of foods and proportion of children provided with sandwiches, fruit, vegetables, dairy food, savoury snacks and confectionery in each packed lunch. Levels of nutrients provided including energy, total fat, saturated fat, protein, non-milk extrinsic sugar, sodium, calcium, iron, folate, zinc, vitamin A and vitamin C. Moderately higher weights of fruit, vegetables, dairy and starchy food and lower weights of savoury snacks were provided to children in the intervention group. Children in the intervention group were provided with slightly higher levels of vitamin A and folate. 11% more children were provided with vegetables/salad in their packed lunch, and 13% fewer children were provided with savoury snacks (crisps). Children in the intervention group were more likely to be provided with packed lunches meeting the government school meal standards. The SMART lunch box intervention, targeting parents and children, led to small improvements in the food and nutrient content of children's packed lunches. Further interventions are required to bring packed lunches in line with the new government standards for school meals. Current controlled trials ISRCTN77710993.

Design report for shielded glove box

International Nuclear Information System (INIS)

Ku, J. H.; Lee, J. C.; Seo, K. S.; Bang, K. S.; Lee, D. W.; Kim, J. H.; Min, D. K.; Park, S. W.

1999-05-01

For the examination of spent fuels and high radioactive specimens using a specially equipped scanning electron microscope, a shielded glove box was designed and constructed at PIE facility of KAERI. This glove box consisted of shielding walls, containment box, lead glasses, manipulators, gloves, ventilation systems, doors, hot-cell specimen cask adapter, etc. It was emphasized that both the easy operation and radiation safety are important factors in the shielded glove box were installed also considered as a important factor to build the basic concept of the assembling. Two sliding doors and one hinge-type door were installed for the easy installation, operation and maintenance of scanning electron microscope. Containment box which confines the radioactive material into the box consisted of reinforced transparent glasses, aluminum frames and stainless steel plate liner. Therefore everything beyond the containment box can be seen through the lead glass which installed at the front shielding wall. All shielding walls and doors were introduced separately into the room and assembled by bolting. (author). 3 refs., 5 tabs., 18 figs

SMRT has tissue-specific isoform profiles that include a form containing one CoRNR box

International Nuclear Information System (INIS)

Short, Stephen; Malartre, Marianne; Sharpe, Colin

2005-01-01

SMRT acts as a corepressor for a range of transcription factors. The amino-terminal part of the protein includes domains that mainly mediate transcriptional repression whilst the carboxy-terminal part includes domains that interact with nuclear receptors using up to three motifs called CoRNR boxes. The region of the SMRT primary transcript encoding the interaction domains is subject to alternative splicing that varies the inclusion of the third CoRNR box. The profile in mice includes an abundant, novel SMRT isoform that possesses just one CoRNR box. Mouse tissues therefore express SMRT isoforms containing one, two or three CoRNR boxes. In frogs, the SMRT isoform profile is tissue-specific. The mouse also shows distinct profiles generated by differential expression levels of the SMRT transcript isoforms. The formation of multiple SMRT isoforms and their tissue-specific regulation indicates a mechanism, whereby cells can define the repertoire of transcription factors regulated by SMRT

Box-particle probability hypothesis density filtering

OpenAIRE

Schikora, M.; Gning, A.; Mihaylova, L.; Cremers, D.; Koch, W.

2014-01-01

This paper develops a novel approach for multitarget tracking, called box-particle probability hypothesis density filter (box-PHD filter). The approach is able to track multiple targets and estimates the unknown number of targets. Furthermore, it is capable of dealing with three sources of uncertainty: stochastic, set-theoretic, and data association uncertainty. The box-PHD filter reduces the number of particles significantly, which improves the runtime considerably. The small number of box-p...

The Polerovirus silencing suppressor P0 targets ARGONAUTE proteins for degradation.

Science.gov (United States)

Baumberger, Nicolas; Tsai, Ching-Hsui; Lie, Miranda; Havecker, Ericka; Baulcombe, David C

2007-09-18

Plant and animal viruses encode suppressor proteins of an adaptive immunity mechanism in which viral double-stranded RNA is processed into 21-25 nt short interfering (si)RNAs. The siRNAs guide ARGONAUTE (AGO) proteins so that they target viral RNA. Most viral suppressors bind long dsRNA or siRNAs and thereby prevent production of siRNA or binding of siRNA to AGO. The one exception is the 2b suppressor of Cucumoviruses that binds to and inhibits AGO1. Here we describe a novel suppressor mechanism in which a Polerovirus-encoded F box protein (P0) targets the PAZ motif and its adjacent upstream sequence in AGO1 and mediates its degradation. F box proteins are components of E3 ubiquitin ligase complexes that add polyubiquitin tracts on selected lysine residues and thereby mark a protein for proteasome-mediated degradation. With P0, however, the targeted degradation of AGO is insensitive to inhibition of the proteasome, indicating that the proteasome is not involved. We also show that P0 does not block a mobile signal of silencing, indicating that the signal molecule does not have AGO protein components. The ability of P0 to block silencing without affecting signal movement may contribute to the phloem restriction of viruses in the Polerovirus group.

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: 3.057, year: 2015

High-mobility group box 1 released by autophagic cancer-associated fibroblasts maintains the stemness of luminal breast cancer cells.

Science.gov (United States)

Zhao, Xi-Long; Lin, Yong; Jiang, Jun; Tang, Zhuo; Yang, Shuai; Lu, Lu; Liang, Yan; Liu, Xue; Tan, Jiao; Hu, Xu-Gang; Niu, Qin; Fu, Wen-Juan; Yan, Ze-Xuan; Guo, De-Yu; Ping, Yi-Fang; Wang, Ji Ming; Zhang, Xia; Kung, Hsiang-Fu; Bian, Xiu-Wu; Yao, Xiao-Hong

2017-11-01

Cancer stem cells/cancer-initiating cells (CICs) and their microenvironmental niche play a vital role in malignant tumour recurrence and metastasis. Cancer-associated fibroblasts (CAFs) are major components of the niche of breast cancer-initiating cells (BCICs), and their interactions may profoundly affect breast cancer progression. Autophagy has been considered to be a critical process for CIC maintenance, but whether it is involved in the cross-talk between CAFs and CICs to affect tumourigenesis and pathological significance has not been determined. In this study, we found that the presence of CAFs containing high levels of microtubule-associated protein 1 light chain 3 (LC3II), a marker of autophagosomes, was associated with more aggressive luminal human breast cancer. CAFs in human luminal breast cancer tissues with high autophagy activity enriched BCICs with increased tumourigenicity. Mechanistically, autophagic CAFs released high-mobility group box 1 (HMGB1), which activated its receptor, Toll-like receptor (TLR) 4, expressed by luminal breast cancer cells, to enhance their stemness and tumourigenicity. Furthermore, immunohistochemistry of 180 luminal breast cancers revealed that high LC3II/TLR4 levels predicted an increased relapse rate and a poorer prognosis. Our findings demonstrate that autophagic CAFs play a critical role in promoting the progression of luminal breast cancer through an HMGB1-TLR4 axis, and that both autophagy in CAFs and TLR4 on breast cancer cells constitute potential therapeutic targets. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Channel box dimension measuring method

International Nuclear Information System (INIS)

Oshima, Hirotake; Jo, Hiroto.

1994-01-01

The present invention provides a method for measuring the entire length of a channel box of a fuel assembly of a BWR type reactor. Namely, four sensors are used as one set that generate ultrasonic waves from oblique upper portion, oblique lower portion, upper portion and lower portion of the channel box respectively. The distances between the four sensors and each of the portions of the channel box are measured respectively for both of a reference member and a member to be measured. The entire length of the channel box is measured by calculating the measured values and the angles of the obliquely disposed sensors according to a predetermined formula. According to the method of the present invention, the inclination of the channel box to be measured can be corrected. In addition, accuracy of the measurement is improved and the measuring time is saved as well as the measuring device and operation can be simplified. (I.S.)

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...

Protein Kinase R Degradation Is Essential for Rift Valley Fever Virus Infection and Is Regulated by SKP1-CUL1-F-box (SCF)FBXW11-NSs E3 Ligase.

Science.gov (United States)

Mudhasani, Rajini; Tran, Julie P; Retterer, Cary; Kota, Krishna P; Whitehouse, Chris A; Bavari, Sina

2016-02-01

Activated protein kinase R (PKR) plays a vital role in antiviral defense primarily by inhibiting protein synthesis and augmenting interferon responses. Many viral proteins have adopted unique strategies to counteract the deleterious effects of PKR. The NSs (Non-structural s) protein which is encoded by Rift Valley fever virus (RVFV) promotes early PKR proteasomal degradation through a previously undefined mechanism. In this study, we demonstrate that NSs carries out this activity by assembling the SCF (SKP1-CUL1-F-box)(FBXW11) E3 ligase. NSs binds to the F-box protein, FBXW11, via the six amino acid sequence DDGFVE called the degron sequence and recruits PKR through an alternate binding site to the SCF(FBXW11) E3 ligase. We further show that disrupting the assembly of the SCF(FBXW11-NSs) E3 ligase with MLN4924 (a small molecule inhibitor of SCF E3 ligase activity) or NSs degron viral mutants or siRNA knockdown of FBXW11 can block PKR degradation. Surprisingly, under these conditions when PKR degradation was blocked, NSs was essential and sufficient to activate PKR causing potent inhibition of RVFV infection by suppressing viral protein synthesis. These antiviral effects were antagonized by the loss of PKR expression or with a NSs deleted mutant virus. Therefore, early PKR activation by disassembly of SCF(FBXW11-NSs) E3 ligase is sufficient to inhibit RVFV infection. Furthermore, FBXW11 and BTRC are the two homologues of the βTrCP (Beta-transducin repeat containing protein) gene that were previously described to be functionally redundant. However, in RVFV infection, among the two homologues of βTrCP, FBXW11 plays a dominant role in PKR degradation and is the limiting factor in the assembly of the SCF(FBXW11) complex. Thus, FBXW11 serves as a master regulator of RVFV infection by promoting PKR degradation. Overall these findings provide new insights into NSs regulation of PKR activity and offer potential opportunities for therapeutic intervention of RVFV infection.

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

manner. Demographic data, comorbidity, routine biochemistry, microbiological data, infection focus, severity score and mortality on day 28 were recorded. Plasma and serum were sampled within 24 hours after admission. Levels of all studied markers (HMGB1, LBP, PCT, IL-6, C-reactive protein, white blood...... patients compared with nonbacteraemic patients (P white blood cell count and neutrophils (P ... (HMGB1, LBP, PCT, IL-6) and infection markers (C-reactive protein, white blood cell count, neutrophils) were elevated among bacteraemic patients. PCT performed best as a diagnostic test marker for bacteraemia. Udgivelsesdato: 2007-null...

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.

Innovations in Los Alamos alpha box design

International Nuclear Information System (INIS)

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

Protein-protein interactions in the regulation of WRKY transcription factors.

Science.gov (United States)

Chi, Yingjun; Yang, Yan; Zhou, Yuan; Zhou, Jie; Fan, Baofang; Yu, Jing-Quan; Chen, Zhixiang

2013-03-01

It has been almost 20 years since the first report of a WRKY transcription factor, SPF1, from sweet potato. Great progress has been made since then in establishing the diverse biological roles of WRKY transcription factors in plant growth, development, and responses to biotic and abiotic stress. Despite the functional diversity, almost all analyzed WRKY proteins recognize the TTGACC/T W-box sequences and, therefore, mechanisms other than mere recognition of the core W-box promoter elements are necessary to achieve the regulatory specificity of WRKY transcription factors. Research over the past several years has revealed that WRKY transcription factors physically interact with a wide range of proteins with roles in signaling, transcription, and chromatin remodeling. Studies of WRKY-interacting proteins have provided important insights into the regulation and mode of action of members of the important family of transcription factors. It has also emerged that the slightly varied WRKY domains and other protein motifs conserved within each of the seven WRKY subfamilies participate in protein-protein interactions and mediate complex functional interactions between WRKY proteins and between WRKY and other regulatory proteins in the modulation of important biological processes. In this review, we summarize studies of protein-protein interactions for WRKY transcription factors and discuss how the interacting partners contribute, at different levels, to the establishment of the complex regulatory and functional network of WRKY transcription factors.

Complementarity in the Einstein-Bohr photon box

NARCIS (Netherlands)

Dieks, D.G.B.J.; Lam, S

2008-01-01

The Bohr-Einstein photon box thought experiment is a forerunner of the EPR experiment: a packet of radiation escapes from a box, and the box-plus-radiation state remains entangled. Hence, a measurement on the box makes a difference for the state of the far-away radiation long after its escape. This

Dustproof cooling of the electrical box

Directory of Open Access Journals (Sweden)

Nemec Patrik

2018-01-01

Full Text Available In present are electrical boxes cooled by air through the intake hole on the bottom electrical box to the box space with electrotechnical elements and exhaust through the hole at the top to the surrounding by natural convection. This cooling method is effective but operate with the risk of contamination electrotechnical elements by dust sucking from surrounding air. The goal of this work is solution of the dustproof cooling of the electrical box by natural convection. The work deal with design of the device with the heat transfer by the phase change of the working fluid and experimental measuring its thermal performance at the cooling electrotechnical elements loaded by heat 1 200 W in the dustproof electrical box.

bHLH106 Integrates Functions of Multiple Genes through Their G-Box to Confer Salt Tolerance on Arabidopsis.

Science.gov (United States)

Ahmad, Aftab; Niwa, Yasuo; Goto, Shingo; Ogawa, Takeshi; Shimizu, Masanori; Suzuki, Akane; Kobayashi, Kyoko; Kobayashi, Hirokazu

2015-01-01

An activation-tagging methodology was applied to dedifferentiated calli of Arabidopsis to identify new genes involved in salt tolerance. This identified salt tolerant callus 8 (stc8) as a gene encoding the basic helix-loop-helix transcription factor bHLH106. bHLH106-knockout (KO) lines were more sensitive to NaCl, KCl, LiCl, ABA, and low temperatures than the wild-type. Back-transformation of the KO line rescued its phenotype, and over-expression (OX) of bHLH106 in differentiated plants exhibited tolerance to NaCl. Green fluorescent protein (GFP) fused with bHLH106 revealed that it was localized to the nucleus. Prepared bHLH106 protein was subjected to electrophoresis mobility shift assays against E-box sequences (5'-CANNTG-3'). The G-box sequence 5'-CACGTG-3' had the strongest interaction with bHLH106. bHLH106-OX lines were transcriptomically analyzed, and resultant up- and down-regulated genes selected on the criterion of presence of a G-box sequence. There were 198 genes positively regulated by bHLH106 and 36 genes negatively regulated; these genes possessed one or more G-box sequences in their promoter regions. Many of these genes are known to be involved in abiotic stress response. It is concluded that bHLH106 locates at a branching point in the abiotic stress response network by interacting directly to the G-box in genes conferring salt tolerance on plants.

Mathematical aspects of molecular replacement. III. Properties of space groups preferred by proteins in the Protein Data Bank.

Science.gov (United States)

Chirikjian, G; Sajjadi, S; Toptygin, D; Yan, Y

2015-03-01

The main goal of molecular replacement in macromolecular crystallography is to find the appropriate rigid-body transformations that situate identical copies of model proteins in the crystallographic unit cell. The search for such transformations can be thought of as taking place in the coset space Γ\\G where Γ is the Sohncke group of the macromolecular crystal and G is the continuous group of rigid-body motions in Euclidean space. This paper, the third in a series, is concerned with viewing nonsymmorphic Γ in a new way. These space groups, rather than symmorphic ones, are the most common ones for protein crystals. Moreover, their properties impact the structure of the space Γ\\G. In particular, nonsymmorphic space groups contain both Bieberbach subgroups and symmorphic subgroups. A number of new theorems focusing on these subgroups are proven, and it is shown that these concepts are related to the preferences that proteins have for crystallizing in different space groups, as observed in the Protein Data Bank.

Box graphs and resolutions I

Directory of Open Access Journals (Sweden)

Andreas P. Braun

2016-04-01

Full Text Available Box graphs succinctly and comprehensively characterize singular fibers of elliptic fibrations in codimension two and three, as well as flop transitions connecting these, in terms of representation theoretic data. We develop a framework that provides a systematic map between a box graph and a crepant algebraic resolution of the singular elliptic fibration, thus allowing an explicit construction of the fibers from a singular Weierstrass or Tate model. The key tool is what we call a fiber face diagram, which shows the relevant information of a (partial toric triangulation and allows the inclusion of more general algebraic blowups. We shown that each such diagram defines a sequence of weighted algebraic blowups, thus providing a realization of the fiber defined by the box graph in terms of an explicit resolution. We show this correspondence explicitly for the case of SU(5 by providing a map between box graphs and fiber faces, and thereby a sequence of algebraic resolutions of the Tate model, which realizes each of the box graphs.

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.

The influence of the boxing stance on performance in professional boxers

Directory of Open Access Journals (Sweden)

Sorokowski Piotr

2014-12-01

Full Text Available In boxing, athletes choose between two strategies: the orthodox stance characteristic of right handed competitors, or the southpaw stance characteristic of left-handers. Despite a conviction popular among the practitioners of this sport that fighting against a southpaw opponent constitutes a handicap, the effectiveness of the type of stance has so far not been examined. We extracted the statistics of the top twenty active male professionals boxing in each of the seventeen weight divisions. Out of the 340 boxers who composed our group, 75% used the orthodox stance and 25% were southpaw. Generally, we found that boxing stance had no effect on the percentage of 340 top professional boxers’ victories. However, both the southpaw and the orthodox athletes had a higher percentage of victories against orthodox boxers than against southpaws.

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…

Injury risk in professional boxing.

Science.gov (United States)

Bledsoe, Gregory H; Li, Guohu; Levy, Fred

2005-10-01

Although a popular endeavor, boxing has fallen under increased scrutiny because of its association with traumatic brain injury. However, few studies have investigated the overall epidemiology of boxing injuries from representative samples, and no study has ever documented the incidence of injuries in female boxers. This study is a review of professional boxing data from the state of Nevada from September 2001 through March 2003. Medical and outcome data for all professional boxing matches occurring in Nevada between September 2001 and March 2003 (n = 524 matches) were analyzed on the basis of a pair-matched, case-control design. Cases were boxers who received an injury during the boxing matches. Boxers who were not injured served as control subjects. Both conditional and unconditional logistic regression models were used to assess risk factors for injury. The overall incidence rate of injury was 17.1 per 100 boxer-matches, or 3.4 per 100 boxer-rounds. Facial laceration accounted for 51% of all injuries, followed by hand injury (17%), eye injury (14%), and nose injury (5%). Male boxers were significantly more likely than female boxers to receive injuries (3.6 versus 1.2 per 100 boxer-rounds, P = 0.01). Male boxing matches also ended in knockouts and technical knockouts more often than did female matches (P boxing matches is high, particularly among male boxers. Superficial facial lacerations are the most common injury reported. Male boxers have a higher rate of knockout and technical knockouts than female boxers. Further research is necessary to determine the outcomes of injury, particularly the long-term neurologic outcome differences between sexes.

Comparative Human and Automatic Evaluation of Glass-Box and Black-Box Approaches to Interactive Translation Prediction

Directory of Open Access Journals (Sweden)

Torregrosa Daniel

2017-06-01

Full Text Available Interactive translation prediction (ITP is a modality of computer-aided translation that assists professional translators by offering context-based computer-generated continuation suggestions as they type. While most state-of-the-art ITP systems follow a glass-box approach, meaning that they are tightly coupled to an adapted machine translation system, a black-box approach which does not need access to the inner workings of the bilingual resources used to generate the suggestions has been recently proposed in the literature: this new approach allows new sources of bilingual information to be included almost seamlessly. In this paper, we compare for the first time the glass-box and the black-box approaches by means of an automatic evaluation of translation tasks between related languages such as English–Spanish and unrelated ones such as Arabic–English and English–Chinese, showing that, with our setup, 20%–50% of keystrokes could be saved using either method and that the black-box approach outperformed the glass-box one in five out of six scenarios operating under similar conditions. We also performed a preliminary human evaluation of English to Spanish translation for both approaches. On average, the evaluators saved 10% keystrokes and were 4% faster with the black-box approach, and saved 15% keystrokes and were 12% slower with the glass-box one; but they could have saved 51% and 69% keystrokes respectively if they had used all the compatible suggestions. Users felt the suggestions helped them to translate faster and easier. All the tools used to perform the evaluation are available as free/open–source software.

Patterns of MADS-box gene expression mark flower-type development in Gerbera hybrida (Asteraceae

Directory of Open Access Journals (Sweden)

Teeri Teemu H

2006-06-01

Full Text Available Abstract Background The inflorescence of the cut-flower crop Gerbera hybrida (Asteraceae consists of two principal flower types, ray and disc, which form a tightly packed head, or capitulum. Despite great interest in plant morphological evolution and the tractability of the gerbera system, very little is known regarding genetic mechanisms involved in flower type specification. Here, we provide comparative staging of ray and disc flower development and microarray screening for differentially expressed genes, accomplished via microdissection of hundreds of coordinately developing flower primordia. Results Using a 9K gerbera cDNA microarray we identified a number of genes with putative specificity to individual flower types. Intrestingly, several of these encode homologs of MADS-box transcription factors otherwise known to regulate flower organ development. From these and previously obtained data, we hypothesize the functions and protein-protein interactions of several gerbera MADS-box factors. Conclusion Our RNA expression results suggest that flower-type specific MADS protein complexes may play a central role in differential development of ray and disc flowers across the gerbera capitulum, and that some commonality is shared with known protein functions in floral organ determination. These findings support the intriguing conjecture that the gerbera flowering head is more than a mere floral analog at the level of gene regulation.

Opto-Box

CERN Document Server

AUTHOR|(INSPIRE)INSPIRE-00377159; The ATLAS collaboration

2016-01-01

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.

Math in the Box

Science.gov (United States)

DeYoung, Mary J.

2009-01-01

This article describes how to make an origami paper box and explores the algebra, geometry, and other mathematics that unfolds. A set of origami steps that transforms the paper into an open box can hold mathematical surprises for both students and teachers. An origami lesson can engage students in an open-ended exploration of the relationship…

ALUMINUM BOX BUNDLING PRESS

Directory of Open Access Journals (Sweden)

Iosif DUMITRESCU

2015-05-01

Full Text Available In municipal solid waste, aluminum is the main nonferrous metal, approximately 80- 85% of the total nonferrous metals. The income per ton gained from aluminum recuperation is 20 times higher than from glass, steel boxes or paper recuperation. The object of this paper is the design of a 300 kN press for aluminum box bundling.

Box-Cox transformation for QTL mapping.

Science.gov (United States)

Yang, Runqing; Yi, Nengjun; Xu, Shizhong

2006-01-01

The maximum likelihood method of QTL mapping assumes that the phenotypic values of a quantitative trait follow a normal distribution. If the assumption is violated, some forms of transformation should be taken to make the assumption approximately true. The Box-Cox transformation is a general transformation method which can be applied to many different types of data. The flexibility of the Box-Cox transformation is due to a variable, called transformation factor, appearing in the Box-Cox formula. We developed a maximum likelihood method that treats the transformation factor as an unknown parameter, which is estimated from the data simultaneously along with the QTL parameters. The method makes an objective choice of data transformation and thus can be applied to QTL analysis for many different types of data. Simulation studies show that (1) Box-Cox transformation can substantially increase the power of QTL detection; (2) Box-Cox transformation can replace some specialized transformation methods that are commonly used in QTL mapping; and (3) applying the Box-Cox transformation to data already normally distributed does not harm the result.

T box riboswitches in Actinobacteria: Translational regulation via novel tRNA interactions

Science.gov (United States)

Sherwood, Anna V.; Grundy, Frank J.; Henkin, Tina M.

2015-01-01

The T box riboswitch regulates many amino acid-related genes in Gram-positive bacteria. T box riboswitch-mediated gene regulation was shown previously to occur at the level of transcription attenuation via structural rearrangements in the 5′ untranslated (leader) region of the mRNA in response to binding of a specific uncharged tRNA. In this study, a novel group of isoleucyl-tRNA synthetase gene (ileS) T box leader sequences found in organisms of the phylum Actinobacteria was investigated. The Stem I domains of these RNAs lack several highly conserved elements that are essential for interaction with the tRNA ligand in other T box RNAs. Many of these RNAs were predicted to regulate gene expression at the level of translation initiation through tRNA-dependent stabilization of a helix that sequesters a sequence complementary to the Shine–Dalgarno (SD) sequence, thus freeing the SD sequence for ribosome binding and translation initiation. We demonstrated specific binding to the cognate tRNAIle and tRNAIle-dependent structural rearrangements consistent with regulation at the level of translation initiation, providing the first biochemical demonstration, to our knowledge, of translational regulation in a T box riboswitch. PMID:25583497

Y-box Binding Protein-1 Enhances Oncogenic Transforming Growth Factor β Signaling in Breast Cancer Cells via Triggering Phospho-Activation of Smad2.

Science.gov (United States)

Stope, Matthias B; Weiss, Martin; Koensgen, Dominique; Popp, Simone L; Joffroy, Christian; Mustea, Alexander; Buck, Miriam B; Knabbe, Cornelius

2017-12-01

Transforming growth factor β (TGFβ) plays a role in diverse oncogenic pathways including cell proliferation and cell motility and is regulated by the pleiotropic factor Y-box binding protein-1 (YB-1). In breast cancer, Sma/Mad related protein 2 (Smad2) represents the most common downstream transducer in TGFβ signaling. Here, YB-1's impact on Smad2 phospho-activation was characterized by incubation of the breast cancer cell line MCF-7 with or without TGFβ1 in the absence or presence of overexpressed YB-1 protein. The phospho-status of Smad2 was assessed via western blotting. Analysis of MCF-7 cells revealed no induction of total Smad2 neither in the presence of TGFβ1, nor during YB-1 overexpression. In contrast, incubation with TGFβ1 led to an increase of phosphorylated Smad2 forms which was significantly amplified by simultaneously overexpressed YB-1 (2.8±0.2-fold). Oncogenic YB-1 indirectly enhances TGFβ signaling cascades via Smad2 phospho-activation and may represent a promising factor for future diagnosis and therapy of breast cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Structural Isosteres of Phosphate Groups in the Protein Data Bank.

Science.gov (United States)

Zhang, Yuezhou; Borrel, Alexandre; Ghemtio, Leo; Regad, Leslie; Boije Af Gennäs, Gustav; Camproux, Anne-Claude; Yli-Kauhaluoma, Jari; Xhaard, Henri

2017-03-27

We developed a computational workflow to mine the Protein Data Bank for isosteric replacements that exist in different binding site environments but have not necessarily been identified and exploited in compound design. Taking phosphate groups as examples, the workflow was used to construct 157 data sets, each composed of a reference protein complexed with AMP, ADP, ATP, or pyrophosphate as well other ligands. Phosphate binding sites appear to have a high hydration content and large size, resulting in U-shaped bioactive conformations recurrently found across unrelated protein families. A total of 16 413 replacements were extracted, filtered for a significant structural overlap on phosphate groups, and sorted according to their SMILES codes. In addition to the classical isosteres of phosphate, such as carboxylate, sulfone, or sulfonamide, unexpected replacements that do not conserve charge or polarity, such as aryl, aliphatic, or positively charged groups, were found.

Urinary levels of high mobility group box-1 are associated with disease activity in antineutrophil cytoplasmic autoantibody-associated vasculitis.

Directory of Open Access Journals (Sweden)

Tian-Tian Ma

Full Text Available High mobility group box-1 (HMGB1, a kind of pro-inflammatory mediator, is associated with inflammatory conditions and tissue damage. Our previous study demonstrated that the circulating levels of HMGB1 correlated with disease activity of antineutrophil cytoplasmic antibody (ANCA-associated vasculitis (AAV. In the current study, we aimed to measure urinary levels of HMGB1 in AAV patients, correlated them to clinical activity index and analysed the immunohistochemical HMGB1 staining in kidney specimens.50 patients with AAV in active stage and 56 patients with AAV in remission were recruited. The urinary levels of HMGB1 were determined by enzyme-linked immunosorbent assay. Moreover, renal biopsy specimens from 27 patients with active AAV were randomly collected to evaluate the deposition of HMGB1.Urinary HMGB1 levels in AAV patients in active stage were significantly higher than those in AAV patients in remission and healthy controls (1.46 [0.56-3.43] versus 0.38 [0.10-1.35] mg/μmolCr, P=0.001; 1.46 [0.56-3.43] versus 0.48 [0.40-0.60] mg/μmolCr, P=0.000, respectively. Further analysis found that urinary levels of HMGB1 correlated with erythrocyte sedimentation rate (r=0.354, p=0.012, C-reactive protein (r=0.289, p=0.042, and Birmingham Vasculitis Activity Score (r=0.350, p=0.013. Renal tissue of active AAV patients showed HMGB1 was mainly expressed in the cytoplasm and the extracellular space. The percentage of HMGB1-negative nuclei in renal tissue of patients with active AAV was significantly higher than that in normal controls (60.6±20.2 % versus 2.7±0.6 %, p<0.01.Urinary levels of HMGB1 may be associated with the disease activity in AAV patients.

Standards and interdisciplinary treatment of boxing injuries of the head in professional boxing on the basis of an IBF World Championship Fight.

Science.gov (United States)

Dragu, Adrian; Unglaub, Frank; Radomirovic, Sinisa; Schnürer, Stefan; Wagner, Walter; Horch, Raymund E; Hell, Berthold

2010-12-01

Boxing injuries are well known in hobby boxing as well as in professional boxing. Especially in professional boxing it is of great importance to implement and follow prevention-, diagnosis- and therapy-standards in order to prevent or at least to minimize injuries of the athlete. The utmost aim would be to establish international prevention-, diagnosis- and therapy-standards for boxing injuries in professional boxing. However, this aim is on a short run unrealistic, as there are too many different professional boxing organisations with different regulations. A realistic short term aim would be to develop a national standard in order to unify the management and medical treatment of boxing injuries in professional boxing. We present the management and interdisciplinary treatment of a professional boxer with a bilateral open fracture of the mandible during a middle weight IBF World Championship Fight. On the basis of this case we want to present and discuss the possibilities of an interdisciplinary and successful medical treatment. In order to prevent or minimize boxing injuries of professional boxers, annual MRI-Scans of the head and neck have to be performed as prevention standard. Furthermore, neurocognitive tests must be performed on a regular basis. Boxing injuries in professional boxing need an interdisciplinary, unbiased and complex analysis directly at the boxing ring. The treatment of the injuries should be only performed in medical centres and thus under constant parameters. The needed qualifications must be learned in mandatory national licence courses of boxing physicians, referees and promoters.

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...

Overexpression of a novel MADS-box gene SlFYFL delays senescence, fruit ripening and abscission in tomato

Science.gov (United States)

Xie, Qiaoli; Hu, Zongli; Zhu, Zhiguo; Dong, Tingting; Zhao, Zhiping; Cui, Baolu; Chen, Guoping

2014-03-01

MADS-domain proteins are important transcription factors involved in many biological processes of plants. In our study, a tomato MADS-box gene, SlFYFL, was isolated. SlFYFL is expressed in all tissues of tomato and significantly higher in mature leave, fruit of different stages, AZ (abscission zone) and sepal. Delayed leaf senescence and fruit ripening, increased storability and longer sepals were observed in 35S:FYFL tomato. The accumulation of carotenoid was reduced, and ethylene content, ethylene biosynthetic and responsive genes were down-regulated in 35S:FYFL fruits. Abscission zone (AZ) did not form normally and abscission zone development related genes were declined in AZs of 35S:FYFL plants. Yeast two-hybrid assay revealed that SlFYFL protein could interact with SlMADS-RIN, SlMADS1 and SlJOINTLESS, respectively. These results suggest that overexpression of SlFYFL regulate fruit ripening and development of AZ via interactions with the ripening and abscission zone-related MADS box proteins.

Glove boxes

International Nuclear Information System (INIS)

Eisert, G.A.

1979-01-01

An arrangement for effecting access for performing work within a glove box comprises an elongate arm-length impermeable flexible sleeve, a fitting having an aperture therethrough, adapted to be secured in sealing relation in a port, in a wall of the glove box, the fitting including an outwardly extending lip having at least one continuous groove extending around its outer periphery, one end of the sleeve extending through the aperture in fitting and being folded back against the outer periphery of the lip, a resilient fastening ring securing the sleeve in sealing engagement in the groove, clamping means securing the sleeves to the lip and a glove secured in sealing relation via a bushing to the other end of the sleeve. (author)

Magnetorotational Dynamo Action in the Shearing Box

Science.gov (United States)

Walker, Justin; Boldyrev, Stanislav

2017-10-01

Magnetic dynamo action caused by the magnetorotational instability is studied in the shearing-box approximation with no imposed net magnetic flux. Consistent with recent studies, the dynamo action is found to be sensitive to the aspect ratio of the box: it is much easier to obtain in tall boxes (stretched in the direction normal to the disk plane) than in long boxes (stretched in the radial direction). Our direct numerical simulations indicate that the dynamo is possible in both cases, given a large enough magnetic Reynolds number. To explain the relatively larger effort required to obtain the dynamo action in a long box, we propose that the turbulent eddies caused by the instability most efficiently fold and mix the magnetic field lines in the radial direction. As a result, in the long box the scale of the generated strong azimuthal (stream-wise directed) magnetic field is always comparable to the scale of the turbulent eddies. In contrast, in the tall box the azimuthal magnetic flux spreads in the vertical direction over a distance exceeding the scale of the turbulent eddies. As a result, different vertical sections of the tall box are permeated by large-scale nonzero azimuthal magnetic fluxes, facilitating the instability. NSF AGS-1261659, Vilas Associates Award, NSF-Teragrid Project TG-PHY110016.

Genome-wide identification, characterisation and expression analysis of the MADS-box gene family in Prunus mume.

Science.gov (United States)

Xu, Zongda; Zhang, Qixiang; Sun, Lidan; Du, Dongliang; Cheng, Tangren; Pan, Huitang; Yang, Weiru; Wang, Jia

2014-10-01

MADS-box genes encode transcription factors that play crucial roles in plant development, especially in flower and fruit development. To gain insight into this gene family in Prunus mume, an important ornamental and fruit plant in East Asia, and to elucidate their roles in flower organ determination and fruit development, we performed a genome-wide identification, characterisation and expression analysis of MADS-box genes in this Rosaceae tree. In this study, 80 MADS-box genes were identified in P. mume and categorised into MIKC, Mα, Mβ, Mγ and Mδ groups based on gene structures and phylogenetic relationships. The MIKC group could be further classified into 12 subfamilies. The FLC subfamily was absent in P. mume and the six tandemly arranged DAM genes might experience a species-specific evolution process in P. mume. The MADS-box gene family might experience an evolution process from MIKC genes to Mδ genes to Mα, Mβ and Mγ genes. The expression analysis suggests that P. mume MADS-box genes have diverse functions in P. mume development and the functions of duplicated genes diverged after the duplication events. In addition to its involvement in the development of female gametophytes, type I genes also play roles in male gametophytes development. In conclusion, this study adds to our understanding of the roles that the MADS-box genes played in flower and fruit development and lays a foundation for selecting candidate genes for functional studies in P. mume and other species. Furthermore, this study also provides a basis to study the evolution of the MADS-box family.

Does box model training improve surgical dexterity and economy of movement during virtual reality laparoscopy? A randomised trial

DEFF Research Database (Denmark)

Clevin, L.; Grantcharov, T.P.

2008-01-01

OBJECTIVE: Laparoscopic box model trainers have been used in training curricula for a long time, however data on their impact on skills acquisition is still limited. Our aim was to validate a low cost box model trainer as a tool for the training of skills relevant to laparoscopic surgery. DESIGN:...... the VR system. Trainees who used the box model trainer showed significant improvement compared to the control group. Box model trainers are valid tools for laparoscopic skills training and should be implemented in the comprehensive training curricula in gynaecology Udgivelsesdato: 2008...

Opportunities in white-box cryptography

NARCIS (Netherlands)

Michiels, W.

White-box cryptography is the discipline of implementing a cryptographic algorithm in software such that an adversary will have difficulty extracting the cryptographic key. This approach assumes that the adversary has full access to and full control over the implementation's execution. White-box

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

Seismic stability of a standalone glove box structure

International Nuclear Information System (INIS)

Saraswat, A.; Reddy, G.R.; Ghosh, S.; Ghosh, A.K.; Kumar, Arun

2014-01-01

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

Combining native MS approaches to decipher archaeal box H/ACA ribonucleoprotein particle structure and activity.

Science.gov (United States)

Saliou, Jean-Michel; Manival, Xavier; Tillault, Anne-Sophie; Atmanene, Cédric; Bobo, Claude; Branlant, Christiane; Van Dorsselaer, Alain; Charpentier, Bruno; Cianférani, Sarah

2015-08-01

Site-specific isomerization of uridines into pseudouridines in RNAs is catalyzed either by stand-alone enzymes or by box H/ACA ribonucleoprotein particles (sno/sRNPs). The archaeal box H/ACA sRNPs are five-component complexes that consist of a guide RNA and the aCBF5, aNOP10, L7Ae, and aGAR1 proteins. In this study, we performed pairwise incubations of individual constituents of archaeal box H/ACA sRNPs and analyzed their interactions by native MS to build a 2D-connectivity map of direct binders. We describe the use of native MS in combination with ion mobility-MS to monitor the in vitro assembly of the active H/ACA sRNP particle. Real-time native MS was used to monitor how box H/ACA particle functions in multiple-turnover conditions. Native MS also unambiguously revealed that a substrate RNA containing 5-fluorouridine (f(5) U) was hydrolyzed into 5-fluoro-6-hydroxy-pseudouridine (f(5) ho(6) Ψ). In terms of enzymatic mechanism, box H/ACA sRNP was shown to catalyze the pseudouridylation of a first RNA substrate, then to release the RNA product (S22 f(5) ho(6) ψ) from the RNP enzyme and reload a new substrate RNA molecule. Altogether, our native MS-based approaches provide relevant new information about the potential assembly process and catalytic mechanism of box H/ACA RNPs. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

GLASS BOX

National Research Council Canada - National Science Library

Curtis, Laura

2008-01-01

The goals of this effort were to develop Glass Box capabilities to allow for the capturing of analyst activities and the associated data resources, track and log the results of automated processing...

Acquisition of fundamental laparoscopic skills: is a box really as good as a virtual reality trainer?

Science.gov (United States)

Vitish-Sharma, P; Knowles, J; Patel, B

2011-01-01

Laparoscopic surgery requires working in a three-dimensional environment with a two-dimensional view. Skills such as depth perception, hand to eye co-ordination and bimanual manipulation are crucial to its efficacy. To compare the efficiency of training in laparoscopic skills on a VR simulator with a traditional box trainer. Twenty medical students were recruited. An initial training session on the relevant anatomy and steps of a laparoscopic cholecystectomy was given. Baseline skills were recorded using a pre-training laparoscopic cholecystectomy on the VR trainer. Parameters measured were: (1) total time taken (mins); (2) number of movements right and left instrument; (3) path length (cms) of right and left instrument was recorded. Ten students trained on a VR simulator, and ten on a box trainer, for three hours each. The box trainer group exercises were based on the Royal College of Surgeons core laparoscopic skills course, and the VR trainer exercises were based on the Simbionix LapMentor basic skills tasks. Following this both groups were reassessed by a laparoscopic cholecystectomy on the VR trainer. Both groups showed improvement in all measured parameters. A student T-test at 95% confidence interval showed no statistically significant difference between the two groups pre and post training. Both the VR and box trainer are effective in the acquisition of laparoscopic skills. Copyright © 2011 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

[Roles of Y box-binding protein 1 in SK-BR-3 breast cancer proliferation].

Science.gov (United States)

Shi, Jianhong; Lü, Xinrui; Wang, Bing; Daudan, Lin; Yanan, Wang; Yuhui, Bu; Zhenfeng, Ma

2014-09-30

To explore the roles of Y box-binding protein 1 (YB-1) in breast cancer cell proliferation. Twenty cases of surgical removal of breast cancer tissue (diagnosed with invasive ductal carcinoma, stage II, by postoperative paraffin pathology) and normal breast tissues adjacent to carcinoma were collected during June 2013 to August 2013.Quantitative real-time PCR (qRT-PCR) was performed to detect the YB1 mRNA levels. Cultured mammary epithelial cells (HBL-100) and breast cancer cells (MCF7, MDA-MB-231 & SK-BR-3 cells) were harvested and qRT-PCR was performed to detect the YB1 mRNA levels.SK-BR-3 cells were stimulated with various concentrations of PDGF-BB and YB1 expression levels were detected by qRT-PCR. Down-regulation or over-expression of YB1 by si-YB1 or Ad-GFP-YB1 was detected in SK-BR-3 cells. And MTS cell proliferation assay kit was used to detect cell proliferation. YB1 mRNA levels were significantly higher in breast cancer tissues and MDA-MB-231 and SK-BR-3 breast cancer cell lines than that in adjacent normal breast tissues and HBL-100 mammary epithelial cells respectively (P BR-3 cells in a dose-dependent manner. A down-regulation of endogenous YB1 decreases and an over-expression of exogenous YB1 promotes the proliferation activity in SK-BR-3 cells.

SimpleBox 4.0: Improving the model while keeping it simple….

Science.gov (United States)

Hollander, Anne; Schoorl, Marian; van de Meent, Dik

2016-04-01

Chemical behavior in the environment is often modeled with multimedia fate models. SimpleBox is one often-used multimedia fate model, firstly developed in 1986. Since then, two updated versions were published. Based on recent scientific developments and experience with SimpleBox 3.0, a new version of SimpleBox was developed and is made public here: SimpleBox 4.0. In this new model, eight major changes were implemented: removal of the local scale and vegetation compartments, addition of lake compartments and deep ocean compartments (including the thermohaline circulation), implementation of intermittent rain instead of drizzle and of depth dependent soil concentrations, adjustment of the partitioning behavior for organic acids and bases as well as of the value for enthalpy of vaporization. In this paper, the effects of the model changes in SimpleBox 4.0 on the predicted steady-state concentrations of chemical substances were explored for different substance groups (neutral organic substances, acids, bases, metals) in a standard emission scenario. In general, the largest differences between the predicted concentrations in the new and the old model are caused by the implementation of layered ocean compartments. Undesirable high model complexity caused by vegetation compartments and a local scale were removed to enlarge the simplicity and user friendliness of the model. Copyright © 2016 Elsevier Ltd. All rights reserved.

The lithium vapor box divertor

International Nuclear Information System (INIS)

Goldston, R J; Schwartz, J; Myers, R

2016-01-01

It has long been recognized that volumetric dissipation of the plasma heat flux from a fusion power system is preferable to its localized impingement on a material surface. Volumetric dissipation mitigates both the anticipated very high heat flux and intense particle-induced damage due to sputtering. Recent projections to a tokamak demonstration power plant suggest an immense upstream parallel heat flux, of order 20 GW m −2 , implying that fully detached operation may be a requirement for the success of fusion power. Building on pioneering work on the use of lithium by Nagayama et al and by Ono et al as well as earlier work on the gas box divertor by Watkins and Rebut, we present here a concept for a lithium vapor box divertor, in which lithium vapor extracts momentum and energy from a fusion-power-plant divertor plasma, using fully volumetric processes. At the high powers and pressures that are projected this requires a high density of lithium vapor, which must be isolated from the main plasma in order to avoid lithium build-up on the chamber walls or in the plasma. Isolation is achieved through a powerful multi-box differential pumping scheme available only for condensable vapors. The preliminary box-wise calculations are encouraging, but much more work is required to demonstrate the practical viability of this scheme, taking into account at least 2D plasma and vapor flows within and between the vapor boxes and out of the vapor boxes to the main plasma. (paper)

Policy statement—Boxing participation by children and adolescents.

Science.gov (United States)

Purcell, Laura; LeBlanc, Claire M A

2011-09-01

Thousands of boys and girls younger than 19 years 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 neurologic injuries. Concussions are one of the most common injuries that occur with boxing. Because of the risk of head and facial injuries, the American Academy of Pediatrics and the Canadian Paediatric Society oppose boxing as a sport for children and adolescents. These organizations recommend that physicians vigorously oppose boxing in youth and encourage patients to participate in alternative sports in which intentional head blows are not central to the sport.

Spirit Boxes: Expressions of Culture.

Science.gov (United States)

DeMuro, Ted

1984-01-01

After studying the culture and art of the ancient civilizations of South America, Mesopotamia, Greece, and Egypt, secondary level art students made spirit boxes as expressions of the various cultures. How to make the boxes and how to prepare the face molds are described. (RM)

Decontamination of TRU glove boxes

International Nuclear Information System (INIS)

Crawford, J.H.

1978-03-01

Two glove boxes that had been used for work with transuranic nuclides (TRU) for about 12 years were decontaminated in a test program to collect data for developing a decontamination facility for large equipment highly contaminated with alpha emitters. A simple chemical technique consisting of a cycle of water flushes and alkaline permanganate and oxalic acid washes was used for both boxes. The test showed that glove boxes and similar equipment that are grossly contaminated with transuranic nuclides can be decontaminated to the current DIE nonretrievable disposal guide of <10 nCi TRU/g with a moderate amount of decontamination solution and manpower. Decontamination of the first box from an estimated 1.3 Ci to about 5 mCi (6 nCi/g) required 1.3 gallons of decontamination solution and 0.03 man-hour of work for each square foot of surface area. The second box was decontaminated from an estimated 3.4 Ci to about 2.8 mCi (4.2 nCi/g) using 0.9 gallon of decontamination solution and 0.02 man-hour for each square foot of surface area. Further reductions in contamination were achieved by repetitive decontamination cycles, but the effectiveness of the technique decreased sharply after the initial cycle

Electrostatic potentials of the S-locus F-box proteins contribute to the pollen S specificity in self-incompatibility in Petunia hybrida.

Science.gov (United States)

Li, Junhui; Zhang, Yue; Song, Yanzhai; Zhang, Hui; Fan, Jiangbo; Li, Qun; Zhang, Dongfen; Xue, Yongbiao

2017-01-01

Self-incompatibility (SI) is a self/non-self discrimination system found widely in angiosperms and, in many species, is controlled by a single polymorphic S-locus. In the Solanaceae, Rosaceae and Plantaginaceae, the S-locus encodes a single S-RNase and a cluster of S-locus F-box (SLF) proteins to control the pistil and pollen expression of SI, respectively. Previous studies have shown that their cytosolic interactions determine their recognition specificity, but the physical force between their interactions remains unclear. In this study, we show that the electrostatic potentials of SLF contribute to the pollen S specificity through a physical mechanism of 'like charges repel and unlike charges attract' between SLFs and S-RNases in Petunia hybrida. Strikingly, the alteration of a single C-terminal amino acid of SLF reversed its surface electrostatic potentials and subsequently the pollen S specificity. Collectively, our results reveal that the electrostatic potentials act as a major physical force between cytosolic SLFs and S-RNases, providing a mechanistic insight into the self/non-self discrimination between cytosolic proteins in angiosperms. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Loss of Hda activity stimulates replication initiation from I-box, but not R4 mutant origins in Escherichia coli.

Science.gov (United States)

Riber, Leise; Fujimitsu, Kazuyuki; Katayama, Tsutomu; Løbner-Olesen, Anders

2009-01-01

Initiation of chromosome replication in Escherichia coli is limited by the initiator protein DnaA associated with ATP. Within the replication origin, binding sites for DnaA associated with ATP or ADP (R boxes) and the DnaA(ATP) specific sites (I-boxes, tau-boxes and 6-mer sites) are found. We analysed chromosome replication of cells carrying mutations in conserved regions of oriC. Cells carrying mutations in DnaA-boxes I2, I3, R2, R3 and R5 as well as FIS and IHF binding sites resembled wild-type cells with respect to origin concentration. Initiation of replication in these mutants occurred in synchrony or with slight asynchrony only. Furthermore, lack of Hda stimulated initiation in all these mutants. The DnaA(ATP) containing complex that leads to initiation can therefore be formed in the absence of several of the origin DnaA binding sites including both DnaA(ATP) specific I-boxes. However, competition between I-box mutant and wild-type origins, revealed a positive role of I-boxes on initiation. On the other hand, mutations affecting DnaA-box R4 were found to be compromised for initiation and could not be augmented by an increase in cellular DnaA(ATP)/DnaA(ADP) ratio. Compared with the sites tested here, R4 therefore seems to contribute to initiation most critically.

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...

Packing a cake into a box

KAUST Repository

Skopenkov, Mikhail

2011-01-01

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.

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.

Protein: MPB2 [TP Atlas

Lifescience Database Archive (English)

Full Text Available MPB2 Ubiquitin ligases STUB1 CHIP STUB1 E3 ubiquitin-protein ligase CHIP Antigen NY...-CO-7, CLL-associated antigen KW-8, Carboxy terminus of Hsp70-interacting protein, STIP1 homology and U box-containing pr

Decision boxes for clinicians to support evidence-based practice and shared decision making: the user experience

Directory of Open Access Journals (Sweden)

Giguere Anik

2012-08-01

Full Text Available Abstract Background This project engages patients and physicians in the development of Decision Boxes, short clinical topic summaries covering medical questions that have no single best answer. Decision Boxes aim to prepare the clinician to communicate the risks and benefits of the available options to the patient so they can make an informed decision together. Methods Seven researchers (including four practicing family physicians selected 10 clinical topics relevant to primary care practice through a Delphi survey. We then developed two one-page prototypes on two of these topics: prostate cancer screening with the prostate-specific antigen test, and prenatal screening for trisomy 21 with the serum integrated test. We presented the prototypes to purposeful samples of family physicians distributed in two focus groups, and patients distributed in four focus groups. We used the User Experience Honeycomb to explore barriers and facilitators to the communication design used in Decision Boxes. All discussions were transcribed, and three researchers proceeded to thematic content analysis of the transcriptions. The coding scheme was first developed from the Honeycomb’s seven themes (valuable, usable, credible, useful, desirable, accessible, and findable, and included new themes suggested by the data. Prototypes were modified in light of our findings. Results Three rounds were necessary for a majority of researchers to select 10 clinical topics. Fifteen physicians and 33 patients participated in the focus groups. Following analyses, three sections were added to the Decision Boxes: introduction, patient counseling, and references. The information was spread to two pages to try to make the Decision Boxes less busy and improve users’ first impression. To try to improve credibility, we gave more visibility to the research institutions involved in development. A statement on the boxes’ purpose and a flow chart representing the shared decision

Ion-wake Field inside a Glass Box

OpenAIRE

Chen, Mudi; Dropmann, Michael; 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 ex...

Water-cooled target-box design at LAMPF

International Nuclear Information System (INIS)

Grisham, D.; Lambert, J.

1983-01-01

The target boxes in the main experimental beam line (Line A) at the Clinton P. Anderson Meson Physics Facility (LAMPF) have operated since 1976. A program of replacing the boxes is underway. This paper will present past history, design considerations, calculational results and the final box design

Construction of dry-boxes for plutonium metallurgy

International Nuclear Information System (INIS)

Grison, E.; Pascard, R.

1958-01-01

The dry-boxes used at Chatillon are of two main types: a) boxes with a metal frame work of welded angle-pieces, panels of plexiglass, bakelite, duralumin, etc... They include a standard panel which enables them to be connected up to the contaminated repairs workshop; b) boxes made entirely of welded plastic. The working face only is of plexiglas held by screw clamps to a pure rubber joint. These boxes, which cannot be connected to the contaminated workshop, are generally reserved for small pieces of chemical apparatus. None has yet been used for working under argon, although their airtightness is excellent. After an interval of several hours, in fact, no decrease in the pressure inside the box can be detected. Several means can be adopted to ensure that the joints between panels and mountings are absolutely air-tight. Up to the present we are using three types of box with metal framework at the same time, without being able to make a definitive choice. (author) [fr

A DEAD box protein facilitates HIV-1 replication as a cellular co-factor of Rev

International Nuclear Information System (INIS)

Fang Jianhua; Kubota, Satoshi; Yang Bin; Zhou Naiming; Zhang Hui; Godbout, Roseline; Pomerantz, Roger J.

2004-01-01

HIV-1 Rev escorts unspliced viral mRNAs out of the nucleus of infected cells, which allows formation of infectious HIV-1 virions. We have identified a putative DEAD box (Asp-Glu-Ala-Asp) RNA helicase, DDX1, as a cellular co-factor of Rev, through yeast and mammalian two-hybrid systems using the N-terminal motif of Rev as 'bait'. DDX1 is not a functional homolog of HIV-1 Rev, but down-regulation of DDX1 resulted in an alternative splicing pattern of Rev-responsive element (RRE)-containing mRNA, and attenuation of Gag p24 antigen production from HLfb rev(-) cells rescued by exogenous Rev. Co-transfection of a DDX1 expression vector with HIV-1 significantly increased viral production. DDX1 binding to Rev, as well as to the RRE, strongly suggest that DDX1 affects Rev function through the Rev-RRE axis. Moreover, down-regulation of DDX1 altered the steady state subcellular distribution of Rev, from nuclear/nucleolar to cytoplasmic dominance. These findings indicate that DDX1 is a critical cellular co-factor for Rev function, which maintains the proper subcellular distribution of this lentiviral regulatory protein. Therefore, alterations in DDX1-Rev interactions could induce HIV-1 persistence and targeting DDX1 may lead to rationally designed and novel anti-HIV-1 strategies and therapeutics

49 CFR 178.515 - Standards for reconstituted wood boxes.

Science.gov (United States)

2010-10-01

... 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 water... 49 Transportation 2 2010-10-01 2010-10-01 false Standards for reconstituted wood boxes. 178.515...

Calmodulin-dependent nuclear import of HMG-box family nuclear factors: importance of the role of SRY in sex reversal.

Science.gov (United States)

Kaur, Gurpreet; Delluc-Clavieres, Aurelie; Poon, Ivan K H; Forwood, Jade K; Glover, Dominic J; Jans, David A

2010-08-15

The HMG (high-mobility group)-box-containing chromatin-remodelling factor SRY (sex-determining region on the Y chromosome) plays a key role in sex determination. Its role in the nucleus is critically dependent on two NLSs (nuclear localization signals) that flank its HMG domain: the C-terminally located 'beta-NLS' that mediates nuclear transport through Impbeta1 (importin beta1) and the N-terminally located 'CaM-NLS' which is known to recognize the calcium-binding protein CaM (calmodulin). In the present study, we examined a number of missense mutations in the SRY CaM-NLS from human XY sex-reversed females for the first time, showing that they result in significantly reduced nuclear localization of GFP (green fluorescent protein)-SRY fusion proteins in transfected cells compared with wild-type. The CaM antagonist CDZ (calmidazolium chloride) was found to significantly reduce wild-type SRY nuclear accumulation, indicating dependence of SRY nuclear import on CaM. Intriguingly, the CaM-NLS mutants were all resistant to CDZ's effects, implying a loss of interaction with CaM, which was confirmed by direct binding experiments. CaM-binding/resultant nuclear accumulation was the only property of SRY found to be impaired by two of the CaM-NLS mutations, implying that inhibition of CaM-dependent nuclear import is the basis of sex reversal in these cases. Importantly, the CaM-NLS is conserved in other HMG-box-domain-containing proteins such as SOX-2, -9, -10 and HMGN1, all of which were found for the first time to rely on CaM for optimal nuclear localization. CaM-dependent nuclear translocation is thus a common mechanism for this family of important transcription factors.

The dsRNA binding protein RDE-4 interacts with RDE-1, DCR-1, and a DExH-box helicase to direct RNAi in C. elegans.

Science.gov (United States)

Tabara, Hiroaki; Yigit, Erbay; Siomi, Haruhiko; Mello, Craig C

2002-06-28

Double-stranded (ds) RNA induces potent gene silencing, termed RNA interference (RNAi). At an early step in RNAi, an RNaseIII-related enzyme, Dicer (DCR-1), processes long-trigger dsRNA into small interfering RNAs (siRNAs). DCR-1 is also required for processing endogenous regulatory RNAs called miRNAs, but how DCR-1 recognizes its endogenous and foreign substrates is not yet understood. Here we show that the C. elegans RNAi pathway gene, rde-4, encodes a dsRNA binding protein that interacts during RNAi with RNA identical to the trigger dsRNA. RDE-4 protein also interacts in vivo with DCR-1, RDE-1, and a conserved DExH-box helicase. Our findings suggest a model in which RDE-4 and RDE-1 function together to detect and retain foreign dsRNA and to present this dsRNA to DCR-1 for processing.

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 [IBACOS Inc., 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.

The F-box-containing protein UFO and AGAMOUS participate in antagonistic pathways governing early petal development in Arabidopsis.

Science.gov (United States)

Durfee, Tim; Roe, Judith L; Sessions, R Allen; Inouye, Carla; Serikawa, Kyle; Feldmann, Kenneth A; Weigel, Detlef; Zambryski, Patricia C

2003-07-08

The UNUSUAL FLORAL ORGANS (UFO) gene is required for multiple processes in the developing Arabidopsis flower, including the proper patterning and identity of both petals and stamens. The gene encodes an F-box-containing protein, UFO, which interacts physically and genetically with the Skp1 homolog, ASK1. In this report, we describe four ufo alleles characterized by the absence of petals, which uncover another role for UFO in promoting second whorl development. This UFO-dependent pathway is required regardless of the second whorl organ to be formed, arguing that it affects a basic process acting in parallel with those establishing organ identity. However, the pathway is dispensable in the absence of AGAMOUS (AG), a known inhibitor of petal development. In situ hybridization results argue that AG is not transcribed in the petal region, suggesting that it acts non-cell-autonomously to inhibit second whorl development in ufo mutants. These results are combined into a genetic model explaining early second whorl initiation/proliferation, in which UFO functions to inhibit an AG-dependent activity.

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 a...

Nonneurologic emergencies in boxing.

Science.gov (United States)

Coletta, Domenic F

2009-10-01

Professional boxing has done an admirable job in promoting safety standards in its particular sport. However, injuries occur during the normal course of competition and, unfortunately, an occasional life-threatening emergency may arise. Although most common medical emergencies in boxing are injuries from closed head trauma, in this article those infrequent but potentially catastrophic nonneurologic conditions are reviewed along with some less serious emergencies that the physician must be prepared to address.

Y-box-binding protein 1 interacts with hepatitis C virus NS3/4A and influences the equilibrium between viral RNA replication and infectious particle production.

Science.gov (United States)

Chatel-Chaix, Laurent; Melançon, Pierre; Racine, Marie-Ève; Baril, Martin; Lamarre, Daniel

2011-11-01

The hepatitis C virus (HCV) NS3/4A protein has several essential roles in the virus life cycle, most probably through dynamic interactions with host factors. To discover cellular cofactors that are co-opted by HCV for its replication, we elucidated the NS3/4A interactome using mass spectrometry and identified Y-box-binding protein 1 (YB-1) as an interacting partner of NS3/4A protein and HCV genomic RNA. Importantly, silencing YB-1 expression decreased viral RNA replication and severely impaired the propagation of the infectious HCV molecular clone JFH-1. Immunofluorescence studies further revealed a drastic HCV-dependent redistribution of YB-1 to the surface of the lipid droplets, an important organelle for HCV assembly. Core and NS3 protein-dependent polyprotein maturation were shown to be required for YB-1 relocalization. Unexpectedly, YB-1 knockdown cells showed the increased production of viral infectious particles while HCV RNA replication was impaired. Our data support that HCV hijacks YB-1-containing ribonucleoparticles and that YB-1-NS3/4A-HCV RNA complexes regulate the equilibrium between HCV RNA replication and viral particle production.

Barriers and facilitators to implementing Decision Boxes in primary healthcare teams to facilitate shared decisionmaking: a study protocol

Directory of Open Access Journals (Sweden)

Giguere Anik

2012-08-01

Full Text Available Abstract Background Decision Boxes are summaries of the most important benefits and harms of health interventions provided to clinicians before they meet the patient, to prepare them to help patients make informed and value-based decisions. Our objective is to explore the barriers and facilitators to using Decision Boxes in clinical practice, more precisely factors stemming from (1 the Decision Boxes themselves, (2 the primary healthcare team (PHT, and (3 the primary care practice environment. Methods/design A two-phase mixed methods study will be conducted. Eight Decision Boxes relevant to primary care, and written in both English and in French, will be hosted on a website together with a tutorial to introduce the Decision Box. The Decision Boxes will be delivered as weekly emails over a span of eight weeks to clinicians of PHTs (family physicians, residents and nurses in five primary care clinics located across two Canadian provinces. Using a web-questionnaire, clinicians will rate each Decision Box with the Information Assessment Method (cognitive impacts, relevance, usefulness, expected benefits and with a questionnaire based on the Theory of Planned Behavior to study the determinants of clinicians’ intention to use what they learned from that Decision Box in their patient encounter (attitude, social norm, perceived behavioral control. Web-log data will be used to monitor clinicians’ access to the website. Following the 8-week intervention, we will conduct semi-structured group interviews with clinicians and individual interviews with clinic administrators to explore contextual factors influencing the use of the Decision Boxes. Data collected from questionnaires, focus groups and individual interviews will be combined to identify factors potentially influencing implementation of Decision Boxes in clinical practice by clinicians of PHTs. Conclusions This project will allow tailoring of Decision Boxes and their delivery to overcome the

Glove boxes. Dimensions and requirements. Draft

International Nuclear Information System (INIS)

1985-07-01

The standard is to be applied to work done in glove-boxes, whereby either the personnel need to be protected from the damaging effects of the materials being handled, or the materials from the effects of the environment. It is to be applied to glove-boxes in which substances are handled which emit ionising radiation (radioactive substances). This norm is not restricted to glove-boxes in which processes are carried out on a technique scale. In accordance with this norm, only those pressures and temperatures are allowed to be present in the glove-boxes, that do not offer significantly from the work areas. Alongside the stipulations of this standard regard is also always to be taken of the regulations in the radiation protection ordinance. (orig./HP) [de

Using rap music to promote adolescent health: pilot study of VoxBox.

Science.gov (United States)

Paukste, Ernesta; Harris, Neil

2015-04-01

Alcohol, tobacco and other drugs (ATODs) usage among adolescents, particularly those living in lower socioeconomic communities, is a population health problem in Australia that requires innovative health promotion strategies. There is a growing recognition of the potential of arts-based approaches to engage youth in health promoting activities. This paper presents the process evaluation of the pilot VoxBox intervention that used rap to build adolescents' awareness of risks associated with ATODs. The VoxBox intervention was piloted in Logan, Queensland, at five high schools with 18 adolescents completing the intervention. Data collection methods included observation, focus groups, semi-structured interviews and a survey of adolescent participants. The intervention was well received by participants and stakeholders. Three factors characterising the project's successful engagement of adolescents were: participate - go with the flow, learning from the real deal and resourced to make some noise. In VoxBox, the emphasis on engaging adolescents in an activity of real interest that was appropriately resourced and delivered was central to credibility and success. SO WHAT?: The findings highlight the importance of interventions matching the interests of the targeted population group.

Introduction to the Box Particle Filtering

OpenAIRE

Gning, Amadou; Ristic, B; Mihaylova, Lyudmila; Abdallah, F.

2013-01-01

This paper presents a novel method for solving nonlinear filtering problems. This approach is particularly appealing in practical situations involving imprecise stochastic measurements, thus resulting in very broad posterior densities. It relies on the concept of a box particle, which occupies a small and controllable rectangular region having a non-zero volume in the state space. Key advantages of the box particle filter (Box-PF) against the standard particle filter (PF) are in its reduced c...

Alternative Sources Of Protein And Bulking Agent For Mass Rearing Of The Mediterranean Fruit Fly, Ceratitis Capitata (WIED.), For The Sterile Insect Technique (SIT)

International Nuclear Information System (INIS)

SHOMAN, A.A.

2009-01-01

The objective of this study was to develop suitable and economic diets for mass rearing of the Mediterranean fruit fly, Ceratitis capitata (Wied.) (Diptera: Tephritidae), larvae by testing alternative sources of protein and bulking agent. Two larval diet groups for laboratory rearing of the medfly were conducted in addition to the control diet. The first group kept the sources of bulking agent constant (wheat bran) while the kind and the ratio of sources of protein were changed (brewer's yeast, soybean, schemed milk and agar). In the second group, the fiber (used for filling the pillows) and a paste of cardboard eggs box trays were used instead of wheat bran as bulking agent against the yeast and soybean as protein sources. To investigate the effect of the new sources of bulking agent and the kind or the ratio of the protein sources on the development and viability of the medfly, larval duration, pupal recovery, pupal weight, adult emergence, and flight ability were checked. The larval duration, pupal weight, adult recovery and flight ability were unaffected when soybean or a mixture from yeast, soybean, schemed milk and agar as protein sources for larval diet were used. The larvae reared on diets based on schemed milk or agar as sources of protein did not complete their life cycle. The percent of pupal recovery of larvae reread on diets of soybean or a mixture of protein sources were not affected except when larvae were reared on diets based on a mixture of soybean and schemed milk or schemed milk and agar. Larval duration was extended by one to two days more than the control when the fiber or a mixture of it with bran or paste of cardboard of eggs box was used as bulking agent. A paste of cardboard eggs box as bulking agent led to the extension of the larval duration by more than four days than in control. Pupal recovery was significantly decreased at all diets of the second group except the diet containing a mixture of 4 % fiber and 10 % bran as bulking agent

Amateur boxing: physical and physiological attributes.

Science.gov (United States)

Chaabène, Helmi; Tabben, Montassar; Mkaouer, Bessem; Franchini, Emerson; Negra, Yassine; Hammami, Mehrez; Amara, Samiha; Chaabène, Raja Bouguezzi; Hachana, Younés

2015-03-01

Boxing is one of the oldest combat sports. The aim of the current review is to critically analyze the amateur boxer's physical and physiological characteristics and to provide practical recommendations for training as well as new areas of scientific research. High-level male and female boxers show a propensity for low body fat levels. Although studies on boxer somatotypes are limited, the available information shows that elite-level male boxers are characterized by a higher proportion of mesomorphy with a well-developed muscle mass and a low body fat level. To help support the overall metabolic demands of a boxing match and to accelerate the recovery process between rounds, athletes of both sexes require a high level of cardiorespiratory fitness. International boxers show a high peak and mean anaerobic power output. Muscle strength in both the upper and lower limbs is paramount for a fighter's victory and is one of the keys to success in boxing. As boxing punches are brief actions and very dynamic, high-level boxing performance requires well-developed muscle power in both the upper and lower limbs. Albeit limited, the available studies reveal that isometric strength is linked to high-level boxing performance. Future investigations into the physical and physiological attributes of boxers are required to enrich the current data set and to help create a suitable training program.

Influence of dimension box differences and time differences during operations of red box for motorcycles at signalized intersection

Science.gov (United States)

Mulyadi, Agah Muhammad

2017-11-01

Performance of signalized intersection has declined due to a large number of motorcycles. The number of motorcycles reached 98.2 million units and the composition of motorcycles has reached around 81.7% of the total composition of vehicles in Indonesia (AISI, 2017). To solve that problem, the red box for motorcycles are provided at the signalized intersection. Red box for the motorcycle at signalized intersections was developed from the concept of Advance Stop Line (ASL) for bicycles. The Red Box was developed to split the queue between motorcycles and other vehicles when waiting at red light. This paper aims to evaluate the influence of the red box dimension and red time operation differences. The survey was conducted as many as 30 cycles of traffic signals per day. The data were analyzed using software IBM SPSS Statistics 20 by using Analysis of Variance (ANOVA) to obtain p-value (significant). The analysis shows that there are insignificant influences between the occupancy rates to the dimension of Red Box. Furthermore, that there is a significant difference that shows the dependency of only motorcycles in the Red Box Area towards red time operation.

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 as...

Relativistic particle in a box

OpenAIRE

Alberto, P.; Fiolhais, Carlos; Gil, Victor

1996-01-01

The problem of a relativistic spin 1/2 particle confined to a one-dimensional box is solved in a way that resembles closely the solution of the well known quantum-mechanical textbook problem of a non-relativistic particle in a box. The energy levels and probability density are computed and compared with the non-relativistic case

What Makes a Better Box?

Science.gov (United States)

Moyer, Richard; Everett, Susan

2010-01-01

Every morning, many Americans start their day with a bowl of cereal. Some spend time while they eat breakfast reading the back of the cereal box, but few consider its size, shape, and construction, or realize that it was designed by an engineer. This article describes a lesson in which students design, build, and critique cereal boxes. The lesson…

Infectious disease and boxing.

Science.gov (United States)

King, Osric S

2009-10-01

There are no unique boxing diseases but certain factors contributing to the spread of illnesses apply strongly to the boxer, coach, and the training facility. This article examines the nature of the sport of boxing and its surrounding environment, and the likelihood of spread of infection through airborne, contact, or blood-borne routes of transmission. Evidence from other sports such as running, wrestling, and martial arts is included to help elucidate the pathophysiologic elements that could be identified in boxers.

The applicability of a multitask boxing program using the BoxMaster ® for Parkinson’s disease

OpenAIRE

Domingos, Josefa; Loureiro, Rita; Godinho, Catarina; Dean, John; Ferreira, Joaquim J.

2016-01-01

Poster presented at the 4th World Parkinson Congress. Portland, Oregon, 20-23 September 2016 "Objective: To test the applicability of a multitasking boxing program using the BoxMaster® in individuals with Parkinson’s disease that combines motor, cognitive and vocal exercises." N/A

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 is not just for faces anymore— ...

Fuel assembly and fuel channel box

International Nuclear Information System (INIS)

Sakuma, Toraki; Hirakawa, Hiromasa; Ishizaki, Hideaki; Nakajima, Junjiro; Aizawa, Yasuhiro.

1992-01-01

A fuel channel box has a square cylindrical shape and, in the transversal cross sectional shape, the wall thickness of a corner portion is greater than that of a central portion of the side wall except for an upper portion thereof. The upper portion of the channel box includes a region to be in contact with an upper lattice plate and a region to attach a channel spacer. Then, the wall thickness of these regions is uniform in the transversal cross section and they have the same wall thickness with that of the corner portion which has the increased wall thickness. With such a constitution, the upper portion of the channel box receives a counter force applied from the upper lattice plate upon occurrence of earthquakes and moderate it to reduce local stresses and deformation. Further, a similar region with increased wall thickness is disposed also to the lower portion of the channel box, thereby enabling to suppress the amount of coolants leaked from a portion between the lower portion and a lower tie plate, and improve the mechanical integrity of the channel box. (I.N.)

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

Spacer for supporting fuel element boxes

International Nuclear Information System (INIS)

Wild, E.

1979-01-01

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

Arabidopsis AtbHLH112 regulates the expression of genes involved in abiotic stress tolerance by binding to their E-box and GCG-box motifs.

Science.gov (United States)

Liu, Yujia; Ji, Xiaoyu; Nie, Xianguang; Qu, Min; Zheng, Lei; Tan, Zilong; Zhao, Huimin; Huo, Lin; Liu, Shengnan; Zhang, Bing; Wang, Yucheng

2015-08-01

Plant basic helix-loop-helix (bHLH) transcription factors play essential roles in abiotic stress tolerance. However, most bHLHs have not been functionally characterized. Here, we characterized the functional role of a bHLH transcription factor from Arabidopsis, AtbHLH112, in response to abiotic stress. AtbHLH112 is a nuclear-localized protein, and its nuclear localization is induced by salt, drought and abscisic acid (ABA). In addition, AtbHLH112 serves as a transcriptional activator, with the activation domain located at its N-terminus. In addition to binding to the E-box motifs of stress-responsive genes, AtbHLH112 binds to a novel motif with the sequence 'GG[GT]CC[GT][GA][TA]C' (GCG-box). Gain- and loss-of-function analyses showed that the transcript level of AtbHLH112 is positively correlated with salt and drought tolerance. AtbHLH112 mediates stress tolerance by increasing the expression of P5CS genes and reducing the expression of P5CDH and ProDH genes to increase proline levels. AtbHLH112 also increases the expression of POD and SOD genes to improve reactive oxygen species (ROS) scavenging ability. We present a model suggesting that AtbHLH112 is a transcriptional activator that regulates the expression of genes via binding to their GCG- or E-boxes to mediate physiological responses, including proline biosynthesis and ROS scavenging pathways, to enhance stress tolerance. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Sport medicine and the ethics of boxing

Science.gov (United States)

Leclerc, S.; Herrera, C. D.

1999-01-01

In the light of medical evidence of the health risks associated with boxing, a watchful agnostic position among sport physicians is no longer justifiable. The normal activity in a boxing match places the athletes at risk of head injury, some of which may be difficult to detect and impossible to repair. This suggests that sport physicians and others expert in the prevention and diagnosis of such injuries should take a public stand against boxing, as other medical associations have. Although there is a need for continuing research into the health risks, doctors can in the interim take steps to increase public awareness of these risks. Sport physicians in particular can make a strong public statement by also ending their professional involvement with boxing. This need not be interpreted as paternalism; doctors are qualified neither to make laws nor to restrict private behaviour. Sport physicians are, however, well equipped to advise those who do make laws and those who choose to engage in boxing. In the end, because this stance against boxing will probably reduce the number of brain injuries in certain athletes, autonomy will be preserved, rather than restricted. 


 PMID:10597855

North American box turtles: A natural history

Science.gov (United States)

Dodd, C. Kenneth

2002-01-01

Once a familiar backyard visitor in many parts of the United States and Mexico, the box turtle is losing the battle against extinction. In North American Box Turtles, C. Kenneth Dodd, Jr., has written the first book-length natural history of the twelve species and subspecies of this endangered animal. This volume includes comprehensive information on the species’ evolution, behavior, courtship and reproduction, habitat use, diet, population structure, systematics, and disease. Special features include color photos of all species, subspecies, and their habitats; a simple identification guide to both living and fossil species; and a summary of information on fossil Terrapene and Native uses of box turtles. End-of-chapter sections highlight future research directions, including the need for long-term monitoring and observation of box turtles within their natural habitat and conservation applications. A glossary and a bibliography of literature on box turtles accompany the text.

Community-based group exercise for persons with Parkinson disease: a randomized controlled trial.

Science.gov (United States)

Combs, Stephanie A; Diehl, M Dyer; Chrzastowski, Casey; Didrick, Nora; McCoin, Brittany; Mox, Nicholas; Staples, William H; Wayman, Jessica

2013-01-01

The purpose of this study was to compare group boxing training to traditional group exercise on function and quality of life in persons with Parkinson disease (PD). A convenience sample of adults with PD (n = 31) were randomly assigned to boxing training or traditional exercise for 24-36 sessions, each lasting 90 minutes, over 12 weeks. Boxing training included: stretching, boxing (e.g. lateral foot work, punching bags), resistance exercises, and aerobic training. Traditional exercise included: stretching, resistance exercises, aerobic training, and balance activities. Participants were tested before and after completion of training on balance, balance confidence, mobility, gait velocity, gait endurance, and quality of life. The traditional exercise group demonstrated significantly greater gains in balance confidence than the boxing group (p effect size for the gait endurance (d = 0.65). Both groups demonstrated significant improvements with the balance, mobility, and quality of life with large within-group effect sizes (d ≥ 0.80). While groups significantly differed in balance confidence after training, both groups demonstrated improvements in most outcome measures. Supporting options for long-term community-based group exercise for persons with PD will be an important future consideration for rehabilitation professionals.

Box-Particle Cardinality Balanced Multi-Target Multi-Bernoulli Filter

OpenAIRE

L. Song; X. Zhao

2014-01-01

As a generalized particle filtering, the box-particle filter (Box-PF) has a potential to process the measurements affected by bounded error of unknown distributions and biases. Inspired by the Box-PF, a novel implementation for multi-target tracking, called box-particle cardinality balanced multi-target multi-Bernoulli (Box-CBMeMBer) filter is presented in this paper. More important, to eliminate the negative effect of clutters in the estimation of the numbers of targets, an improved generali...

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 more...

Sequence-specific DNA binding by MYC/MAX to low-affinity non-E-box motifs.

Directory of Open Access Journals (Sweden)

Michael Allevato

Full Text Available The MYC oncoprotein regulates transcription of a large fraction of the genome as an obligatory heterodimer with the transcription factor MAX. The MYC:MAX heterodimer and MAX:MAX homodimer (hereafter MYC/MAX bind Enhancer box (E-box DNA elements (CANNTG and have the greatest affinity for the canonical MYC E-box (CME CACGTG. However, MYC:MAX also recognizes E-box variants and was reported to bind DNA in a "non-specific" fashion in vitro and in vivo. Here, in order to identify potential additional non-canonical binding sites for MYC/MAX, we employed high throughput in vitro protein-binding microarrays, along with electrophoretic mobility-shift assays and bioinformatic analyses of MYC-bound genomic loci in vivo. We identified all hexameric motifs preferentially bound by MYC/MAX in vitro, which include the low-affinity non-E-box sequence AACGTT, and found that the vast majority (87% of MYC-bound genomic sites in a human B cell line contain at least one of the top 21 motifs bound by MYC:MAX in vitro. We further show that high MYC/MAX concentrations are needed for specific binding to the low-affinity sequence AACGTT in vitro and that elevated MYC levels in vivo more markedly increase the occupancy of AACGTT sites relative to CME sites, especially at distal intergenic and intragenic loci. Hence, MYC binds diverse DNA motifs with a broad range of affinities in a sequence-specific and dose-dependent manner, suggesting that MYC overexpression has more selective effects on the tumor transcriptome than previously thought.

Grey Box Modelling of Hydrological Systems

DEFF Research Database (Denmark)

Thordarson, Fannar Ørn

of two papers where the stochastic differential equation based model is used for sewer runoff from a drainage system. A simple model is used to describe a complex rainfall-runoff process in a catchment, but the stochastic part of the system is formulated to include the increasing uncertainty when...... rainwater flows through the system, as well as describe the lower limit of the uncertainty when the flow approaches zero. The first paper demonstrates in detail the grey box model and all related transformations required to obtain a feasible model for the sewer runoff. In the last paper this model is used......The main topic of the thesis is grey box modelling of hydrologic systems, as well as formulation and assessment of their embedded uncertainties. Grey box model is a combination of a white box model, a physically-based model that is traditionally formulated using deterministic ordinary differential...

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...... and the strength of the bounds that can be proven in such a model. In particular, the original black-box model provides for well-known benchmark problems relatively small lower bounds, which seem unrealistic in certain cases and are typically not met by popular search heuristics.In this paper, we introduce a more...... restricted black-box model for optimisation of pseudo-Boolean functions which we claim captures the working principles of many randomised search heuristics including simulated annealing, evolutionary algorithms, randomised local search, and others. The key concept worked out is an unbiased variation operator...

Leak detection in turbo group condensers using helium

International Nuclear Information System (INIS)

Gomez Cores, C.; Lloret, J.

1997-01-01

This method allows a rapid location of leaks (small or not) in the pipelines of a turbo group condenser, before opening the condenser boxes and no need of stooping the turbo group operation. This operation can last two hours maximum depending on the volume of the box or semi box. The technique consists of injecting helium into the water side and detecting it in the steam side, in the outlet of not condensable gases of the ejector. In the same way, probable air inlet to the condenser can be proved (auxiliary systems, turbo group joints to the condenser, etc.) in order to improve the vacuum and/or reduce the quantity of oxygen dissolved in the water of the steam side. (author) [es

Evaluation method for the deformation of channel box

International Nuclear Information System (INIS)

Sadaoka, Noriyuki; Kumahora, Hiroki; Miki, Kazuyoshi.

1990-01-01

In a BWR type nuclear reactor, a channel box undergoes creep deformation due to the effects of a pressure difference between inside and outside of the channel box and a reactor water temperature, which is accelerated by the irradiation of radiation rays and the extent of which depends on the loading position. Then, there are provided a step of determining the extent of the deformation of the channel box in a burning period in the past, a step of setting the loading position for the channel box in the reactor core, a step of forecasting the extent of the deformation of the channel box based on the data of reactor core characteristics, the date of the physical properties of the materials and the shape of the channel box, the data of the loading pattern of fuel assemblies and the extent of deformation, and a step of estimating whether the forecast deforming extent is within an allowable range or not. As a result, the deforming extent for each of the channel boxes can be forecast and, accordingly, the interference with the control rods can be estimated accurately. (N.H.)

Fuel element box inspection device

International Nuclear Information System (INIS)

Ortmayer, R.M.; Pick, W.

1985-01-01

The invention concerns a device for inspecting the outer geometry of a long fuel element box by measuring the surface contours over its longitudinal crossection and along its length by sensors. These are kept in a sledge which can be moved along the fuel element guide in a slot guide. The measurement signals reach an evaluation device outside the longitudinal box. (orig./HP) [de

Dynamics of TBP binding to the TATA box

Science.gov (United States)

Schluesche, Peter; Heiss, Gregor; Meisterernst, Michael; Lamb, Don C.

2008-02-01

Gene expression is highly controlled and regulated in living cells. One of the first steps in gene transcription is recognition of the promoter site by the TATA box Binding Protein (TBP). TBP recruits other transcriptions factors and eventually the RNA polymerase II to transcribe the DNA in mRNA. We developed a single pair Förster Resonance Energy Transfer (spFRET) assay to investigate the mechanism of gene regulation. Here, we apply this assay to investigate the initial binding process of TBP to the adenovirus major late (AdML) promoter site. From the spFRET measurements, we were able to identify two conformations of the TBP-DNA complex that correspond to TBP bound in the correct and the opposite orientation. Increased incubation times or the presence of the transcription factor TFIIA improved the alignment of TBP on the promoter site. Binding of TBP to the TATA box shows a rich dynamics with abrupt transitions between multiple FRET states. A frame-wise histogram analysis revealed the presence of at least six discrete states, showing that TBP binding is more complicated than previously thought. Hence, the spFRET assay is very sensitive to the conformation of the TBP-DNA complex and is very promising tool for investigating the pathway of TBP binding in detail.

30 CFR 18.49 - Connection boxes on machines.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Connection boxes on machines. 18.49 Section 18..., AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.49 Connection boxes on machines. Connection boxes used to facilitate replacement...

49 CFR 178.513 - Standards for boxes of natural wood.

Science.gov (United States)

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Standards for boxes of natural wood. 178.513... natural wood. (a) The following are the identification codes for boxes of natural wood: (1) 4C1 for an ordinary box; and (2) 4C2 for a box with sift-proof walls. (b) Construction requirements for boxes of...

Structural testing of the technology integration box beam

Science.gov (United States)

Griffin, C. F.

1992-01-01

A full-scale section of a transport aircraft wing box was designed, analyzed, fabricated, and tested. The wing box section, which was called the technology integration box beam, contained blade stiffened covers and T-stiffened channel spars constructed using graphite/epoxy materials. Covers, spars, and the aluminum ribs were assembled using mechanical fasteners. The box beam was statically tested for several loading conditions to verify the stiffness and strength characteristics of the composite wing design. Failure of the box beam occurred at 125 percent of design limit load during the combined upbending and torsion ultimate design load test. It appears that the failure initiated at a stiffener runout location in the upper cover which resulted in rupture of the upper cover and portions of both spars.

Fosrenol for Enhancing Dietary Protein Intake in Hypoalbuminemic Dialysis Patients (FrEDI Study

Directory of Open Access Journals (Sweden)

Tara Koontz

2012-06-01

Full Text Available Protein-energy wasting (PEW, reflected by serum albumin 5.5 mg/dL is also common and is associated with high death risk. The traditional dietary approach to control hyperphosphatemia by limiting protein foods may cause or worsen PEW. We hypothesized that provision of a high protein diet including during HD treatment results in favorable outcomes if a potent phosphorus binder such as lanthanum carbonate (Fosrenol™ can control phosphorus simultaneously and conducted a pilot/feasibility randomized controlled trial in 110 hypoalbuminemic (<4.0 mg/dL MHD patients in several dialysis clinics. After a washout period and upon 1:1 randomization, we provided the INTERVENTION group with 8 weeks of high protein meals as prepared meal boxes (50 g protein, 850 Cal, phosphorus to protein ratio <10 mg/gm during each HD treatment, along with 0.5 to 1.5 g Fosrenol (titrated as needed plus dietary counseling to maintain a high dietary protein intake at home. The CONTROL group received meal boxes containing low calorie (<50 Cal and almost no protein (<1 g, such as salads during each HD treatment and continued non-Fosrenol binders. We examined combined change in serum albumin with remaining in target phosphorus range of 3.5-<5.5 mg/dL over the 8 weeks of intervention. Among the 51 intervention and 55 control subjects who qualified for the intention-to-treat analyses, the combined rise in albumin ≥0.2 g/dL while maintaining phosphorus in 3.5-<5.5 mg/dL range was achieved in 25.5% and 9.8%, respectively (χ² p-value 0.036. No serious adverse events were reported, and patients reported satisfaction with high protein meals during HD. Hence, provision of high protein meals combined with Fosrenol™ during HD is safe and may improve albumin while controlling serum phosphorus. ClinicalTrials.gov # NCT0111694

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…

Construction and properties of Box-Behnken designs

OpenAIRE

Jo, Jinnam

1992-01-01

Box-Behnken designs are used to estimate parameters in a second-order response surface model (Box and Behnken, 1960). These designs are formed by combining ideas from incomplete block designs (BIBD or PBIBD) and factorial experiments, specifically 2k full or 2k-1 fractional factorials. In this dissertation, a more general mathematical formulation of the Box-Behnken method is provided, a general expression for the coefficient matrix in the least squares analysis for estimatin...

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.

Plutonium glove boxes - metrology and operational states

International Nuclear Information System (INIS)

Thyer, A.M.

2001-01-01

The main objective was to undertake a literature review in support of NII's ongoing work in improving safety in the nuclear industry to help define suitable standards of cleanliness for plutonium glove boxes. This is to cover the following areas: existing or proposed national/international standards relating to plutonium glove box cleanliness management; practicable metrology options for assessing the plutonium content of glove boxes; any available dose information relating to the operation of modern and 'old design'; current contamination levels of specific significance (i.e. any accepted level in decommissioning/waste terms, typical criticality limits (if available), any box plutonium loadings that are documented with corresponding operator doses etc.); and, techniques for the decontamination of plutonium glove boxes and their relative effectiveness. This should then form the basis of any further development work undertaken by the UK nuclear industry. Main recommendations are as follows: 1) No information could be found in open literature on acceptable levels of contamination in boxes and action levels for cleanup. If these are not available in closed publications the 2) Where possible, the decontamination methods identified should be tested and dose information recorded against each method to allow informed decisions on which is the optimum technique for a particular form of contamination. 3) Consideration should be given to utilisation of metrology options which have the lowest potential for exposure of operators. Preferred options, may be detection from the outside of boxes using hand-held or permanently located radiation detectors, or semi-intrusive methods such as air-ionisation readings which would require one-off installation of detectors in ductwork

Designing key-dependent chaotic S-box with larger key space

International Nuclear Information System (INIS)

Yin Ruming; Yuan Jian; Wang Jian; Shan Xiuming; Wang Xiqin

2009-01-01

The construction of cryptographically strong substitution boxes (S-boxes) is an important concern in designing secure cryptosystems. The key-dependent S-boxes designed using chaotic maps have received increasing attention in recent years. However, the key space of such S-boxes does not seem to be sufficiently large due to the limited parameter range of discretized chaotic maps. In this paper, we propose a new key-dependent S-box based on the iteration of continuous chaotic maps. We explore the continuous-valued state space of chaotic systems, and devise the discrete mapping between the input and the output of the S-box. A key-dependent S-box is constructed with the logistic map in this paper. We show that its key space could be much larger than the current key-dependent chaotic S-boxes.

Design of strong wooden box coated with fiberglass reinforced resin for shipping and burial of contaminated glove boxes. Final report

International Nuclear Information System (INIS)

1982-01-01

The project scope of work included the complete decontamination and decommissioning (D and D) of the Westinghouse ARD Fuel Laboratories at the Cheswick Site in the shortest possible time. This has been accomplished in the following four phases: (1) preparation of documents and necessary paperwork; packaging and shipping of all special nuclear materials in an acceptable form to a reprocessing agency; (2) decontamination of all facilities, glove boxes and equipment; loading of generated waste into bins, barrels and strong wooden boxes; (3) shipping of al bins, barrels and boxes containing waste to the designated burial site; removal of all utility services from the laboratories; and (4) final survey of remaining facilities and certification for nonrestricted use; preparation of final report. This attachment contains design of strong wooden box coated with fiberglass reinforced resin for shipping and burial of contaminated glove boxes

Light Therapy Boxes for Seasonal Affective Disorder

Science.gov (United States)

Seasonal affective disorder treatment: Choosing a light therapy box Light therapy boxes can offer an effective treatment for seasonal affective disorder. Features such as light intensity, safety, cost and ...

F-box protein FBXO31 is a dedicated checkpoint protein to facilitate cell cycle arrest through activation of regulators in radiation induced DNA damage

International Nuclear Information System (INIS)

Santra, Manas Kumar

2017-01-01

In response to radiation-induced DNA damage, eukaryotic cells initiate a complex signalling pathway, termed the DNA damage response (DDR), which coordinates cell cycle arrest with DNA repair. Previous study showed that induction of G1 arrest in response to radiation induced DNA damage is minimally a two-step process: a fast p53-independent initiation of G1 arrest mediated by cyclin D1 proteolysis and a slower maintenance of arrest resulting from increased p53 stability. We elucidated the molecular mechanism of slow and fast response of radiation induced DDR. We showed that FBXO31, a member of F-box family proteins, plays important role in DDR induced by ionizing radiation. We show that FBXO31 is responsible for promoting MDM2 degradation following radiation. FBXO31 interacts with and directs the degradation of MDM2 in ATM dependent phosphorylation of MDM2. FBXO31-mediated loss of MDM2 leads to elevated levels of p53, resulting in growth arrest. In cells depleted of FBXO31, MDM2 is not degraded and p53 levels do not increase following genotoxic stress. Thus, FBXO31 is essential for the classic robust increase in p53 levels following DNA damage

Implementation of T-box/T/sup -1/-box based AES design on latest xilinx fpga

International Nuclear Information System (INIS)

Kundi, D.E.; Aziz, A.

2015-01-01

This work presents an efficient implementation of the AES (Advance Encryption Standard) based on Tbox/T-1-box design for both the encryption and decryption on FPGA (Field Programmable Gate Array). The proposed architecture not only make efficient use of full capacity of dedicated 32 Kb BRAM (Block RAM) of latest Xilinx FPGAs (Virtex-5, Virtex-6 and 7 Series) but also saves considerable amount of BRAM and logical resources by using multiple accesses from single BRAM in one cycle of system clock as compared to conventional LUT (Look-Up-Table) techniques. The proposed T-box/T-1-box based AES design for both the encryption and decryption fits into just 4 BRAMs on FPGA and results in good efficiency TPS (Throughput per Slice) with less power consumption. (author)

Essential roles of high-mobility group box 1 in the development of murine colitis and colitis-associated cancer

International Nuclear Information System (INIS)

Maeda, Shin; Hikiba, Yohko; Shibata, Wataru; Ohmae, Tomoya; Yanai, Ayako; Ogura, Keiji; Yamada, Shingo; Omata, Masao

2007-01-01

High-mobility group box 1 (HMGB1) is a nuclear factor released extracellularly as a proinflammatory cytokine. We measured the HMGB1 concentration in the sera of mice with chemically induced colitis (DSS; dextran sulfate sodium salt) and found a marked increase. Inhibition of HMGB1 by neutralizing anti-HMGB1 antibody resulted in reduced inflammation in DSS-treated colons. In macrophages, HMGB1 induces several proinflammatory cytokines, such as IL-6, which are regulated by NF-κB activation. Two putative sources of HMGB1 were explored: in one, bacterial factors induce HMGB1 secretion from macrophages and in the other, necrotic epithelial cells directly release HMGB1. LPS induced a small amount of HMGB1 in macrophages, but macrophages incubated with supernatant prepared from necrotic cells and containing large amounts of HMGB1 activated NF-κB and induced IL-6. Using the colitis-associated cancer model, we demonstrated that neutralizing anti-HMGB1 antibody decreases tumor incidence and size. These observations suggest that HMGB1 is a potentially useful target for IBD treatment and the prevention of colitis-associated cancer

Hydrogen atom within spherical boxes with penetrable walls

International Nuclear Information System (INIS)

Ley-Koo, E.; Rubinstein, S.

1979-01-01

We study a model for the hydrogen atom confined within spherical boxes with penetrable walls. The potential consists of the Coulomb potential inside the box and a constant potential outside the box; the Schroedinger equation admits analytical solutions in both regions. The energy eigenvalues and eigenfunctions for the lowest states of the system are determined numerically for boxes of different sizes and penetrabilities. In addition, we also evaluate the hyperfine splitting, nuclear magnetic shielding, polarizability and pressure of the system and investigate the effect of the confinement on these atomic properties

A novel heuristic method for obtaining S-boxes

International Nuclear Information System (INIS)

Chen Guo

2008-01-01

An efficient algorithm named chaotic multi-swapping and simulated annealing (CMSSA) for obtaining cryptographically strong 8 x 8 S-boxes is presented. The method is based on chaotic maps and simulated annealing. In addition, cryptographic properties such as bijectivity, strict avalanche criterion, nonlinearity, output bits independence criterion and equiprobable input/output XOR distribution are analyzed in detail for the S-box produced. The results of numerical analysis show that the box has nearly fulfilled the criteria for a cryptographically strong S-box and can effectively resist several attacks

Electrical requirements for unshielded glove boxes

International Nuclear Information System (INIS)

1978-02-01

The specification relates to the general design and installation of electrical services required in unshielded glove boxes in which atmospheres of air, argon or nitrogen etc. may exist either temporarily or permanently. The specification does not apply to electrical services for glove boxes with flammable explosive atmospheres. (author)

Boxing Injuries from an Instructional Program.

Science.gov (United States)

Welch, Michael J.; And Others

1986-01-01

This paper describes the safeguards as well as the injury pattern of the boxing program at the US Military Academy at West Point from 1983 to 1985. About 2,100 cadets received boxing instruction during this period with an injury rate of less than four percent. (Author/MT)

TATA-binding protein and the retinoblastoma gene product bind to overlapping epitopes on c-Myc and adenovirus E1A protein

NARCIS (Netherlands)

Hateboer, G.; Timmers, H.T.M.; Rustgi, A.K.; Billaud, Marc; Veer, L.J. Van 't; Bernards, R.A.

1993-01-01

Using a protein binding assay, we show that the amino-teminal 204 amino acids of the c-Myc protein interact di y with a key component of the basal p tdon factor TFID, the TATA box-binding protein (TBP). Essentialy the same region of the c-Myc protein alo binds the product of the retinoblatoma

Prohibiting Headgear for Safety in Amateur Boxing? Opinion of the Canadian Boxing Community: an Online Poll.

Science.gov (United States)

Dickinson, Philip; Rempel, Philip

In 2013, the Amateur International Boxing Association (AIBA) introduced a rule banning headgear for male-senior open class boxers during competition. The AIBA has defended the rule change as motivated by safety and supported by internal unpublished studies. As a result, in 2018, the AIBA plans to universally prohibit headgear in competition: for all competitors (male and female), all ages and all levels. Within Canada, this ruling has generated controversy in the boxing community, yet there has been no overall measure of opinion. To address this, we instituted a voluntary, anonymous, online open-access poll to allow members of the boxing community to express their stance on headgear use in competition. In total, 636 responses were received. A total of 71.5 % of Canadian respondents believed headgear should be mandatory at all levels. Only 5.8 % agreed that headgear should be prohibited, as planned for 2018. Estimating results on a representative breakdown of boxing membership in Canada, a similar pattern emerged, whereby 68.2 % concurred with mandatory headgear while only 4.95 % supported its prohibition. Parents of boxers were almost unanimously against banning headgear, stating they would change sports as a result. Similarly, only 1.7 % of women believed headgear should be prohibited. The consensus of the Canadian boxing community largely opposes the rule changes that the AIBA has implemented. The results highlight risks posed to the long-term viability of the sport, if significant grassroots safety concerns are disregarded.

49 CFR 178.514 - Standards for plywood boxes.

Science.gov (United States)

2010-10-01

... identification code for a plywood box is 4D. (b) Construction requirements for plywood boxes are as follows: (1..., commercially dry and free from defects that would materially lessen the strength of the box. The strength of the material used and the method of construction must be appropriate to the capacity and intended use...

47 CFR 90.241 - Radio call box operations.

Science.gov (United States)

2010-10-01

... remains on for a period in excess of three minutes. The automatic cutoff system must be designed so the... Public Safety Pool for highway call box systems subject to the following requirements: (1) Call box... effective radiated power (ERP). (3) The height of a call box antenna may not exceed 6.1 meters (20 feet...

A Comprehensive Study of Neutralizing Antigenic Sites on the Hepatitis E Virus (HEV) Capsid by Constructing, Clustering, and Characterizing a Tool Box*

Science.gov (United States)

Zhao, Min; Li, Xiao-Jing; Tang, Zi-Min; Yang, Fan; Wang, Si-Ling; Cai, Wei; Zhang, Ke; Xia, Ning-Shao; Zheng, Zi-Zheng

2015-01-01

The hepatitis E virus (HEV) ORF2 encodes a single structural capsid protein. The E2s domain (amino acids 459–606) of the capsid protein has been identified as the major immune target. All identified neutralizing epitopes are located on this domain; however, a comprehensive characterization of antigenic sites on the domain is lacking due to its high degree of conformation dependence. Here, we used the statistical software SPSS to analyze cELISA (competitive ELISA) data to classify monoclonal antibodies (mAbs), which recognized conformational epitopes on E2s domain. Using this novel analysis method, we identified various conformational mAbs that recognized the E2s domain. These mAbs were distributed into 6 independent groups, suggesting the presence of at least 6 epitopes. Twelve representative mAbs covering the six groups were selected as a tool box to further map functional antigenic sites on the E2s domain. By combining functional and location information of the 12 representative mAbs, this study provided a complete picture of potential neutralizing epitope regions and immune-dominant determinants on E2s domain. One epitope region is located on top of the E2s domain close to the monomer interface; the other is located on the monomer side of the E2s dimer around the groove zone. Besides, two non-neutralizing epitopes were also identified on E2s domain that did not stimulate neutralizing antibodies. Our results help further the understanding of protective mechanisms induced by the HEV vaccine. Furthermore, the tool box with 12 representative mAbs will be useful for studying the HEV infection process. PMID:26085097

Molecular dissection of the APC/C inhibitor Rca1 shows a novel F-box-dependent function

OpenAIRE

Zielke, Norman; Querings, Silvia; Grosskortenhaus, Ruth; Reis, Tânia; Sprenger, Frank

2006-01-01

Rca1 (regulator of Cyclin A)/Emi (early mitotic inhibitor) proteins are essential inhibitors of the anaphase-promoting complex/cyclosome (APC/C). In Drosophila, Rca1 is required during G2 to prevent premature cyclin degradation by the Fizzy-related (Fzr)-dependent APC/C activity. Here, we present a structure and function analysis of Rca1 showing that a carboxy-terminal fragment is sufficient for APC/C inhibition. Rca1/Emi proteins contain a conserved F-box and interact with components of the ...

Cation-π interactions: computational analyses of the aromatic box motif and the fluorination strategy for experimental evaluation.

Science.gov (United States)

Davis, Matthew R; Dougherty, Dennis A

2015-11-21

Cation-π interactions are common in biological systems, and many structural studies have revealed the aromatic box as a common motif. With the aim of understanding the nature of the aromatic box, several computational methods were evaluated for their ability to reproduce experimental cation-π binding energies. We find the DFT method M06 with the 6-31G(d,p) basis set performs best of several methods tested. The binding of benzene to a number of different cations (sodium, potassium, ammonium, tetramethylammonium, and guanidinium) was studied. In addition, the binding of the organic cations NH4(+) and NMe4(+) to ab initio generated aromatic boxes as well as examples of aromatic boxes from protein crystal structures were investigated. These data, along with a study of the distance dependence of the cation-π interaction, indicate that multiple aromatic residues can meaningfully contribute to cation binding, even with displacements of more than an angstrom from the optimal cation-π interaction. Progressive fluorination of benzene and indole was studied as well, and binding energies obtained were used to reaffirm the validity of the "fluorination strategy" to study cation-π interactions in vivo.

Influence of nest box environment on kit survival

DEFF Research Database (Denmark)

Lund, V.H.; Malmkvist, Jens

2012-01-01

females divided into 4 groups, non-pregnant females (NON), pregnant females with access to one resource of nest building material (RES-1), pregnant females with access to three resources (RES-3), and pregnant females with access to one resource but which were moved into a climate-controlled facility...... died from day 1-7, and only ~5% in RES-3. The risk of dying was approx. 4 times higher for a kit live-born into the one resource environment. RES-3 females were building better nests and stayed in the nest box longer around parturition than RES-1, which could explain the higher mortality in this group...

Interspecific and intraspecific spatial separation by birds breeding in nest boxes

Directory of Open Access Journals (Sweden)

Denis C. Deeming

2017-12-01

Full Text Available Nest boxes can be seen as a conservation tool for improving low-grade nesting habitat but it is unclear how sympatric species using boxes establish a spatial distribution relative to conspecifics and heterospecifics. This study determined the distances between nest boxes occupied by Blue Tits (Cyanistes caeruleus and Great Tits (Parus major in two British woodlands to ascertain whether spatial distribution was affected by species and, if it was, whether there were reproductive consequences of this breeding distribution. Occupancy of nest boxes at two woodland sites were recorded on an annual basis between 2010 and 2014, inclusive. Distances between nest boxes, and reproductive activity, were recorded. Even if nest boxes showed a clumped distribution in the woodlands, the occupancy of the boxes was random. Not all boxes were used and the minimum distance between occupied boxes was at least twice the distance between boxes in general. Blue Tits tended to have greater distances between boxes containing conspecifics but distances between boxes containing heterospecifics were generally of comparable lengths. Reproductive output was only affected in relation to clutch size for Blue Tits nesting at one site. Nest boxes that aim to improve habitats that lack suitable nesting sites should be placed to reflect actual dispersal distances of the focal bird species.

Two particle states in an asymmetric box

OpenAIRE

Li, Xin; Liu, Chuan

2004-01-01

The exact two-particle energy eigenstates in an asymmetric rectangular box with periodic boundary conditions in all three directions are studied. Their relation with the elastic scattering phases of the two particles in the continuum are obtained. These results can be viewed as a generalization of the corresponding formulae in a cubic box obtained by L\\"uscher before. In particular, the s-wave scattering length is related to the energy shift in the finite box. Possible applications of these f...

Two particle states in an asymmetric box

International Nuclear Information System (INIS)

Li Xin; Liu Chuan

2004-01-01

The exact two-particle energy eigenstates in an asymmetric rectangular box with periodic boundary conditions in all three directions are studied. Their relation with the elastic scattering phases of the two particles in the continuum are obtained. These results can be viewed as a generalization of the corresponding formulae in a cubic box obtained by Luescher before. In particular, the s-wave scattering length is related to the energy shift in the finite box. Possible applications of these formulae are also discussed

New approaches to glove box design at Hanford

International Nuclear Information System (INIS)

Lini, D.C.; Fisher, F.D.; Walters, F.F.

1986-01-01

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

Design of housing file box of fire academy based on RFID

Science.gov (United States)

Li, Huaiyi

2018-04-01

This paper presents a design scheme of intelligent file box based on RFID. The advantages of RFID file box and traditional file box are compared and analyzed, and the feasibility of RFID file box design is analyzed based on the actual situation of our university. After introducing the shape and structure design of the intelligent file box, the paper discusses the working process of the file box, and explains in detail the internal communication principle of the RFID file box and the realization of the control system. The application of the RFID based file box will greatly improve the efficiency of our school's archives management.

CASAS: A Smart Home in a Box

OpenAIRE

Cook, Diane J.; Crandall, Aaron S.; Thomas, Brian L.; Krishnan, Narayanan C.

2012-01-01

While the potential benefits of smart home technology are widely recognized, a lightweight design is needed for the benefits to be realized at a large scale. We introduce the CASAS “smart home in a box”, a lightweight smart home design that is easy to install and provides smart home capabilities out of the box with no customization or training. We discuss types of data analysis that have been performed by the CASAS group and can be pursued in the future by using this approach to designing and...

Dendrimer-encapsulated nanoparticle-core micelles as a modular strategy for particle-in-a-box-in-a-box nanostructures

NARCIS (Netherlands)

Hove, ten J.B.; Wang, J.; Leeuwen, van F.W.B.; Velders, A.H.

2017-01-01

The hierarchically controlled synthesis and characterization of self-assembling macromolecules and particles are key to explore and exploit new nanomaterials. Here we present a versatile strategy for constructing particle-in-a-box-in-a-box systems by assembling dendrimer-encapsulated gold

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...

Box- or Virtual-Reality Trainer: Which Tool Results in Better Transfer of Laparoscopic Basic Skills?-A Prospective Randomized Trial.

Science.gov (United States)

Brinkmann, Christian; Fritz, Mathias; Pankratius, Ulrich; Bahde, Ralf; Neumann, Philipp; Schlueter, Steffen; Senninger, Norbert; Rijcken, Emile

Simulation training improves laparoscopic performance. Laparoscopic basic skills can be learned in simulators as box- or virtual-reality (VR) trainers. However, there is no clear recommendation for either box or VR trainers as the most appropriate tool for the transfer of acquired laparoscopic basic skills into a surgical procedure. Both training tools were compared, using validated and well-established curricula in the acquirement of basic skills, in a prospective randomized trial in a 5-day structured laparoscopic training course. Participants completed either a box- or VR-trainer curriculum and then applied the learned skills performing an ex situ laparoscopic cholecystectomy on a pig liver. The performance was recorded on video and evaluated offline by 4 blinded observers using the Global Operative Assessment of Laparoscopic Skills (GOALS) score. Learning curves of the various exercises included in the training course were compared and the improvement in each exercise was analyzed. Surgical Skills Lab of the Department of General and Visceral Surgery, University Hospital Muenster. Surgical novices without prior surgical experience (medical students, n = 36). Posttraining evaluation showed significant improvement compared with baseline in both groups, indicating acquisition of laparoscopic basic skills. Learning curves showed almost the same progression with no significant differences. In simulated laparoscopic cholecystectomy, total GOALS score was significantly higher for the box-trained group than the VR-trained group (box: 15.31 ± 3.61 vs. VR: 12.92 ± 3.06; p = 0.039; Hedge׳s g* = 0.699), indicating higher technical skill levels. Despite both systems having advantages and disadvantages, they can both be used for simulation training for laparoscopic skills. In the setting with 2 structured, validated and almost identical curricula, the box-trained group appears to be superior in the better transfer of basic skills into an experimental but structured

Black holes in a box

International Nuclear Information System (INIS)

Witek, Helvi; Cardoso, Vitor; Nerozzi, Andrea; Gualtieri, Leonardo; Herdeiro, Carlos; Zilhao, Miguel; Sperhake, Ulrich

2010-01-01

The evolution of BHs in 'confining boxes' is interesting for a number of reasons, particularly because it mimics some aspects of anti-de Sitter spacetimes. These admit no Cauchy surface and are a simple example of a non-globally hyperbolic spacetime. We are here interested in the potential role that boundary conditions play in the evolution of a BH system. For that, we imprison a binary BH in a box, at which boundary we set mirror-like boundary conditions.

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.

Air-tighten test for used glove boxes

International Nuclear Information System (INIS)

Itoh, Masanori; Kashiro, Kashio; Matsumoto, Masaki; Ogiya, Takashi; Nakata, Keiji; Gohda, Masahiko

2000-05-01

All of the glove boxes in Plutonium Fuel Fabrication facilities are operated after confirming their condition by conducting negative pressure maintenance test and air-tighten test. Although we check the negative pressure maintenance condition before operating glove boxes in a daily basis, we have not been conducted the air-tighten test. Hence, we have conduct air-tighten test using the glove box that will be dismantled in the near future. In order to compare the present data to the criteria of licensing and to the measurement data for new glove box, the test was conducted by leak tightness vessel which is used the competent authority's test for newly constructed equipments. We also have confirmed the leakage condition in case failure of keeping negative pressure. The main results are as follows: 1. No leakage was detected after leaving the glove box 21 days in case failure of keeping negative pressure condition. 2. The measurement result of the air-tighten test was 0.025 vol%/h, and it was confirmed that this result is within the range of licensing criteria (-0.04 - 0.06 vol%/h). 3. The measurement result was also within the error of leak tightness vessel, and it was confirmed that the air-tighten condition was in force within this past 10 years after installing this glove box (the corresponding value for used the competent authority test for newly constructed equipments was 0.019 vol%/h). (author)

Integrated Box Interrogation System (IBIS) Preliminary Design Study

CERN Document Server

Croft, S; Chard-Mj, P; Estop, J R; Martancik, D; Sheila-Melton; Young, B

2003-01-01

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-nucli...

Eye trauma in boxing.

Science.gov (United States)

Corrales, Gustavo; Curreri, Anthony

2009-10-01

In boxing, along with a few other sports, trauma is inherent to the nature of the sport; therefore it is considered a high-risk sport for ocular injuries. The long-term morbidity of ocular injuries suffered by boxers is difficult to estimate due to the lack of structured long-term follow-up of these athletes. Complications of blunt ocular trauma may develop years after the athlete has retired from the ring and is no longer considered to be at risk for boxing-related injuries. This article describes the wide range of eye injuries a boxer can sustain, and their immediate and long-term clinical management.

The activation of p38 MAPK primarily contributes to UV-induced RhoB expression by recruiting the c-Jun and p300 to the distal CCAAT box of the RhoB promoter

International Nuclear Information System (INIS)

Ahn, Jiwon; Choi, Jeong-Hae; Won, Misun; Kang, Chang-Mo; Gyun, Mi-Rang; Park, Hee-Moon; Kim, Chun-Ho; Chung, Kyung-Sook

2011-01-01

Highlights: → Regulation of transcriptional activation of RhoB is still unclear. → We examine the effect of p38 MAPK inhibition, and c-Jun and RhoB depletion on UV-induced RhoB expression and apoptosis. → We identify the regions of RhoB promoter necessary to confer UV responsiveness using pRhoB-luciferase reporter assays. → c-Jun, ATF2 and p300 are dominantly associated with NF-Y on the distal CCAAT box. → The activation of p38 MAPK primarily contribute to UV-induced RhoB expression by recruiting the c-Jun and p300 proteins on distal CCAAT box of RhoB promoter. -- Abstract: The Ras-related small GTP-binding protein RhoB is rapidly induced in response to genotoxic stresses caused by ionizing radiation. It is known that UV-induced RhoB expression results from the binding of activating transcription factor 2 (ATF2) via NF-Y to the inverted CCAAT box (-23) of the RhoB promoter. Here, we show that the association of c-Jun with the distal CCAAT box (-72) is primarily involved in UV-induced RhoB expression and p38 MAPK regulated RhoB induction through the distal CCAAT box. UV-induced RhoB expression and apoptosis were markedly attenuated by pretreatment with the p38 MAPK inhibitor. siRNA knockdown of RhoB, ATF2 and c-Jun resulted in decreased RhoB expression and eventually restored the growth of UV-irradiated Jurkat cells. In the reporter assay using luciferase under the RhoB promoter, inhibition of RhoB promoter activity by the p38 inhibitor and knockdown of c-Jun using siRNA occurred through the distal CCAAT box. Immunoprecipitation and DNA affinity protein binding assays revealed the association of c-Jun and p300 via NF-YA and the dissociation of histone deacetylase 1 (HDAC1) via c-Jun recruitment to the CCAAT boxes of the RhoB promoter. These results suggest that the activation of p38 MAPK primarily contributes to UV-induced RhoB expression by recruiting the c-Jun and p300 proteins to the distal CCAAT box of the RhoB promoter in Jurkat cells.

Fuel assembly, channel box of fuel assembly, fuel spacer of fuel assembly and method of manufacturing channel box

International Nuclear Information System (INIS)

Chaki, Masao; Kanazawa, Toru; Orii, Akihito; Nagayoshi, Takuji; Nishida, Koji; Kawasaki, Terufumi.

1997-01-01

In a fuel assembly of a BWR type reactor, fuel rods disposed at corners of side walls of a channel box or in the periphery of the side walls are partially removed, and recessed portions are formed on the side walls of the channel box from which the fuel rods are removed. Spaces closed at the sides are formed in the inner side of the corner portions. Openings are formed for communicating the closed space with the outside of the channel box. Then, the channel area of the outer side of the channel box is increased, through which much water flows to increase the amount of water in the reactor core thereby promoting the moderation of neutrons and providing thermal neutrons suitable to nuclear fission. The degree of freedom for distribution of the spaces in the reactor core is increased to improve neutron economy thereby enabling to utilize reactor fuels effectively. (N.H.)

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. ...

Decontamination and dismantling of large plutonium-contamined glove boxes

International Nuclear Information System (INIS)

Draulans, J.

1991-01-01

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 CO 2 blasting tests on non active samples

Purification, crystallization and X-ray diffraction analysis of a novel ring-cleaving enzyme (BoxCC) from Burkholderia xenovorans LB400

International Nuclear Information System (INIS)

Bains, Jasleen; Boulanger, Martin J.

2008-01-01

Preliminary X-ray diffraction studies of a novel ring-cleaving enzyme from B. xenovorans LB400 encoded by the benzoate-oxidation (box) pathway. The assimilation of aromatic compounds by microbial species requires specialized enzymes to cleave the thermodynamically stable ring. In the recently discovered benzoate-oxidation (box) pathway in Burkholderia xenovorans LB400, this is accomplished by a novel dihydrodiol lyase (BoxC C ). Sequence analysis suggests that BoxC C is part of the crotonase superfamily but includes an additional uncharacterized region of approximately 115 residues that is predicted to mediate ring cleavage. Processing of X-ray diffraction data to 1.5 Å resolution revealed that BoxC C crystallized with two molecules in the asymmetric unit of the P2 1 2 1 2 1 space group, with a solvent content of 47% and a Matthews coefficient of 2.32 Å 3 Da −1 . Selenomethionine BoxC C has been purified and crystals are currently being refined for anomalous dispersion studies

Role of protein-bound carbonyl groups in the formation of advanced glycation endproducts.

Science.gov (United States)

Liggins, J; Furth, A J

1997-08-22

Several mechanisms have been postulated for the formation of advanced glycation endproducts (AGEs) from glycated proteins; they all feature protein-bound carbonyl intermediates. Using 2,4-dinitrophenylhydrazine (DNPH), we have detected these intermediates on bovine serum albumin, lysozyme and beta-lactoglobulin after in vitro glycation by glucose or fructose. Carbonyls were formed in parallel with AGE-fluorophores, via oxidative Maillard reactions. Neither Amadori nor Heyns products contributed to the DNPH reaction. Fluorophore and carbonyl yields were much enhanced in lipid-associated proteins, but both groups could also be detected in lipid-free proteins. When pre-glycated proteins were incubated in the absence of free sugar, carbonyl groups were rapidly lost in a first-order reaction, while fluorescence continued to develop beyond the 21 days of incubation. Another unexpected finding was that not all carbonyl groups were blocked by aminoguanidine, although there was complete inhibition of reactions leading to AGE-fluorescence. It is suggested that carbonyls acting as fluorophore precursors react readily with aminoguanidine, while others are resistant to this hydrazine, possibly because they are involved in ring closure. Factors influencing the relative rates of acyclisation and hydrazone formation are discussed, together with possible implications for antiglycation therapy.

Injury and injury rates in Muay Thai kick boxing.

Science.gov (United States)

Gartland, S; Malik, M H; Lovell, M E

2001-10-01

To determine the type and number of injuries that occur during the training and practice of Muay Thai kick boxing and to compare the data obtained with those from previous studies of karate and taekwondo. One to one interviews using a standard questionnaire on injuries incurred during training and practice of Muay Thai kick boxing were conducted at various gyms and competitions in the United Kingdom and a Muay Thai gala in Holland. A total of 152 people were questioned, 132 men and 20 women. There were 19 beginners, 82 amateurs, and 51 professionals. Injuries to the lower extremities were the most common in all groups. Head injuries were the second most common in professionals and amateurs. Trunk injuries were the next most common in beginners. The difference in injury distribution among the three groups was significant (pinjury in the three groups. Fractures were the second most common in professionals, and in amateurs and beginners it was sprains and strains (pinjury rates were: beginners, 13.5/1000 participants; amateurs, 2.43/1000 participants; professionals, 2.79/1000 participants. For beginners, 7% of injuries resulted in seven or more days off training; for amateurs and professionals, these values were 4% and 5.8% respectively. The results are similar to those found for karate and taekwondo with regard to injury distribution, type, and rate. The percentage of injuries resulting in time off training is less.

Diabetes-Induced Oxidative Stress in Endothelial Progenitor Cells May Be Sustained by a Positive Feedback Loop Involving High Mobility Group Box-1

Directory of Open Access Journals (Sweden)

Han Wu

2016-01-01

Full Text Available Oxidative stress is considered to be a critical factor in diabetes-induced endothelial progenitor cell (EPC dysfunction, although the underlying mechanisms are not fully understood. In this study, we investigated the role of high mobility group box-1 (HMGB-1 in diabetes-induced oxidative stress. HMGB-1 was upregulated in both serum and bone marrow-derived monocytes from diabetic mice compared with control mice. In vitro, advanced glycation end productions (AGEs induced, expression of HMGB-1 in EPCs and in cell culture supernatants in a dose-dependent manner. However, inhibition of oxidative stress with N-acetylcysteine (NAC partially inhibited the induction of HMGB-1 induced by AGEs. Furthermore, p66shc expression in EPCs induced by AGEs was abrogated by incubation with glycyrrhizin (Gly, while increased superoxide dismutase (SOD activity in cell culture supernatants was observed in the Gly treated group. Thus, HMGB-1 may play an important role in diabetes-induced oxidative stress in EPCs via a positive feedback loop involving the AGE/reactive oxygen species/HMGB-1 pathway.

Motif III in superfamily 2 "helicases" helps convert the binding energy of ATP into a high-affinity RNA binding site in the yeast DEAD-box protein Ded1.

Science.gov (United States)

Banroques, Josette; Doère, Monique; Dreyfus, Marc; Linder, Patrick; Tanner, N Kyle

2010-03-05

Motif III in the putative helicases of superfamily 2 is highly conserved in both its sequence and its structural context. It typically consists of the sequence alcohol-alanine-alcohol (S/T-A-S/T). Historically, it was thought to link ATPase activity with a "helicase" strand displacement activity that disrupts RNA or DNA duplexes. DEAD-box proteins constitute the largest family of superfamily 2; they are RNA-dependent ATPases and ATP-dependent RNA binding proteins that, in some cases, are able to disrupt short RNA duplexes. We made mutations of motif III (S-A-T) in the yeast DEAD-box protein Ded1 and analyzed in vivo phenotypes and in vitro properties. Moreover, we made a tertiary model of Ded1 based on the solved structure of Vasa. We used Ded1 because it has relatively high ATPase and RNA binding activities; it is able to displace moderately stable duplexes at a large excess of substrate. We find that the alanine and the threonine in the second and third positions of motif III are more important than the serine, but that mutations of all three residues have strong phenotypes. We purified the wild-type and various mutants expressed in Escherichia coli. We found that motif III mutations affect the RNA-dependent hydrolysis of ATP (k(cat)), but not the affinity for ATP (K(m)). Moreover, mutations alter and reduce the affinity for single-stranded RNA and subsequently reduce the ability to disrupt duplexes. We obtained intragenic suppressors of the S-A-C mutant that compensate for the mutation by enhancing the affinity for ATP and RNA. We conclude that motif III and the binding energy of gamma-PO(4) of ATP are used to coordinate motifs I, II, and VI and the two RecA-like domains to create a high-affinity single-stranded RNA binding site. It also may help activate the beta,gamma-phosphoanhydride bond of ATP. (c) 2009 Elsevier Ltd. All rights reserved.

Outside the box

International Nuclear Information System (INIS)

Pichon, Max

2011-01-01

Full text: Queensland-based Hydrasyst wants to take its motto of 'Do more with less' into the greywater sector with a new water recycling and energy recovery technology launched in November, called The Grey Box. The company is initially targeting large industrial laundries as they are major generators of greywater and heavy energy users, but it has ambitions well beyond that. The average commercial laundry consumes 1-5ML of water a week, using about 16 litres for every 1kg of clothing washed. Hydrasyst director Stephen Balemi said The Grey Box can slash the volume by 80 per cent. While he was reluctant to disclose too much technical detail, he claimed it is the only technology serving the $1 billion a year laundry sector that combines microfiltration / ultrafiltration membrane technology and energy reduction components. The heart of the system is a ceramic hollow fibre membrane. Balemi said it produces higher filtrate quality than competitors, meaning the recycled water can be reused more often, and can process feed water of up to 70°C compared to typical ultrafiltration membranes that cap out at about 38°C. This means the recycled water can be reused at higher temperatures, with the heat in it recovered by a precise steam heater built into The Grey Box. “As an overall measure, it saves 80 per cent of the water that is processed and saves 20 per cent of the energy,” Balemi said. Four systems have already been installed, with one going into a large commercial laundry in south Queensland and another to AMP's state-of-the-art 6 Green Star building in Brisbane. “We can modify them slightly to suit the industry, depending on the quality of raw water they are trying to recycle and also depending on the size of the project,,” said Balemi. Where many organisations build systems to specification, The Grey Box is offered in three standard sizes: the HY20 (20kL per day, based on a 10 hour day), HY80 (80kL per day) and HY130 (130kL per day). They can be used

[Study on immunogenicity of group A and group C meningococcal conjugate vaccine with coupling group B meningococcal outer membrane protein].

Science.gov (United States)

Ma, Fu-Bao; Tao, Hong; Wang, Hong-Jun

2009-10-01

To evaluate the Immunogenicity of Group A and Group C Meningococcal conjugate Vaccine with coupling Group B Meningococcal Outer Membrane Protein (Men B-OMP). 458 healthy children aged 3-5 months, 6-23 months, 2-6 years and 7-24 years were given the Groups A and C conjugate Vaccine with MenB-OMP or other vaccine as control group to measure the pre-and post-vaccination Men A and C and B by Serum Bactericidal Assay (SBA) in the double-blind randomized controlled trial. 97.65%-100% were 4 times or greater increase in SBA titer for the healthy children given the Groups A and C conjugate Vaccine with MenB-OMP, The geometric mean titer of SBA were 1:194-1:420, which significantly higber than controls. The Group A and C conjugate Vaccine with MenB-OMP was safe and well immunogenic.

MADS-box gene evolution - structure and transcription patterns

DEFF Research Database (Denmark)

Johansen, Bo; Pedersen, Louise Buchholt; Skipper, Martin

2002-01-01

Mads-box genes, ABC model, Evolution, Phylogeny, Transcription patterns, Gene structure, Conserved motifs......Mads-box genes, ABC model, Evolution, Phylogeny, Transcription patterns, Gene structure, Conserved motifs...

A Lithium Vapor Box Divertor Similarity Experiment

Science.gov (United States)

Cohen, Robert A.; Emdee, Eric D.; Goldston, Robert J.; Jaworski, Michael A.; Schwartz, Jacob A.

2017-10-01

A lithium vapor box divertor offers an alternate means of managing the extreme power density of divertor plasmas by leveraging gaseous lithium to volumetrically extract power. The vapor box divertor is a baffled slot with liquid lithium coated walls held at temperatures which increase toward the divertor floor. The resulting vapor pressure differential drives gaseous lithium from hotter chambers into cooler ones, where the lithium condenses and returns. A similarity experiment was devised to investigate the advantages offered by a vapor box divertor design. We discuss the design, construction, and early findings of the vapor box divertor experiment including vapor can construction, power transfer calculations, joint integrity tests, and thermocouple data logging. Heat redistribution of an incident plasma-based heat flux from a typical linear plasma device is also presented. This work supported by DOE Contract No. DE-AC02-09CH11466 and The Princeton Environmental Institute.

Fire test of DOT 7A Boxes

International Nuclear Information System (INIS)

Jensen, J.D.

1979-05-01

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

Developing and user-testing Decision boxes to facilitate shared decision making in primary care - a study protocol

Directory of Open Access Journals (Sweden)

Rousseau François

2011-03-01

Full Text Available Abstract Background Applying evidence is one of the most challenging steps of evidence-based clinical practice. Healthcare professionals have difficulty interpreting evidence and translating it to patients. Decision boxes are summaries of the most important benefits and harms of diagnostic, therapeutic, and preventive health interventions provided to healthcare professionals before they meet the patient. Our hypothesis is that Decision boxes will prepare clinicians to help patients make informed value-based decisions. By acting as primers, the boxes will enhance the application of evidence-based practices and increase shared decision making during the clinical encounter. The objectives of this study are to provide a framework for developing Decision boxes and testing their value to users. Methods/Design We will begin by developing Decision box prototypes for 10 clinical conditions or topics based on a review of the research on risk communication. We will present two prototypes to purposeful samples of 16 family physicians distributed in two focus groups, and 32 patients distributed in four focus groups. We will use the User Experience Model framework to explore users' perceptions of the content and format of each prototype. All discussions will be transcribed, and two researchers will independently perform a hybrid deductive/inductive thematic qualitative analysis of the data. The coding scheme will be developed a priori from the User Experience Model's seven themes (valuable, usable, credible, useful, desirable, accessible and findable, and will include new themes suggested by the data (inductive analysis. Key findings will be triangulated using additional publications on the design of tools to improve risk communication. All 10 Decision boxes will be modified in light of our findings. Discussion This study will produce a robust framework for developing and testing Decision boxes that will serve healthcare professionals and patients alike. It

Hadron scattering in an asymmetric box

International Nuclear Information System (INIS)

Li Xin; Chen Ying; Meng Guozhan; Feng Xu; Gong Ming; He Song; Li Gang; Liu Chuan; Liu Yubin; Ma Jianping; Meng Xiangfei; Shen Yan; Zhang Jianbo

2007-01-01

We propose to study hadron-hadron scattering using lattice QCD in an asymmetric box which allows one to access more non-degenerate low-momentum modes for a given volume. The conventional Luescher's formula applicable in a symmetric box is modified accordingly. To illustrate the feasibility of this approach, pion-pion elastic scattering phase shifts in the I = 2, J = 0 channel are calculated within quenched approximation using improved gauge and Wilson fermion actions on anisotropic lattices in an asymmetric box. After the chiral and continuum extrapolation, we find that our quenched results for the scattering phase shifts in this channel are consistent with the experimental data when the three-momentum of the pion is below 300MeV. Agreement is also found when compared with previous theoretical results from lattice and other means. Moreover, with the usage of asymmetric volume, we are able to compute the scattering phases in the low-momentum range (pion three momentum less than about 350MeV in the center of mass frame) for over a dozen values of the pion three-momenta, much more than using the conventional symmetric box with comparable volume

All 17 S-locus F-box proteins of the S2 - and S3 -haplotypes of Petunia inflata are assembled into similar SCF complexes with a specific function in self-incompatibility.

Science.gov (United States)

Li, Shu; Williams, Justin S; Sun, Penglin; Kao, Teh-Hui

2016-09-01

The collaborative non-self-recognition model for S-RNase-based self-incompatibility predicts that multiple S-locus F-box proteins (SLFs) produced by pollen of a given S-haplotype collectively mediate ubiquitination and degradation of all non-self S-RNases, but not self S-RNases, in the pollen tube, thereby resulting in cross-compatible pollination but self-incompatible pollination. We had previously used pollen extracts containing GFP-fused S2 -SLF1 (SLF1 with an S2 -haplotype) of Petunia inflata for co-immunoprecipitation (Co-IP) and mass spectrometry (MS), and identified PiCUL1-P (a pollen-specific Cullin1), PiSSK1 (a pollen-specific Skp1-like protein) and PiRBX1 (a conventional Rbx1) as components of the SCF(S) (2-) (SLF) (1) complex. Using pollen extracts containing PiSSK1:FLAG:GFP for Co-IP/MS, we identified two additional SLFs (SLF4 and SLF13) that were assembled into SCF(SLF) complexes. As 17 SLF genes (SLF1 to SLF17) have been identified in S2 and S3 pollen, here we examined whether all 17 SLFs are assembled into similar complexes and, if so, whether these complexes are unique to SLFs. We modified the previous Co-IP/MS procedure, including the addition of style extracts from four different S-genotypes to pollen extracts containing PiSSK1:FLAG:GFP, to perform four separate experiments. The results taken together show that all 17 SLFs and an SLF-like protein, SLFLike1 (encoded by an S-locus-linked gene), co-immunoprecipitated with PiSSK1:FLAG:GFP. Moreover, of the 179 other F-box proteins predicted by S2 and S3 pollen transcriptomes, only a pair with 94.9% identity and another pair with 99.7% identity co-immunoprecipitated with PiSSK1:FLAG:GFP. These results suggest that SCF(SLF) complexes have evolved specifically to function in self-incompatibility. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

DFBX boxes -- electrical and cryogenic distribution boxes for the superconducting magnets in the LHC straight sections

International Nuclear Information System (INIS)

Zbasnik, Jon P.; Corradi, Carol A.; Gourlay, S.A.; Green, MichaelA.; Hafalia, Aurelio Q.; Kajiyama, Yoichi Jr.; Knolls, Michael J.; LaMantia, Roberto F.; Rasson, Joseph E.; Reavill, Dulie; Turner, William C.

2002-01-01

DFBX distribution boxes provide cryogenic and electrical services to superconducting quadrupoles and to a superconducting dipole at either end of four of the long straight sections in the LHC. The DFBX boxes also provide instrumentation and quench protection to the magnets. Current for the quadrupole and the dipole magnet is delivered through leads that combine HTS and gas cooled leads. Current for the 600 A and 120 A correction magnets is provided by pure gas-cooled leads. The bus bars from the leads to the magnets pass through low leak-rate lambda plugs between 1.8 K and 4.4 K. The heat leak into the 1.9 K region from the liquid helium tank is determined by the design of the lambda plugs. This paper describes the DFBX boxes and their function of delivering current and instrumentation signals to the magnets

Generation of 3D templates of active sites of proteins with rigid prosthetic groups.

Science.gov (United States)

Nebel, Jean-Christophe

2006-05-15

With the increasing availability of protein structures, the generation of biologically meaningful 3D patterns from the simultaneous alignment of several protein structures is an exciting prospect: active sites could be better understood, protein functions and protein 3D structures could be predicted more accurately. Although patterns can already be generated at the fold and topological levels, no system produces high-resolution 3D patterns including atom and cavity positions. To address this challenge, our research focuses on generating patterns from proteins with rigid prosthetic groups. Since these groups are key elements of protein active sites, the generated 3D patterns are expected to be biologically meaningful. In this paper, we present a new approach which allows the generation of 3D patterns from proteins with rigid prosthetic groups. Using 237 protein chains representing proteins containing porphyrin rings, our method was validated by comparing 3D templates generated from homologues with the 3D structure of the proteins they model. Atom positions were predicted reliably: 93% of them had an accuracy of 1.00 A or less. Moreover, similar results were obtained regarding chemical group and cavity positions. Results also suggested our system could contribute to the validation of 3D protein models. Finally, a 3D template was generated for the active site of human cytochrome P450 CYP17, the 3D structure of which is unknown. Its analysis showed that it is biologically meaningful: our method detected the main patterns of the cytochrome P450 superfamily and the motifs linked to catalytic reactions. The 3D template also suggested the position of a residue, which could be involved in a hydrogen bond with CYP17 substrates and the shape and location of a cavity. Comparisons with independently generated 3D models comforted these hypotheses. Alignment software (Nestor3D) is available at http://www.kingston.ac.uk/~ku33185/Nestor3D.html

Lightweight S-Box Architecture for Secure Internet of Things

Directory of Open Access Journals (Sweden)

A. Prathiba

2018-01-01

Full Text Available Lightweight cryptographic solutions are required to guarantee the security of Internet of Things (IoT pervasiveness. Cryptographic primitives mandate a non-linear operation. The design of a lightweight, secure, non-linear 4 × 4 substitution box (S-box suited to Internet of Things (IoT applications is proposed in this work. The structure of the 4 × 4 S-box is devised in the finite fields GF (24 and GF ((222. The finite field S-box is realized by multiplicative inversion followed by an affine transformation. The multiplicative inverse architecture employs Euclidean algorithm for inversion in the composite field GF ((222. The affine transformation is carried out in the field GF (24. The isomorphic mapping between the fields GF (24 and GF ((222 is based on the primitive element in the higher order field GF (24. The recommended finite field S-box architecture is combinational and enables sub-pipelining. The linear and differential cryptanalysis validates that the proposed S-box is within the maximal security bound. It is observed that there is 86.5% lesser gate count for the realization of sub field operations in the composite field GF ((222 compared to the GF (24 field. In the PRESENT lightweight cipher structure with the basic loop architecture, the proposed S-box demonstrates 5% reduction in the gate equivalent area over the look-up-table-based S-box with TSMC 180 nm technology.

Cloning and analysis of two Ceratopteris thalictroides MADS-box genes

Directory of Open Access Journals (Sweden)

XU Daolan

2014-06-01

Full Text Available MADS-box transcription factors,as a large gene family,play an important role in plant growth and development,especially act as key regulators in controlling the identities of floral organs in flowering plants.They are also significant in the evolutionary revelation.In order to understand MADS-box genes,we need more information of MADS-box genes in non flowering plant.MADS-box genes of Ceratopteris thalictroides were selected to clone and analysis by using RACE method.Two MADS-box genes,designated CtMADS1 and CtMADS2 in C. thalictroides,were cloned.Analysis indicates that CtMADS1 is belonged to MIKC*-clade,while CtMADS2 is belonged to MIKCc-clade.Phylogeny suggests that these two MADS-box genes of C. thalictroides have a close relationship with flowering plants,the data indicates that at least two different MADS-box genes are homologous to floral homeotic genes existed in the last common ancestor of contemporary vascular plants.

Inhibition of Y-box binding protein-1 slows the growth of glioblastoma multiforme and sensitizes to temozolomide independent O6-methylguanine-DNA methyltransferase.

Science.gov (United States)

Gao, Yuanyuan; Fotovati, Abbas; Lee, Cathy; Wang, Michelle; Cote, Gilbert; Guns, Emma; Toyota, Brian; Faury, Damien; Jabado, Nada; Dunn, Sandra E

2009-12-01

Glioblastoma multiforme (GBM) is an aggressive type of brain tumor where 5 years. In adults, GBM is the most common type of brain tumor. It is rarer in children, where it constitutes approximately 15% of all brain tumors diagnosed. These tumors are often invasive, making surgical resection difficult. Further, they can be refractory to current therapies such as temozolomide. The current dogma is that temozolomide resistance rests on the expression of O6-methylguanine-DNA methyltransferase (MGMT) because it cleaves methylated DNA adducts formed by the drug. Our laboratory recently reported that another drug resistance gene known as the Y-box binding protein-1 (YB-1) is highly expressed in primary GBM but not in normal brain tissues based on the evaluation of primary tumors. We therefore questioned whether GBM depend on YB-1 for growth and/or response to temozolomide. Herein, we report that YB-1 inhibition reduced tumor cell invasion and growth in monolayer as well as in soft agar. Moreover, blocking this protein ultimately delayed tumor onset in mice. Importantly, inhibiting YB-1 enhanced temozolomide sensitivity in a manner that was independent of MGMT in models of adult and pediatric GBM. In conclusion, inhibiting YB-1 may be a novel way to improve the treatment of GBM.

Boxing against drones : Drones in sports education

NARCIS (Netherlands)

Zwaan, S.G.; Barakova, E.I.

2016-01-01

This paper investigates how drones could be integrated into the context of sports, boxing in particular. The goal of this project is to design a drone application that allows direct and embodied interaction. The sport of boxing provides a very interesting setting, because the intimidating and

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 bearing...

Test procedure for boxed waste assay system

International Nuclear Information System (INIS)

Wachter, J.

1994-01-01

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

Earthquake resistance test of full-scale glove box

International Nuclear Information System (INIS)

Fujita, T.; Ohtani, K.; Hayashi, M.; Kozeki, M.; Ide, T.; Sakuno, K.

1989-01-01

A glove box used at nuclear facilities must confine radioactive materials. High airtightness and negative internal pressure are used to prevent leaks. The allowable leakage rate of air is 0.1% vol/hr or less at the pre-service inspection. The negative pressure value is kept at - 30 mm H 2 O in normal operation. The glove box structural strength and its confinement reliability during an earthquake are major concerns. The verification of aseismic analysis methods and assumptions for a glove box are thus of great importance. Data on the dynamic behavior of giant glove boxes was recently obtained in large shaker experiments. This paper describes these experimental results and the appropriateness of aseismic analysis methods used in current design

A simple biosynthetic method for stereospecific resonance assignment of prochiral methyl groups in proteins

International Nuclear Information System (INIS)

Plevin, Michael J.; Hamelin, Olivier; Boisbouvier, Jérôme; Gans, Pierre

2011-01-01

A new method for stereospecific assignment of prochiral methyl groups in proteins is presented in which protein samples are produced using U-[ 13 C]glucose and subsaturating amounts of 2-[ 13 C]methyl-acetolactate. The resulting non-uniform labeling pattern allows proR and proS methyl groups to be easily distinguished by their different phases in a constant-time two-dimensional 1 H- 13 C correlation spectra. Protein samples are conveniently prepared using the same media composition as the main uniformly-labeled sample and contain higher levels of isotope-enrichment than fractional labeling approaches. This new strategy thus represents an economically-attractive, robust alternative for obtaining isotopically-encoded stereospecific NMR assignments of prochiral methyl groups.

DISTORTION ANALYSIS OF TILL -WALLED BOX GIRDERS

African Journals Online (AJOL)

NIJOTECH

bridges, buildings, motor vehicles, ships and aircrafts. Due to thinness of the box walls, generalized loads applied to this structure give rise to warping and distortion of ..... Recommendation for Design of. Intermediate Diaphragms in Box. Girders, Transactions of Japanese. Society of Civil Engineers, Vol. 14,1984, pp 121-126.

Boxing It Up-a Cross-curricular Approach.

Science.gov (United States)

Till, Wesley

1996-01-01

Reports on a class project that examined the manufacture of boxes and packaging to teach about design and technology. The class discovered basic manufacturing techniques by examining and disassembling cereal boxes. Field trips to stores provided more examples. Appraises the children's final projects and discusses acquiring materials. (MJP)

Prediction of functional sites in proteins using conserved functional group analysis.

Science.gov (United States)

Innis, C Axel; Anand, A Prem; Sowdhamini, R

2004-04-02

A detailed knowledge of a protein's functional site is an absolute prerequisite for understanding its mode of action at the molecular level. However, the rapid pace at which sequence and structural information is being accumulated for proteins greatly exceeds our ability to determine their biochemical roles experimentally. As a result, computational methods are required which allow for the efficient processing of the evolutionary information contained in this wealth of data, in particular that related to the nature and location of functionally important sites and residues. The method presented here, referred to as conserved functional group (CFG) analysis, relies on a simplified representation of the chemical groups found in amino acid side-chains to identify functional sites from a single protein structure and a number of its sequence homologues. We show that CFG analysis can fully or partially predict the location of functional sites in approximately 96% of the 470 cases tested and that, unlike other methods available, it is able to tolerate wide variations in sequence identity. In addition, we discuss its potential in a structural genomics context, where automation, scalability and efficiency are critical, and an increasing number of protein structures are determined with no prior knowledge of function. This is exemplified by our analysis of the hypothetical protein Ydde_Ecoli, whose structure was recently solved by members of the North East Structural Genomics consortium. Although the proposed active site for this protein needs to be validated experimentally, this example illustrates the scope of CFG analysis as a general tool for the identification of residues likely to play an important role in a protein's biochemical function. Thus, our method offers a convenient solution to rapidly and automatically process the vast amounts of data that are beginning to emerge from structural genomics projects.

Conformational responses to changes in the state of ionization of titrable groups in proteins

Science.gov (United States)

Richman, Daniel Eric

Electrostatic energy links the structural properties of proteins with some of their important biological functions, including catalysis, energy transduction, and binding and recognition. Accurate calculation of electrostatic energy is essential for predicting and for analyzing function from structure. All proteins have many ionizable residues at the protein-water interface. These groups tend to have ionization equilibria (pK a values) shifted slightly relative to their values in water. In contrast, groups buried in the hydrophobic interior usually have highly anomalous p Ka values. These shifts are what structure-based calculations have to reproduce to allow examination of contributions from electrostatics to stability, solubility and interactions of proteins. Electrostatic energies are challenging to calculate accurately because proteins are heterogeneous dielectric materials. Any individual ionizable group can experience very different local environments with different dielectric properties. The studies in this thesis examine the hypothesis that proteins reorganize concomitant with changes in their state of ionization. It appears that the pKa value measured experimentally reflects the average of pKa values experienced in the different electrostatic environments corresponding to different conformational microstates. Current computational models fail to sample conformational reorganization of the backbone correctly. Staphyloccocal nuclease (SNase) was used as a model protein in nuclear magnetic resonance (NMR) spectroscopy studies to characterize the conformational rearrangements of the protein coupled to changes in the ionization state of titrable groups. One set of experiments tests the hypothesis that proton binding to surface Asp and Glu side chains drives local unfolding by stabilizing less-native, more water-solvated conformations in which the side chains have normalized pKa values. Increased backbone flexibility in the ps-ns timescale, hydrogen bond (H

Temperature, pressure, and electrochemical constraints on protein speciation: Group additivity calculation of the standard molal thermodynamic properties of ionized unfolded proteins

Directory of Open Access Journals (Sweden)

J. M. Dick

2006-01-01

Full Text Available Thermodynamic calculations can be used to quantify environmental constraints on the speciation of proteins, such as the pH and temperature dependence of ionization state, and the relative chemical stabilities of proteins in different biogeochemical settings. These calculations depend in part on values of the standard molal Gibbs energies of proteins and their ionization reactions as a function of temperature and pressure. Because these values are not generally available, we calculated values of the standard molal thermodynamic properties at 25°C and 1 bar as well as the revised Helgeson-Kirkham-Flowers equations of state parameters of neutral and charged zwitterionic reference model compounds including aqueous amino acids, polypeptides, and unfolded proteins. The experimental calorimetric and volumetric data for these species taken from the literature were combined with group additivity algorithms to calculate the properties and parameters of neutral and ionized sidechain and backbone groups in unfolded proteins. The resulting set of group contributions enables the calculation of the standard molal Gibbs energy, enthalpy, entropy, isobaric heat capacity, volume, and isothermal compressibility of unfolded proteins in a range of proton ionization states to temperatures and pressures exceeding 100°C and 1000 bar. This approach provides a useful frame of reference for thermodynamic studies of protein folding and complexation reactions. It can also be used to assign provisional values of the net charge and Gibbs energy of ionized proteins as a function of temperature and pH. Using these values, an Eh-pH diagram for a reaction representing the speciation of extracellular proteins from Pyrococcus furiosus and Bacillus subtilis was generated. The predicted predominance limits of these proteins correspond with the different electrochemical conditions of hydrothermal vents and soils. More comprehensive calculations of this kind may reveal pervasive

Prognostic implications of the nuclear localization of Y-box-binding protein-1 and CXCR4 expression in ovarian cancer: their correlation with activated Akt, LRP/MVP and P-glycoprotein expression.

Science.gov (United States)

Oda, Yoshinao; Ohishi, Yoshihiro; Basaki, Yuji; Kobayashi, Hiroaki; Hirakawa, Toshio; Wake, Norio; Ono, Mayumi; Nishio, Kazuto; Kuwano, Michihiko; Tsuneyoshi, Masazumi

2007-07-01

The nuclear localization of Y-box-binding protein-1 (YB-1) is known to be a poor prognostic factor in several human malignancies, including ovarian carcinoma. Following on from our basic study dealing with microarray analyses of YB-1-associated gene expression in ovarian cancer cells, we examined whether nuclear localization of YB-1 is associated with the expression of CXCR4, a vault protein named lung resistance-related vault protein (LRP/MVP), phosphorylated Akt (p-Akt) or P-glycoprotein (P-gp) in human ovarian carcinoma. Fifty-three surgically resected ovarian carcinomas treated with paclitaxel and carboplatin were examined immunohistochemically for nuclear YB-1 expression and intrinsic expression of p-Akt, P-gp, LRP/MVP and CXCR4. Nuclear expression of YB-1 demonstrated significant correlation with p-Akt, P-gp and LRP expression, but no relationship with CXCR4 expression. By multivariate analysis, only YB-1 nuclear expression and CXCR4 expression were independent prognostic factors with regard to overall survival. These results indicate that YB-1 nuclear expression and CXCR4 expression are important prognostic factors in ovarian carcinoma.

A sealed enclosure of the glove box type

International Nuclear Information System (INIS)

Moreels, Pierre.

1974-01-01

The invention relates to a sealed enclosure of the glove-box type. According to the invention, the box-frame comprises: angle-bars having a right-angled cross-section, sealing joints, tightening bars and fastening means [fr

Deep Cuboid Detection: Beyond 2D Bounding Boxes

OpenAIRE

Dwibedi, Debidatta; Malisiewicz, Tomasz; Badrinarayanan, Vijay; Rabinovich, Andrew

2016-01-01

We present a Deep Cuboid Detector which takes a consumer-quality RGB image of a cluttered scene and localizes all 3D cuboids (box-like objects). Contrary to classical approaches which fit a 3D model from low-level cues like corners, edges, and vanishing points, we propose an end-to-end deep learning system to detect cuboids across many semantic categories (e.g., ovens, shipping boxes, and furniture). We localize cuboids with a 2D bounding box, and simultaneously localize the cuboid's corners,...

An Introduction to Plum Blossom Boxing: History, Culture and Practice

Directory of Open Access Journals (Sweden)

Guodong Zhang

2012-07-01

Full Text Available Meihuaquan (“Plum Blossom Fist [Boxing]” has traditionally been practiced as vernacular (folk art practiced among the Han ethnic group residing in the Shandong, Henan and Hebei Provinces of China. Historical documentation dates Plum Blossom Boxing to the seventeenth century. The classic Chinese novel, Shuǐhǔ Zhuàn (Marsh Chronicles recounts the martial exploits of Shandong’s twelfth century outlaw heroes who may have been Mei Boxers, also. Thus, for perhaps a millennium, the region has been noted for vernacular martial arts and social banditry. The region’s rampant lawlessness promoted highly-developed martial prowess among both lawbreakers and those who were required to protect themselves against the brigands. Cultural, economic, and environmental factors in the region gave rise to heterodox political and religious beliefs that frequently served as a catalyst for martial sects, most notably the “Boxers” who at the turn of the twentieth century, came into conflict with the imperial government. These factors laid the groundwork for the “character traits” of the art while Taoism, the Five Elements theory, and a concept of predictable change shaped Plum Boxing’s strategic and mechanical principles. In the past decade, there have been efforts to globalize this vernacular martial art. Rather than driving Plum Boxing to extinction it is likely that the folk and the “larger than local” will co-exist.

A multi-layer box model of carbon dynamics in soil

International Nuclear Information System (INIS)

Kuc, T.

2005-01-01

A multi-layer box model (MLB) for quantification of carbon fluxes between soil and atmosphere has been developed. In the model, soil carbon reservoir is represented by two boxes: fast decomposition box (FDB) and slow decomposition box (SDB), characterised by substantially different turnover time (TT) of carbon compounds. Each box has an internal structure (sub-compartments) accounting for carbon deposited in consecutive time intervals. The rate of decomposition of carbon compounds in each sub-compartment is proportional to the carbon content. With the aid of the MLB model and the 14 C signature of carbon dioxide, the fluxes entering and leaving the boxes, turnover time of carbon in each box, and the ratio of mass of carbon in the slow and fast box (M s /M f ) were calculated. The MBL model yields the turnover time of carbon in the FDB (TT f ) ca. 14 for typical investigated soils of temperate climate ecosystems. The calculated contribution of the CO 2 flux originating from the slow box (F s ) to the total CO 2 flux into the atmosphere ranges from 12% to 22%. These values are in agreement with experimental observations at different locations. Assuming that the input flux of carbon (F i n) to the soil system is doubled within the period of 100 years, the soil buffering capacity for excess carbon predicted by the MLB model for typical soil parameters may vary in the range between 26% and 52%. The highest values are obtained for soils characterised by long TTf, and well developed old carbon pool. (author)

A Comparison of Energy Expenditure During "Wii Boxing" Versus Heavy Bag Boxing in Young Adults.

Science.gov (United States)

Perusek, Kristen; Sparks, Kenneth; Little, Kathleen; Motley, Mary; Patterson, Sheila; Wieand, Jennifer

2014-02-01

Traditional computer videogames are sedentary, whereas new computer videogames, such as the Nintendo(®) (Redmond, WA) "Wii™ Sports" games, allow users to physically interact while playing the sport. Energy expenditure (EE), heart rate (HR), and rating of perceived exertion (RPE) during heavy bag boxing versus the Nintendo "Wii Boxing" game were compared. Fifteen males and 14 females (mean age, 25.6 years; height, 171.3 cm; weight, 71.8 kg) randomly selected (by a coin toss) heavy bag boxing or "Wii Boxing" for their first test session and completed the other protocol at their second session at least 2 days later. Each session lasted for a total duration of 30 minutes and consisted of 10 3-minute exercise bouts with measurements of HR, RPE, and EE obtained from indirect calorimetry. A paired-samples t test was used to analyze the results. Significant differences were found for HR (bag, 156 beats per minute; Wii, 138 beats per minute; P=0.001) and RPE (bag, 13.8; Wii, 11.4; P=0.0001) but not for EE (bag, 8.0 kcal/minute; Wii, 7.1 kcal/minute; bag, 241 total kcal; Wii, 213 total kcal; P=0.078). The results suggest that computer active videogames, such as the Nintendo Wii, have the potential to provide similar EE as their traditional forms of exercise and may be a sufficient replacement for traditional target HR zone activities, especially in less fit individuals. Further research is needed to compare EE for different "Wii Sports" games with those for their traditional forms of exercise.

The chimeric ubiquitin ligase SH2-U-box inhibits the growth of imatinib-sensitive and resistant CML by targeting the native and T315I-mutant BCR-ABL.

Science.gov (United States)

Ru, Yi; Wang, Qinhao; Liu, Xiping; Zhang, Mei; Zhong, Daixing; Ye, Mingxiang; Li, Yuanchun; Han, Hua; Yao, Libo; Li, Xia

2016-06-22

Chronic myeloid leukemia (CML) is characterized by constitutively active fusion protein tyrosine kinase BCR-ABL. Although the tyrosine kinase inhibitor (TKI) against BCR-ABL, imatinib, is the first-line therapy for CML, acquired resistance almost inevitably emerges. The underlying mechanism are point mutations within the BCR-ABL gene, among which T315I is notorious because it resists to almost all currently available inhibitors. Here we took use of a previously generated chimeric ubiquitin ligase, SH2-U-box, in which SH2 from the adaptor protein Grb2 acts as a binding domain for activated BCR-ABL, while U-box from CHIP functions as an E3 ubiquitin ligase domain, so as to target the ubiquitination and degradation of both native and T315I-mutant BCR-ABL. As such, SH2-U-box significantly inhibited proliferation and induced apoptosis in CML cells harboring either the wild-type or T315I-mutant BCR-ABL (K562 or K562R), with BCR-ABL-dependent signaling pathways being repressed. Moreover, SH2-U-box worked in concert with imatinib in K562 cells. Importantly, SH2-U-box-carrying lentivirus could markedly suppress the growth of K562-xenografts in nude mice or K562R-xenografts in SCID mice, as well as that of primary CML cells. Collectively, by degrading the native and T315I-mutant BCR-ABL, the chimeric ubiquitin ligase SH2-U-box may serve as a potential therapy for both imatinib-sensitive and resistant CML.

BOX-COX REGRESSION METHOD IN TIME SCALING

Directory of Open Access Journals (Sweden)

ATİLLA GÖKTAŞ

2013-06-01

Full Text Available Box-Cox regression method with λj, for j = 1, 2, ..., k, power transformation can be used when dependent variable and error term of the linear regression model do not satisfy the continuity and normality assumptions. The situation obtaining the smallest mean square error  when optimum power λj, transformation for j = 1, 2, ..., k, of Y has been discussed. Box-Cox regression method is especially appropriate to adjust existence skewness or heteroscedasticity of error terms for a nonlinear functional relationship between dependent and explanatory variables. In this study, the advantage and disadvantage use of Box-Cox regression method have been discussed in differentiation and differantial analysis of time scale concept.

Cloning and Functional Analysis of the MADS-box CiMADS9 Gene from Carya illinoinensis

Directory of Open Access Journals (Sweden)

Zhang Jiyu

2015-07-01

Full Text Available A MADS-box gene, CiMADS9, was cloned from the male flowers of Carya illinoinensis by rapid amplification of cDNA ends. The gene was 1 077 bp with a 768 bp open reading frame encoding 255 amino acids. Multiple sequence comparisons revealed that CiMADS9 is a typical MIKC-type MADS-box gene with a MADS-box domain and a K semi-conserved region. Phylogenetic analysis indicated that CiMADS9 belongs to the AGL15 group of the MADS-box gene family. Quantitative reverse transcription polymerase chain reaction analysis indicated that the expression levels in reproductive organs (i.e., flowers and young fruits were considerably higher than in vegetative tissues (i.e., leaves and branches. The highest expression levels were observed in male flowers. An overexpression vector for CiMADS9 was constructed and the gene was inserted into the Arabidopsis thaliana genome. CiMADS9 expression was confirmed in all transgenic lines. Compared with wild-type plants, transgenic A. thaliana plants overexpressing CiMADS9 exhibited delayed flowering and an increased number of leaves.

Ballast system for maintaining constant pressure in a glove box

Science.gov (United States)

Shlichta, Paul J.

1989-09-01

A ballast system is disclosed for a glove box including a fixed platform on which is mounted an inflatable bag on top of which resides a cover and a weight. The variable gas volume of the inflatable bag communicates with that of the glove box via a valved tube. The weight and the gas volume are selected to maintain a relatively constant pressure in the glove box despite variations in the glove box volume while avoiding the use of complicated valving apparatus.

British Box Business: A History of OCL

DEFF Research Database (Denmark)

Poulsen, René Taudal

2018-01-01

Book review of British Box Business: A History of OCL / edited by A. Bott SCARA, Goldaming, 2009, £17 (hb) 288 pages, illustrations, bibliography, index iSBn 139780955922701......Book review of British Box Business: A History of OCL / edited by A. Bott SCARA, Goldaming, 2009, £17 (hb) 288 pages, illustrations, bibliography, index iSBn 139780955922701...

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

Analysis of S-box in Image Encryption Using Root Mean Square Error Method

Science.gov (United States)

Hussain, Iqtadar; Shah, Tariq; Gondal, Muhammad Asif; Mahmood, Hasan

2012-07-01

The use of substitution boxes (S-boxes) in encryption applications has proven to be an effective nonlinear component in creating confusion and randomness. The S-box is evolving and many variants appear in literature, which include advanced encryption standard (AES) S-box, affine power affine (APA) S-box, Skipjack S-box, Gray S-box, Lui J S-box, residue prime number S-box, Xyi S-box, and S8 S-box. These S-boxes have algebraic and statistical properties which distinguish them from each other in terms of encryption strength. In some circumstances, the parameters from algebraic and statistical analysis yield results which do not provide clear evidence in distinguishing an S-box for an application to a particular set of data. In image encryption applications, the use of S-boxes needs special care because the visual analysis and perception of a viewer can sometimes identify artifacts embedded in the image. In addition to existing algebraic and statistical analysis already used for image encryption applications, we propose an application of root mean square error technique, which further elaborates the results and enables the analyst to vividly distinguish between the performances of various S-boxes. While the use of the root mean square error analysis in statistics has proven to be effective in determining the difference in original data and the processed data, its use in image encryption has shown promising results in estimating the strength of the encryption method. In this paper, we show the application of the root mean square error analysis to S-box image encryption. The parameters from this analysis are used in determining the strength of S-boxes

S-Boxes Based on Affine Mapping and Orbit of Power Function

Science.gov (United States)

Khan, Mubashar; Azam, Naveed Ahmed

2015-06-01

The demand of data security against computational attacks such as algebraic, differential, linear and interpolation attacks has been increased as a result of rapid advancement in the field of computation. It is, therefore, necessary to develop such cryptosystems which can resist current cryptanalysis and more computational attacks in future. In this paper, we present a multiple S-boxes scheme based on affine mapping and orbit of the power function used in Advanced Encryption Standard (AES). The proposed technique results in 256 different S-boxes named as orbital S-boxes. Rigorous tests and comparisons are performed to analyse the cryptographic strength of each of the orbital S-boxes. Furthermore, gray scale images are encrypted by using multiple orbital S-boxes. Results and simulations show that the encryption strength of the orbital S-boxes against computational attacks is better than that of the existing S-boxes.

Properties of Human Embryonic Stem Cells and Their Differentiated Derivatives Depend on Nonhistone DNA-Binding HMGB1 and HMGB2 Proteins

Czech Academy of Sciences Publication Activity Database

Bagherpoor, Alireza Jian; Doležalová, D.; Bárta, T.; Kučírek, Martin; Sani, Soodabeh Abbasi; Esner, M.; Bosakova, M.K.; Vinařský, V.; Peškova, L.; Hampl, A.; Štros, Michal

2017-01-01

Roč. 26, č. 5 (2017), s. 328-340 ISSN 1547-3287 R&D Projects: GA ČR GA15-01354S Grant - others:GA ČR(CZ) GA15-23033S Institutional support: RVO:68081707 Keywords : group box 1 * chromatin protein * expression Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 3.562, year: 2016

"Light-box" accelerated growth of poinsettias: LED-only illumination

Science.gov (United States)

Weerasuriya, Charitha; Detez, Stewart; Hock Ng, Soon; Hughes, Andrew; Callaway, Michael; Harrison, Iain; Katkus, Tomas; Juodkazis, Saulius

2018-01-01

For the current commercialized agricultural industry which requires a reduced product lead time to customer and supply all year round, an artificial light emitting diodes (LEDs)-based illumination has high potential due to high efficiency of electrical-to-light conversion. The main advantage of the deployed Red Green Blue Amber LED lighting system is colour mixing capability, which means ability to generate all the colours in the spectrum by using three or four primary colours LEDs. The accelerated plant growth was carried out in a "light-box" which was made to generate an artificial day/night cycle by moving the colour mixing ratio along the colour temperature curve of the chromaticity diagram. The control group of plants form the same initial batch was grown on the same shelf in a greenhouse at the same conditions with addition of artificial illumination by incandescent lamps for few hours. Costs and efficiency projections of LED lamps for horticultural applications is discussed together with required capital investment. The total cost of the "light-box" including LED lamps and electronics was 850 AUD.