Nuclear factor-κB is a common upstream signal for growth differentiation factor-5 expression in brown adipocytes exposed to pro-inflammatory cytokines and palmitate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hinoi, Eiichi; Iezaki, Takashi; Ozaki, Kakeru

Highlights: • GDF5 expression is up-regulated by IL-1β, TNF-α and palmitate in brown pre-adipocytes. • NF-κB stimulates promoter activity and expression of GDF5 in brown pre-adipocytes. • Recruitment of NF-κB to the GDF5 promoter is facilitated in BAT from ob/ob mice. • An NF-κB inhibitor prevents upregulation of GDF5 expression in brown pre-adipocytes. - Abstract: We have previously demonstrated that genetic and acquired obesity similarly led to drastic upregulation in brown adipose tissue (BAT), rather than white adipose tissue, of expression of both mRNA and corresponding protein for the bone morphogenic protein/growth differentiation factor (GDF) member GDF5 capable of promotingmore » brown adipogenesis. In this study, we evaluated expression profiles of GDF5 in cultured murine brown pre-adipocytes exposed to pro-inflammatory cytokines and free fatty acids (FFAs), which are all shown to play a role in the pathogenesis of obesity. Both interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were effective in up-regulating GDF5 expression in a concentration-dependent manner, while similar upregulation was seen in cells exposed to the saturated FFA palmitate, but not to the unsaturated FFA oleate. In silico analysis revealed existence of the putative nuclear factor-κB (NF-κB) binding site in the 5′-flanking region of mouse GDF5, whereas introduction of NF-κB subunits drastically facilitated both promoter activity and expression of GDF5 in brown pre-adipocytes. Chromatin immunoprecipitation analysis confirmed significant facilitation of the recruitment of NF-κB to the GDF5 promoter in lysed extracts of BAT from leptin-deficient ob/ob obese mice. Upregulation o GDF5 expression was invariably inhibited by an NF-κB inhibitor in cultured brown pre-adipocytes exposed to IL-1β, TNF-α and palmitate. These results suggest that obesity leads to upregulation of GDF5 expression responsible for the promotion of brown adipogenesis through a

Study of the weak annihilation contributions in charmless \\varvec{B_s→ VV} decays

NASA Astrophysics Data System (ADS)

Chang, Qin; Li, Xiaonan; Li, Xin-Qiang; Sun, Junfeng

2017-06-01

In this paper, in order to probe the spectator-scattering and weak annihilation contributions in charmless B_s→ VV (where V stands for a light vector meson) decays, we perform the χ ^2-analyses for the endpoint parameters within the QCD factorization framework, under the constraints from the measured \\bar{B}s→ ρ ^0φ , φ K^{*0}, φ φ and K^{*0}\\bar{K}^{*0} decays. The fitted results indicate that the endpoint parameters in the factorizable and nonfactorizable annihilation topologies are non-universal, which is also favored by the charmless B→ PP and PV (where P stands for a light pseudo-scalar meson) decays observed in previous work. Moreover, the abnormal polarization fractions f_{L,\\bot }(\\bar{B}s→ K^{*0}\\bar{K}^{*0})=(20.1± 7.0)%,(58.4± 8.5)% measured by the LHCb collaboration can be reconciled through the weak annihilation corrections. However, the branching ratio of \\bar{B}s→ φ K^{*0} decay exhibits a tension between the data and theoretical result, which dominates the contributions to χ _min^2 in the fits. Using the fitted endpoint parameters, we update the theoretical results for the charmless B_s→ VV decays, which will be further tested by the LHCb and Belle-II experiments in the near future.

The B-cell identity factor Pax5 regulates distinct transcriptional programmes in early and late B lymphopoiesis

PubMed Central

Revilla-i-Domingo, Roger; Bilic, Ivan; Vilagos, Bojan; Tagoh, Hiromi; Ebert, Anja; Tamir, Ido M; Smeenk, Leonie; Trupke, Johanna; Sommer, Andreas; Jaritz, Markus; Busslinger, Meinrad

2012-01-01

Pax5 controls the identity and development of B cells by repressing lineage-inappropriate genes and activating B-cell-specific genes. Here, we used genome-wide approaches to identify Pax5 target genes in pro-B and mature B cells. In these cell types, Pax5 bound to 40% of the cis-regulatory elements defined by mapping DNase I hypersensitive (DHS) sites, transcription start sites and histone modifications. Although Pax5 bound to 8000 target genes, it regulated only 4% of them in pro-B and mature B cells by inducing enhancers at activated genes and eliminating DHS sites at repressed genes. Pax5-regulated genes in pro-B cells account for 23% of all expression changes occurring between common lymphoid progenitors and committed pro-B cells, which identifies Pax5 as an important regulator of this developmental transition. Regulated Pax5 target genes minimally overlap in pro-B and mature B cells, which reflects massive expression changes between these cell types. Hence, Pax5 controls B-cell identity and function by regulating distinct target genes in early and late B lymphopoiesis. PMID:22669466

The 10B(p,α)7Be S(E)-factor from 5 keV to 1.5 MeV using the Trojan Horse Method

NASA Astrophysics Data System (ADS)

Puglia, Sebastiana Maria Regina; Spitaleri, Claudio; La Cognata, Marco; Lamia, Livio; Broggini, Carlo; Caciolli, Antonio; Carlin, Nelson; Cherubini, Silvio; Cvetinovic, Alexandra; D'Agata, Giuseppe; Dell'aquila, Daniele; Depalo, Rosanna; Gulino, Marisa; Guardo, Giovanni Luca; Indelicato, Iolanda; Lombardo, Ivano; Menegazzo, Roberto; Munhoz, Marcelo Gimenez; Pizzone, Rosario Gianluca; Rapisarda, Giuseppe Gabriele; Rigato, Valentino; Romano, Stefano; Sergi, Maria Letizia; Souza, Francisco; Sparta, Roberta; Tudisco, Salvo; Tumino, Aurora

2018-01-01

The 10B(p,α)7Be reaction is the main responsible for the 10B destruction in stellar interior [1]. In such environments this p-capture process occurs at a Gamow energy of 10 keV and takes places mainly through a resonant state (Ex = 8.701 MeV) of the compound 11C nucleus. Thus a resonance right in the region of the Gamow peak is expected to significantly influence the behavior of the astrophysical S(E)-factor. The 10B(p,α)7Be reaction was studied via the Trojan Horse Method (THM) applied to the 2H(10B,α7Be)n in order to extract the astrophysical S(E)-factor in a wide energy range from 5 keV to 1.5 MeV.

Interleukin-5 regulates genes involved in B-cell terminal maturation.

PubMed

Horikawa, Keisuke; Takatsu, Kiyoshi

2006-08-01

Interleukin (IL)-5 induces CD38-activated splenic B cells to differentiate into immunoglobulin M-secreting cells and undergo micro to gamma 1 class switch recombination (CSR) at the DNA level, resulting in immunoglobulin G1 (IgG1) production. Interestingly, IL-4, a well-known IgG1-inducing factor does not induce immunoglobulin production or micro to gamma 1 CSR in CD38-activated B cells. In the present study, we implemented complementary DNA microarrays to investigate the contribution of IL-5-induced gene expression in CD38-stimulated B cells to immunoglobulin-secreting cell differentiation and micro to gamma 1 CSR. IL-5 and IL-4 stimulation of CD38-activated B cells induced the expression of 418 and 289 genes, respectively, that consisted of several clusters. Surprisingly, IL-5-inducible 78 genes were redundantly regulated by IL-4. IL-5 and IL-4 also suppressed the gene expression of 319 and 325 genes, respectively, 97 of which were overlapped. Genes critically regulated by IL-5 include immunoglobulin-related genes such as J chain and immunoglobulinkappa, and genes involved in B-cell maturation such as BCL6, activation-induced cytidine deaminase (Aid) and B lymphocyte-induced maturation protein-1 (Blimp-1) and tend to be induced slowly after IL-5 stimulation. Intriguingly, among genes, the retroviral induction of Blimp-1 and Aid in CD38-activated B cells could induce IL-4-dependent maturation to Syndecan-1+ antibody-secreting cells and micro to gamma 1 CSR, respectively, in CD38-activated B cells. Taken together, preferential Aid and Blimp-1 expression plays a critical role in IL-5-induced immunoglobulin-secreting cell differentiation and micro to gamma 1 CSR in CD38-activated B cells.

Signal transducer and activator of transcription 5B (STAT5B) modulates adipocyte differentiation via MOF.

PubMed

Gao, Peng; Zhang, Yuchao; Liu, Yuantao; Chen, Jicui; Zong, Chen; Yu, Cong; Cui, Shang; Gao, Weina; Qin, Dandan; Sun, Wenchuan; Li, Xia; Wang, Xiangdong

2015-12-01

The role and mechanism of signal transducer and activator of transcription 5B (STAT5B) in adipogenesis remain unclear. In this study, our data showed that Males absent on the first (MOF) protein expression was increased during 3 T3-L1 preadipocytes differentiation accompanied with STAT5B expression increasing. Over-expression STAT5B enhanced MOF promoter trans-activation in HeLa cells. Mutagenesis assay and ChIP analysis exhibited that STAT5B was able to bind MOF promoter. Knocking-down STAT5B in 3 T3-L1 preadipocytes led to decreased expression of MOF, but resulted in increased expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα) and fatty acid-binding protein 4 (Fabp4), which were important factors or enzymes for adipogenesis. We also found that knocking-down MOF in 3 T3-L1 preadipocytes resulted in increased expression of PPARγ, C/EBPα and Fabp4, which was in the same trend as STAT5B knocking-down. Over-expression MOF resulted in reduced promoter trans-activation activity of C/EBPα. These results suggest that STAT5B and MOF work as negative regulators in adipogenesis, and STAT5B modulates preadipocytes differentiation partially by regulating MOF expression. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Possible involvement of nuclear factor erythroid 2-related factor 2 in the gene expression of Cyp2b10 and Cyp2a5☆

PubMed Central

Ashino, Takashi; Ohkubo-Morita, Haruyo; Yamamoto, Masayuki; Yoshida, Takemi; Numazawa, Satoshi

2014-01-01

Cytochrome P450 gene expression is altered by various chemical compounds. In this study, we used nuclear factor erythroid 2-related factor 2 (Nrf2)–deficient (Nrf2−⧸−) mice to investigate the involvement of Nrf2 in Cyp2b10 and Cyp2a5 gene expression. Phorone, an Nrf2 activator, strongly increased Cyp2b10 and Cyp2a5 mRNA as well as Nrf2 target genes, including NAD(P)H-quinone oxidoreductase-1 and heme oxygenase-1, in wild-type mouse livers 8 h after treatment. The phorone-induced mRNA levels in Nrf2−⧸− mouse livers were lower than that in wild-type mouse livers. Nrf2−⧸− mice showed attenuated Cyp2b10 and Cyp2a5 induction by phenobarbital, a classical Cyp2b inducer. These findings suggest that the Nrf2 pathway is involved in Cyp2b10 and Cyp2a5 gene expression. PMID:24494203

Frequency of pediatric medication administration errors and contributing factors.

PubMed

Ozkan, Suzan; Kocaman, Gulseren; Ozturk, Candan; Seren, Seyda

2011-01-01

This study examined the frequency of pediatric medication administration errors and contributing factors. This research used the undisguised observation method and Critical Incident Technique. Errors and contributing factors were classified through the Organizational Accident Model. Errors were made in 36.5% of the 2344 doses that were observed. The most frequent errors were those associated with administration at the wrong time. According to the results of this study, errors arise from problems within the system.

UV-B Radiation Contributes to Amphibian Population Declines

NASA Astrophysics Data System (ADS)

Blaustein, Andrew

2007-05-01

UV-B (280-315 nm) radiation is the most significant biologically damaging radiation at the terrestrial surface. At the organismal level, UV-B radiation can slow growth rates, cause immune dysfunction and result in sublethal damage. UV-B radiation can lead to mutations and cell death. Over evolutionary time, UV radiation has been an important stressor on living organisms. Natural events, including impacts from comets and asteroids, volcanic activity, supernova explosions and solar flares, can cause large-scale ozone depletion with accompanying increases in UV radiation. However, these natural events are transient. Moreover, the amount of ozone damage due to natural events depends upon a number of variables, including the magnitude of the event. This is different from modern-day human-induced production of chlorofluorocarbons (CFCs) and other chemicals that deplete stratospheric ozone continuously, resulting in long-term increases in UV-B radiation at the surface of the earth. We will briefly review the effects of UV-B exposure in one group of aquatic organisms_amphibians. UV-B has been implicated as a possible factor contributing to global declines and range reductions in amphibian populations.

Maternal factors contributing to under-five mortality at birth order 1 to 5 in India: a comprehensive multivariate study.

PubMed

Singh, Rajvir; Tripathi, Vrijesh

2013-01-01

The objective of the study is to assess maternal factors contributing to under-five mortality at birth order 1 to 5 in India. Data for this study was derived from the children's record of the 2007 India National Family Health Survey, which is a nationally representative cross-sectional household survey. Data is segregated according to birth order 1 to 5 to assess mother's occupation, Mother's education, child's gender, Mother's age, place of residence, wealth index, mother's anaemia level, prenatal care, assistance at delivery , antenatal care, place of delivery and other maternal factors contributing to under-five mortality. Out of total 51555 births, analysis is restricted to 16567 children of first birth order, 14409 of second birth order, 8318 of third birth order, 5021 of fourth birth order and 3034 of fifth birth order covering 92% of the total births taken place 0-59 months prior to survey. Mother's average age in years for birth orders 1 to 5 are 23.7, 25.8, 27.4, 29 and 31 years, respectively. Most mothers whose children died are Hindu, with no formal education, severely anaemic and working in the agricultural sector. In multivariate logistic models, maternal education, wealth index and breastfeeding are protective factors across all birth orders. In birth order model 1 and 2, mother's occupation is a significant risk factor. In birth order models 2 to 5, previous birth interval of lesser than 24 months is a risk factor. Child's gender is a risk factor in birth order 1 and 5. Information regarding complications in pregnancy and prenatal care act as protective factors in birth order 1, place of delivery and immunization in birth order 2, and child size at birth in birth order 4. Prediction models demonstrate high discrimination that indicates that our models fit the data. The study has policy implications such as enhancing the Information, Education and Communication network for mothers, especially at higher birth orders, in order to reduce under

45 CFR 1627.5 - Contributions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Contributions. 1627.5 Section 1627.5 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION SUBGRANTS AND MEMBERSHIP FEES OR DUES § 1627.5 Contributions. Any contributions or gifts of Corporation funds to another organization or to an individual are prohibited...

A novel NFIA-NFκB feed-forward loop contributes to glioblastoma cell survival

PubMed Central

Lee, JunSung; Hoxha, Edlira

2017-01-01

Abstract Background. The nuclear factor I-A (NFIA) transcription factor promotes glioma growth and inhibits apoptosis in glioblastoma (GBM) cells. Here we report that the NFIA pro-survival effect in GBM is mediated in part via a novel NFIA–nuclear factor-kappaB (NFκB) p65 feed-forward loop. Methods. We examined effects of gain- and loss-of-function manipulations of NFIA and NFκB p65 on each other’s transcription, cell growth, apoptosis and sensitivity to chemotherapy in patient-derived GBM cells and established GBM cell lines. Results. NFIA enhanced apoptosis evasion by activating NFκB p65 and its downstream anti-apoptotic factors tumor necrosis factor receptor-associated factor 1 (TRAF1) and cellular inhibitor of apoptosis proteins (cIAPs). Induction of NFκB by NFIA was required to protect cells from apoptosis, and inhibition of NFκB effectively reversed the NFIA anti-apoptotic effect. Conversely, NFIA knockdown decreased expression of NFκB and anti-apoptotic genes TRAF1 and cIAPs, and increased baseline apoptosis. NFIA positively regulated NFκB transcription and NFκB protein level. Interestingly, NFκB also activated the NFIA promoter and increased NFIA level, and knockdown of NFIA was sufficient to attenuate the NFκB pro-survival effect, suggesting a reciprocal regulation between NFIA and NFκB in governing GBM cell survival. Supporting this, NFIA and NFκB expression levels were highly correlated in human GBM and patient-derived GBM cells. Conclusions. These data define a previously unknown NFIA-NFκB feed-forward regulation that may contribute to GBM cell survival. PMID:27994064

Nuclear Factor-kappaB in Autoimmunity: Man and Mouse

PubMed Central

Miraghazadeh, Bahar; Cook, Matthew C.

2018-01-01

NF-κB (nuclear factor-kappa B) is a transcription complex crucial for host defense mediated by innate and adaptive immunity, where canonical NF-κB signaling, mediated by nuclear translocation of RelA, c-Rel, and p50, is important for immune cell activation, differentiation, and survival. Non-canonical signaling mediated by nuclear translocation of p52 and RelB contributes to lymphocyte maturation and survival and is also crucial for lymphoid organogenesis. We outline NF-κB signaling and regulation, then summarize important molecular contributions of NF-κB to mechanisms of self-tolerance. We relate these mechanisms to autoimmune phenotypes described in what is now a substantial catalog of immune defects conferred by mutations in NF-κB pathways in mouse models. Finally, we describe Mendelian autoimmune syndromes arising from human NF-κB mutations, and speculate on implications for understanding sporadic autoimmune disease. PMID:29686669

Renormalization group analysis of B →π form factors with B -meson light-cone sum rules

NASA Astrophysics Data System (ADS)

Shen, Yue-Long; Wei, Yan-Bing; Lü, Cai-Dian

2018-03-01

Within the framework of the B -meson light-cone sum rules, we review the calculation of radiative corrections to the three B →π transition form factors at leading power in Λ /mb. To resum large logarithmic terms, we perform the complete renormalization group evolution of the correlation function. We employ the integral transformation which diagonalizes evolution equations of the jet function and the B -meson light-cone distribution amplitude to solve these evolution equations and obtain renormalization group improved sum rules for the B →π form factors. Results of the form factors are extrapolated to the whole physical q2 region and are compared with that of other approaches. The effect of B -meson three-particle light-cone distribution amplitudes, which will contribute to the form factors at next-to-leading power in Λ /mb at tree level, is not considered in this paper.

Celecoxib restores angiogenic factor expression at the maternal-fetal interface in the BPH/5 mouse model of preeclampsia.

PubMed

Reijnders, Dorien; Liu, Chin-Chi; Xu, Xinjing; Zhao, Anna M; Olson, Kelsey N; Butler, Scott D; Douglas, Nataki C; Sones, Jenny L

2018-05-01

Preeclampsia (PE), a hypertensive disease of pregnancy, is a leading cause of fetal and maternal morbidity/mortality. Early angiogenic and inflammatory disturbances within the placenta are thought to underlie the development of the maternal PE syndrome and poor pregnancy outcomes. However, the exact etiology remains largely unknown. Here, we use the BPH/5 mouse model of PE to elucidate the way in which inflammation early in pregnancy contributes to abnormal expression of angiogenic factors at the maternal-fetal interface. We have previously described improvement in maternal hypertension and fetal growth restriction in this model after treatment with the anti-inflammatory cyclooxygenase-2 (Cox2) specific inhibitor celecoxib. To further characterize the mechanisms by which celecoxib improves poor pregnancy outcomes in BPH/5 mice, we determined expression of angiogenic factors and complement pathway components after celecoxib. In BPH/5 implantation sites there was increased hypoxia inducible factor-1α ( Hif1α), heme oxygenase-1 ( Ho-1), and stem cell factor ( Scf) mRNA concomitant with elevated prostaglandin synthase 2 ( Ptgs2), encoding Cox2, and elevated VEGF protein. Angiopoietin 1 ( Ang1), tunica interna endothelial cell kinase-2 receptor ( Tie2), complement factor 3 ( C3), and complement factor B ( CfB) were increased in midgestation BPH/5 placentae. Whereas BPH/5 expression levels of VEGF, Ang1, and Tie2 normalized after celecoxib, placental C3 and CfB mRNA remained unchanged. However, celecoxib did reduce the pregnancy-specific circulating soluble fms-like tyrosine kinase-1 (sFlt-1) rise in BPH/5 mice at midgestation. These data show that elevated Cox2 during implantation contributes to placental angiogenic factor imbalances in the BPH/5 mouse model of PE.

Study of the individual cytochrome b5 and cytochrome b5 reductase domains of Ncb5or reveals a unique heme pocket and a possible role of the CS domain.

PubMed

Deng, Bin; Parthasarathy, Sudharsan; Wang, WenFang; Gibney, Brian R; Battaile, Kevin P; Lovell, Scott; Benson, David R; Zhu, Hao

2010-09-24

NADH cytochrome b(5) oxidoreductase (Ncb5or) is found in animals and contains three domains similar to cytochrome b(5) (b(5)), CHORD-SGT1 (CS), and cytochrome b(5) reductase (b(5)R). Ncb5or has an important function, as suggested by the diabetes and lipoatrophy phenotypes in Ncb5or null mice. To elucidate the structural and functional properties of human Ncb5or, we generated its individual b(5) and b(5)R domains (Ncb5or-b(5) and Ncb5or-b(5)R, respectively) and compared them with human microsomal b(5) (Cyb5A) and b(5)R (Cyb5R3). A 1.25 Å x-ray crystal structure of Ncb5or-b(5) reveals nearly orthogonal planes of the imidazolyl rings of heme-ligating residues His(89) and His(112), consistent with a highly anisotropic low spin EPR spectrum. Ncb5or is the first member of the cytochrome b(5) family shown to have such a heme environment. Like other b(5) family members, Ncb5or-b(5) has two helix-loop-helix motifs surrounding heme. However, Ncb5or-b(5) differs from Cyb5A with respect to location of the second heme ligand (His(112)) and of polypeptide conformation in its vicinity. Electron transfer from Ncb5or-b(5)R to Ncb5or-b(5) is much less efficient than from Cyb5R3 to Cyb5A, possibly as a consequence of weaker electrostatic interactions. The CS linkage probably obviates the need for strong interactions between b(5) and b(5)R domains in Ncb5or. Studies with a construct combining the Ncb5or CS and b(5)R domains suggest that the CS domain facilitates docking of the b(5) and b(5)R domains. Trp(114) is an invariant surface residue in all known Ncb5or orthologs but appears not to contribute to electron transfer from the b(5)R domain to the b(5) domain.

Anti-inflammatory activity of Cymbopogon citratus leaves infusion via proteasome and nuclear factor-κB pathway inhibition: contribution of chlorogenic acid.

PubMed

Francisco, Vera; Costa, Gustavo; Figueirinha, Artur; Marques, Carla; Pereira, Paulo; Miguel Neves, Bruno; Celeste Lopes, Maria; García-Rodríguez, Carmen; Teresa Cruz, Maria; Teresa Batista, Maria

2013-06-21

Cymbopogon citratus (DC.) Stapf leaves infusion is used in traditional medicine for the treatment of inflammatory conditions, however little is known about their bioactive compounds. Investigate the compounds responsible for anti-inflammatory potential of Cymbopogon citratus (Cy) on cytokines production induced by lipopolysaccharide (LPS) in human and mouse macrophages, and the action mechanisms involved. An essential oil-free infusion of Cy was prepared and polyphenol-rich fractions (PFs) were obtained from it by column chromatography. Chlorogenic acid (CGA) was identified, by HPLC/PDA/ESI-MS(n). The expression of cytokines, namely TNF-α and CCL5, was analyzed by real-time RT-PCR, on LPS-stimulated human macrophages. Activation of nuclear factor (NF)-κB, a master regulator of inflammation, was investigated by western blot and gene reporter assay. Proteasome activity was assessed using a fluorogenic peptide. Cymbopogon citratus extract and its polyphenols inhibited the cytokine production on human macrophages. This supports the anti-inflammatory activity of Cy polyphenols in physiologically relevant cells. Concerning the effect on the activation of NF-κB pathway, the results pointed to an inhibition of LPS-induced NF-κB activation by Cy and PFs. CGA was identified, by HPLC/PDA/ESI-MS(n), as the main phenolic acid of the Cy infusion, and it demonstrated to be, at least in part, responsible by that effect. Additionally, it was verified for the first time that Cy and PFs inhibited the proteasome activity, a complex that controls NF-κB activation, having CGA a strong contribution. The results evidenced, for the first time, the anti-inflammatory properties of Cymbopogon citratus through proteasome inhibition and, consequently NF-κB pathway and cytokine expression. Additionally, Cy polyphenols, in particular chlorogenic acid, were highlighted as bioactive compounds. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Muc5b is required for airway defence

NASA Astrophysics Data System (ADS)

Roy, Michelle G.; Livraghi-Butrico, Alessandra; Fletcher, Ashley A.; McElwee, Melissa M.; Evans, Scott E.; Boerner, Ryan M.; Alexander, Samantha N.; Bellinghausen, Lindsey K.; Song, Alfred S.; Petrova, Youlia M.; Tuvim, Michael J.; Adachi, Roberto; Romo, Irlanda; Bordt, Andrea S.; Bowden, M. Gabriela; Sisson, Joseph H.; Woodruff, Prescott G.; Thornton, David J.; Rousseau, Karine; de La Garza, Maria M.; Moghaddam, Seyed J.; Karmouty-Quintana, Harry; Blackburn, Michael R.; Drouin, Scott M.; Davis, C. William; Terrell, Kristy A.; Grubb, Barbara R.; O'Neal, Wanda K.; Flores, Sonia C.; Cota-Gomez, Adela; Lozupone, Catherine A.; Donnelly, Jody M.; Watson, Alan M.; Hennessy, Corinne E.; Keith, Rebecca C.; Yang, Ivana V.; Barthel, Lea; Henson, Peter M.; Janssen, William J.; Schwartz, David A.; Boucher, Richard C.; Dickey, Burton F.; Evans, Christopher M.

2014-01-01

Respiratory surfaces are exposed to billions of particulates and pathogens daily. A protective mucus barrier traps and eliminates them through mucociliary clearance (MCC). However, excessive mucus contributes to transient respiratory infections and to the pathogenesis of numerous respiratory diseases. MUC5AC and MUC5B are evolutionarily conserved genes that encode structurally related mucin glycoproteins, the principal macromolecules in airway mucus. Genetic variants are linked to diverse lung diseases, but specific roles for MUC5AC and MUC5B in MCC, and the lasting effects of their inhibition, are unknown. Here we show that mouse Muc5b (but not Muc5ac) is required for MCC, for controlling infections in the airways and middle ear, and for maintaining immune homeostasis in mouse lungs, whereas Muc5ac is dispensable. Muc5b deficiency caused materials to accumulate in upper and lower airways. This defect led to chronic infection by multiple bacterial species, including Staphylococcus aureus, and to inflammation that failed to resolve normally. Apoptotic macrophages accumulated, phagocytosis was impaired, and interleukin-23 (IL-23) production was reduced in Muc5b-/- mice. By contrast, in mice that transgenically overexpress Muc5b, macrophage functions improved. Existing dogma defines mucous phenotypes in asthma and chronic obstructive pulmonary disease (COPD) as driven by increased MUC5AC, with MUC5B levels either unaffected or increased in expectorated sputum. However, in many patients, MUC5B production at airway surfaces decreases by as much as 90%. By distinguishing a specific role for Muc5b in MCC, and by determining its impact on bacterial infections and inflammation in mice, our results provide a refined framework for designing targeted therapies to control mucin secretion and restore MCC.

Transcription factor Stat5a/b as a therapeutic target protein for prostate cancer

PubMed Central

Liao, Zhiyong; Lutz, Jacqueline; Nevalainen, Marja T.

2009-01-01

Prostate cancer is the most common non-cutaneous cancer in Western males. The majority of prostate cancer fatalities are caused by development of castration-resistant growth and metastatic spread of the primary tumor. The average duration of the response of primary prostate cancer to hormonal ablation is less than 3 years, and 75% of prostate cancers in the United States progress to hormone-refractory disease. The existing pharmacological therapies for metastatic and/or hormone-refractory prostate cancer do not provide significant survival benefit. This review summarizes the importance of transcription factor Stat5 signaling in the pathogenesis of prostate cancer and discusses the molecular basis why inhibition of Stat5a/b could be used as a therapeutic strategy for prostate cancer. PMID:19914392

STAT5A and STAT5B have opposite correlations with drug response gene expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lamba, V., E-mail: vlamba@ufl.edu; Jia, B.; Liang, F.

Introduction: STAT5A and STAT5B are important transcription factors that play a key role in regulation of several important physiological processes including proliferation, survival, mediation of responses to cytokines and in regulating gender differences in drug response genes such as the hepatic cytochrome P450s (CYPs) that are responsible for a large majority of drug metabolism reactions in the human body. STAT5A and STAT5b have a high degree of sequence homology and have been reported to have largely similar functions. Recent studies have, however, indicated that they can also often have distinct and unique roles in regulating gene expression. Objective: In thismore » study, we evaluated the association of STAT5A and STAT5B mRNA expression levels with those of several key hepatic cytochrome P450s (CYPs) and hepatic transcription factors (TFs) and evaluated the potential roles of STAT5A and 5b in mediating gender differences in these CYPs and TFs. Methods: Expression profiling for major hepatic CYP isoforms and transcription factors was performed using RNA sequencing (RNA-seq) in 102 human liver samples (57 female, 45 male). Real time PCR gene expression data for selected CYPs and TFs was available on a subset of 50 human liver samples (25 female, 25 male) and was used to validate the RNA-seq findings. Results: While STAT5A demonstrated significant negative correlation with expression levels of multiple hepatic transcription factors (including NR1I2 and HNF4A) and DMEs such as CYP3A4 and CYP2C19, STAT5B expression was observed to demonstrate positive associations with several CYPs and TFs analyzed. As STAT5A and STAT5B have been shown to be important in regulation of gender differences in CYPs, we also analyzed STAT5A and 5b associations with CYPs and TFs separately in males and females and observed gender dependent differential associations of STATs with several CYPs and TFs. Results from the real time PCR validation largely supported our RNA-seq findings

Contribution of Salmonella Enteritidis virulence factors to intestinal colonization and systemic dissemination in 1-day-old chickens.

PubMed

Addwebi, Tarek M; Call, Douglas R; Shah, Devendra H

2014-04-01

Salmonella enterica serovar Enteritidis is one of the most common serovars associated with poultry and poultry product contamination in the United States. We previously identified 14 mutant strains of Salmonella Enteritidis phage type 4 (PT4) with significantly reduced invasiveness in human intestinal epithelial cells (Caco-2), chicken macrophages (HD-11), and chicken hepatocellular epithelial cells (LMH). These included Salmonella Enteritidis mutants with transposon insertions in 6 newly identified Salmonella Enteritidis-specific genes (pegD and SEN1393), and genes or genomic islands common to most other Salmonella serovars (SEN0803, SEN0034, SEN2278, and SEN3503) along with 8 genes previously known to contribute to enteric infection (hilA, pipA, fliH, fljB, csgB, spvR, and rfbMN). We hypothesized that Salmonella Enteritidis employs both common Salmonella enterica colonization factors and Salmonella Enteritidis-specific traits to establish infection in chickens. Four Salmonella Enteritidis mutants (SEN0034::Tn5, fliH::Tn5, SEN1393::Tn5, and spvR::Tn5) were indistinguishable from the isogenic wild-type strain when orally inoculated in 1-d-old chickens, whereas 2 mutants (CsgB::Tn5 and PegD::Tn5) were defective for intestinal colonization (P < 0.05) and 8 mutants (hilA::Tn5, SEN3503::Tn5, SEN0803::Tn5, SEN2278::Tn5, fljB::Tn5, rfbM::Tn5, rfbN::Tn5, and pipA::Tn5) showed significant in vivo attenuation in more than one organ (P < 0.05). Complementation studies confirmed the role of rfbN and SEN3503 during infection. This study should contribute to a better understanding of the mechanisms involved in Salmonella Enteritidis pathogenesis, and the target genes identified here could potentially serve as targets for the development of live-attenuated or subunit vaccine.

Brain-derived neurotrophic factor (BDNF) in the rostral anterior cingulate cortex (rACC) contributes to neuropathic spontaneous pain-related aversion via NR2B receptors.

PubMed

Zhang, Le; Wang, Gongming; Ma, Jinben; Liu, Chengxiao; Liu, Xijiang; Zhan, Yufeng; Zhang, Mengyuan

2016-10-01

The rostral anterior cingulate cortex (rACC) plays an important role in pain affect. Previous investigations have reported that the rACC mediates the negative affective component of inflammatory pain and contributed to the aversive state of nerve injury-induced neuropathic pain. Brain-derived neurotrophic factor (BDNF), an activity-dependent neuromodulator in the adult brain, is believed to play a role in the development and maintenance of inflammatory and neuropathic pain in the spinal cord. However, whether and how BDNF in the rACC regulates pain-related aversion due to peripheral nerve injury is largely unknown. Behaviorally, using conditioned place preference (CPP) training in rats, which is thought to reveal spontaneous pain-related aversion, we found that CPP was acquired following spinal clonidine in rats with partial sciatic nerve transection. Importantly, BDNF was upregulated within the rACC in of rats with nerve injury and enhanced the CPP acquisition, while a local injection of a BDNF-tropomyosin receptor kinase B (TrkB) antagonist into the rACC completely blocked this process. Finally, we demonstrated that the BDNF/TrkB pathway exerted its function by activating the NR2B receptor, which is widely accepted to be a crucial factor contributing to pain affect. In conclusion, our results demonstrate that the BDNF/TrkB-mediated signaling pathway in the rACC is involved in the development of neuropathic spontaneous pain-related aversion and that this process is dependent upon activation of NR2B receptors. These findings suggest that suppression of the BDNF-related signaling pathway in the rACC may provide a novel strategy to overcome pain-related aversion. Copyright © 2016 Elsevier Inc. All rights reserved.

Free factor XIII activation peptide (fAP-FXIII) is a regulator of factor XIII activity via factor XIII-B.

PubMed

Dodt, Johannes; Pasternack, Ralf; Seitz, Rainer; Volkers, Peter

2016-02-01

In a factor XIIIa (FXIIIa) generation assay with recombinant FXIII-A2 (rFXIII-A2 ) free FXIII activation peptide (fAP-FXII) prolonged the time to peak (TTP) but did not affect the area under the curve (AUC) or concentration at peak (CP). Addition of recombinant factorXIII-B2 (rFXIII-B2 ) restored the characteristics of the FXIIIa generation parameters (AUC, TTP and CP) to those observed for plasma FXIII (FXIII-A2 B2 ). FXIII-A2 B2 reconstituted from rFXIII-A2 and rFXIII-B2 showed a similar effect on AUC, TTP and CP in the presence of fAP-FXII as observed for plasma FXIII-A2 B2 , indicating a role for FXIII-B in this observation. An effect of fAP-FXIII on thrombin, the proteolytic activator of FXIII, was excluded by thrombin generation assays and clotting experiments. In a purified system, fAP-FXIII did not interfere with the FXIIIa activity development of thrombin-cleaved rFXIII-A2 (rFXIII-A2 ') also excluding direct inhibition of FXIIIa. However, FXIIIa activity development of FXIII-A2 'B2 was inhibited in a concentration-dependent manner by fAP-FXIII, indicating that an interaction between AP-FXIII and FXIII-B2 contributes to the overall stability of FXIII-A2 'B2 . In addition to its well-known role, FXIII-B also contributes to FXIII-A2 B2 stability or dissociation depending on fAP-FXIII and calcium concentrations. © 2015 John Wiley & Sons Ltd.

B =5 Skyrmion as a two-cluster system

NASA Astrophysics Data System (ADS)

Gudnason, Sven Bjarke; Halcrow, Chris

2018-06-01

The classical B =5 Skyrmion can be approximated by a two-cluster system in which a B =1 Skyrmion is attached to a core B =4 Skyrmion. We quantize this system, allowing the B =1 to freely orbit the core. The configuration space is 11 dimensional but simplifies significantly after factoring out the overall spin and isospin degrees of freedom. We exactly solve the free quantum problem and then include an interaction potential between the Skyrmions numerically. The resulting energy spectrum is compared to the corresponding nuclei—the helium-5/lithium-5 isodoublet. We find approximate parity doubling not seen in the experimental data. In addition, we fail to obtain the correct ground-state spin. The framework laid out for this two-cluster system can readily be modified for other clusters and in particular for other B =4 n +1 nuclei, of which B =5 is the simplest example.

Differential Splicing of Oncogenes and Tumor Suppressor Genes in African- and Caucasian-American Populations: Contributing Factor in Prostate Cancer Disparities

DTIC Science & Technology

2015-10-01

Populations: Contributing Factor in Prostate Cancer Disparities? PRINCIPAL INVESTIGATOR: Norman H Lee, Ph.D. CONTRACTING ORGANIZATION: George Washington...Prostate Cancer Disparities? 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Norman H Lee, PhD; Bi-Dar Wang, PhD; Jacqueline Olender (PhD graduate...suppressor genes in prostate cancer disparities between African American (AA) and Caucasian American (CA) prostate cancer (PCa). In year 1 of this award

5 CFR 1620.42 - Processing TSP contribution elections.

Code of Federal Regulations, 2010 CFR

2010-01-01

... she must make a new contribution election to begin current contributions. (b) Makeup contribution... within 60 days of the participant's reemployment or return to pay status. (c) Makeup contributions. Makeup contributions will be processed as follows: (1) If the employee had a valid contribution election...

Granulocyte and monocyte CD11b expression during plasma separation is dependent on complement factor 5 (C5) - an ex vivo study with blood from a C5-deficient individual.

PubMed

Hardersen, Randolf; Enebakk, Terje; Christiansen, Dorte; Bergseth, Grethe; Brekke, Ole-Lars; Mollnes, Tom Eirik; Lappegård, Knut Tore; Hovland, Anders

2018-04-01

The aim of the study was to investigate the role of complement factor 5 (C5) in reactions elicited by plasma separation using blood from a C5-deficient (C5D) individual, comparing it to C5-deficient blood reconstituted with C5 (C5DR) and blood from healthy donors. Blood was circulated through an ex vivo plasma separation model. Leukocyte CD11b expression and leukocyte-platelet conjugates were measured by flow cytometry during a 30-min period. Other markers were assessed during a 240-min period. Granulocyte and monocyte CD11b expression did not increase in C5D blood during plasma separation. In C5DR samples granulocytes CD11b expression, measured by mean fluorescence intensity (MFI), increased from 10481 ± 6022 (SD) to 62703 ± 4936, and monocytes CD11b expression changed from 13837 ± 7047 to 40063 ± 713. Granulocyte-platelet conjugates showed a 2.5-fold increase in the C5DR sample compared to the C5D sample. Monocyte-platelet conjugates increased independently of C5. In the C5D samples, platelet count decreased from 210 × 10 9 /L (201-219) (median and range) to 51 × 10 9 /L (50-51), and C3bc increased from 14 CAU/mL (21-7) to 198 CAU/mL (127-269), whereas TCC formation was blocked during plasma separation. In conclusion, up-regulation of granulocyte and monocyte CD11b during plasma separation was C5-dependent. The results also indicate C5 dependency in granulocyte-platelet conjugates formation. © 2018 APMIS. Published by John Wiley & Sons Ltd.

The antimicrobial peptide derived from insulin-like growth factor-binding protein 5, AMP-IBP5, regulates keratinocyte functions through Mas-related gene X receptors.

PubMed

Chieosilapatham, Panjit; Niyonsaba, François; Kiatsurayanon, Chanisa; Okumura, Ko; Ikeda, Shigaku; Ogawa, Hideoki

2017-10-01

In addition to their microbicidal properties, host defense peptides (HDPs) display various immunomodulatory functions, including keratinocyte production of cytokines/chemokines, proliferation, migration and wound healing. Recently, a novel HDP named AMP-IBP5 (antimicrobial peptide derived from insulin-like growth factor-binding protein 5) was shown to exhibit antimicrobial activity against numerous pathogens, even at concentrations comparable to those of human β-defensins and LL-37. However, the immunomodulatory role of AMP-IBP5 in cutaneous tissue remains unknown. To investigate whether AMP-IBP5 triggers keratinocyte activation and to clarify its mechanism. Production of cytokines/chemokines and growth factors was determined by appropriate ELISA kits. Cell migration was assessed by in vitro wound closure assay, whereas cell proliferation was analyzed using BrdU incorporation assay complimented with XTT assay. MAPK and NF-κB activation was determined by Western blotting. Intracellular cAMP levels were assessed using cAMP enzyme immunoassay kit. Among various cytokines/chemokines and growth factors tested, AMP-IBP5 selectively increased the production of IL-8 and VEGF. Moreover, AMP-IBP5 markedly enhanced keratinocyte migration and proliferation. AMP-IBP5-induced keratinocyte activation was mediated by Mrg X1-X4 receptors with MAPK and NF-κB pathways working downstream, as evidenced by the inhibitory effects of MrgX1-X4 siRNAs and ERK-, JNK-, p38- and NF-κB-specific inhibitors. We confirmed that AMP-IBP5 indeed induced MAPK and NF-κB activation. Furthermore, AMP-IBP5-induced VEGF but not IL-8 production correlated with an increase in intracellular cAMP. Our findings suggest that in addition to its antimicrobial function, AMP-IBP5 might contribute to wound healing process through activation of keratinocytes. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

34 CFR 636.5 - What are the matching contribution and planning consortium requirements?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 3 2010-07-01 2010-07-01 false What are the matching contribution and planning... PROGRAM General § 636.5 What are the matching contribution and planning consortium requirements? (a) The... agreed to by the members of a planning consortium. (Authority: 20 U.S.C. 1136b, 1136e) ...

Draft Genome Sequence of Lactobacillus delbrueckii subsp. bulgaricus LBB.B5.

PubMed

Urshev, Zoltan; Hajo, Karima; Lenoci, Leonardo; Bron, Peter A; Dijkstra, Annereinou; Alkema, Wynand; Wels, Michiel; Siezen, Roland J; Minkova, Svetlana; van Hijum, Sacha A F T

2016-10-06

Lactobacillus delbrueckii subsp. bulgaricus LBB.B5 originates from homemade Bulgarian yogurt and was selected for its ability to form a strong association with Streptococcus thermophilus The genome sequence will facilitate elucidating the genetic background behind the contribution of LBB.B5 to the taste and aroma of yogurt and its exceptional protocooperation with S. thermophilus. Copyright © 2016 Urshev et al.

Serotonin Signaling Through the 5-HT1B Receptor and NADPH Oxidase 1 in Pulmonary Arterial Hypertension.

PubMed

Hood, Katie Y; Mair, Kirsty M; Harvey, Adam P; Montezano, Augusto C; Touyz, Rhian M; MacLean, Margaret R

2017-07-01

Serotonin can induce human pulmonary artery smooth muscle cell (hPASMC) proliferation through reactive oxygen species (ROS), influencing the development of pulmonary arterial hypertension (PAH). We hypothesize that in PASMCs, serotonin induces oxidative stress through NADPH-oxidase-derived ROS generation and reduced Nrf-2 (nuclear factor [erythroid-derived 2]-like 2) antioxidant systems, promoting vascular injury. HPASMCs from controls and PAH patients, and PASMCs from Nox1 -/- mice, were stimulated with serotonin in the absence/presence of inhibitors of Src kinase, the 5-HT 1B receptor, and NADPH oxidase 1 (Nox1). Markers of fibrosis were also determined. The pathophysiological significance of our findings was examined in vivo in serotonin transporter overexpressing female mice, a model of pulmonary hypertension. We confirmed thatserotonin increased superoxide and hydrogen peroxide production in these cells. For the first time, we show that serotonin increased oxidized protein tyrosine phosphatases and hyperoxidized peroxiredoxin and decreased Nrf-2 and catalase activity in hPASMCs. ROS generation was exaggerated and dependent on cellular Src-related kinase, 5-HT 1B receptor, and the serotonin transporter in human pulmonary artery smooth muscle cells from PAH subjects. Proliferation and extracellular matrix remodeling were exaggerated in human pulmonary artery smooth muscle cells from PAH subjects and dependent on 5-HT 1B receptor signaling and Nox1, confirmed in PASMCs from Nox1 -/- mice. In serotonin transporter overexpressing mice, SB216641, a 5-HT 1B receptor antagonist, prevented development of pulmonary hypertension in a ROS-dependent manner. Serotonin can induce cellular Src-related kinase-regulated Nox1-induced ROS and Nrf-2 dysregulation, contributing to increased post-translational oxidative modification of proteins and activation of redox-sensitive signaling pathways in hPASMCs, associated with mitogenic responses. 5-HT 1B receptors contribute to

Serotonin Signaling Through the 5-HT1B Receptor and NADPH Oxidase 1 in Pulmonary Arterial Hypertension

PubMed Central

Hood, Katie Y.; Mair, Kirsty M.; Harvey, Adam P.; Montezano, Augusto C.; Touyz, Rhian M.

2017-01-01

Objective— Serotonin can induce human pulmonary artery smooth muscle cell (hPASMC) proliferation through reactive oxygen species (ROS), influencing the development of pulmonary arterial hypertension (PAH). We hypothesize that in PASMCs, serotonin induces oxidative stress through NADPH-oxidase–derived ROS generation and reduced Nrf-2 (nuclear factor [erythroid-derived 2]-like 2) antioxidant systems, promoting vascular injury. Approach and Results— HPASMCs from controls and PAH patients, and PASMCs from Nox1−/− mice, were stimulated with serotonin in the absence/presence of inhibitors of Src kinase, the 5-HT1B receptor, and NADPH oxidase 1 (Nox1). Markers of fibrosis were also determined. The pathophysiological significance of our findings was examined in vivo in serotonin transporter overexpressing female mice, a model of pulmonary hypertension. We confirmed thatserotonin increased superoxide and hydrogen peroxide production in these cells. For the first time, we show that serotonin increased oxidized protein tyrosine phosphatases and hyperoxidized peroxiredoxin and decreased Nrf-2 and catalase activity in hPASMCs. ROS generation was exaggerated and dependent on cellular Src-related kinase, 5-HT1B receptor, and the serotonin transporter in human pulmonary artery smooth muscle cells from PAH subjects. Proliferation and extracellular matrix remodeling were exaggerated in human pulmonary artery smooth muscle cells from PAH subjects and dependent on 5-HT1B receptor signaling and Nox1, confirmed in PASMCs from Nox1−/− mice. In serotonin transporter overexpressing mice, SB216641, a 5-HT1B receptor antagonist, prevented development of pulmonary hypertension in a ROS-dependent manner. Conclusions— Serotonin can induce cellular Src-related kinase–regulated Nox1-induced ROS and Nrf-2 dysregulation, contributing to increased post-translational oxidative modification of proteins and activation of redox-sensitive signaling pathways in hPASMCs, associated with

Hepatitis B virus-triggered autophagy targets TNFRSF10B/death receptor 5 for degradation to limit TNFSF10/TRAIL response.

PubMed

Shin, Gu-Choul; Kang, Hong Seok; Lee, Ah Ram; Kim, Kyun-Hwan

2016-12-01

Death receptors of TNFSF10/TRAIL (tumor necrosis factor superfamily member 10) contribute to immune surveillance against virus-infected or transformed cells by promoting apoptosis. Many viruses evade antiviral immunity by modulating TNFSF10 receptor signaling, leading to persistent infection. Here, we report that hepatitis B virus (HBV) X protein (HBx) restricts TNFSF10 receptor signaling via macroautophagy/autophagy-mediated degradation of TNFRSF10B/DR5, a TNFSF10 death receptor, and thus permits survival of virus-infected cells. We demonstrate that the expression of the TNFRSF10B protein is dramatically reduced both in liver tissues of chronic hepatitis B patients and in cell lines transfected with HBV or HBx. HBx-mediated downregulation of TNFRSF10B is caused by the lysosomal, but not proteasomal, degradation pathway. Immunoblotting analysis of LC3B and SQSTM1, and microscopy analysis of tandem-fluorescence-tagged LC3B revealed that HBx promotes complete autophagy. Inhibition of autophagy with a pharmacological inhibitor and LC3B knockdown revealed that HBx-induced autophagy is crucial for TNFRSF10B degradation. Immunoprecipitation and GST affinity isolation assays showed that HBx directly interacts with TNFRSF10B and recruits it to phagophores, the precursors to autophagosomes. We confirmed that autophagy activation is related to the downregulation of the TNFRSF10B protein in liver tissues of chronic hepatitis B patients. Inhibition of autophagy enhanced the susceptibility of HBx-infected hepatocytes to TNFSF10. These results identify the dual function of HBx in TNFRSF10B degradation: HBx plays a role as an autophagy receptor-like molecule, which promotes the association of TNFRSF10B with LC3B; HBx is also an autophagy inducer. Our data suggest a molecular mechanism for HBV evasion from TNFSF10-mediated antiviral immunity, which may contribute to chronic HBV infection.

A descriptive study of noise in the neonatal intensive care unit: ambient levels and perceptions of contributing factors.

PubMed

Darcy, Ashley E; Hancock, Lauren E; Ware, Emily J

2008-10-01

To examine the baseline acoustic environment in several mid-Atlantic region neonatal intensive care units (NICUs) and investigate the perceived factors contributing to noise levels in these NICUs. Quantitative data were collected from 3 urban, mid-Atlantic level IIIB and level IIIC NICUs. Qualitative data were collected via interview from 2 RNs employed in each of the study NICUs. This was an exploratory descriptive study utilizing a mixed-methods approach. A quantitative method was used for sound-level data collection, and a qualitative method was utilized during interviews with nurses to examine perceptions of factors contributing to noise. Ambient sound levels, measured in decibels, were taken at 5-minute intervals over a 2-hour period during both day and night shifts in a central location at each NICU. In addition, nurses were interviewed using a standardized interview questionnaire, and these interviews were then reviewed to determine themes regarding perceived factors contributing to sound levels. Hourly mean sound levels in each NICU ranged from 53.9 dB to 60.6 dB, with no statistically significant difference between noise levels recorded on day shift versus night shift, and no statistically significant difference among sites. Qualitative data showed that nurses' believed day shift to be louder than night shift and many perceived their own NICU as "pretty quiet." Key contributing factors to increased sound levels were stated as monitors or alarms, performing invasive procedures, presence of family, nurses or doctors giving report or rounds, and ringing phones. Noise levels were found to be above the American Academy of Pediatrics-recommended 45-dB level and often louder than the 50-dB level, which should not be exceeded more than 10% of the time. The recommended impulse maximum of 65 dB was also exceeded. Environmental Protection Agency recommendations for hospitals include sound levels no louder than 35 dB on night shift; this standard was also violated

A descriptive study of noise in the neonatal intensive care unit. Ambient levels and perceptions of contributing factors.

PubMed

Darcy, Ashley E; Hancock, Lauren E; Ware, Emily J

2008-06-01

To examine the baseline acoustic environment in several mid-Atlantic region neonatal intensive care units (NICUs) and investigate the perceived factors contributing to noise levels in these NICUs. Quantitative data were collected from 3 urban, mid-Atlantic level IIIB and level IIIC NICUs. Qualitative data were collected via interview from 2 RNs employed in each of the study NICUs. This was an exploratory descriptive study utilizing a mixed-methods approach. A quantitative method was used for sound-level data collection, and a qualitative method was utilized during interviews with nurses to examine perceptions of factors contributing to noise. Ambient sound levels, measured in decibels, were taken at 5-minute intervals over a 2-hour period during both day and night shifts in a central location at each NICU. In addition, nurses were interviewed using a standardized interview questionnaire, and these interviews were then reviewed to determine themes regarding perceived factors contributing to sound levels. Hourly mean sound levels in each NICU ranged from 53.9 dB to 60.6 dB, with no statistically significant difference between noise levels recorded on day shift versus night shift, and no statistically significant difference among sites. Qualitative data showed that nurses' believed day shift to be louder than night shift and many perceived their own NICU as "pretty quiet." Key contributing factors to increased sound levels were stated as monitors or alarms, performing invasive procedures, presence of family, nurses or doctors giving report or rounds, and ringing phones. Noise levels were found to be above the American Academy of Pediatrics--recommended 45-dB level and often louder than the 50-dB level, which should not be exceeded more than 10% of the time. The recommended impulse maximum of 65 dB was also exceeded. Environmental Protection Agency recommendations for hospitals include sound levels no louder than 35 dB on night shift; this standard was also violated

26 CFR 1.403(b)-3 - Exclusion for contributions to purchase section 403(b) contracts.

Code of Federal Regulations, 2011 CFR

2011-04-01

... designated Roth contributions; see paragraph (c) of this section and § 1.403(b)-7(e) for special taxation... eligible employer other than a church, the contract is purchased under a plan that satisfies section 403(b... paragraph (b)(3) applies to contributions to an annuity contract by a church only if the annuity is part of...

26 CFR 1.403(b)-3 - Exclusion for contributions to purchase section 403(b) contracts.

Code of Federal Regulations, 2010 CFR

2010-04-01

... designated Roth contributions; see paragraph (c) of this section and § 1.403(b)-7(e) for special taxation... eligible employer other than a church, the contract is purchased under a plan that satisfies section 403(b... paragraph (b)(3) applies to contributions to an annuity contract by a church only if the annuity is part of...

26 CFR 1.403(b)-3 - Exclusion for contributions to purchase section 403(b) contracts.

Code of Federal Regulations, 2012 CFR

2012-04-01

... designated Roth contributions; see paragraph (c) of this section and § 1.403(b)-7(e) for special taxation... eligible employer other than a church, the contract is purchased under a plan that satisfies section 403(b... paragraph (b)(3) applies to contributions to an annuity contract by a church only if the annuity is part of...

26 CFR 1.403(b)-3 - Exclusion for contributions to purchase section 403(b) contracts.

Code of Federal Regulations, 2013 CFR

2013-04-01

... designated Roth contributions; see paragraph (c) of this section and § 1.403(b)-7(e) for special taxation... eligible employer other than a church, the contract is purchased under a plan that satisfies section 403(b... paragraph (b)(3) applies to contributions to an annuity contract by a church only if the annuity is part of...

26 CFR 1.403(b)-3 - Exclusion for contributions to purchase section 403(b) contracts.

Code of Federal Regulations, 2014 CFR

2014-04-01

... designated Roth contributions; see paragraph (c) of this section and § 1.403(b)-7(e) for special taxation... eligible employer other than a church, the contract is purchased under a plan that satisfies section 403(b... paragraph (b)(3) applies to contributions to an annuity contract by a church only if the annuity is part of...

Contributing factors to disease outbreaks associated with untreated groundwater.

PubMed

Wallender, Erika K; Ailes, Elizabeth C; Yoder, Jonathan S; Roberts, Virginia A; Brunkard, Joan M

2014-01-01

Disease outbreaks associated with drinking water drawn from untreated groundwater sources represent a substantial proportion (30.3%) of the 818 drinking water outbreaks reported to CDC's Waterborne Disease and Outbreak Surveillance System (WBDOSS) during 1971 to 2008. The objectives of this study were to identify underlying contributing factors, suggest improvements for data collection during outbreaks, and inform outbreak prevention efforts. Two researchers independently reviewed all qualifying outbreak reports (1971 to 2008), assigned contributing factors and abstracted additional information (e.g., cases, etiology, and water system attributes). The 248 outbreaks resulted in at least 23,478 cases of illness, 390 hospitalizations, and 13 deaths. The majority of outbreaks had an unidentified etiology (n = 135, 54.4%). When identified, the primary etiologies were hepatitis A virus (n = 21, 8.5%), Shigella spp. (n = 20, 8.1%), and Giardia intestinalis (n = 14, 5.7%). Among the 172 (69.4%) outbreaks with contributing factor data available, the leading contamination sources included human sewage (n = 57, 33.1%), animal contamination (n = 16, 9.3%), and contamination entering via the distribution system (n = 12, 7.0%). Groundwater contamination was most often facilitated by improper design, maintenance or location of the water source or nearby waste water disposal system (i.e., septic tank; n = 116, 67.4%). Other contributing factors included rapid pathogen transport through hydrogeologic formations (e.g., karst limestone; n = 45, 26.2%) and preceding heavy rainfall or flooding (n = 36, 20.9%). This analysis underscores the importance of identifying untreated groundwater system vulnerabilities through frequent inspection and routine maintenance, as recommended by protective regulations such as Environmental Protection Agency's (EPA's) Groundwater Rule, and the need for special consideration of the local hydrogeology. Published

25 CFR Appendix B to Subpart C - Population Adjustment Factor

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Population Adjustment Factor B Appendix B to Subpart C...—Population Adjustment Factor 1. The Population Adjustment Factor allows for participation in the IRR Program... Distribution factor* Number of tribes** Funding amount per tribe Less than 25 1 N1 MBA*** × 1 25-100 3.5 N2 MBA...

5 CFR 1600.22 - Maximum contributions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Maximum contributions. 1600.22 Section... ELECTIONS AND CONTRIBUTION ALLOCATIONS Program of Contributions § 1600.22 Maximum contributions. (a) Regular...) FERS percentage limit. The maximum employee contribution from basic pay for a FERS participant for 2005...

14 CFR Appendix B to Part 1215 - Factors Affecting Standard Charges

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Factors Affecting Standard Charges B Appendix B to Part 1215 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION TRACKING AND DATA RELAY SATELLITE SYSTEM (TDRSS) Pt. 1215, App. B Appendix B to Part 1215—Factors Affecting Standard...

Role of nuclear factor-kappa B activation in the adverse effects induced by air pollution particulate matter (PM2.5) in human epithelial lung cells (L132) in culture.

PubMed

Dagher, Zeina; Garçon, Guillaume; Billet, Sylvain; Verdin, Anthony; Ledoux, Frédéric; Courcot, Dominique; Aboukais, Antoine; Shirali, Pirouz

2007-01-01

To contribute to improving knowledge on the adverse health effects induced by particulate matter (PM) air pollution, an extensive investigation was undertaken of the underlying mechanisms of action activated by PM(2.5) air pollution collected in Dunkerque, a strongly industrialized French seaside city. Their chemical and physical characteristics have been previously determined, and earlier in vitro short-term studies have shown them to cause dose-dependent and time-dependent oxidative damage, gene expression and protein secretion of inflammatory mediators, and apoptotic events in human lung epithelial cells (L132) in culture. Hence, this work studied the activation of nuclear factor-kappa B (NF-kappaB)/inhibitory kappa B (IkappaB) by Dunkerque city PM(2.5) in these target cells, by determination of phosphorylated p65 and phosphorylated IkappaBalpha protein levels in cytoplasmic extracts, and p65 and p50 DNA binding in nuclear extracts. In PM-exposed L132 cells, there were concentration- and/or time-dependent increases in nuclear p65 and cytoplasmic IkB-alpha phosphorylation, and nuclear p65 and p50 DNA binding. Taken together, these results showed that Dunkerque city PM(2.5) were involved in the activation of the NF-kappaB/IkappaB complex, notably through the occurrence of oxidative stress conditions, and, therefore, in the gene expression and protein secretion of inflammatory mediators in target L132 cells. Hence, these findings suggested that the activation of the NF-kappaB/IkappaB complex preceded cytotoxicity in Dunkerque city PM-exposed L132 cells. (c) 2007 John Wiley & Sons, Ltd.

Fabrication of an Fe80.5Si7.5B6Nb5Cu Amorphous-Nanocrystalline Powder Core with Outstanding Soft Magnetic Properties

NASA Astrophysics Data System (ADS)

Zhang, Zongyang; Liu, Xiansong; Feng, Shuangjiu; Rehman, Khalid Mehmood Ur

2018-03-01

In this study, the melt spinning method was used to develop Fe80.5Si7.5B6Nb5Cu amorphous ribbons in the first step. Then, the Fe80.5Si7.5B6Nb5Cu amorphous-nanocrystalline core with a compact microstructure was obtained by multiple processes. The main properties of the magnetic powder core, such as micromorphology, thermal behavior, permeability, power loss and quality factor, have been analyzed. The obtained results show that an Fe80.5Si7.5B6Nb5Cu amorphous-nanocrystalline duplex core has high permeability (54.8-57), is relatively stable at different frequencies and magnetic fields, and the maximum power loss is only 313 W/kg; furthermore, it has a good quality factor.

Disconnected-Sea Quarks Contribution to Nucleon Electromagnetic Form Factors

NASA Astrophysics Data System (ADS)

Sufian, Raza Sabbir

We present comprehensive analysis of the light and strange disconnected-sea quarks contribution to the nucleon electric and magnetic form factors. The lattice QCD estimates of strange quark magnetic moment GsM (0) = -0.064(14)(09) microN and the mean squared charge radius E = -0.0043(16)(14) fm2 are more precise than any existing experimental measurements and other lattice calculations. The lattice QCD calculation includes ensembles across several lattice volumes and lattice spacings with one of the ensembles at the physical pion mass. We have performed a simultaneous chiral, infinite volume, and continuum extrapolation in a global fit to calculate results in the continuum limit. We find that the combined light-sea and strange quarks contribution to the nucleon magnetic moment is -0.022(11)(09) microN and to the nucleon mean square charge radius is -0.019(05)(05) fm 2. The most important outcome of this lattice QCD calculation is that while the combined light-sea and strange quarks contribution to the nucleon magnetic moment is small at about 1%, a negative 2.5(9)% contribution to the proton charge radius and a relatively larger positive 16.3(6.1)% contribution to the neutron charge radius come from the sea quarks in the nucleon. For the first time, by performing global fits, we also give predictions of the light-sea and strange quarks contributions to the nucleon electric and magnetic form factors at the physical point and in the continuum and infinite volume limits in the momentum transfer range of 0 ≤ Q2 ≤ 0.5 GeV2.

5 CFR 890.501 - Government contributions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Government contributions. 890.501 Section... (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Contributions and Withholdings § 890.501 Government contributions. (a) The Government contribution toward subscription charges under all health benefits plans, for...

5 CFR 890.501 - Government contributions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Government contributions. 890.501 Section... (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Contributions and Withholdings § 890.501 Government contributions. (a) The Government contribution toward subscription charges under all health benefits plans, for...

5 CFR 890.501 - Government contributions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false Government contributions. 890.501 Section... (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Contributions and Withholdings § 890.501 Government contributions. (a) The Government contribution toward subscription charges under all health benefits plans, for...

5 CFR 890.501 - Government contributions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Government contributions. 890.501 Section... (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Contributions and Withholdings § 890.501 Government contributions. (a) The Government contribution toward subscription charges under all health benefits plans, for...

5 CFR 890.501 - Government contributions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Government contributions. 890.501 Section... (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Contributions and Withholdings § 890.501 Government contributions. (a) The Government contribution toward subscription charges under all health benefits plans, for...

TH-CD-BRA-05: First Water Calorimetric Dw Measurement and Direct Measurement of Magnetic Field Correction Factors, KQ,B, in a 1.5 T B-Field of An MRI Linac

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prez, L de; Pooter, J de; Jansen, B

2016-06-15

Purpose: Reference dosimetry in MR-guided radiotherapy is performed in the presence of a B-field. As a consequence the response of ionization chambers changes considerably and depends on parameters not considered in traditional reference dosimetry. Therefore future Codes of Practices need ionization chamber correction factors to correct for both the change in beam quality and the presence of a B-field. The objective was to study the feasibility of water calorimetric absorbed-dose measurements in a 1.5 T B-field of an MRLinac and the direct measurement of kQ,B calibration of ionization chambers. Methods: Calorimetric absorbed dose to water Dw was measured with amore » new water calorimeter in the bore of an MRLinac (TPR20,10 of 0.702). Two waterproof ionization chambers (PTW 30013, IBA FC-65G) were calibrated inside the calorimeter phantom (ND,w,Q,B). Both measurements were normalized to a monitor ionization chamber. Ionization chamber measurements were corrected for conventional influence parameter. Based on the chambers’ Co-60 calibrations (ND,w,Q0), measured directly against the calorimeter. In this study the correction factors kQ,B was determined as the ratio of the calibration coefficients in the MRLinac and in Co-60. Additionally, kB was determined based on kQ values obtained with the IAEA TRS-398 Code of Practice. Results: The kQ,B factors of the ionization chambers mentioned above were respectively 0.9488(8) and 0.9445(8) with resulting kB factors of 0.961(13) and 0.952(13) with standard uncertainties on the least significant digit(s) between brackets. Conclusion: Calorimetric Dw measurements and calibration of waterproof ionization chambers were successfully carried out in the 1.5 T B-field of an MRLinac with a standard uncertainty of 0.7%. Preliminary kQ,B and kB factors were determined with standard uncertainties of respectively 0.8% and 1.3%. The kQ,B agrees with an alternative method within 0.4%. The feasibility of water calorimetry in the presence

Activation of the UNC5B receptor by Netrin-1 inhibits sprouting angiogenesis.

PubMed

Larrivée, Bruno; Freitas, Catarina; Trombe, Marc; Lv, Xiang; Delafarge, Benjamin; Yuan, Li; Bouvrée, Karine; Bréant, Christiane; Del Toro, Raquel; Bréchot, Nicolas; Germain, Stéphane; Bono, Françoise; Dol, Frédérique; Claes, Filip; Fischer, Christian; Autiero, Monica; Thomas, Jean-Léon; Carmeliet, Peter; Tessier-Lavigne, Marc; Eichmann, Anne

2007-10-01

Netrins are secreted molecules with roles in axonal growth and angiogenesis. The Netrin receptor UNC5B is required during embryonic development for vascular patterning, suggesting that it may also contribute to postnatal and pathological angiogenesis. Here we show that unc5b is down-regulated in quiescent adult vasculature, but re-expressed during sprouting angiogenesis in matrigel and tumor implants. Stimulation of UNC5B-expressing neovessels with an agonist (Netrin-1) inhibits sprouting angiogenesis. Genetic loss of function of unc5b reduces Netrin-1-mediated angiogenesis inhibition. Expression of UNC5B full-length receptor also triggers endothelial cell repulsion in response to Netrin-1 in vitro, whereas a truncated UNC5B lacking the intracellular signaling domain fails to induce repulsion. These data show that UNC5B activation inhibits sprouting angiogenesis, thus identifying UNC5B as a potential anti-angiogenic target.

Activation of the UNC5B receptor by Netrin-1 inhibits sprouting angiogenesis

PubMed Central

Larrivée, Bruno; Freitas, Catarina; Trombe, Marc; Lv, Xiang; DeLafarge, Benjamin; Yuan, Li; Bouvrée, Karine; Bréant, Christiane; Del Toro, Raquel; Bréchot, Nicolas; Germain, Stéphane; Bono, Françoise; Dol, Frédérique; Claes, Filip; Fischer, Christian; Autiero, Monica; Thomas, Jean-Léon; Carmeliet, Peter; Tessier-Lavigne, Marc; Eichmann, Anne

2007-01-01

Netrins are secreted molecules with roles in axonal growth and angiogenesis. The Netrin receptor UNC5B is required during embryonic development for vascular patterning, suggesting that it may also contribute to postnatal and pathological angiogenesis. Here we show that unc5b is down-regulated in quiescent adult vasculature, but re-expressed during sprouting angiogenesis in matrigel and tumor implants. Stimulation of UNC5B-expressing neovessels with an agonist (Netrin-1) inhibits sprouting angiogenesis. Genetic loss of function of unc5b reduces Netrin-1-mediated angiogenesis inhibition. Expression of UNC5B full-length receptor also triggers endothelial cell repulsion in response to Netrin-1 in vitro, whereas a truncated UNC5B lacking the intracellular signaling domain fails to induce repulsion. These data show that UNC5B activation inhibits sprouting angiogenesis, thus identifying UNC5B as a potential anti-angiogenic target. PMID:17908930

Activation of complement factor B contributes to murine and human myocardial ischemia/reperfusion injury

PubMed Central

Hou, Yunfang; Wong, Karen A.; Lee, Daniel; Rushbrook, Julie I.; Gulaya, Karan; Hines, Roberta; Hollis, Tamika; Nistal Nuno, Beatriz; Mangi, Abeel A.; Hashim, Sabet; Pekna, Marcela; Catalfamo, Amy; Chin, Hsiao-ying; Patel, Foramben; Rayala, Sravani; Shevde, Ketan; Heeger, Peter S.

2017-01-01

The pathophysiology of myocardial injury that results from cardiac ischemia and reperfusion (I/R) is incompletely understood. Experimental evidence from murine models indicates that innate immune mechanisms including complement activation via the classical and lectin pathways are crucial. Whether factor B (fB), a component of the alternative complement pathway required for amplification of complement cascade activation, participates in the pathophysiology of myocardial I/R injury has not been addressed. We induced regional myocardial I/R injury by transient coronary ligation in WT C57BL/6 mice, a manipulation that resulted in marked myocardial necrosis associated with activation of fB protein and myocardial deposition of C3 activation products. In contrast, in fB-/- mice, the same procedure resulted in significantly reduced myocardial necrosis (% ventricular tissue necrotic; fB-/- mice, 20 ± 4%; WT mice, 45 ± 3%; P < 0.05) and diminished deposition of C3 activation products in the myocardial tissue (fB-/- mice, 0 ± 0%; WT mice, 31 ± 6%; P<0.05). Reconstitution of fB-/- mice with WT serum followed by cardiac I/R restored the myocardial necrosis and activated C3 deposition in the myocardium. In translational human studies we measured levels of activated fB (Bb) in intracoronary blood samples obtained during cardio-pulmonary bypass surgery before and after aortic cross clamping (AXCL), during which global heart ischemia was induced. Intracoronary Bb increased immediately after AXCL, and the levels were directly correlated with peripheral blood levels of cardiac troponin I, an established biomarker of myocardial necrosis (Spearman coefficient = 0.465, P < 0.01). Taken together, our results support the conclusion that circulating fB is a crucial pathophysiological amplifier of I/R-induced, complement-dependent myocardial necrosis and identify fB as a potential therapeutic target for prevention of human myocardial I/R injury. PMID:28662037

Activation of complement factor B contributes to murine and human myocardial ischemia/reperfusion injury.

PubMed

Chun, Nicholas; Haddadin, Ala S; Liu, Junying; Hou, Yunfang; Wong, Karen A; Lee, Daniel; Rushbrook, Julie I; Gulaya, Karan; Hines, Roberta; Hollis, Tamika; Nistal Nuno, Beatriz; Mangi, Abeel A; Hashim, Sabet; Pekna, Marcela; Catalfamo, Amy; Chin, Hsiao-Ying; Patel, Foramben; Rayala, Sravani; Shevde, Ketan; Heeger, Peter S; Zhang, Ming

2017-01-01

The pathophysiology of myocardial injury that results from cardiac ischemia and reperfusion (I/R) is incompletely understood. Experimental evidence from murine models indicates that innate immune mechanisms including complement activation via the classical and lectin pathways are crucial. Whether factor B (fB), a component of the alternative complement pathway required for amplification of complement cascade activation, participates in the pathophysiology of myocardial I/R injury has not been addressed. We induced regional myocardial I/R injury by transient coronary ligation in WT C57BL/6 mice, a manipulation that resulted in marked myocardial necrosis associated with activation of fB protein and myocardial deposition of C3 activation products. In contrast, in fB-/- mice, the same procedure resulted in significantly reduced myocardial necrosis (% ventricular tissue necrotic; fB-/- mice, 20 ± 4%; WT mice, 45 ± 3%; P < 0.05) and diminished deposition of C3 activation products in the myocardial tissue (fB-/- mice, 0 ± 0%; WT mice, 31 ± 6%; P<0.05). Reconstitution of fB-/- mice with WT serum followed by cardiac I/R restored the myocardial necrosis and activated C3 deposition in the myocardium. In translational human studies we measured levels of activated fB (Bb) in intracoronary blood samples obtained during cardio-pulmonary bypass surgery before and after aortic cross clamping (AXCL), during which global heart ischemia was induced. Intracoronary Bb increased immediately after AXCL, and the levels were directly correlated with peripheral blood levels of cardiac troponin I, an established biomarker of myocardial necrosis (Spearman coefficient = 0.465, P < 0.01). Taken together, our results support the conclusion that circulating fB is a crucial pathophysiological amplifier of I/R-induced, complement-dependent myocardial necrosis and identify fB as a potential therapeutic target for prevention of human myocardial I/R injury.

Neurotensin stimulates mitogenesis of prostate cancer cells through a novel c-Src/Stat5b pathway.

PubMed

Amorino, G P; Deeble, P D; Parsons, S J

2007-02-01

Neuroendocrine (NE)-like cells are hypothesized to contribute to the progression of prostate cancer by producing factors that enhance the growth, survival or metastatic capabilities of surrounding tumor cells. Many of the factors known to be secreted by NE-like cells, such as neurotensin (NT), parathyroid hormone-related peptide, serotonin, bombesin, etc., are agonists for G-protein-coupled receptors, but the signaling pathways activated by these agonists in prostate tumor cells are not fully defined. Identification of such pathways could provide insights into novel methods of treating late-stage disease. Using conditioned culture medium (CM) from LNCaP-derived NE-like cells (as a source of these agonists) or NT (a prototypical component of CM) to treat PC3 cells, we found that the epidermal growth factor (EGF) receptor (EGFR) was transactivated and that such activation was required for maximal PC3 cell mitogenesis, as measured by 5-bromo-2'-deoxy-uridine incorporation or cell number. NT also induced a time-dependent increase in EGFR Tyr(845) phosphorylation and phosphorylation of c-Src and signal transducer and activator of transcription 5b (Stat5b) (a downstream effector of Tyr(845)), events that were blocked by specific inhibition of c-Src (which mediates Tyr(845) phosphorylation of EGFR) or of EGFR. Introduction of mutant forms of EGFR (Tyr(845)) or Stat5b in PC3 cells, or treatment with selective, catalytic inhibitors of EGFR, c-Src and matrix metalloproteinases (MMPs) resulted in the loss of NT-induced stimulation of DNA synthesis, relative to wild-type controls. These data indicate that the mitogenic effect of NT on prostate cancer cells requires transactivation of the EGFR by MMPs and a novel downstream pathway involving c-Src, phosphorylation of EGFR Tyr(845) and activation of Stat5b.

Factors Contributing to Institutions Achieving Environmental Sustainability

ERIC Educational Resources Information Center

James, Matthew; Card, Karen

2012-01-01

Purpose: The purpose of this paper is to determine what factors contributed to three universities achieving environmental sustainability. Design/methodology/approach: A case study methodology was used to determine how each factor contributed to the institutions' sustainability. Site visits, fieldwork, document reviews, and interviews with…

Cytochrome P450 1B1 contributes to angiotensin II-induced hypertension and associated pathophysiology.

PubMed

Jennings, Brett L; Sahan-Firat, Seyhan; Estes, Anne M; Das, Kanak; Farjana, Nasreen; Fang, Xiao R; Gonzalez, Frank J; Malik, Kafait U

2010-10-01

Hypertension is the leading cause of cardiovascular diseases, and angiotensin II is one of the major components of the mechanisms that contribute to the development of hypertension. However, the precise mechanisms for the development of hypertension are unknown. Our recent study showing that angiotensin II-induced vascular smooth muscle cell growth depends on cytochrome P450 1B1 led us to investigate its contribution to hypertension caused by this peptide. Angiotensin II was infused via miniosmotic pump into rats (150 ng/kg per minute) or mice (1000 μg/kg per day) for 13 days resulting in increased blood pressure, increased cardiac and vascular hypertrophy, increased vascular reactivity to vasoconstrictor agents, increased vascular reactive oxygen species production, and endothelial dysfunction in both species. The increase in blood pressure and associated pathophysiological changes were minimized by the cytochrome P450 1B1 inhibitor 2,3',4,5'-tetramethoxystilbene in both species and was markedly reduced in Cyp1b1(-/-) mice. These data suggest that cytochrome P450 1B1 contributes to angiotensin II-induced hypertension and associated pathophysiological changes. Moreover, 2,3',4,5'-tetramethoxystilbene, which prevents both cytochrome P450 1B1-dependent and -independent components of angiotensin II-induced hypertension and inhibits associated pathophysiological changes could be clinically useful in the treatment of hypertension and associated cardiovascular and inflammatory diseases.

CYTOCHROME P450 1B1 CONTRIBUTES TO ANGIOTENSIN II-INDUCED HYPERTENSION AND ASSOCIATED PATHOPHYSIOLOGY

PubMed Central

Jennings, Brett L.; Sahan-Firat, Seyhan; Estes, Anne M.; Das, Kanak; Farjana, Nasreen; Fang, Xiao R.; Gonzalez, Frank J.; Malik, Kafait U.

2010-01-01

Hypertension is the leading cause of cardiovascular diseases, and angiotensin II is one of the major components of the mechanisms that contribute to the development of hypertension. However, the precise mechanisms for the development of hypertension are unknown. Our recent study that angiotensin II-induced vascular smooth muscle cell growth is dependent on cytochrome P450 1B1 led us to investigate its contribution to hypertension caused by this peptide. Angiotensin II was infused via miniosmotic pump into rats (150 ng/kg/min) or mice (1000 μg/kg/day) for 13 days resulting in increased blood pressure, increased cardiac and vascular hypertrophy, increased vascular reactivity to vasoconstrictor agents, increased reactive oxygen species production, and endothelial dysfunction in both species. The increase in blood pressure and associated pathophysiological changes were minimized by the cytochrome P450 1B1 inhibitor, 2,3′,4,5′-tetramethoxystilbene in both species and was markedly reduced in Cyp1b1-/- mice. These data suggest that cytochrome P450 1B1 contributes to angiotensin II-induced hypertension and associated pathophysiological changes. Moreover, 2,3′,4,5′-tetramethoxystilbene which prevents both cytochrome P450 1B1-dependent and independent components of angiotensin II-induced hypertension and inhibits associated pathophysiological changes could be clinically useful in the treatment of hypertension and associated cardiovascular and inflammatory diseases. PMID:20805442

Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies

PubMed Central

Gambhir, Sahil; Vyas, Dinesh; Hollis, Michael; Aekka, Apporva; Vyas, Arpita

2015-01-01

Nuclear factor kappa B (NF-κB) has an established role in the regulation of innate immunity and inflammation. NF-κB is also involved in critical mechanisms connecting inflammation and cancer development. Recent investigations suggest that the NF-κB signaling cascade may be the central mediator of gastrointestinal malignancies including esophageal, gastric and colorectal cancers. This review will explore NF-κB’s function in inflammation-associated gastrointestinal malignancies, highlighting its oncogenic contribution to each step of carcinogenesis. NF-κB’s role in the inflammation-to-carcinoma sequence in gastrointestinal malignancies warrants stronger emphasis upon targeting this pathway in achieving greater therapeutic efficacy. PMID:25805923

Social isolation stress induces ATF-7 phosphorylation and impairs silencing of the 5-HT 5B receptor gene

PubMed Central

Maekawa, Toshio; Kim, Seungjoon; Nakai, Daisuke; Makino, Chieko; Takagi, Tsuyoshi; Ogura, Hiroo; Yamada, Kazuyuki; Chatton, Bruno; Ishii, Shunsuke

2010-01-01

Many symptoms induced by isolation rearing of rodents may be relevant to neuropsychiatric disorders, including depression. However, identities of transcription factors that regulate gene expression in response to chronic social isolation stress remain elusive. The transcription factor ATF-7 is structurally related to ATF-2, which is activated by various stresses, including inflammatory cytokines. Here, we report that Atf-7-deficient mice exhibit abnormal behaviours and increased 5-HT receptor 5B (Htr5b) mRNA levels in the dorsal raphe nuclei. ATF-7 silences the transcription of Htr5B by directly binding to its 5′-regulatory region, and mediates histone H3-K9 trimethylation via interaction with the ESET histone methyltransferase. Isolation-reared wild-type (WT) mice exhibit abnormal behaviours that resemble those of Atf-7-deficient mice. Upon social isolation stress, ATF-7 in the dorsal raphe nucleus is phosphorylated via p38 and is released from the Htr5b promoter, leading to the upregulation of Htr5b. Thus, ATF-7 may have a critical role in gene expression induced by social isolation stress. PMID:19893493

Evidence for activation of nuclear factor kappaB in obstructive sleep apnea.

PubMed

Yamauchi, Motoo; Tamaki, Shinji; Tomoda, Koichi; Yoshikawa, Masanori; Fukuoka, Atsuhiko; Makinodan, Kiyoshi; Koyama, Noriko; Suzuki, Takahiro; Kimura, Hiroshi

2006-12-01

Obstructive sleep apnea (OSA) is a risk factor for atherosclerosis, and atherosclerosis evolves from activation of the inflammatory cascade. We propose that activation of the nuclear factor kappaB (NF-kappaB), a key transcription factor in the inflammatory cascade, occurs in OSA. Nine age-matched, nonsmoking, and non-hypertensive men with OSA symptoms and seven similar healthy subjects were recruited for standard polysomnography followed by the collection of blood samples for monocyte nuclear p65 concentrations (OSA and healthy groups). In the OSA group, p65 and of monocyte production of tumor necrosis factor alpha (TNF-alpha) were measured at the same time and after the next night of continuous positive airway pressure (CPAP). p65 Concentrations in the OSA group were significantly higher than in the control group [median, 0.037 ng/microl (interquartile range, 0.034 to 0.051) vs 0.019 ng/microl (interquartile range, 0.013 to 0.032); p = 0.008], and in the OSA group were significantly correlated with apnea-hypopnea index and time spent below an oxygen saturation of 90% (r = 0.77 and 0.88, respectively) after adjustment for age and BMI. One night of CPAP resulted in a reduction in p65 [to 0.020 ng/mul (interquartile range, 0.010 to 0.036), p = 0.04] and levels of TNF-alpha production in cultured monocytes [16.26 (interquartile range, 7.75 to 24.85) to 7.59 ng/ml (interquartile range, 5.19 to 12.95), p = 0.01]. NF-kappaB activation occurs with sleep-disordered breathing. Such activation of NF-kappaB may contribute to the pathogenesis of atherosclerosis in OSA patients.

Decrement of miR-199a-5p contributes to the tumorigenesis of bladder urothelial carcinoma by regulating MLK3/NF-κB pathway

PubMed Central

Song, Tao; Zhang, Xu; Yang, Guoqiang; Song, Yong; Cai, Wei

2015-01-01

Aberrant miRNA expression is implicated in tumorigenesis. However, the role of miRNAs in bladder urothelial carcinoma still remains largely unknown. In this study, miR-199a-5p was validated to be significantly down-regulated in bladder urothelial carcinoma. In addition, restoring expression of miR-199a-5p inhibited the tumorigenesis of bladder urothelial carcinoma in vitro and in vivo by inducing the apoptosis and suppressing the proliferation of bladder cancerous cells. Further investigation reported that MLK3 was a direct target of miR-199a-5p. Moreover, the expression level of miR-199a-5p was conversely correlated with MLK3 in bladder cancerous cells. In addition, reintroduction of MLK3 was identified to promote the proliferation and inhibit the apoptotic rate of cells, which have been altered by miR-199a-5p through activating the NF-κB pathway. All together, decrement of miR-199a-5p contributes to the tumorigenesis of bladder cancer by directly regulating MLK3/NF-κB pathway and miR-199a-5p might be developed as a therapeutic target for treatment of the bladder urothelial carcinoma. PMID:26885275

5 CFR 891.401 - Government contributions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Government contributions. 891.401 Section... (CONTINUED) RETIRED FEDERAL EMPLOYEES HEALTH BENEFITS Contributions and Withholdings § 891.401 Government... receive a Government contribution toward his or her cost of coverage for: (A) A private health insurance...

5 CFR 891.401 - Government contributions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Government contributions. 891.401 Section... (CONTINUED) RETIRED FEDERAL EMPLOYEES HEALTH BENEFITS Contributions and Withholdings § 891.401 Government... receive a Government contribution toward his or her cost of coverage for: (A) A private health insurance...

5 CFR 891.401 - Government contributions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Government contributions. 891.401 Section... (CONTINUED) RETIRED FEDERAL EMPLOYEES HEALTH BENEFITS Contributions and Withholdings § 891.401 Government... receive a Government contribution toward his or her cost of coverage for: (A) A private health insurance...

5 CFR 891.401 - Government contributions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false Government contributions. 891.401 Section... (CONTINUED) RETIRED FEDERAL EMPLOYEES HEALTH BENEFITS Contributions and Withholdings § 891.401 Government... receive a Government contribution toward his or her cost of coverage for: (A) A private health insurance...

5 CFR 891.401 - Government contributions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Government contributions. 891.401 Section... (CONTINUED) RETIRED FEDERAL EMPLOYEES HEALTH BENEFITS Contributions and Withholdings § 891.401 Government... receive a Government contribution toward his or her cost of coverage for: (A) A private health insurance...

Observational Insights into N2O5 Heterogeneous Chemistry: Influencing Factors and Contribution to Wintertime Air Pollution

NASA Astrophysics Data System (ADS)

McDuffie, E. E.; Fibiger, D. L.; Womack, C.; Dube, W. P.; Lopez-Hilfiker, F.; Goldberger, L.; Thornton, J. A.; Shah, V.; Jaegle, L.; Guo, H.; Weber, R. J.; Schroder, J. C.; Campuzano Jost, P.; Jimenez, J. L.; Franchin, A.; Middlebrook, A. M.; Baasandorj, M.; Brown, S. S.

2017-12-01

Chemical mechanisms that underlie wintertime air pollution, including tropospheric ozone and aerosol nitrate, are poorly characterized. Due to colder temperatures and fewer hours of solar radiation, nocturnal heterogeneous uptake of N2O5 plays a relatively larger role during wintertime in controlling the oxidation of NOx (=NO+NO2) and its influence on ozone and soluble nitrate. After uptake to aerosol, N2O5 can act as both a nocturnal NOx reservoir and sink depending on the partitioning between its nitric acid and photo labile, ClNO2 reaction products. In addition, N2O5 itself can act as a NOx reservoir if the aerosol uptake coefficient is small. As a result, the nocturnal fate of N2O5 dictates the amount of NOx in an air parcel and the subsequent formation of aerosol nitrate and following-day ozone. Models of winter air pollution therefore require accurate parameterization of the N2O5 uptake coefficient, as well as factors that control its magnitude and N2O5 product partitioning. There are currently only a small number of ambient N2O5 and ClNO2 observations during the winter season concurrent with measurements of relevant variables such as aerosol size distributions and composition. The Wintertime INvestigation of Transport, Emissions, and Reactivity (WINTER) campaign conducted 10 nighttime research flights with the NCAR C-130 over the eastern U.S. during February and March, 2015. The more recent Utah Wintertime Fine Particulate Study (UWFPS) conducted over 20 research flights with the NOAA twin otter aircraft during January-February 2017 in three mountain basins near and including Salt Lake City, Utah. The two campaigns were similarly instrumented and have provided the first aircraft observations of N2O5, ClNO2, and aerosol composition in the wintertime boundary layer in these urban-influenced regions. Analysis of heterogeneous chemistry under a wide range of real environmental conditions provides insight into the factors controlling the N2O5 uptake coefficient

Study of B c  → J/ψV and {B}_{c}^{* } \\rightarrow {\\eta }_{c}V decays within the QCD factorization

NASA Astrophysics Data System (ADS)

Chang, Qin; Chen, Li-Li; Xu, Shuai

2018-07-01

In this paper, we study the non-leptonic B c → J/ψV and {B}c* \\to {η }cV (V=ρ ,{K}* ) weak decays in the framework of QCD factorization. In the evaluation, the form factors are calculated using the Bauer–Stech–Wirbel model and the light-front quark model, respectively. Besides the longitudinal amplitude, the power-suppressed transverse contributions are also evaluated at next-to-leading order. The predictions for the observables of B c → J/ψV and {B}c* \\to {η }cV decays are presented. We find that the NLO QCD contribution presents about 8% correction to the branching ratios, and the longitudinal polarization fractions of these decays are at the level of (80 ∼ 90)%. In addition, we suggest direct measurements on some useful ratios, {R}{K* /ρ }(λ =0) and {\\widetilde{R}}{K* /ρ }(λ =0), which are very suitable to test the consistence between theoretical prediction and data because their theoretical uncertainties can be well controlled.

TRIB3 mediates the expression of Wnt5a and activation of nuclear factor-κB in Porphyromonas endodontalis lipopolysaccharide-treated osteoblasts.

PubMed

Yu, Y; Qiu, L; Guo, J; Yang, D; Qu, L; Yu, J; Zhan, F; Xue, M; Zhong, M

2015-08-01

Porphyromonas endodontalis lipopolysaccharide (LPS) is considered to be correlated with the progression of bone resorption in periodontal and periapical diseases. Wnt5a has recently been implicated in inflammatory processes, but its role is unclear as a P. endodontalis LPS-induced mediator in osteoblasts. Tribbles homolog 3 (TRIB3) encodes a pseudokinase and has been linked to inflammation in certain situations. Here, we found that P. endodontalis LPS induced Wnt5a expression in a dose- and time-dependent manner and it also upregulated translocation, phosphorylation and transcriptional activity of nuclear factor-κB (NF-κB) in MC3T3-E1 cells. Bay 11-7082 blocked the translocation of NF-κB and Wnt5a expression induced by P. endodontalis LPS. Chromatin immunoprecipitation assay further established that induction of Wnt5a by P. endodontalis LPS was mediated through the NF-κB p65 subunit. Additionally, P. endodontalis LPS increased expression of TRIB3 in osteoblasts after 10 h simulated time. Overexpression of TRIB3 enhanced NF-κB phosphorylation and Wnt5a induction, whereas knockdown of TRIB3 inhibited NF-κB phosphorylation and Wnt5a expression in P. endodontalis LPS-stimulated osteoblasts. These results suggest that P. endodontalis LPS has the ability to promote the expression of Wnt5a in mouse osteoblasts, and this induction is mainly mediated by NF-κB pathway. TRIB3 seems to modulate the sustained expression of Wnt5a in osteoblasts stimulated by P. endodontalis LPS, as well as regulating NF-κB phosphorylation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The bZIP transcription factor MdHY5 regulates anthocyanin accumulation and nitrate assimilation in apple.

PubMed

An, Jian-Ping; Qu, Feng-Jia; Yao, Ji-Fang; Wang, Xiao-Na; You, Chun-Xiang; Wang, Xiao-Fei; Hao, Yu-Jin

2017-01-01

The basic leucine zipper (bZIP) transcription factor HY5 plays a multifaceted role in plant growth and development. Here the apple MdHY5 gene was cloned based on its homology with Arabidopsis HY5 . Expression analysis demonstrated that MdHY5 transcription was induced by light and abscisic acid treatments. Electrophoretic mobility shift assays and transient expression assays subsequently showed that MdHY5 positively regulated both its own transcription and that of MdMYB10 by binding to E-box and G-box motifs, respectively. Furthermore, we obtained transgenic apple calli that overexpressed the MdHY5 gene, and apple calli coloration assays showed that MdHY5 promoted anthocyanin accumulation by regulating expression of the MdMYB10 gene and downstream anthocyanin biosynthesis genes. In addition, the transcript levels of a series of nitrate reductase genes and nitrate uptake genes in both wild-type and transgenic apple calli were detected. In association with increased nitrate reductase activities and nitrate contents, the results indicated that MdHY5 might be an important regulator in nutrient assimilation. Taken together, these results indicate that MdHY5 plays a vital role in anthocyanin accumulation and nitrate assimilation in apple.

The identification of the heat-stable microsomal protein required for methoxyflurane metabolism as cytochrome b5.

PubMed

Canova-Davis, E; Waskell, L

1984-02-25

Methoxyflurane is an anesthetic whose metabolism by cytochrome P-450LM2 has been shown to be dependent upon a heat-stable microsomal protein (Canova-Davis, E., and Waskell, L. A. (1982) Biochem. Biophys. Res. Commun. 108, 1264-1270). Treatment of this protein with diethylpyrocarbonate, which modifies selected amino acids, caused a dose-dependent loss in its ability to effect the metabolism of methoxyflurane by purified cytochrome P-450LM2. This protein factor has been identified as cytochrome b5 by demonstrating that cytochrome b5 and the heat-stable factor coelute during cytochrome b5 purification. Neither ferriheme nor apocytochrome b5 was able to substitute for the activating factor, while cytochrome b5 reconstituted from apocytochrome b5 and heme exhibited an activity similar to that of native b5. Examination of the cytochrome b5 molecule by computer graphics suggested that diethylpyrocarbonate did not inactivate b5 by reacting with the anionic surface of the cytochrome b5 molecule. Maximal rates of methoxyflurane metabolism were obtained at a ratio of 1:1:1 of the three proteins, cytochrome P-450LM2:reductase:cytochrome b5. In summary, it has been demonstrated that the heat-stable protein, cytochrome b5, is obligatory for the metabolism of methoxyflurane by cytochrome P-450LM2. These data also suggest that cytochrome b5 may be acting as an electron donor to P-450LM2 in the O-demethylation of methoxyflurane.

Reductive Detoxication of Arylhydroxylamine Carcinogens by Human NADH Cytochrome b5 Reductase and Cytochrome b5

PubMed Central

Kurian, Joseph R.; Chin, Nathaniel A.; Longlais, Brett J.; Hayes, Kristie L.; Trepanier, Lauren A.

2008-01-01

Heterocyclic and aromatic amine carcinogens are thought to lead to tumor initiation via the formation of DNA adducts, and bioactivation to arylhydroxylamine metabolites is necessary for reactivity with DNA. Carcinogenic arylhydroxylamine metabolites are cleared by a microsomal, NADH-dependent, oxygen-insensitive reduction pathway in humans, which may be a source of inter-individual variability in response to aromatic amine carcinogens. The purpose of this study was to characterize the identity of this reduction pathway in human liver. Based on our findings with structurally similar arylhydroxylamine metabolites of therapeutic drugs, we hypothesized that the reductive detoxication of arylhydroxylamine carcinogens was catalyzed by NADH cytochrome b5 reductase (b5R) and cytochrome b5 (cyt b5). We found that reduction of the carcinogenic hydroxylamines of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette smoke) and the heterocyclic amine 2- amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system containing only human b5R and cyt b5. Specific activities were 56 to 346-fold higher in the purified system compared to human liver microsomes (HLM), with similar Michaelis-Menten constants (Km values) in both systems. The stoichiometry for b5R and cyt b5 that yielded the highest activity in the purified system was also similar to that found in native HLM (∼1:8 to 1:10). Polyclonal antisera to either b5R or cyt b5 significantly inhibited N-hydroxy-4-aminobiphenyl (NHOH-4-ABP) reduction by 95 and 89%, respectively, and immunoreactive cyt b5 protein content in individual HLM was significantly correlated with individual reduction of both NHOH-4-ABP and N-hydroxy-PhIP (NHOH-PhIP). Finally, titration of HLM into the purified b5R/cyt b5 system did not enhance the efficiency of reduction activity. We conclude that b5R and cyt b5 are together solely capable of the reduction of arylhydroxylamine carcinogens

LOXL4 Is Induced by Transforming Growth Factor β1 through Smad and JunB/Fra2 and Contributes to Vascular Matrix Remodeling

PubMed Central

Busnadiego, Oscar; González-Santamaría, José; Lagares, David; Guinea-Viniegra, Juan; Pichol-Thievend, Cathy; Muller, Laurent

2013-01-01

Transforming growth factor β1 (TGF-β1) is a pleiotropic factor involved in the regulation of extracellular matrix (ECM) synthesis and remodeling. In search for novel genes mediating the action of TGF-β1 on vascular ECM, we identified the member of the lysyl oxidase family of matrix-remodeling enzymes, lysyl oxidase-like 4 (LOXL4), as a direct target of TGF-β1 in aortic endothelial cells, and we dissected the molecular mechanism of its induction. Deletion mapping and mutagenesis analysis of the LOXL4 promoter demonstrated the absolute requirement of a distal enhancer containing an activator protein 1 (AP-1) site and a Smad binding element for TGF-β1 to induce LOXL4 expression. Functional cooperation between Smad proteins and the AP-1 complex composed of JunB/Fra2 accounted for the action of TGF-β1, which involved the extracellular signal-regulated kinase (ERK)-dependent phosphorylation of Fra2. We furthermore provide evidence that LOXL4 was extracellularly secreted and significantly contributed to ECM deposition and assembly. These results suggest that TGF-β1-dependent expression of LOXL4 plays a role in vascular ECM homeostasis, contributing to vascular processes associated with ECM remodeling and fibrosis. PMID:23572561

MicroRNA-29b-2-5p inhibits cell proliferation by directly targeting Cbl-b in pancreatic ductal adenocarcinoma.

PubMed

Li, Ce; Dong, Qian; Che, Xiaofang; Xu, Ling; Li, Zhi; Fan, Yibo; Hou, Kezuo; Wang, Shuo; Qu, Jinglei; Xu, Lu; Wen, Ti; Yang, Xianghong; Qu, Xiujuan; Liu, Yunpeng

2018-06-25

MicroRNAs can be used in the prognosis of malignancies; however, their regulatory mechanisms are unknown, especially in pancreatic ductal adenocarcinoma (PDAC). In 120 PDAC specimens, miRNA levels were assessed by quantitative real time polymerase chain reaction (qRT-PCR). Then, the role of miR-29b-2-5p in cell proliferation was evaluated both in vitro (Trypan blue staining and cell cycle analysis in the two PDAC cell lines SW1990 and Capan-2) and in vivo using a xenograft mouse model. Next, bioinformatics methods, a luciferase reporter assay, Western blot, and immunohistochemistry (IHC) were applied to assess the biological effects of Cbl-b inhibition by miR-29b-2-5p. Moreover, the relationship between Cbl-b and p53 was evaluated by immunoprecipitation (IP), Western blot, and immunofluorescence. From the 120 PDAC patients who underwent surgical resection, ten patients with longest survival and ten with shortest survival were selected. We found that high miR-29b-2-5p expression was associated with good prognosis (p = 0.02). The validation cohort confirmed miR-29b-2-5p as an independent prognostic factor in PDAC (n = 100, 95% CI = 0.305-0.756, p = 0.002). Furthermore, miR-29b-2-5p inhibited cell proliferation, induced cell cycle arrest, and promoted apoptosis both in vivo and in vitro. Interestingly, miR-29b-2-5p directly bound the Cbl-b gene, down-regulating its expression and reducing Cbl-b-mediated degradation of p53. Meanwhile, miR-29b-2-5p expression was negatively correlated with Cbl-b in PDAC tissues (r = - 0.33, p = 0.001). Taken together, these findings indicated that miR-29b-2-5p improves prognosis in PDAC by targeting Cbl-b to promote p53 expression, and would constitute an important prognostic factor in PDAC.

5 CFR 831.1004 - Agency contributions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Agency contributions. 831.1004 Section 831.1004 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT CSRS Offset § 831.1004 Agency contributions. The employing agency, the Secretary of...

5 CFR 831.1004 - Agency contributions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Agency contributions. 831.1004 Section 831.1004 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT CSRS Offset § 831.1004 Agency contributions. The employing agency, the Secretary of...

Increased levels of CCR7(lo)PD-1(hi) CXCR5+ CD4+ T cells, and associated factors Bcl-6, CXCR5, IL-21 and IL-6 contribute to repeated implantation failure.

PubMed

Gong, Qiaoqiao; Zhu, Yuejie; Pang, Nannan; Ai, Haiquan; Gong, Xiaoyun; La, Xiaolin; Ding, Jianbing

2017-12-01

In vitro fertilization-embryo transfer (IVF-ET) can be used by infertile couples to assist with reproduction; however, failure of the embryo to implant into the endometrial lining results in failure of the IVF treatment. The present study investigated the expression of chemokine receptor 7 (CCR7)(lo) programmed death-1(PD-1)(hi) chemokine receptor type 5 (CXCR5) + cluster of differentiation 4 (CD4) + T cells and associated factors in patients with repeated implantation failure (RIF). A total of 30 females with RIF and 30 healthy females were enrolled in the current study. Flow cytometry was used to detect the proportion of CCR7(lo)PD-1(hi) CXCR5 + CD4 + T cells in the peripheral blood. Cytokine bead arrays were performed to detect the levels of interleukin (IL)-6, -4 and -2 in the serum. ELISAs were used to detect the level of IL-21 in the serum. Quantitative real time polymerase chain reaction analysis and immunohistochemistry were used to investigate the expression of B-cell lymphoma 6 (Bcl-6), chemokine receptor type 5 (CXCR5) and IL-21 in the endometrium. The results revealed that the percentage of CCR7(lo)PD-1(hi) CXCR5 + CD4 + T cells was increased in the RIF group compared with the control group during the mid luteal phase. The mRNA and protein levels of Bcl-6, IL-21 and CXCR5 in the endometrium and the concentrations of IL-21 and IL-6 in the serum were significantly increased in the RIF group; however, no significant difference was observed between the two groups in regards to the expression of IL-4 and IL-2. Furthermore, a significant positive correlation was identified between the percentage of CCR7(lo)PD-1(hi) CXCR5 + CD4 + T cells and IL-21 and IL-6 levels. The expression of IL-21 also had a positive correlation with Bcl-6 and CXCR5 expression in the RIF group. These results suggest that increased levels of CCR7(lo)PD-1(hi) CXCR5 + CD4 + T cells and associated factors contribute to RIF and could therefore be a potential therapeutic target.

Circulating CD4+CXCR5+ T cells contribute to proinflammatory responses in multiple ways in coronary artery disease.

PubMed

Ding, Ru; Gao, Wenwu; He, Zhiqing; Wu, Feng; Chu, Yang; Wu, Jie; Ma, Lan; Liang, Chun

2017-11-01

Coronary artery disease (CAD) is a common subtype of cardiovascular disease. The major contributing event is atherosclerosis, which is a progressive inflammatory condition resulting in the thickening of the arterial wall and the formation of atheromatous plaques. Recent evidence suggests that circulating CD4 + CXCR5 + T cells can contribute to inflammatory reactions. In this study, the frequency, phenotype, and function of circulating CD4 + CXCR5 + T cells in CAD patients were examined. Data showed that circulating CD4 + CXCR5 + T cells in CAD patients were enriched with a PD-1 + CCR7 - subset, which was previously identified as the most potent in B cell help. The CD4 + CXCR5 + T cells in CAD patients also secreted significantly higher levels of IFN-γ, IL-17A, and IL-21 than those from healthy controls. Depleting the PD-1 + population significantly reduced the cytokine secretion. Interestingly, the CD4 + CXCR5 + PD-1 - T cells significantly upregulated PD-1 following anti-CD3/CD28 or SEB stimulation. CD4 + CXCR5 + T cells from CAD patients also demonstrated more potent capacity to stimulate B cell inflammation than those from healthy individuals. The phosphorylation of STAT1 and STAT3 were significantly higher in B cells incubated with CD4 + CXCR5 + T cells from CAD than controls. The IL-6 and IFN-γ expression were also significantly higher in B cells incubated with CD4 + CXCR5 + T cells from CAD. Together, this study demonstrated that CAD patients presented a highly activated CD4 + CXCR5 + T cell subset that could contribute to proinflammatory responses in multiple ways. The possibility of using CD4 + CXCR5 + T cells as a therapeutic target should therefore be examined in CAD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Experimental tests of factorization in charmless nonleptonic two-body B decays

NASA Astrophysics Data System (ADS)

Ali, A.; Kramer, G.; Lü, Cai-Dian

1998-11-01

Using a theoretical framework based on the next-to-leading-order QCD-improved effective Hamiltonian and a factorization ansatz for the hadronic matrix elements of the four-quark operators, we reassess branching fractions in two-body nonleptonic decays B-->PP,PV,VV, involving the lowest-lying light pseudoscalar (P) and vector (V) mesons in the standard model. We work out the parametric dependence of the decay rates, making use of the currently available information on the weak mixing matrix elements, form factors, decay constants, and quark masses. Using the sensitivity of the decay rates on the effective number of colors, Nc, as a criterion of theoretical predictivity, we classify all the current-current (tree) and penguin transitions in five different classes. The recently measured charmless two-body B-->PP decays (B+-->K+η', B0-->K0η', B0-->K+π-, B+-->π+K0, and charge conjugates) are dominated by the Nc-stable QCD penguin transitions (class-IV transitions) and their estimates are consistent with the data. The measured charmless B-->PV (B+-->ωK+, B+-->ωh+) and B-->VV transition (B-->φK*), on the other hand, belong to the penguin (class-V) and tree (class-III) transitions. The class-V penguin transitions are Nc sensitive and/or involve large cancellations among competing amplitudes, making their decay rates in general more difficult to predict. Some of these transitions may also receive significant contributions from annihilation and/or final state interactions. We propose a number of tests of the factorization framework in terms of the ratios of branching ratios for some selected B-->h1h2 decays involving light hadrons h1 and h2, which depend only moderately on the form factors. We also propose a set of measurements to determine the effective coefficients of the current-current and QCD penguin operators. The potential impact of B-->h1h2 decays on the CKM phenomenology is emphasized by analyzing a number of decay rates in the factorization framework.

Some NASA contributions to human factors engineering: A survey

NASA Technical Reports Server (NTRS)

Behan, R. A.; Wendhausen, H. W.

1973-01-01

This survey presents the NASA contributions to the state of the art of human factors engineering, and indicates that these contributions have a variety of applications to nonaerospace activities. Emphasis is placed on contributions relative to man's sensory, motor, decisionmaking, and cognitive behavior and on applications that advance human factors technology.

5 CFR 890.1306 - Government premium contributions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Government premium contributions. 890... Health Benefits Program Demonstration Project § 890.1306 Government premium contributions. The Secretary of Defense is responsible for the government contribution for enrolled eligible beneficiaries and...

5 CFR 890.1306 - Government premium contributions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Government premium contributions. 890... Health Benefits Program Demonstration Project § 890.1306 Government premium contributions. The Secretary of Defense is responsible for the government contribution for enrolled eligible beneficiaries and...

Homeobox a5 Promotes White Adipose Tissue Browning Through Inhibition of the Tenascin C/Toll-Like Receptor 4/Nuclear Factor Kappa B Inflammatory Signaling in Mice.

PubMed

Cao, Weina; Huang, Hongtao; Xia, Tianyu; Liu, Chenlong; Muhammad, Saeed; Sun, Chao

2018-01-01

Lipopolysaccharide (LPS) induces rapid increase in systemic inflammatory factors. As adipose tissue is a key contributor to the inflammatory response to numerous metabolic stimuli, it is important to understand the mechanism behind the LPS-induced inflammation in white adipose tissue (WAT). Homeobox a5 (Hoxa5) is an important transcription factor, which is highly expressed in adipose tissue, and its mRNA expression is increased at cold exposure in mice. So far, the function of Hoxa5 in adipose tissue browning has been poorly understood. So, the objective of this study was conducted to determine the role of Hoxa5 in adipose inflammatory response and white adipose browning in mice. LPS-induced inflammatory and cold-induced browning model were conducted. We compared the coordinated role of Hoxa5 in inflammation and thermogenesis of mice adipose. Transcriptional and methylation regulation was determined by luciferase assay, electrophoretic mobility shift assay, and bisulfite conversion experiment. Hoxa5 and tenascin C (TNC) were involved in WAT inflammation and browning in mice with LPS injection. Furthermore, Hoxa5 inhibited the TNC-involved activation of Toll-like receptor (TLR) 4/nuclear factor kappa B (NF-κB) signal pathway and promoted WAT browning. Moreover, we found that a BMP4/Smad1 signal, closely related to browning, was activated by Hoxa5. Hoxa5 relieved adipocyte inflammation by decreasing TNC-mediated TLR4 transducer and activator of the NF-κB pathway. Interestingly, descended methylation level increased Hoxa5 expression in cold exposure. Our findings demonstrated that Hoxa5 alleviated inflammation and enhanced browning of adipose tissue via negative control of TNC/TLR4/NF-κB inflammatory signaling and activating BMP4/Smad1 pathway. These findings indicated a novel potential means for the regulation of inflammation in adipocytes to prevent obesity and other inflammatory diseases.

Analysis of the strong coupling form factors of ΣbNB and ΣcND in QCD sum rules

NASA Astrophysics Data System (ADS)

Yu, Guo-Liang; Wang, Zhi-Gang; Li, Zhen-Yu

2017-08-01

In this article, we study the strong interaction of the vertices Σ b NB and Σ c ND using the three-point QCD sum rules under two different Dirac structures. Considering the contributions of the vacuum condensates up to dimension 5 in the operation product expansion, the form factors of these vertices are calculated. Then, we fit the form factors into analytical functions and extrapolate them into time-like regions, which gives the coupling constants. Our analysis indicates that the coupling constants for these two vertices are G ΣbNB = 0.43±0.01 GeV-1 and G ΣcND = 3.76±0.05 GeV-1. Supported by Fundamental Research Funds for the Central Universities (2016MS133)

Zinc-induced Self-association of Complement C3b and Factor H

PubMed Central

Nan, Ruodan; Tetchner, Stuart; Rodriguez, Elizabeth; Pao, Po-Jung; Gor, Jayesh; Lengyel, Imre; Perkins, Stephen J.

2013-01-01

The sub-retinal pigment epithelial deposits that are a hallmark of age-related macular degeneration contain both C3b and millimolar levels of zinc. C3 is the central protein of complement, whereas C3u is formed by the spontaneous hydrolysis of the thioester bridge in C3. During activation, C3 is cleaved to form active C3b, then C3b is inactivated by Factor I and Factor H to form the C3c and C3d fragments. The interaction of zinc with C3 was quantified using analytical ultracentrifugation and x-ray scattering. C3, C3u, and C3b associated strongly in >100 μm zinc, whereas C3c and C3d showed weak association. With zinc, C3 forms soluble oligomers, whereas C3u and C3b precipitate. We conclude that the C3, C3u, and C3b association with zinc depended on the relative positions of C3d and C3c in each protein. Computational predictions showed that putative weak zinc binding sites with different capacities exist in all five proteins, in agreement with experiments. Factor H forms large oligomers in >10 μm zinc. In contrast to C3b or Factor H alone, the solubility of the central C3b-Factor H complex was much reduced at 60 μm zinc and even more so at >100 μm zinc. The removal of the C3b-Factor H complex by zinc explains the reduced C3u/C3b inactivation rates by zinc. Zinc-induced precipitation may contribute to the initial development of sub-retinal pigment epithelial deposits in the retina as well as reducing the progression to advanced age-related macular degeneration in higher risk patients. PMID:23661701

26 CFR 1.403(b)-5 - Nondiscrimination rules.

Code of Federal Regulations, 2010 CFR

2010-04-01

...)(1) of this section, an employee is not treated as being permitted to have section 403(b) elective... under the contract with the largest limitation, and applies to part-time employees as well as full-time...) General rule. Under section 403(b)(12)(A)(i), employer contributions and after-tax employee contributions...

Contribution of B2 receptors for bradykinin in Arthus reaction-induced plasma extravasation in wild-type or B2 transgenic knockout mice

PubMed Central

Samadfam, R; Teixeira, C; Bkaily, G; Sirois, P; de Brum-Fernandes, A; D'Orleans-Juste, P

2000-01-01

The aim of the present study was to investigate the contribution of bradykinin (BK) B1 and B2 receptors in a model of type III hypersensitivity, the reverse passive Arthus reaction (RPA), in wild-type mice and transgenic B2 knockout littermates.BK (10 μg mouse−1) or bovine serum albumin (0.5 mg mouse−1) induced a sustained Evans blue extravasation for more than 80 min in naive or rabbit anti-bovine serum albumin-treated mice (RPA model), respectively. The response to the two stimuli was prevented by the B2 receptor antagonist, HOE-140, but not by [Leu8]desArg9-BK (B1 receptor antagonist).In contrast to the wild-type littermates, RPA and bradykinin were unable to trigger an increase in plasma extravasation in B2 knockout mice.Furthermore, endothelin-1 (5 μg mouse−1) and a selective NK-1 receptor agonist [Sar9,Met (O2)11]-SP (20 μg mouse−1), triggered a significant increase in peritoneal plasma extravasation in both wild-type and B2 knockout animals.A pretreatment with indomethacin (200 μg mouse−1) significantly reduced the RPA-induced but not the BK-induced increase in Evans blue extravasation. Furthermore, RPA, but not BK, triggered a significant indomethacin-sensitive increase in peritoneal prostaglandin E2 content.Our results suggest a pivotal role for B2 receptors in the mechanism of plasma extravasation which occurs during the reverse passive Arthus reaction in the mouse. Moreover, our results suggest an important contribution of prostanoids in the plasma leakage mechanisms triggered by RPA but not by bradykinin. PMID:10780980

Synthesis of Substituted 2,3,5,6-tetraarylbenzo(1,2-b:5,4-b')difurans

NASA Technical Reports Server (NTRS)

Abdul-Aziz, Mahmoud; Auping, Judith V.; Meador, Michael A.

1995-01-01

A series of substituted 2,3,5,6-tetraarylbenzo(l,2-b:5,4-b')difurans 1 was synthesized. This synthesis is based upon the photocyclization of 2,5-dibenzoylresorcinol dibenzyl ethers to the corresponding tetrahydrobenzo(1,2-b:5,4-b')difurans. Treatment of the photoproducts with methanesulfonyl chloride in pyridine afforded 1 in overall yields ranging from 30-72%. A number of these compounds have high fluorescence quantum yields (of phi(sub f) = 0.76-0.90), and their fluorescence spectra exhibit large solvatochromic shifts. These compounds may be suitable for use as fluorescent probes.

Chemical and Hormonal Effects on STAT5b-Dependent Sexual Dimorphism of the Liver Transcriptome.

EPA Science Inventory

The growth hormone (GH)-activated transcription factor signal transducer and activator of transcription 5b (STAT5b) is a key regulator of sexually dimorphic gene expression in the liver. Suppression of hepatic STAT5b signaling is associated with lipid metabolic dysfunction leadi...

Qatar Exoplanet Survey : Qatar-3b, Qatar-4b, and Qatar-5b

NASA Astrophysics Data System (ADS)

Alsubai, Khalid; Mislis, Dimitris; Tsvetanov, Zlatan I.; Latham, David W.; Bieryla, Allyson; Buchhave, Lars A.; Esquerdo, Gilbert A.; Bramich, D. M.; Pyrzas, Stylianos; Vilchez, Nicolas P. E.; Mancini, Luigi; Southworth, John; Evans, Daniel F.; Henning, Thomas; Ciceri, Simona

2017-04-01

We report the discovery of Qatar-3b, Qatar-4b, and Qatar-5b, three new transiting planets identified by the Qatar Exoplanet Survey. The three planets belong to the hot Jupiter family, with orbital periods of {P}{{Q}3{{b}}} = 2.50792 days, {P}{{Q}4{{b}}} = 1.80539 days, and {P}{{Q}5{{b}}} = 2.87923 days. Follow-up spectroscopic observations reveal the masses of the planets to be {M}{{Q}3{{b}}} = 4.31 ± 0.47 {M}{{J}}, {M}{{Q}4{{b}}} = 6.10 ± 0.54 {M}{{J}}, and {M}{{Q}5{{b}}} = 4.32 ± 0.18 {M}{{J}}, while model fits to the transit light curves yield radii of {R}{{Q}3{{b}}} = 1.096 ± 0.14 {R}{{J}}, {R}{{Q}4{{b}}} = 1.135 ± 0.11 {R}{{J}}, and {R}{{Q}5{{b}}} = 1.107 ± 0.064 {R}{{J}}. The host stars are low-mass main sequence stars with masses and radii M Q3 = 1.145 ± 0.064 M ⊙, M Q4 = 0.896 ± 0.048 M ⊙, M Q5 = 1.128 ± 0.056 M ⊙ and R Q3 = 1.272 ± 0.14 R ⊙, R Q4 = 0.849 ± 0.063 R ⊙, and R Q5 = 1.076 ± 0.051 R ⊙ for Qatar-3, 4, and 5 respectively. The V magnitudes of the three host stars are V Q3 = 12.88, V Q4 = 13.60, and V Q5 = 12.82. All three new planets can be classified as heavy hot Jupiters (M > 4 M J).

Molecular role of the PAX5-ETV6 oncoprotein in promoting B-cell acute lymphoblastic leukemia.

PubMed

Smeenk, Leonie; Fischer, Maria; Jurado, Sabine; Jaritz, Markus; Azaryan, Anna; Werner, Barbara; Roth, Mareike; Zuber, Johannes; Stanulla, Martin; den Boer, Monique L; Mullighan, Charles G; Strehl, Sabine; Busslinger, Meinrad

2017-03-15

PAX5 is a tumor suppressor in B-ALL, while the role of PAX5 fusion proteins in B-ALL development is largely unknown. Here, we studied the function of PAX5-ETV6 and PAX5-FOXP1 in mice expressing these proteins from the Pax5 locus. Both proteins arrested B-lymphopoiesis at the pro-B to pre-B-cell transition and, contrary to their proposed dominant-negative role, did not interfere with the expression of most regulated Pax5 target genes. Pax5-Etv6, but not Pax5-Foxp1, cooperated with loss of the Cdkna2a/b tumor suppressors in promoting B-ALL development. Regulated Pax5-Etv6 target genes identified in these B-ALLs encode proteins implicated in pre-B-cell receptor (BCR) signaling and migration/adhesion, which could contribute to the proliferation, survival, and tissue infiltration of leukemic B cells. Together with similar observations made in human PAX5-ETV6 + B-ALLs, these data identified PAX5-ETV6 as a potent oncoprotein that drives B-cell leukemia development. © 2017 The Authors.

Porcine reproductive and respiratory syndrome virus nonstructural protein 2 contributes to NF-κB activation.

PubMed

Fang, Ying; Fang, Liurong; Wang, Yang; Lei, Yingying; Luo, Rui; Wang, Dang; Chen, Huanchun; Xiao, Shaobo

2012-04-30

Nuclear factor-kappaB (NF-κB) is an inducible transcription factor that plays a key role in inflammation and immune responses, as well as in the regulation of cell proliferation and survival. Previous studies by our group and others have demonstrated that porcine reproductive and respiratory syndrome virus (PRRSV) infection could activate NF-κB in MARC-145 cells and alveolar macrophages. The nucleocapsid (N) protein was identified as an NF-κB activator among the structural proteins encoded by PRRSV; however, it remains unclear whether the nonstructural proteins (Nsps) contribute to NF-κB activation. In this study, we identified which Nsps can activate NF-κB and investigated the potential mechanism(s) by which they act. By screening the individual Nsps of PRRSV strain WUH3, Nsp2 exhibited great potential to activate NF-κB in MARC-145 and HeLa cells. Overexpression of Nsp2 induced IκBα degradation and nuclear translocation of NF-κB. Furthermore, Nsp2 also induced NF-κB-dependent inflammatory factors, including interleukin (IL)-6, IL-8, COX-2, and RANTES. Compared with the Nsp2 of the classical PRRSV strain, the Nsp2 of highly pathogenic PRRSV (HP-PRRSV) strains that possess a 30 amino acid (aa) deletion in Nsp2 displayed greater NF-κB activation. However, the 30-aa deletion was demonstrated to not be associated with NF-κB activation. Further functional domain analyses revealed that the hypervariable region (HV) of Nsp2 was essential for NF-κB activation. Taken together, these data indicate that PRRSV Nsp2 is a multifunctional protein participating in the modulation of host inflammatory response, which suggests an important role of Nsp2 in pathogenesis and disease outcomes.

24 CFR Appendix I to Subpart B of... - Annual Contributions Contract

Code of Federal Regulations, 2011 CFR

2011-04-01

..., Subpt. B, App. I Appendix I to Subpart B of Part 904—Annual Contributions Contract (Subpart B... initial purchase price of the dwelling unit. The term “initial purchase price” as used in these Special...

24 CFR Appendix I to Subpart B of... - Annual Contributions Contract

Code of Federal Regulations, 2010 CFR

2010-04-01

..., Subpt. B, App. I Appendix I to Subpart B of Part 904—Annual Contributions Contract (Subpart B... initial purchase price of the dwelling unit. The term “initial purchase price” as used in these Special...

Identification of the human factors contributing to maintenance failures in a petroleum operation.

PubMed

Antonovsky, Ari; Pollock, Clare; Straker, Leon

2014-03-01

This research aimed to identify the most frequently occurring human factors contributing to maintenance-related failures within a petroleum industry organization. Commonality between failures will assist in understanding reliability in maintenance processes, thereby preventing accidents in high-hazard domains. Methods exist for understanding the human factors contributing to accidents. Their application in a maintenance context mainly has been advanced in aviation and nuclear power. Maintenance in the petroleum industry provides a different context for investigating the role that human factors play in influencing outcomes. It is therefore worth investigating the contributing human factors to improve our understanding of both human factors in reliability and the factors specific to this domain. Detailed analyses were conducted of maintenance-related failures (N = 38) in a petroleum company using structured interviews with maintenance technicians. The interview structure was based on the Human Factor Investigation Tool (HFIT), which in turn was based on Rasmussen's model of human malfunction. A mean of 9.5 factors per incident was identified across the cases investigated.The three most frequent human factors contributing to the maintenance failures were found to be assumption (79% of cases), design and maintenance (71%), and communication (66%). HFIT proved to be a useful instrument for identifying the pattern of human factors that recurred most frequently in maintenance-related failures. The high frequency of failures attributed to assumptions and communication demonstrated the importance of problem-solving abilities and organizational communication in a domain where maintenance personnel have a high degree of autonomy and a wide geographical distribution.

FACTORS CONTRIBUTING TO STUDENT ACHIEVEMENT.

ERIC Educational Resources Information Center

Ohio State Dept. of Education, Columbus. Trade and Industrial Education Service.

FACTORS WHICH MIGHT CONTRIBUTE SIGNIFICANTLY TOWARD STUDENT ACHIEVEMENT IN SELECTED TRADE AND INDUSTRIAL EDUCATION AREAS WERE EXAMINED -- WHAT IS THE BACKGROUND AND PREPARATION OF OHIO'S TEACHER IN TRADE AND INDUSTRIAL EDUCATION, IS THERE ANY RELATIONSHIP BETWEEN THE AMOUNT OF MONEY SPENT PER STUDENT AND QUALITY PROGRAMS, DO LOCAL SUPERVISORS'…

In-situ X-ray diffraction studies of the phase transformations and structural states of B2, R and B19′ phases in Ti{sub 49.5}Ni{sub 50.5} alloy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ostapenko, Marina G., E-mail: artifakt@ispms.tsc.ru; National Research Tomsk Polytechnic University, Tomsk, 634050; Meisner, Ludmila L., E-mail: llm@ispms.tsc.ru

2015-10-27

The martensitic transformation, Debye–Waller factor, mean-square atomic displacements and the coefficient of thermal expansion on cooling of the Ti{sub 49.5}Ni{sub 50.5} shape memory alloy were examined using in-situ X-ray diffraction. It was revealed B2→R (T{sub R} ≡ T = 273 ± 10 K) along with B2→B19’ (M{sub s} ≡ T = 273 ± 10 K) transitions occur. It was found that Debye–Waller factor and mean-square displacement of B2 phase undergo significant increase as functions of temperature when phase transition B2→R and B2→B19’ take place. The analysis of the thermal expansion coefficient of the B2 phase indicates that the value of a increasesmore » almost linearly while cooling.« less

Fatty acid-binding protein 5 (FABP5) promotes lipolysis of lipid droplets, de novo fatty acid (FA) synthesis and activation of nuclear factor-kappa B (NF-κB) signaling in cancer cells.

PubMed

Senga, Shogo; Kobayashi, Narumi; Kawaguchi, Koichiro; Ando, Akira; Fujii, Hiroshi

2018-06-12

Fatty acid-binding proteins (FABPs) are involved in binding and storing hydrophobic ligands such as long-chain fatty acids, as well as transporting them to the appropriate compartments in the cell. Epidermal fatty acid-binding protein (FABP5) is an intracellular lipid-binding protein that is abundantly expressed in adipocytes and macrophages. Previous studies have revealed that the FABP5 expression level is closely related to malignancy in various types of cancer. However, its precise functions in the metabolisms of cancer cells remain unclear. Here, we revealed that FABP5 knockdown significantly induced downregulation of the genes expression, such as hormone-sensitive lipase (HSL), monoacylglycerol lipase (MAGL), elongation of long-chain fatty acid member 6 (Elovl6), and acyl-CoA synthetase long-chain family member 1 (ACSL1), which are involved in altered lipid metabolism, lipolysis, and de novo FA synthesis in highly aggressive prostate and breast cancer cells. Moreover, we demonstrated that FABP5 induced inflammation and cytokine production through the nuclear factor-kappa B signaling pathway activated by reactive oxygen species and protein kinase C in PC-3 and MDA-MB-231 cells. Thus, FABP5 might regulate lipid quality and/or quantity to promote aggressiveness such as cell growth, invasiveness, survival, and inflammation in prostate and breast cancer cells. In the present study, we have revealed for the first time that high expression of FABP5 plays a critical role in alterations of lipid metabolism, leading to cancer development and metastasis in highly aggressive prostate and breast cancer cells. Copyright © 2018. Published by Elsevier B.V.

miR-146b-5p promotes the neural conversion of pluripotent stem cells by targeting Smad4

PubMed Central

Zhang, Nianping; Lyu, Ying; Pan, Xuebing; Xu, Liping; Xuan, Aiguo; He, Xiaosong; Huang, Wandan; Long, Dahong

2017-01-01

Pluripotent stem cells (PSCs) are regarded as potential sources that provide specific neural cells for cell therapy in some nervous system diseases. However, the mechanisms underlying the neural differentiation of PSCs remain largely unknown. MicroRNAs (miRNAs or miRs) are a class of small non-protein-coding RNAs that act as critical regulatory molecules in many cellular processes. In this study, we found that miR-146b-5p expression was markedly increased following the neural induction of mouse embryonic stem cells (ESCs) or induced PSCs (iPSCs). In this study, to further identify the role of miR-146b-5p, we generated stable miR-146b-5p- overexpressing ESC and iPSC cell lines, and induced the differentiation of these cells by the adherent monolayer culture method. In the miR-146b-5p-overexpressing ESC- or iPSC- derived cultures, RT-qPCR analysis revealed that the mRNA expression levels of neuroectoderm markers, such as Sox1, Nestin and Pax6, were markedly increased, and flow cytometric analysis verified that the number of Nestin-positive cells was higher in the miR-146b-5p-overexpressing compared with the control cells. Mechanistically, the miR-146b-5p-overexpressing ESCs or iPSCs exhibited a significant reduction in Oct4 expression, which may be an explanation for these cells having a tendency to differentiate towards the neural lineage. Moreover, we confirmed that miR-146b-5p directly targeted Smad4 and negatively regulated the transforming growth factor (TGF)-β signaling pathway, which contributed to the neural commitment of PSCs. Collectively, our findings uncover the essential role of miR-146b-5p in the neural conversion of PSCs. PMID:28713933

Inhibition of IκB Kinase-Nuclear Factor-κB Signaling Pathway by 3,5-Bis(2-flurobenzylidene)piperidin-4-one (EF24), a Novel Monoketone Analog of Curcumin*

PubMed Central

Kasinski, Andrea L.; Du, Yuhong; Thomas, Shala L.; Zhao, Jing; Sun, Shi-Yong; Khuri, Fadlo R.; Wang, Cun-Yu; Shoji, Mamoru; Sun, Aiming; Snyder, James P.; Liotta, Dennis; Fu, Haian

2009-01-01

The nuclear factor-κB (NF-κB) signaling pathway has been targeted for therapeutic applications in a variety of human diseases, includuing cancer. Many naturally occurring substances, including curcumin, have been investigated for their actions on the NF-κB pathway because of their significant therapeutic potential and safety profile. A synthetic monoketone compound termed 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) was developed from curcumin and exhibited potent anticancer activity. Here, we report a mechanism by which EF24 potently suppresses the NF-κB signaling pathway through direct action on IκB kinase (IKK). We demonstrate that 1) EF24 induces death of lung, breast, ovarian, and cervical cancer cells, with a potency about 10 times higher than that of curcumin; 2) EF24 rapidly blocks the nuclear translocation of NF-κB, with an IC50 value of 1.3 μM compared with curcumin, with an IC50 value of 13 μM; 3) EF24 effectively inhibits tumor necrosis factor (TNF)-α-induced IκB phosphorylation and degradation, suggesting a role of this compound in targeting IKK; and 4) EF24 indeed directly inhibits the catalytic activity of IKK in an in vitro-reconstituted system. Our study identifies IKK as an effective target for EF24 and provides a molecular explanation for a superior activity of EF24 over curcumin. The effective inhibition of TNF-α-induced NF-κB signaling by EF24 extends the therapeutic application of EF24 to other NF-κB-dependent diseases, including inflammatory diseases such as rheumatoid arthritis. PMID:18577686

Inhibition of IkappaB kinase-nuclear factor-kappaB signaling pathway by 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24), a novel monoketone analog of curcumin.

PubMed

Kasinski, Andrea L; Du, Yuhong; Thomas, Shala L; Zhao, Jing; Sun, Shi-Yong; Khuri, Fadlo R; Wang, Cun-Yu; Shoji, Mamoru; Sun, Aiming; Snyder, James P; Liotta, Dennis; Fu, Haian

2008-09-01

The nuclear factor-kappaB (NF-kappaB) signaling pathway has been targeted for therapeutic applications in a variety of human diseases, includuing cancer. Many naturally occurring substances, including curcumin, have been investigated for their actions on the NF-kappaB pathway because of their significant therapeutic potential and safety profile. A synthetic monoketone compound termed 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) was developed from curcumin and exhibited potent anticancer activity. Here, we report a mechanism by which EF24 potently suppresses the NF-kappaB signaling pathway through direct action on IkappaB kinase (IKK). We demonstrate that 1) EF24 induces death of lung, breast, ovarian, and cervical cancer cells, with a potency about 10 times higher than that of curcumin; 2) EF24 rapidly blocks the nuclear translocation of NF-kappaB, with an IC(50) value of 1.3 microM compared with curcumin, with an IC(50) value of 13 microM; 3) EF24 effectively inhibits tumor necrosis factor (TNF)-alpha-induced IkappaB phosphorylation and degradation, suggesting a role of this compound in targeting IKK; and 4) EF24 indeed directly inhibits the catalytic activity of IKK in an in vitro-reconstituted system. Our study identifies IKK as an effective target for EF24 and provides a molecular explanation for a superior activity of EF24 over curcumin. The effective inhibition of TNF-alpha-induced NF-kappaB signaling by EF24 extends the therapeutic application of EF24 to other NF-kappaB-dependent diseases, including inflammatory diseases such as rheumatoid arthritis.

Prospective analysis of frequency and contributing factors of nerve injuries following third-molar surgery.

PubMed

Janakiraman, Eswari Natt; Alexander, Mohan; Sanjay, Pasupathy

2010-05-01

The objective of this prospective study was to determine the incidence of injury to the inferior alveolar and lingual nerves following surgical removal of impacted mandibular third molars and to evaluate the various factors contributing to the same. A total of 119 patients underwent mandibular third-molar removal during the period of 11 months. Of 119, 3 inferior alveolar nerve and 5 lingual nerve injuries were encountered. Various factors such as lingual retraction, surgical time, operator experience, radiologic findings contributing to the injury were correlated and analyzed.

45 CFR 5b.3 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Policy. 5b.3 Section 5b.3 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PRIVACY ACT REGULATIONS § 5b.3 Policy. It is... public is entitled to have under the Freedom of Information Act, 5 U.S.C. 552, and part 5 of this title. ...

Skeletal muscle growth and fiber composition in mice are regulated through the transcription factors STAT5a/b: linking growth hormone to the androgen receptor.

PubMed

Klover, Peter; Chen, Weiping; Zhu, Bing-Mei; Hennighausen, Lothar

2009-09-01

In skeletal muscle, STAT5a/b transcription factors are critical for normal postnatal growth, whole-animal glucose homeostasis, and local IGF-1 production. These observations have led us to hypothesize that STAT5a/b are critical for maintenance of normal muscle mass and function. To investigate this, mice with a skeletal muscle-specific deletion of the Stat5a/b genes (Stat5MKO) were used. Stat5MKO mice displayed reduced muscle mass, altered fiber-type distribution and reduced activity. On a molecular level, gene expression in skeletal muscle of Stat5MKO and control mice was analyzed by microarrays and real-time PCR, both in the presence and absence of growth hormone (GH) stimulation. Expression of several genes involved in muscle growth and fiber type were significantly changed. Specifically, in the quadriceps, a muscle almost exclusively composed of type II fibers, the absence of STAT5a/b led to increased expression of several genes associated with type I fibers and the de novo appearance of type I fibers. In addition, it is shown here that expression of the androgen receptor gene (Ar) is controlled by GH through STAT5a/b. The link between STAT5a/b and Ar gene is likely through direct transcriptional regulation, as chromatin immunoprecipitaion of the Ar promoter region in C2C12 myoblasts was accomplished by antibodies against STAT5a. These experiments demonstrate an important role for STAT5a/b in skeletal muscle physiology, and they provide a direct link to androgen signaling.

UV-B light contributes directly to the synthesis of chiloglottone floral volatiles

PubMed Central

Amarasinghe, Ranamalie; Poldy, Jacqueline; Matsuba, Yuki; Barrow, Russell A.; Hemmi, Jan M.; Pichersky, Eran; Peakall, Rod

2015-01-01

Background and Aims Australian sexually deceptive Chiloglottis orchids attract their specific male wasp pollinators by means of 2,5-dialkylcyclohexane-1,3-diones or ‘chiloglottones’, representing a newly discovered class of volatiles with unique structures. This study investigated the hypothesis that UV-B light at low intensities is directly required for chiloglottone biosynthesis in Chiloglottis trapeziformis. Methods Chiloglottone production occurs only in specific tissue (the callus) of the labellum. Cut buds and flowers, and whole plants with buds and flowers, sourced from the field, were kept in a growth chamber and interactions between growth stage of the flowers and duration and intensity of UV-B exposure on chiloglottone production were studied. The effects of the protein synthesis inhibitor cycloheximide were also examined. Key Results Chiloglottone was not present in buds, but was detected in buds that were manually opened and then exposed to sunlight, or artificial UV-B light for ≥5 min. Spectrophotometry revealed that the sepals and petals blocked UV-B light from reaching the labellum inside the bud. Rates of chiloglottone production increased with developmental stage, increasing exposure time and increasing UV-B irradiance intensity. Cycloheximide did not inhibit the initial production of chiloglottone within 5 min of UV-B exposure. However, inhibition of chiloglottone production by cycloheximide occurred over 2 h of UV-B exposure, indicating a requirement for de novo protein synthesis to sustain chiloglottone production under UV-B. Conclusions The sepals and petals of Chiloglottis orchids strongly block UV-B wavelengths of light, preventing chiloglottone production inside the bud. While initiation of chiloglottone biosynthesis requires only UV-B light, sustained chiloglottone biosynthesis requires both UV-B and de novo protein biosynthesis. The internal amounts of chiloglottone in a flower reflect the interplay between developmental stage

3,4,5-Tricaffeoylquinic acid inhibits tumor necrosis factor-α-stimulated production of inflammatory mediators in keratinocytes via suppression of Akt- and NF-κB-pathways.

PubMed

Lee, Chung Soo; Lee, Seon Ae; Kim, Yun Jeong; Seo, Seong Jun; Lee, Min Won

2011-11-01

Keratinocytes may play an important role in the pathogenesis of skin disease in atopic dermatitis. Caffeoyl derivatives are demonstrated to have anti-inflammatory and anti-oxidant effects. However, the effect of 3,4,5-tricaffeoylquinic acid prepared from Aconium koreanum on the pro-inflammatory cytokine-stimulated keratinocyte responses remains uncertain. In human keratinocytes, we investigated the effect of 3,4,5-tricaffeoylquinic acid on the tumor necrosis factor (TNF)-α-stimulated production of inflammatory mediators in relation to the nuclear factor (NF)-κB and cell signaling Akt, which regulates the transcription genes involved in immune and inflammatory responses. 3,4,5-Tricaffeoylquinic acid inhibited the TNF-α-stimulated production of cytokines (IL-1β and IL-8) and chemokine (CCL17 and CCL27) in keratinocytes. Bay 11-7085 (an inhibitor of NF-κB activation) and Akt inhibitor attenuated the TNF-α-induced formation of inflammatory mediators. 3,4,5-Tricaffeoylquinic acid, Bay 11-7085, Akt inhibitor and N-acetylcysteine inhibited the TNF-α-induced activation of NF-κB, activation of Akt, and formation of reactive oxygen and nitrogen species. The results show that 3,4,5-tricaffeoylquinic acid seems to attenuate the TNF-α-stimulated inflammatory mediator production in keratinocytes by suppressing the activation of Akt and NF-κB pathways which may be mediated by reactive oxygen species. The findings suggest that 3,4,5-tricaffeoylquinic acid may exert an inhibitory effect against the pro-inflammatory mediator-induced skin disease. Copyright © 2011 Elsevier B.V. All rights reserved.

Molecular characterization of Myf5 and comparative expression patterns of myogenic regulatory factors in Siniperca chuatsi.

PubMed

Zhu, Xin; Li, Yu-Long; Liu, Li; Wang, Jian-Hua; Li, Hong-Hui; Wu, Ping; Chu, Wu-Ying; Zhang, Jian-She

2016-01-01

Myogenic regulatory factors (MRFs) are muscle-specific basic helix-loop-helix (bHLH) transcription factor that plays an essential role in regulating skeletal muscle development and growth. To investigate molecular characterization of Myf5 and compare the expressional patterns of the four MRFs, we cloned the Myf5 cDNA sequence and analyzed the MRFs expressional patterns using quantitative real-time polymerase chain reaction in Chinese perch (Siniperca chuatsi). Sequence analysis indicated that Chinese perch Myf5 and other MRFs shared a highly conserved bHLH domain with those of other vertebrates. Sequence alignment and phylogenetic tree showed that Chinese perch MRFs had the highest identity with the MRFs of Epinephelus coioides. Spatio-temporal expressional patterns revealed that the MRFs were primarily expressed in muscle, especially in white muscle. During embryonic development period, Myf5, MyoD and MyoG mRNAs had a steep increase at neurula stage, and their highest expressional level was predominantly observed at hatching period. Whereas the highest expressional level of the MRF4 was observed at the muscular effect stage. The expressional patterns of post-embryonic development showed that the Myf5, MyoD and MyoG mRNAs were highest at 90 days post-hatching (dph). Furthermore, starvation and refeeding results showed that the transcription of the MRFs in the fast skeletal muscle of Chinese perch responded quickly to a single meal after 7 days of fasting. It indicated that the MRFs might contribute to muscle recovery after refeeding in Chinese perch. Copyright © 2015 Elsevier B.V. All rights reserved.

SIDS-CDF Hypothesis Revisited: Cause vs. Contributing Factors.

PubMed

Siren, Pontus M A

2016-01-01

The sudden infant death syndrome (SIDS)-critical diaphragm failure (CDF) hypothesis was first published by Siren and Siren in 2011 (1). Since its publication, the hypothesis has continued to generate interest and several colleagues have contributed perspectives and insights to it (2-5). The basic premise of the hypothesis is that the diaphragm is a vital organ that must continuously generate adequate force to maintain ventilation, and that CDF is a terminal event and the cause of death in SIDS. I have argued in two follow-up articles that all SIDS factors either increase the workload of the respiratory muscles, the diaphragm being the primary muscle affected, or reduce its force generating capacity (6, 7). The SIDS-CDF hypothesis posits that SIDS has many contributing factors but only one cause, namely, the failure of the vital respiratory pump. There are several known SIDS factors, such as the prone sleeping position, non-lethal infections, deep sleep, gestational prematurity, low birth weight, cigarette smoke, male gender, and altitude, but of these, some such as the prone sleeping position more significantly both impact diaphragm function and correlate with SIDS. However, SIDS cases are multifactorial and as such can be caused by different combinations of factors. An infection combined with a prone sleeping position and elevated room temperature could lead to SIDS, whereas in other circumstances, low birth weight, cigarette smoke, prone sleeping position, and altitude could result in CDF and SIDS. The SIDS-CDF hypothesis also posits that SIDS does not have a congenital or genetic origin, and that efforts to identify significant genetic anomalies in SIDS victims are unlikely to be successful (8-11).

Intron retention and transcript chimerism conserved across mammals: Ly6g5b and Csnk2b-Ly6g5b as examples

PubMed Central

2013-01-01

Background Alternative splicing (AS) is a major mechanism for modulating gene expression of an organism, allowing the synthesis of several structurally and functionally distinct mRNAs and protein isoforms from a unique gene. Related to AS is the Transcription Induced Chimerism (TIC) or Tandem Chimerism, by which chimeric RNAs between adjacent genes can be found, increasing combinatorial complexity of the proteome. The Ly6g5b gene presents particular behaviours in its expression, involving an intron retention event and being capable to form RNA chimera transcripts with the upstream gene Csnk2b. We wanted to characterise these events more deeply in four tissues in six different mammals and analyse their protein products. Results While canonical Csnk2b isoform was widely expressed, Ly6g5b canonical isoform was less ubiquitous, although the Ly6g5b first intron retained transcript was present in all the tissues and species analysed. Csnk2b-Ly6g5b chimeras were present in all the samples analysed, but with restricted expression patterns. Some of these chimeric transcripts maintained correct structural domains from Csnk2b and Ly6g5b. Moreover, we found Csnk2b, Ly6g5b, and Csnk2b-Ly6g5b transcripts that present exon skipping, alternative 5' and 3' splice site and intron retention events. These would generate truncated or aberrant proteins whose role remains unknown. Some chimeric transcripts would encode CSNK2B proteins with an altered C-terminus, which could affect its biological function broadening its substrate specificity. Over-expression of human CSNK2B, LY6G5B, and CSNK2B-LY6G5B proteins, show different patterns of post-translational modifications and cell distribution. Conclusions Ly6g5b intron retention and Csnk2b-Ly6g5b transcript chimerism are broadly distributed in tissues of different mammals. PMID:23521802

Associations between errors and contributing factors in aircraft maintenance

NASA Technical Reports Server (NTRS)

Hobbs, Alan; Williamson, Ann

2003-01-01

In recent years cognitive error models have provided insights into the unsafe acts that lead to many accidents in safety-critical environments. Most models of accident causation are based on the notion that human errors occur in the context of contributing factors. However, there is a lack of published information on possible links between specific errors and contributing factors. A total of 619 safety occurrences involving aircraft maintenance were reported using a self-completed questionnaire. Of these occurrences, 96% were related to the actions of maintenance personnel. The types of errors that were involved, and the contributing factors associated with those actions, were determined. Each type of error was associated with a particular set of contributing factors and with specific occurrence outcomes. Among the associations were links between memory lapses and fatigue and between rule violations and time pressure. Potential applications of this research include assisting with the design of accident prevention strategies, the estimation of human error probabilities, and the monitoring of organizational safety performance.

Obligatory role of cytochrome b5 in the microsomal metabolism of methoxyflurane.

PubMed

Canova-Davis, E; Chiang, J Y; Waskell, L

1985-06-01

Cytochrome b5 has recently been shown to be required in the reconstituted cytochrome P-450 system for the metabolism of the volatile anesthetic methoxyflurane [E. Canova-Davis and L. A. Waskell, J. biol. Chem. 259, 2541 (1984)]. To determine whether this observation in the reconstituted system was merely dependent on the particular ratios of the various components or some other fortuitous, unknown factor, or whether cytochrome b5 plays a role in the liver microsomal metabolism of methoxyflurane, the following studies were undertaken. Antibody to rabbit holocytochrome b5 was raised in guinea pigs. The antibody to cytochrome b5 was able to inhibit 75% of the microsomal metabolism of methoxyflurane. This same antibody also inhibited methoxyflurane metabolism in the reconstituted system. When the antibody to cytochrome b5 was treated with purified cytochrome b5 before addition to the microsomes, it did not inhibit methoxyflurane metabolism. Furthermore, the antibody to cytochrome b5 did not inhibit the microsomal metabolism of benzphetamine. This suggests that cytochrome b5 was required for the microsomal metabolism of methoxyflurane. It is possible that cytochrome b5 functioned in the metabolism of methoxyflurane by retaining a specific conformation of cytochrome P-450 and not by transferring the second electron to cytochrome P-450. To explore this possibility, cytochrome b5 was reconstituted with Mn3+-protoporphyrin IX. The Mn3+-protoporphyrin IX derivative retained the conformation of cytochrome b5 but not its electron transfer properties. This manganese derivative of cytochrome b5 was unable to stimulate the metabolism of methoxyflurane. The study demonstrated that cytochrome b5 was obligatory for the microsomal metabolism of methoxyflurane, whereas it was not required for the microsomal N-demethylation of benzphetamine. Moreover, the heme moiety of cytochrome b5 functioned to transfer electrons in this reaction.

A Cross-Industry Review of B2B Critical Success Factors.

ERIC Educational Resources Information Center

Eid, Riyad; Trueman, Myfanwy; Ahmed, Abdel Moneim

2002-01-01

Presents a comprehensive review of B2B (business-to- business) international Internet marketing and identifies 21 critical success factors in five categories: marketing strategy, including management support, strategic goals, and collaboration; Web site factors, including Web site design; global factors, including multilanguage sites and cultural…

Extended Self-Renewal and Accelerated Reprogramming in the Absence of Kdm5b

PubMed Central

Hu, Gangqing; Yu, Zu-Xi; Liu, Chengyu

2013-01-01

Embryonic stem (ES) cell pluripotency is thought to be regulated in part by H3K4 methylation. However, it is unclear how H3K4 demethylation contributes to ES cell function and participates in induced pluripotent stem (iPS) cell reprogramming. Here, we show that KDM5B, which demethylates H3K4, is important for ES cell differentiation and presents a barrier to the reprogramming process. Depletion of Kdm5b leads to an extension in the self-renewal of ES cells in the absence of LIF. Transcriptome analysis revealed the persistent expression of pluripotency genes and underexpression of developmental genes during differentiation in the absence of Kdm5b, suggesting that KDM5B plays a key role in cellular fate changes. We also observed accelerated reprogramming of differentiated cells in the absence of Kdm5b, demonstrating that KDM5B is a barrier to the reprogramming process. Expression analysis revealed that mesenchymal master regulators associated with the epithelial-to-mesenchymal transition (EMT) are downregulated during reprogramming in the absence of Kdm5b. Moreover, global analysis of H3K4me3/2 revealed that enhancers of fibroblast genes are rapidly deactivated in the absence of Kdm5b, and genes associated with EMT lose H3K4me3/2 during the early reprogramming process. These findings provide functional insight into the role for KDM5B in regulating ES cell differentiation and as a barrier to the reprogramming process. PMID:24100015

Porcine circovirus type 2 induces the activation of nuclear factor kappa B by I{kappa}B{alpha} degradation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wei Li; Kwang, Jimmy; Wang Jin

The transcription factor NF-{kappa}B is commonly activated upon virus infection and a key player in the induction and regulation of the host immune response. The present study demonstrated for the first time that porcine circovirus type 2 (PCV2), which is the primary causative agent of an emerging swine disease, postweaning multisystemic wasting syndrome, can activate NF-{kappa}B in PCV2-infected PK15 cells. In PCV2-infected cells, NF-{kappa}B was activated concomitantly with viral replication, which was characterized by increased DNA binding activity, translocation of NF-{kappa}B p65 from the cytoplasm to the nucleus, as well as degradation and phosphorylation of I{kappa}B{alpha} protein. We further demonstratedmore » PCV2-induced activation of NF-{kappa}B and colocalization of p65 nuclear translocation with virus replication in cultured cells. Treatment of cells with CAPE, a selective inhibitor of NF-{kappa}B activation, reduced virus protein expression and progeny production followed by decreasing PCV2-induced apoptotic caspase activity, indicating the involvement of this transcription factor in induction of cell death. Taken together, these data suggest that NF-{kappa}B activation is important for PCV2 replication and contributes to virus-mediated changes in host cells. The results presented here provide a basis for understanding molecular mechanism of PCV2 infection.« less

Combined use of bFGF and GDF-5 enhances the healing of medial collateral ligament injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saiga, Kenta; Furumatsu, Takayuki, E-mail: matino@md.okayama-u.ac.jp; Yoshida, Aki

Research highlights: {yields} bFGF/GDF-5 treatment increases cellular proliferation and migration of MCL fibroblasts. {yields} bFGF/GDF-5 hydrogels stimulate the healing of MCL injury in vivo. {yields} bFGF/GDF-5 hydrogels stimulate Col1a1 expression and type I collagen synthesis. {yields} Combined use of bFGF/GDF-5 enhances MCL healing. -- Abstract: Basic fibroblast growth factor (bFGF) and growth and differentiation factor (GDF)-5 stimulate the healing of medial collateral ligament (MCL) injury. However, the effect of isolated and combined use of bFGF/GDF-5 remains still unclear. We investigated cellular proliferation and migration responding to bFGF/GDF-5 using rabbit MCL fibroblasts. Rabbit MCL injury was treated by bFGF and/or GDF-5more » with peptide hydrogels. Gene expression and deposition of collagens in healing tissues were evaluated. bFGF/GDF-5 treatment additively enhanced cell proliferation and migration. bFGF/GDF-5 hydrogels stimulated Col1a1 expression without increasing Col3a1 expression. Combined use of bFGF/GDF-5 stimulated type I collagen deposition and the reorganization of fiber alignment, and induced better morphology of fibroblasts in healing MCLs. Our study indicates that combined use of bFGF/GDF-5 might enhance MCL healing by increasing proliferation and migration of MCL fibroblasts, and by regulating collagen synthesis and connective fiber alignment.« less

Suicidality among College and University Students: Contributing Factors and Preventive Response.

ERIC Educational Resources Information Center

Jones, Joan Wickham

This paper surveys and evaluates the research since 1975 on college and university student suicidality in the United States. It focuses on factors which contribute to suicidality, preventive responses to suicide and how well the preventive responses address the contributing factors. Contributing factors examined include various feeling states…

Characterization of STAT5B phosphorylation correlating with expression of cytokine-inducible SH2-containing protein (CIS).

PubMed

Cooper, John C; Boustead, Jared N; Yu, Chao-Lan

2006-06-01

Cytokine-inducible SH2-containing protein (CIS) is the first identified member of genes encoding for the suppressor of cytokine signaling (SOCS). CIS is also a well-known target gene of signal transducer and activator of transcription 5 (STAT5) pathways, providing normal negative feedback control of signaling by cytokines and growth factors. Three other SOCS genes, SOCS1, SOCS2, and SOCS3, can be silenced by DNA hypermethylation in human cancers, suggesting a potential mechanism for constitutive STAT activation. However, it is not known whether CIS expression is similarly perturbed in tumor cells. We report here the absence of CIS expression in T lymphoma LSTRA that overexpresses the Lck protein tyrosine kinase and exhibits elevated STAT5 activity. Pervanadate-induced CIS expression and STAT5 binding to the CIS promoter in vivo over a short time course implies that mechanisms other than DNA hypermethylation may contribute to defective CIS expression in LSTRA cells. Comparison with cytokine-dependent BaF3 cells stimulated with interleukin-3 (IL-3) further reveals that CIS induction correlates with specific STAT5b post-translational modifications. It exhibits as the slowest migrating form through SDS-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. This distinctly modified STAT5b is the predominant form that binds to the consensus STAT5 sites in the CIS promoter and accumulates in the nucleus. In vitro phosphatase assays and phosphoamino acid analysis suggest the involvement of phosphorylation on residues other than the highly conserved tyrosine and serine sites in this distinct STAT5b mobility shift. All together, our results provide a novel link between incomplete STAT5b phosphorylation and defective SOCS gene expression in cancer cells.

45 CFR 73b.5 - Hearings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Hearings. 73b.5 Section 73b.5 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION DEBARMENT OR SUSPENSION OF FORMER EMPLOYEES § 73b.5 Hearings. (a) Hearings shall be stenographically recorded and transcribed and the testimony of...

Roadway contributing factors in traffic crashes.

DOT National Transportation Integrated Search

2014-09-01

This project involved an evaluation of the codes which relate to roadway contributing : factors. This included a review of relevant codes used in other states. Crashes with related : codes were summarized and analyzed. A sample of crash sites was ins...

45 CFR 73b.5 - Hearings.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 1 2011-10-01 2011-10-01 false Hearings. 73b.5 Section 73b.5 Public Welfare... § 73b.5 Hearings. (a) Hearings shall be stenographically recorded and transcribed and the testimony of witnesses shall be taken under oath or affirmation. Hearings will be closed unless an open hearing is...

45 CFR 73b.5 - Hearings.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false Hearings. 73b.5 Section 73b.5 Public Welfare... § 73b.5 Hearings. (a) Hearings shall be stenographically recorded and transcribed and the testimony of witnesses shall be taken under oath or affirmation. Hearings will be closed unless an open hearing is...

45 CFR 73b.5 - Hearings.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Hearings. 73b.5 Section 73b.5 Public Welfare... § 73b.5 Hearings. (a) Hearings shall be stenographically recorded and transcribed and the testimony of witnesses shall be taken under oath or affirmation. Hearings will be closed unless an open hearing is...

45 CFR 5b.3 - Policy.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false Policy. 5b.3 Section 5b.3 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PRIVACY ACT REGULATIONS § 5b.3 Policy. It is the policy of the Department to protect the privacy of individuals to the fullest extent possible...

34 CFR 5b.1 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 1 2011-07-01 2011-07-01 false Definitions. 5b.1 Section 5b.1 Education Office of the Secretary, Department of Education PRIVACY ACT REGULATIONS § 5b.1 Definitions. As used in this part: (a... Education. (c) Department means the Department of Education. (d) Disclosure means the availability or...

45 CFR 5b.12 - Contractors.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Contractors. 5b.12 Section 5b.12 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PRIVACY ACT REGULATIONS § 5b.12 Contractors. (a) All contracts entered into on or after September 27, 1975 which require a contractor to maintain...

Risk Factors for Bovine Tuberculosis (bTB) in Cattle in Ethiopia.

PubMed

Dejene, Sintayehu W; Heitkönig, Ignas M A; Prins, Herbert H T; Lemma, Fitsum A; Mekonnen, Daniel A; Alemu, Zelalem E; Kelkay, Tessema Z; de Boer, Willem F

2016-01-01

Bovine tuberculosis (bTB) infection is generally correlated with individual cattle's age, sex, body condition, and with husbandry practices such as herd composition, cattle movement, herd size, production system and proximity to wildlife-including bTB maintenance hosts. We tested the correlation between those factors and the prevalence of bTB, which is endemic in Ethiopia's highland cattle, in the Afar Region and Awash National Park between November 2013 and April 2015. A total of 2550 cattle from 102 herds were tested for bTB presence using the comparative intradermal tuberculin test (CITT). Data on herd structure, herd movement, management and production system, livestock transfer, and contact with wildlife were collected using semi-structured interviews with cattle herders and herd owners. The individual overall prevalence of cattle bTB was 5.5%, with a herd prevalence of 46%. Generalized Linear Mixed Models with a random herd-effect were used to analyse risk factors of cattle reactors within each herd. The older the age of the cattle and the lower the body condition the higher the chance of a positive bTB test result, but sex, lactation status and reproductive status were not correlated with bTB status. At herd level, General Linear Models showed that pastoral production systems with transhumant herds had a higher bTB prevalence than sedentary herds. A model averaging analysis identified herd size, contact with wildlife, and the interaction of herd size and contact with wildlife as significant risk factors for bTB prevalence in cattle. A subsequent Structural Equation Model showed that the probability of contact with wildlife was influenced by herd size, through herd movement. Larger herds moved more and grazed in larger areas, hence the probability of grazing in an area with wildlife and contact with either infected cattle or infected wildlife hosts increased, enhancing the chances for bTB infection. Therefore, future bTB control strategies in cattle in

GEDAE-LaB: A Free Software to Calculate the Energy System Contributions during Exercise

PubMed Central

Bertuzzi, Rômulo; Melegati, Jorge; Bueno, Salomão; Ghiarone, Thaysa; Pasqua, Leonardo A.; Gáspari, Arthur Fernandes; Lima-Silva, Adriano E.; Goldman, Alfredo

2016-01-01

Purpose The aim of the current study is to describe the functionality of free software developed for energy system contributions and energy expenditure calculation during exercise, namely GEDAE-LaB. Methods Eleven participants performed the following tests: 1) a maximal cycling incremental test to measure the ventilatory threshold and maximal oxygen uptake (V˙O2max); 2) a cycling workload constant test at moderate domain (90% ventilatory threshold); 3) a cycling workload constant test at severe domain (110% V˙O2max). Oxygen uptake and plasma lactate were measured during the tests. The contributions of the aerobic (AMET), anaerobic lactic (LAMET), and anaerobic alactic (ALMET) systems were calculated based on the oxygen uptake during exercise, the oxygen energy equivalents provided by lactate accumulation, and the fast component of excess post-exercise oxygen consumption, respectively. In order to assess the intra-investigator variation, four different investigators performed the analyses independently using GEDAE-LaB. A direct comparison with commercial software was also provided. Results All subjects completed 10 min of exercise at moderate domain, while the time to exhaustion at severe domain was 144 ± 65 s. The AMET, LAMET, and ALMET contributions during moderate domain were about 93, 2, and 5%, respectively. The AMET, LAMET, and ALMET contributions during severe domain were about 66, 21, and 13%, respectively. No statistical differences were found between the energy system contributions and energy expenditure obtained by GEDAE-LaB and commercial software for both moderate and severe domains (P > 0.05). The ICC revealed that these estimates were highly reliable among the four investigators for both moderate and severe domains (all ICC ≥ 0.94). Conclusion These findings suggest that GEDAE-LaB is a free software easily comprehended by users minimally familiarized with adopted procedures for calculations of energetic profile using oxygen uptake and lactate

GEDAE-LaB: A Free Software to Calculate the Energy System Contributions during Exercise.

PubMed

Bertuzzi, Rômulo; Melegati, Jorge; Bueno, Salomão; Ghiarone, Thaysa; Pasqua, Leonardo A; Gáspari, Arthur Fernandes; Lima-Silva, Adriano E; Goldman, Alfredo

2016-01-01

The aim of the current study is to describe the functionality of free software developed for energy system contributions and energy expenditure calculation during exercise, namely GEDAE-LaB. Eleven participants performed the following tests: 1) a maximal cycling incremental test to measure the ventilatory threshold and maximal oxygen uptake (V̇O2max); 2) a cycling workload constant test at moderate domain (90% ventilatory threshold); 3) a cycling workload constant test at severe domain (110% V̇O2max). Oxygen uptake and plasma lactate were measured during the tests. The contributions of the aerobic (AMET), anaerobic lactic (LAMET), and anaerobic alactic (ALMET) systems were calculated based on the oxygen uptake during exercise, the oxygen energy equivalents provided by lactate accumulation, and the fast component of excess post-exercise oxygen consumption, respectively. In order to assess the intra-investigator variation, four different investigators performed the analyses independently using GEDAE-LaB. A direct comparison with commercial software was also provided. All subjects completed 10 min of exercise at moderate domain, while the time to exhaustion at severe domain was 144 ± 65 s. The AMET, LAMET, and ALMET contributions during moderate domain were about 93, 2, and 5%, respectively. The AMET, LAMET, and ALMET contributions during severe domain were about 66, 21, and 13%, respectively. No statistical differences were found between the energy system contributions and energy expenditure obtained by GEDAE-LaB and commercial software for both moderate and severe domains (P > 0.05). The ICC revealed that these estimates were highly reliable among the four investigators for both moderate and severe domains (all ICC ≥ 0.94). These findings suggest that GEDAE-LaB is a free software easily comprehended by users minimally familiarized with adopted procedures for calculations of energetic profile using oxygen uptake and lactate accumulation during exercise. By

34 CFR 5b.3 - Policy.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 34 Education 1 2012-07-01 2012-07-01 false Policy. 5b.3 Section 5b.3 Education Office of the Secretary, Department of Education PRIVACY ACT REGULATIONS § 5b.3 Policy. It is the policy of the Department to protect the privacy of individuals to the fullest extent possible while nonetheless permitting the...

12 CFR 261b.5 - Exemptions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Exemptions. 261b.5 Section 261b.5 Banks and... REGARDING PUBLIC OBSERVATION OF MEETINGS § 261b.5 Exemptions. (a) Except in a case where the agency finds that the public interest requires otherwise, the agency may close a meeting or a portion or portions of...

34 CFR 5b.13 - Fees.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Fees. 5b.13 Section 5b.13 Education Office of the Secretary, Department of Education PRIVACY ACT REGULATIONS § 5b.13 Fees. (a) Policy. Where applicable, fees for copying records will be charged in accordance with the schedule set forth in this section. Fees...

34 CFR 5b.12 - Contractors.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Contractors. 5b.12 Section 5b.12 Education Office of the Secretary, Department of Education PRIVACY ACT REGULATIONS § 5b.12 Contractors. (a) All contracts entered into on or after September 27, 1975 which require a contractor to maintain or on behalf of the...

34 CFR 5b.1 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... is a citizen of the United States or an alien lawfully admitted for permanent residence. It does not... 34 Education 1 2010-07-01 2010-07-01 false Definitions. 5b.1 Section 5b.1 Education Office of the Secretary, Department of Education PRIVACY ACT REGULATIONS § 5b.1 Definitions. As used in this part: (a...

Chemical and Hormonal Effects on STAT5b-Dependent Sexual Dimorphism of the Liver Transcriptome

PubMed Central

Oshida, Keiyu; Waxman, David J.; Corton, J. Christopher

2016-01-01

The growth hormone (GH)-activated transcription factor signal transducer and activator of transcription 5b (STAT5b) is a key regulator of sexually dimorphic gene expression in the liver. Suppression of hepatic STAT5b signaling is associated with lipid metabolic dysfunction leading to steatosis and liver cancer. In the companion publication, a STAT5b biomarker gene set was identified and used in a rank-based test to predict both increases and decreases in liver STAT5b activation status/function with high (≥ 97%) accuracy. Here, this computational approach was used to identify chemicals and hormones that activate (masculinize) or suppress (feminize) STAT5b function in a large, annotated mouse liver and primary hepatocyte gene expression compendium. Exposure to dihydrotestosterone and thyroid hormone caused liver masculinization, whereas glucocorticoids, fibroblast growth factor 15, and angiotensin II caused liver feminization. In mouse models of diabetes and obesity, liver feminization was consistently observed and was at least partially reversed by leptin or resveratrol exposure. Chemical-induced feminization of male mouse liver gene expression profiles was a relatively frequent phenomenon: of 156 gene expression biosets from chemically-treated male mice, 29% showed feminization of liver STAT5b function, while <1% showed masculinization. Most (93%) of the biosets that exhibited feminization of male liver were also associated with activation of one or more xenobiotic-responsive receptors, most commonly constitutive activated receptor (CAR) or peroxisome proliferator-activated receptor alpha (PPARα). Feminization was consistently associated with increased expression of peroxisome proliferator-activated receptor gamma (Pparg) but not other lipogenic transcription factors linked to steatosis. GH-activated STAT5b signaling in mouse liver is thus commonly altered by diverse chemicals, and provides a linkage between chemical exposure and dysregulated gene expression

5 CFR 831.405 - Interest on voluntary contributions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Interest on voluntary contributions. 831.405 Section 831.405 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Voluntary Contributions § 831.405 Interest on voluntary contributions. (a...

5 CFR 831.405 - Interest on voluntary contributions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Interest on voluntary contributions. 831.405 Section 831.405 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Voluntary Contributions § 831.405 Interest on voluntary contributions. (a...

Risk factors for non-alcoholic fatty liver disease are common in patients with non-B non-C hepatocellular carcinoma in India.

PubMed

David, Deepu; Raghavendran, Anantharam; Goel, Ashish; Bharath Kumar, C; Kodiatte, Thomas Alex; Burad, Deepak; Abraham, Priya; Ramakrishna, Banumathi; Joseph, Philip; Ramachandran, Jeyamani; Eapen, C E

2017-09-01

The aim of the study was to analyze the prevalence of risk factors for non-alcoholic fatty liver disease (NAFLD) in patients with non-B non-C hepatocellular carcinoma (HCC). Between June 2012 and November 2014, patients with HCC, negative for hepatitis B surface antigen and hepatitis C virus antibody, were included in this study. All patients were assessed for risk factors for NAFLD such as diabetes mellitus (DM), hypertension, dyslipidemia, metabolic syndrome, and obesity. Forty-seven patients with non-B non-C HCC (males, 37; age, 60±10 years; mean±SD) were studied. Model for end-stage liver disease score was 11±4. Twenty-five patients were in Child's class A. History of significant alcohol intake was noted in 11 (23%) patients. Prevalence of risk factors for NAFLD were obesity 24 (51%), DM 22 (47%), metabolic syndrome 21 (45%), hypertension 16 (34%), and dyslipidemia 13 (28%). Forty (85%) patients had at least one risk factor for NAFLD. The mean duration of at least one NAFLD risk factor was 7.5 years, prior to diagnosis of HCC. Thirteen (28%) patients were positive for anti-HBc; however, none of the study patients had detectable HBV DNA in blood. Eighty-five percent of the patients with non-B non-C HCC had at least one risk factor for NAFLD. None of the study patients had occult hepatitis B infection. NAFLD is emerging as the major etiological contributing factor for non-B non-C HCC in India.

Chiral mutagenesis of insulin. Contribution of the B20-B23 beta-turn to activity and stability.

PubMed

Nakagawa, Satoe H; Hua, Qing-xin; Hu, Shi-Quan; Jia, Wenhua; Wang, Shuhua; Katsoyannis, Panayotis G; Weiss, Michael A

2006-08-04

Insulin contains a beta-turn (residues B20-B23) interposed between two receptor-binding elements, the central alpha-helix of the B chain (B9-B19) and its C-terminal beta-strand (B24-B28). The turn contains conserved glycines at B20 and B23. Although insulin exhibits marked conformational variability among crystal forms, these glycines consistently maintain positive phi dihedral angles within a classic type-I beta-turn. Because the Ramachandran conformations of GlyB20 and GlyB23 are ordinarily forbidden to L-amino acids, turn architecture may contribute to structure or function. Here, we employ "chiral mutagenesis," comparison of corresponding D- and L-Ala substitutions, to investigate this turn. Control substitutions are introduced at GluB21, a neighboring residue exhibiting a conventional (negative) phi angle. The D- and L-Ala substitutions at B23 are associated with a marked stereospecific difference in activity. Whereas the D-AlaB23 analog retains native activity, the L analog exhibits a 20-fold decrease in receptor binding. By contrast, D- and L-AlaB20 analogs each exhibit high activity. Stereospecific differences between the thermodynamic stabilities of the analogs are nonetheless more pronounced at B20 (delta deltaG(u) 2.0 kcal/mole) than at B23 (delta deltaG(u) 0.7 kcal/mole). Control substitutions at B21 are well tolerated without significant stereospecificity. Chiral mutagenesis thus defines the complementary contributions of these conserved glycines to protein stability (GlyB20) or receptor recognition (GlyB23).

Zinc finger protein 521 antagonizes early B-cell factor 1 and modulates the B-lymphoid differentiation of primary hematopoietic progenitors.

PubMed

Mega, Tiziana; Lupia, Michela; Amodio, Nicola; Horton, Sarah J; Mesuraca, Maria; Pelaggi, Daniela; Agosti, Valter; Grieco, Michele; Chiarella, Emanuela; Spina, Raffaella; Moore, Malcolm A S; Schuringa, Jan Jacob; Bond, Heather M; Morrone, Giovanni

2011-07-01

Zinc finger protein 521 (EHZF/ZNF521) is a multi-functional transcription co-factor containing 30 zinc fingers and an amino-terminal motif that binds to the nucleosome remodelling and histone deacetylase (NuRD) complex. ZNF521 is believed to be a relevant player in the regulation of the homeostasis of the hematopoietic stem/progenitor cell compartment, however the underlying molecular mechanisms are still largely unknown. Here, we show that this protein plays an important role in the control of B-cell development by inhibiting the activity of early B-cell factor-1 (EBF1), a master factor in B-lineage specification. In particular, our data demonstrate that: (1) ZNF521 binds to EBF1 via its carboxyl-terminal portion and this interaction is required for EBF1 inhibition; (2) NuRD complex recruitment by ZNF521 is not essential for the inhibition of transactivation of EBF1-dependent promoters; (3) ZNF521 represses EBF1 target genes in a human B-lymphoid molecular context; and (4) RNAi-mediated silencing of ZNF521/Zfp521 in primary human and murine hematopoietic progenitors strongly enhances the generation of B-lymphocytes in vitro. Taken together, our data indicate that ZNF521 can antagonize B-cell development and lend support to the notion that it may contribute to conserve the multipotency of primitive lympho-myeloid progenitors by preventing or delaying their EBF1-driven commitment toward the B-cell lineage.

75 FR 23574 - Airworthiness Directives; CFM International, S.A. CFM56-5B1/P, -5B2/P, -5B3/P, -5B3/P1, -5B4/P...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-04

... high-pressure compressor (HPC) of both engines. That AD also requires removing from service any engine... monitoring of EGT margin deterioration on engines in service to prevent two engines on an airplane from... 75 [deg]C; Removes FADEC software version 5.B.Q and earlier versions from the engine as mandatory...

B cells expressing the transcription factor T-bet drive lupus-like autoimmunity

PubMed Central

Rubtsov, Anatoly V.; Thurman, Joshua M.; Mennona, Johanna M.; Kappler, John W.; Marrack, Philippa

2017-01-01

B cells contribute to multiple aspects of autoimmune disorders and may play a role in triggering disease. Thus, targeting B cells may be a promising strategy for treating autoimmune disorders. Better understanding of the B cell subsets that are responsible for the development of autoimmunity will be critical for developing efficient therapies. Here we have reported that B cells expressing the transcription factor T-bet promote the rapid appearance of autoantibodies and germinal centers in spontaneous murine models of systemic lupus erythematosus (SLE). Conditional deletion of T-bet from B cells impaired the formation of germinal centers and mitigated the development of kidney damage and rapid mortality in SLE mice. B cell–specific deletion of T-bet was also associated with lower activation of both B cells and T cells. Taken together, our results suggest that targeting T-bet–expressing B cells may be a potential target for therapy for autoimmune diseases. PMID:28240602

Factors Contributing to the Preference of Korean Patients with Crohn’s Disease When Selecting an Anti-Tumor Necrosis Factor Agent (CHOICE Study)

PubMed Central

Kim, Eun Soo; Kim, Kyeong Ok; Jang, Byung Ik; Lee, Chang Kyun; Kim, Hyo Jong; Lee, Kang-Moon; Kim, You Sun; Eun, Chang Soo; Jung, Sung-Ae; Yang, Suk-Kyun; Lee, Jun; Kim, Tae-Oh; Jung, Yunho; Seo, Geom Seog; Yoon, Soon Man

2016-01-01

Background/Aims Two comparable anti-tumor necrosis factor (TNF) agents with different routes of administration (intravenous [iv] infliximab [IFX] vs subcutaneous [sc] adalimumab [ADA]) are available for patients with Crohn’s disease (CD) in Korea. This study aimed to identify the preferences of Korean CD patients for a specific anti-TNF agent and the factors contributing to the decision. Methods A prospective survey was performed among anti-TNF-naive CD patients in 10 tertiary referral hospitals. A 16-item questionnaire addressed patient preferences and the factors contributing to the decision in favor of a particular anti-TNF agent. A logistic regression was conducted to assess predictive factors for ADA preference. Results Overall, 189 patients (139 males; mean age, 32.47±11.71 years) completed the questionnaire. IFX and ADA were preferred by 63.5% (120/189) and 36.5% (69/189) of patients, respectively. The most influential reason for choosing IFX was ‘doctor’s presence’ (68.3%, 82/120), and ADA was “easy to use” (34.8%, 24/69). Amid various clinicodemographic data, having a >60-minute travel time to the hospital was a significant independent predictive factor for ADA preference. Conclusions A large number of anti-TNF-naive Korean patients with CD preferred anti-TNFs with an iv route of administration. The reassuring effect of a doctor’s presence might be the main contributing factor for this decision. PMID:26347512

ABCB5 promotes melanoma metastasis through enhancing NF-κB p65 protein stability.

PubMed

Wang, Shenghao; Tang, Li; Lin, Junyu; Shen, Zhongliang; Yao, Yikun; Wang, Wei; Tao, Shuai; Gu, Chenjian; Ma, Jie; Xie, Youhua; Liu, Yanfeng

2017-10-07

Melanoma is the most aggressive type of skin cancer. Melanoma has an extremely poor prognosis because of its high potential for vascular invasion, metastasis and recurrence. The mechanism of melanoma metastasis is not well understood. ATP-binding cassette sub-family B member 5 (ABCB5) plays a key role in melanoma growth. However, it is uncertain what function ABCB5 may exert in melanoma metastasis. In this report, we for the first time demonstrate ABCB5 as a crucial factor that promotes melanoma metastasis. ABCB5 positive (ABCB5 + ) malignant melanoma initiating cells (MMICs) display a higher metastatic potential compared with ABCB5 negative (ABCB5 - ) melanoma subpopulation. Knockdown of ABCB5 expression reduces melanoma cell migration and invasion in vitro and melanoma pulmonary metastasis in tumor xenograft mice. ABCB5 and NF-κB p65 expression levels are positively correlated in both melanoma tissues and cell lines. Consequently, ABCB5 activates the NF-κB pathway by inhibiting p65 ubiquitination to enhance p65 protein stability. Our finding highlights ABCB5 as a novel pro-metastasis factor and provides a potential therapeutic target for melanoma. Copyright © 2017 Elsevier Inc. All rights reserved.

Improve regional distribution and source apportionment of PM2.5 trace elements in China using inventory-observation constrained emission factors.

PubMed

Ying, Qi; Feng, Miao; Song, Danlin; Wu, Li; Hu, Jianlin; Zhang, Hongliang; Kleeman, Michael J; Li, Xinghua

2018-05-15

Contributions to 15 trace elements in airborne particulate matter with aerodynamic diameters <2.5μm (PM 2.5 ) in China from five major source sectors (industrial sources, residential sources, transportation, power generation and windblown dust) were determined using a source-oriented Community Multiscale Air Quality (CMAQ) model. Using emission factors in the composite speciation profiles from US EPA's SPECIATE database for the five sources leads to relatively poor model performance at an urban site in Beijing. Improved predictions of the trace elements are obtained by using adjusted emission factors derived from a robust multilinear regression of the CMAQ predicted primary source contributions and observation at the urban site. Good correlations between predictions and observations are obtained for most elements studied with R>0.5, except for crustal elements Al, Si and Ca, particularly in spring. Predicted annual and seasonal average concentrations of Mn, Fe, Zn and Pb in Nanjing and Chengdu are also consistently improved using the adjusted emission factors. Annual average concentration of Fe is as high as 2.0μgm -3 with large contributions from power generation and transportation. Annual average concentration of Pb reaches 300-500ngm -3 in vast areas, mainly from residential activities, transportation and power generation. The impact of high concentrations of Fe on secondary sulfate formation and Pb on human health should be evaluated carefully in future studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Myricetin down-regulates phorbol ester-induced cyclooxygenase-2 expression in mouse epidermal cells by blocking activation of nuclear factor kappa B.

PubMed

Lee, Kyung Mi; Kang, Nam Joo; Han, Jin Hee; Lee, Ki Won; Lee, Hyong Joo

2007-11-14

Abnormal expression of cyclooxygenase-2 (COX-2) has been implicated in the development of cancer. There are multiple lines of evidence that red wine exerts chemopreventive effects, and 3,5,4'-trihydroxy- trans-stilbene (resveratrol), which is a non-flavonoid polyphenol found in red wine, has been reported to be a natural chemopreventive agent. However, other phytochemicals might contribute to the cancer-preventive activities of red wine, and the flavonol content of red wines is about 30 times higher than that of resveratrol. Here we report that 3,3',4',5,5',7-hexahydroxyflavone (myricetin), one of the major flavonols in red wine, inhibits 12-O-tetradecanoylphorbol-13-acetate (phorbol ester)-induced COX-2 expression in JB6 P+ mouse epidermal (JB6 P+) cells by suppressing activation of nuclear factor kappa B (NF-kappaB). Myricetin at 10 and 20 microM inhibited phorbol ester-induced upregulation of COX-2 protein, while resveratrol at the same concentration did not exert significant effects. The phorbol ester-induced production of prostaglandin E 2 was also attenuated by myricetin treatment. Myricetin inhibited both COX-2 and NF-kappaB transactivation in phorbol ester-treated JB6 P+ cells, as determined using a luciferase assay. Myricetin blocked the phorbol ester-stimulated DNA binding activity of NF-kappaB, as determined using an electrophoretic mobility shift assay. Moreover, TPCK (N-tosyl-l-phenylalanine chloromethyl ketone), a NF-kappaB inhibitor, significantly attenuated COX-2 expression and NF-kappaB promoter activity in phorbol ester-treated JB6 P+ cells. In addition, red wine extract inhibited phorbol ester-induced COX-2 expression and NF-kappaB transactivation in JB6 P+ cells. Collectively, these data suggest that myricetin contributes to the chemopreventive effects of red wine through inhibition of COX-2 expression by blocking the activation of NF-kappaB.

A brief tool to differentiate factors contributing to insomnia complaints.

PubMed

Townsend, Donald; Kazaglis, Louis; Savik, Kay; Smerud, Adam; Iber, Conrad

2017-03-01

A complaint of insomnia may have many causes. A brief tool examining contributing factors may be useful for nonsleep specialists. This study describes the development of the Insomnia Symptoms Assessment (ISA) for examining insomnia complaints. ISA questions were designed to identify symptoms that may represent 1 of 8 possible factors contributing to insomnia symptoms, including delayed sleep phase syndrome (DSPS), shift work sleep disorder (SWSD), obstructive sleep apnea (OSA), mental health, chronic pain, restless leg syndrome (RLS), poor sleep hygiene, and psychophysiological insomnia (PI). The ISA was completed by 346 new patients. Patients met with a sleep specialist who determined primary and secondary diagnoses. Mean age was 45 (18-85) years and 51% were male. Exploratory factor analysis (n = 217) and confirmatory factor analysis (n = 129) supported 5 factors with good internal consistency (Cronbach's alpha), including RLS (.72), OSA (.60), SWSD (.67), DSPS (.64), and PI (.80). Thirty percent had 1 sleep diagnosis with a mean of 2.2 diagnoses per patient. No diagnosis was entered for 1.2% of patients. The receiver operating characteristics were examined and the area under the curves calculated as an indication of convergent validity for the primary diagnosis (N = 346) were .97 for SWSD, .78 for OSA, .67 for DSPS, .54 for PI, and .80 for RLS. The ISA demonstrated good internal consistency and corresponds well to expert diagnoses. Next steps include setting sensitivity/specificity cutoffs to suggest initial treatment recommendations for use in other settings. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

FAM5C Contributes to Aggressive Periodontitis

PubMed Central

Carvalho, Flavia M.; Tinoco, Eduardo M. B.; Deeley, Kathleen; Duarte, Poliana M.; Faveri, Marcelo; Marques, Marcelo R.; Mendonça, Adriana C.; Wang, Xiaojing; Cuenco, Karen; Menezes, Renato; Garlet, Gustavo P.; Vieira, Alexandre R.

2010-01-01

Aggressive periodontitis is characterized by a rapid and severe periodontal destruction in young systemically healthy subjects. A greater prevalence is reported in Africans and African descendent groups than in Caucasians and Hispanics. We first fine mapped the interval 1q24.2 to 1q31.3 suggested as containing an aggressive periodontitis locus. Three hundred and eighty-nine subjects from 55 pedigrees were studied. Saliva samples were collected from all subjects, and DNA was extracted. Twenty-one single nucleotide polymorphisms were selected and analyzed by standard polymerase chain reaction using TaqMan chemistry. Non-parametric linkage and transmission distortion analyses were performed. Although linkage results were negative, statistically significant association between two markers, rs1935881 and rs1342913, in the FAM5C gene and aggressive periodontitis (p = 0.03) was found. Haplotype analysis showed an association between aggressive periodontitis and the haplotype A-G (rs1935881-rs1342913; p = 0.009). Sequence analysis of FAM5C coding regions did not disclose any mutations, but two variants in conserved intronic regions of FAM5C, rs57694932 and rs10494634, were found. However, these two variants are not associated with aggressive periodontitis. Secondly, we investigated the pattern of FAM5C expression in aggressive periodontitis lesions and its possible correlations with inflammatory/immunological factors and pathogens commonly associated with periodontal diseases. FAM5C mRNA expression was significantly higher in diseased versus healthy sites, and was found to be correlated to the IL-1β, IL-17A, IL-4 and RANKL mRNA levels. No correlations were found between FAM5C levels and the presence and load of red complex periodontopathogens or Aggregatibacter actinomycetemcomitans. This study provides evidence that FAM5C contributes to aggressive periodontitis. PMID:20383335

Naphtho[1,2-b:5,6-b']dithiophene-Based Conjugated Polymers for Fullerene-Free Inverted Polymer Solar Cells.

PubMed

Jiang, Zhaoyan; Li, Huan; Wang, Zhen; Zhang, Jianqi; Zhang, Yajie; Lu, Kun; Wei, Zhixiang

2018-03-23

Three novel copolymers based on zigzag naphthodithiophene (zNDT) with different aromatic rings as π bridges and different core side substitutions are designed and synthesized (PzNDT-T-1,3-bis(4-(2-ethylhexyl)-thiophen-2-yl)-5,7-bis(2-ethylhexyl)benzo[1,2-c:4,5-c']-dithiophene-4,8-dione (BDD), PzNDT-TT-BDD, and PzNDTP-T-BDD, respectively). The 2D conjugation structure and molecular planarity of the polymers can be effectively altered through the modification of conjugated side chains and π-bridges. These alterations contribute to the variation in energy levels, light absorption capacity, and morphology compatibility of the polymers. When blended with the nonfullerene acceptor (2,2'-[(4,4,9,9-tetrahexyl-4,9-dihydro-sindaceno[1,2-b:5,6-b']dithiophene-2,7-diyl)bis[methylidyne(3-oxo-1H-indene-2,1(3H)-diylidene)

Time-dependent modulation of thioredoxin reductase activity might contribute to sulforaphane-mediated inhibition of NF-kappaB binding to DNA.

PubMed

Heiss, Elke; Gerhäuser, Clarissa

2005-01-01

The chemopreventive agent sulforaphane (SFN) exerts anti-inflammatory activity by thiol-dependent inhibition of nuclear factor kappaB (NF-kappaB) DNA binding. To further analyze the underlying mechanisms, we focused on the thioredoxin/thioredoxin reductase (TrxR) system as a key redox mechanism regulating NF-kappaB DNA binding. Using cultured Raw 264.7 mouse macrophages as a model, 1-chloro-2,4-dinitrobenzene (CDNB), a known inhibitor of TrxR, was identified as an inhibitor of lipopolysaccharide (LPS)-mediated nitric oxide (NO) production and of NF-kappaB DNA binding. CDNB and SFN acted synergistically with respect to inhibition of LPS-induced NO release, and we consequently identified SFN as a novel inhibitor of TrxR enzymatic activity in vitro. Short-term treatment of Raw macrophages with SFN or CDNB resulted in the inhibition of TrxR activity in vivo with half-maximal inhibitory concentration of 25.0 +/- 3.5 microM and 9.4 +/- 3.7 microM, respectively, whereas after a 24-h treatment with 25 microM SFN, TrxR activity was >1.5-fold elevated. In additional experiments, we could exclude that inhibition of trans-activating activity of NF-kappaB contributed to the reduced expression of pro-inflammatory proteins by SFN, based on transient transfection experiments with a (kappaB)(2)- chloramphenicol acetyltransferase construct and a lack of inhibition of protein kinase A activity. These findings further emphasize the importance of redox modulation or thiol reactivity for the regulation of NF-kappaB-dependent transcription by SFN. Antioxid. Redox Signal. 7, 1601-1611. Antioxid. Redox Signal. 7, 1601-1611.

Transcription factor NF-kappaB participates in regulation of epithelial cell turnover in the colon.

PubMed

Inan, M S; Tolmacheva, V; Wang, Q S; Rosenberg, D W; Giardina, C

2000-12-01

The transcription factor nuclear factor (NF)-kappaB regulates the expression of genes that can influence cell proliferation and death. Here we analyze the contribution of NF-kappaB to the regulation of epithelial cell turnover in the colon. Immunohistochemical, immunoblot, and DNA binding analyses indicate that NF-kappaB complexes change as colonocytes mature: p65-p50 complexes predominate in proliferating epithelial cells of the colon, whereas the p50-p50 dimer is prevalent in mature epithelial cells. NF-kappaB1 (p50) knockout mice were used to study the role of NF-kappaB in regulating epithelial cell turnover. Knockout animals lacked detectable NF-kappaB DNA binding activity in isolated epithelial cells and had significantly longer crypts with a more extensive proliferative zone than their wild-type counterparts (as determined by proliferating cell nuclear antigen staining and in vivo bromodeoxyuridine labeling). Gene expression profiling reveals that the NF-kappaB1 knockout mice express the potentially growth-enhancing tumor necrosis factor (TNF)-alpha and nerve growth factor-alpha genes at elevated levels, with in situ hybridization localizing some of the TNF-alpha expression to epithelial cells. TNF-alpha is NF-kappaB regulated, and its upregulation in NF-kappaB1 knockouts may result from an alleviation of p50-p50 repression. NF-kappaB complexes may therefore influence cell proliferation in the colon through their ability to selectively activate and/or repress gene expression.

B. F. Skinner's contributions to applied behavior analysis

PubMed Central

Morris, Edward K.; Smith, Nathaniel G.; Altus, Deborah E.

2005-01-01

Our paper reviews and analyzes B. F. Skinner's contributions to applied behavior analysis in order to assess his role as the field's originator and founder. We found, first, that his contributions fall into five categorizes: the style and content of his science, his interpretations of typical and atypical human behavior, the implications he drew from his science for application, his descriptions of possible applications, and his own applications to nonhuman and human behavior. Second, we found that he explicitly or implicitly addressed all seven dimensions of applied behavior analysis. These contributions and the dimensions notwithstanding, he neither incorporated the field's scientific (e.g., analytic) and social dimensions (e.g., applied) into any program of published research such that he was its originator, nor did he systematically integrate, advance, and promote the dimensions so to have been its founder. As the founder of behavior analysis, however, he was the father of applied behavior analysis. PMID:22478444

Independent regulation of the two Pax5 alleles during B-cell development.

PubMed

Nutt, S L; Vambrie, S; Steinlein, P; Kozmik, Z; Rolink, A; Weith, A; Busslinger, M

1999-04-01

The developmental control genes of the Pax family are frequently associated with mouse mutants and human disease syndromes. The function of these transcription factors is sensitive to gene dosage, as mutation of one allele or a modest increase in gene number results in phenotypic abnormalities. Pax5 has an important role in B-cell and midbrain development. By following the expression of individual Pax5 alleles at the single-cell level, we demonstrate here that Pax5 is subject to allele-specific regulation during B-lymphopoiesis. Pax5 is predominantly transcribed from only one allele in early progenitors and mature B cells, whereas it switches to a biallelic transcription mode in immature B cells. The allele-specific regulation of Pax5 is stochastic, reversible, independent of parental origin and correlates with synchronous replication, in contrast with imprinted and other monoallelically expressed genes. As a consequence, B-lymphoid tissues are mosaics with respect to the transcribed Pax5 allele, and thus mutation of one allele in heterozygous mice results in deletion of the cell population expressing the mutant allele due to loss of Pax5 function at the single-cell level. Similar allele-specific regulation may be a common mechanism causing the haploinsufficiency and frequent association of other Pax genes with human disease.

Interaction between AT1 receptor and NF-κB in hypothalamic paraventricular nucleus contributes to oxidative stress and sympathoexcitation by modulating neurotransmitters in heart failure.

PubMed

Yu, Xiao-Jing; Suo, Yu-Ping; Qi, Jie; Yang, Qing; Li, Hui-Hua; Zhang, Dong-Mei; Yi, Qiu-Yue; Zhang, Jian; Zhu, Guo-Qing; Zhu, Zhiming; Kang, Yu-Ming

2013-12-01

Angiotensin II type 1 receptor (AT1-R) and nuclear factor-kappaB (NF-κB) in the paraventricular nucleus (PVN) play important roles in heart failure (HF); however, the central mechanisms by which AT1-R and NF-κB contribute to sympathoexcitation in HF are yet unclear. In this study, we determined whether interaction between AT1-R and NF-κB in the PVN modulates neurotransmitters and contributes to NAD(P)H oxidase-dependent oxidative stress and sympathoexcitation in HF. Rats were implanted with bilateral PVN cannulae and subjected to coronary artery ligation or sham surgery (SHAM). Subsequently, animals were treated for 4 weeks through bilateral PVN infusion with either vehicle or losartan (LOS, 10 μg/h), an AT1-R antagonist; or pyrrolidine dithiocarbamate (PDTC, 5 μg/h), a NF-κB inhibitor via osmotic minipump. Myocardial infarction (MI) rats had higher levels of glutamate (Glu), norepinephrine (NE) and NF-κB p65 activity, lower levels of gamma-aminobutyric acid (GABA), and more positive neurons for phosphorylated IKKβ and gp91(phox) (a subunit of NAD(P)H oxidase) in the PVN when compared to SHAM rats. MI rats also had higher levels of renal sympathetic nerve activity (RSNA) and plasma proinflammatory cytokines (PICs), NE and epinephrine. PVN infusions of LOS or PDTC attenuated the decreases in GABA and the increases in gp91(phox), NF-κB activity, Glu and NE, in the PVN of HF rats. PVN infusions of LOS or PDTC also attenuated the increases in RSNA and plasma PICs, NE and epinephrine in MI rats. These findings suggest that interaction between AT1 receptor and NF-κB in the PVN contributes to oxidative stress and sympathoexcitation by modulating neurotransmitters in heart failure.

Metabolic Factors that Contribute to Lupus Pathogenesis

PubMed Central

Li, Wei; Sivakumar, Ramya; Titov, Anton A.; Choi, Seung-Chul; Morel, Laurence

2017-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disease in which organ damage is mediated by pathogenic autoantibodies directed against nucleic acids and protein complexes. Studies in SLE patients and in mouse models of lupus have implicated virtually every cell type in the immune system in the induction or amplification of the autoimmune response as well as the promotion of an inflammatory environment that aggravates tissue injury. Here, we review the contribution of CD4+ T cells, B cells, and myeloid cells to lupus pathogenesis and then discuss alterations in the metabolism of these cells that may contribute to disease, given the recent advances in the field of immunometabolism. PMID:27480903

5 CFR 831.406 - Withdrawal of voluntary contributions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Withdrawal of voluntary contributions. 831.406 Section 831.406 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Voluntary Contributions § 831.406 Withdrawal of voluntary...

5 CFR 831.406 - Withdrawal of voluntary contributions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Withdrawal of voluntary contributions. 831.406 Section 831.406 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Voluntary Contributions § 831.406 Withdrawal of voluntary...

[Role of C5b-9 expression in skeletal muscle blood vessels in necrotizing myopathy].

PubMed

Cong, Lu; Pu, Chuanqiang; Mao, Yanling; Liu, Jiexiao; Lu, Xianghui; Wang, Qian

2012-05-01

To investigate the expression of C5b-9 in the skeletal muscle blood vessels in patients with necrotizing myopathy and explore its role in the pathogenesis of this disease. The expression of C5b-9 and MHC-I in the skeletal muscular fibers and blood vessels in 4 patients with necrotizing myopathy was detected using enzymohistochemistry and immunohistochemistry. Focal or dispersive necrotic muscle fibers with obvious phagocytosis were observed in all the 4 patients. No inflammatory cell infiltration was found in the perimysium or perivascular regions. HE staining showed a decreased number of local small blood vessels, and the some small blood vessels showed thickened vascular walls. Immunohistochemistry detected prominent C5b-9 expression in the necrotic muscle fibers and the blood vessels, and diffuse strong C5b-9 expression was found in the vascular walls, vascular endothelial cells and the smooth muscle layer. No MHC-I deposition was detected in the muscular fibers and blood vessels. C5b-9 contributes to the pathogenesis of necrotizing myopathy mediated by pathologies in the blood vessels.

49 CFR 178.33b-5 - Material.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 3 2011-10-01 2011-10-01 false Material. 178.33b-5 Section 178.33b-5 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... Containers, and Linings § 178.33b-5 Material. (a) The receptacles must be constructed of polyethylene...

49 CFR 178.33b-5 - Material.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 3 2013-10-01 2013-10-01 false Material. 178.33b-5 Section 178.33b-5 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... Containers, and Linings § 178.33b-5 Material. (a) The receptacles must be constructed of polyethylene...

49 CFR 178.33b-5 - Material.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 3 2014-10-01 2014-10-01 false Material. 178.33b-5 Section 178.33b-5 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... Containers, and Linings § 178.33b-5 Material. (a) The receptacles must be constructed of polyethylene...

49 CFR 178.33b-5 - Material.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 3 2012-10-01 2012-10-01 false Material. 178.33b-5 Section 178.33b-5 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... Containers, and Linings § 178.33b-5 Material. (a) The receptacles must be constructed of polyethylene...

Multiple Sclerosis and EIF2B5: A Paradox or a Missing Link.

PubMed

Zahoor, Insha; Haq, Ehtishamul; Asimi, Ravouf

2017-01-01

Multiple sclerosis (MS) is an encumbering inflammatory condition of the central nervous system (CNS) caused by axonal demyelination. There is sufficient evidence suggesting role of eukaryotic translation initiation factor 2B (EIF2B) gene family encoding the five subunits of eIF2B complex-α, β, γ, δ and ε respectively, in causing vanishing white matter (VWM) disease of the brain. Incidentally researchers have proposed overlapping between MS and VWM in terms of clinical, biochemical and genetic aspects, which incited us to write this chapter to explore the association between EIF2B5 and MS. eIF2B plays an essential role in translation initiation and its regulation in eukaryotes. Among EIF2B gene family, EIF2B5 gene encodes the catalytic and a crucial epsilon subunit of the eIF2B protein as most of the alterations have been found in this gene. The recent findings on the association between EIF2B5 and MS susceptibility point towards unfathomable and contentious role of EIF2B5 in MS development. This chapter briefly reviews the insights gleaned from recent studies conducted in understanding the association between EIF2B5 and MS risk. The need of hour is to conduct large scale conclusive studies aimed at expounding the mechanisms behind this relationship.

The Case for Pangea B: Paleomagnetic Contributions from Adria

NASA Astrophysics Data System (ADS)

Muttoni, G.

2004-12-01

The pre-drift Wegenerian model of Pangea is almost universally accepted, but debate exists on its pre-Jurassic configuration since Ted Irving introduced Pangea B. We review Permian and recently acquired Jurassic-Cretaceous paleomagnetic data from para-autochthonous regions of Adria such as the Southern Alps, which we show to be broadly consistent with "African" APWPs. Paleomagnetic data from para-autochthonous Adria can therefore be used to bolster the Gondwana APWP in the poorly known Late Permian-Triassic time interval. Adria paleopoles are integrated with the Gondwana and Laurasia APWPs and used to generate a tectonic model for the evolution of Pangea. The Early Permian paleopole of Adria from radiometrically dated igneous rocks, in conjunction with the coeval Gondwana and Laurasia paleopoles again from igneous rocks, support Pangea B. The use of paleomagnetic data strictly from igneous rocks excludes artifacts from sedimentary inclination error as a contributing explanation for Pangea B. The ultimate option to reject Pangea B is to introduce a significant zonal octupole component in the Late Paleozoic time-averaged geomagnetic field. Our dataset consisting entirely of paleomagnetic directions with low inclinations from sampling sites confined to one hemisphere show that the effects of a zonal octupole field contribution cannot explain away the paleomagnetic evidence for Pangea B. We therefore regard the paleomagnetic evidence for an Early Permian Pangea B as robust. Because the Late Permian/Early Triassic and the Middle/early Late Triassic paleopoles from Adria and Laurussia support Pangea A, the phase of transcurrent motion between Laurasia and Gondwana that caused the Pangea B to A transition occurred essentially in the Permian. It took place after the cooling of the Variscan mega-suture and lasted ~20 m.y., with an average relative plate velocity of approximately 15 cm/yr. Finally, we review geological and paleomagnetic evidence in support of an intra

Epistasis between 5-HTTLPR and ADRA2B polymorphisms influences attentional bias for emotional information in healthy volunteers.

PubMed

Naudts, Kris H; Azevedo, Ruben T; David, Anthony S; van Heeringen, Kees; Gibbs, Ayana A

2012-09-01

Individual differences in emotional processing are likely to contribute to vulnerability and resilience to emotional disorders such as depression and anxiety. Genetic variation is known to contribute to these differences but they remain incompletely understood. The serotonin transporter (5-HTTLPR) and α2B-adrenergic autoreceptor (ADRA2B) insertion/deletion polymorphisms impact on two separate but interacting monaminergic signalling mechanisms that have been implicated in both emotional processing and emotional disorders. Recent studies suggest that the 5-HTTLPR s allele is associated with a negative attentional bias and an increased risk of emotional disorders. However, such complex behavioural traits are likely to exhibit polygenicity, including epistasis. This study examined the contribution of the 5-HTTLPR and ADRA2B insertion/deletion polymorphisms to attentional biases for aversive information in 94 healthy male volunteers and found evidence of a significant epistatic effect (p<0.001). Specifically, in the presence of the 5-HTTLPR s allele, the attentional bias for aversive information was attenuated by possession of the ADRA2B deletion variant whereas in the absence of the s allele, the bias was enhanced. These data identify a cognitive mechanism linking genotype-dependent serotonergic and noradrenergic signalling that is likely to have implications for the development of cognitive markers for depression/anxiety as well as therapeutic drug effects and personalized approaches to treatment.

Claudin 5 Expression in Mouse Seminiferous Epithelium Is Dependent upon the Transcription Factor Ets Variant 5 and Contributes to Blood-Testis Barrier Function1

PubMed Central

Morrow, Carla M.K.; Tyagi, Gaurav; Simon, Liz; Carnes, Kay; Murphy, Kenneth M.; Cooke, Paul S.; Hofmann, Marie-Claude C.; Hess, Rex A.

2009-01-01

The blood-testis barrier (BTB) is formed by tight junctions between Sertoli cells. Results of previous studies suggested that the barrier is deficient in ets variant 5 (ETV5) gene-deleted mice; therefore, microarray data were examined for changes in tight junction-associated genes. The tight junctional protein claudin 5 (CLDN5) was decreased in testes of 8-day-old Etv5−/− pups. The study reported herein examined the expression of CLDN5 in wild-type (WT) and Etv5−/− mice and evaluated its contribution to BTB function. CLDN5 protein expression was evaluated in 8-day-old WT and Etv5−/− and adult WT, Etv5−/−, and W/Wv testes by immunohistochemistry and in 8-day-old WT Sertoli cell-enriched and germ cell-enriched fractions by immunocytochemistry. Cldn5 mRNA expression was evaluated in 0- to 20-day-old and adult WT mice and in 8-day-old and adult Etv5−/− mice via quantitative PCR. Tracer studies were performed in adult WT, Etv5−/−, and W/Wv mice. The results indicate the following: 1) CLDN5 was expressed in Sertoli cells, spermatogonia, and preleptotene spermatocytes. 2) Seminiferous epithelial CLDN5 expression depended upon both the presence of germ cells and ETV5. 3) CLDN5 expression in testicular vascular endothelium and rete testis epithelium was ETV5 independent. 4) Cldn5 mRNA expression increased in the testes of juvenile mice at the time of BTB formation. 5) Testes of Etv5−/− and W/Wv mice, which are both deficient in seminiferous epithelial CLDN5 expression, had biotin tracer leakage from the interstitial space into the seminiferous tubule lumen. In conclusion, CLDN5 is expressed in the seminiferous epithelium, appears to be regulated by multiple influences, and contributes to BTB function. PMID:19571261

The contribution of B-cell proliferation to spleen enlargement in Babesia microti-infected mice.

PubMed Central

Inchley, C J

1987-01-01

Flow cytofluorimetric analysis showed that B-cell proliferation makes a major contribution to the enlargement and increased cellularity of the spleen, which are characteristic of Babesia microti infections in mice. Expansion of the B-cell population was accompanied by modulation of the cell surface, which affected most B lymphocytes, and which was detected as a reduction in the density of surface immunoglobulin. This effect was noted as early as Day 7, shortly after the appearance of parasites in the circulation and the onset of gross spleen changes. In contrast to the results for B cells, the frequency of splenic T cells declined, and when the data were transformed into absolute numbers it became clear that only limited T-cell proliferation had occurred. There was no evidence to suggest that the balance of T-cell subsets was shifted in favour of suppressor T cells. The relationships of these results to reports of immunosuppression by this parasite are discussed. Images Figure 2 Figure 5 PMID:3493207

CFH Y402H polymorphism and the complement activation product C5a: effects on NF-κB activation and inflammasome gene regulation.

PubMed

Cao, Sijia; Wang, Jay Ching Chieh; Gao, Jiangyuan; Wong, Matthew; To, Elliott; White, Valerie A; Cui, Jing Z; Matsubara, Joanne A

2016-05-01

The Y402H polymorphism in the complement factor H (CFH) gene is an important risk factor for age-related macular degeneration (AMD). Complement activation products and proinflammatory cytokines are associated with this polymorphism at the systemic level, but less is known of the associations in the outer retina of the genotyped eye. Here we investigate complement activation products and their role in nuclear factor (NF)-κB activation and gene expression of the NLRP3 inflammasome pathway. Postmortem donor eyes were genotyped for the CFH Y402H polymorphism and assessed for complement C3a, C5a, interleukin (IL)-18 and tumour necrosis factor (TNF)-α. ARPE19 cells were stimulated basolaterally with C5a or TNF-α in polarised cultures. NF-κB activation was assessed with a reporter cell line. Gene expression of inflammasome-related (NLRP3, caspase-1, IL-1β and IL-18) and classic inflammatory (IL-6 and IL-8) genes was studied. The distribution of inflammasome products, IL-1β and IL-18, was studied in postmortem donor eyes with AMD pathologies. Eyes with the homozygous at-risk variant demonstrated higher levels of C5a, IL-18 and TNF-α in Bruch's membrane and choroid. C5a promoted NF-κB activation and upregulation of IL-18 in polarised ARPE19. TNF-α promoted NF-κB activation and gene expression of caspase-1, IL-1β, IL-18, IL-6 and IL-8, but downregulated NLRP3. In eyes with geographic atrophy, strong immunoreactivity was observed for inflammasome products IL-1β and IL-18 compared with age-matched controls. The at-risk polymorphism of the CFH Y402H may contribute to AMD disease process through increased complement and NF-κB activation, and the upregulation of IL-18, a product of inflammasome activation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

18 CFR 1b.5 - Formal investigations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Formal investigations. 1b.5 Section 1b.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.5 Formal investigations. The...

18 CFR 1b.5 - Formal investigations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Formal investigations. 1b.5 Section 1b.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.5 Formal investigations. The...

18 CFR 1b.5 - Formal investigations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Formal investigations. 1b.5 Section 1b.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.5 Formal investigations. The...

18 CFR 1b.5 - Formal investigations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Formal investigations. 1b.5 Section 1b.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.5 Formal investigations. The...

Gully erosion: A comparison of contributing factors in two catchments in South Africa

NASA Astrophysics Data System (ADS)

Mararakanye, Ndifelani; Sumner, Paul D.

2017-07-01

Gully erosion is an environmental, agricultural and social problem requiring extensive research and mitigation actions to control. This study assesses the influence of factors contributing to gully erosion using Geographic Information System (GIS) and Information Value (InfVal) statistics from two catchments coded X12 and W55 in the Mpumalanga province of South Africa. Existing spatial data representing contributing factors; soil, geology, vegetation and land use were analyzed. Topographic variables were extracted from a 10 m Digital Elevation Model (DEM) interpolated from map contours, and gullies were mapped from aerial photos with 0.5 m spatial resolution. A zonal approach was used to extract the proportion of gullies in each of the contributing factor classes using GIS software packages, and InfVal weighting was performed to determine the influence of each class. Comparison of the results shows the variation in the level of influence of factors contributing to gully erosion. The findings in catchment X12 support a commonly held assumption that gully formation is influenced by duplex soils underlain by colluvium and alluvial deposits on a lower slope position where overland flow converges and accumulates, resulting in high soil moisture. Gullies were also influenced by soils developed over weathered granite, gneiss and ultramafic rocks. The influence of a granite rock was further highlighted in catchment W55 where there is a variable thickness of very deep Hutton dominant soil form and shallow Lithosols with sandy texture, on an area of moderate to steep slopes where overland flow converges and accumulates, with high stream power in overgrazed grassland. An understanding of these factors will assist future modelling of the vulnerability to gully erosion over a wider geographical area.

17 CFR 260.10b-5 - Content.

Code of Federal Regulations, 2010 CFR

2005-04-01

... 17 Commodity and Securities Exchanges 3 2005-04-01 2005-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a) Each...

17 CFR 260.10b-5 - Content.

Code of Federal Regulations, 2010 CFR

2012-04-01

... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a) Each...

17 CFR 260.10b-5 - Content.

Code of Federal Regulations, 2010 CFR

2011-04-01

... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a) Each...

Reduced serpinB9-mediated caspase-1 inhibition can contribute to autoinflammatory disease.

PubMed

van der Burgh, Robert; Meeldijk, Jan; Jongeneel, Lieneke; Frenkel, Joost; Bovenschen, Niels; van Gijn, Mariëlle; Boes, Marianne

2016-04-12

Patients who suffer from autoinflammatory disease (AID) exhibit seemingly uncontrolled release of interleukin (IL)-1β. The presence of this inflammatory cytokine triggers immune activation in absence of pathogens and foreign material. The mechanisms that contribute to 'sterile inflammation' episodes in AID patients are not fully understood, although for some AIDs underlying genetic causes have been identified. We show that the serine protease inhibitor B9 (serpinB9) regulates IL-1β release in human monocytes. SerpinB9 function is more commonly known for its role in control of granzyme B. SerpinB9 however also serves to restrain IL-1β maturation through caspase-1 inhibition. We here describe an autoinflammatory disease-associated serpinB9 (c.985G>T, A329S) variant, which we discovered in a patient with unknown AID. Using patient cells and serpinB9 overexpressing monocytic cells, we show the A329S variant of serpinB9 exhibits unobstructed granzyme B inhibition, but compromised caspase-1 inhibition. SerpinB9 gene variants might contribute to AID development.

15 CFR 8b.5 - Assurances required.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Assurances required. 8b.5 Section 8b.5 Commerce and Foreign Trade Office of the Secretary of Commerce PROHIBITION OF DISCRIMINATION AGAINST THE HANDICAPPED IN FEDERALLY ASSISTED PROGRAMS OPERATED BY THE DEPARTMENT OF COMMERCE General Provisions § 8b.5...

15 CFR 8b.5 - Assurances required.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Assurances required. 8b.5 Section 8b.5 Commerce and Foreign Trade Office of the Secretary of Commerce PROHIBITION OF DISCRIMINATION AGAINST THE HANDICAPPED IN FEDERALLY ASSISTED PROGRAMS OPERATED BY THE DEPARTMENT OF COMMERCE General Provisions § 8b.5...

15 CFR 8b.5 - Assurances required.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 15 Commerce and Foreign Trade 1 2012-01-01 2012-01-01 false Assurances required. 8b.5 Section 8b.5 Commerce and Foreign Trade Office of the Secretary of Commerce PROHIBITION OF DISCRIMINATION AGAINST THE HANDICAPPED IN FEDERALLY ASSISTED PROGRAMS OPERATED BY THE DEPARTMENT OF COMMERCE General Provisions § 8b.5...

15 CFR 8b.5 - Assurances required.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 15 Commerce and Foreign Trade 1 2014-01-01 2014-01-01 false Assurances required. 8b.5 Section 8b.5 Commerce and Foreign Trade Office of the Secretary of Commerce PROHIBITION OF DISCRIMINATION AGAINST THE HANDICAPPED IN FEDERALLY ASSISTED PROGRAMS OPERATED BY THE DEPARTMENT OF COMMERCE General Provisions § 8b.5...

15 CFR 8b.5 - Assurances required.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 15 Commerce and Foreign Trade 1 2013-01-01 2013-01-01 false Assurances required. 8b.5 Section 8b.5 Commerce and Foreign Trade Office of the Secretary of Commerce PROHIBITION OF DISCRIMINATION AGAINST THE HANDICAPPED IN FEDERALLY ASSISTED PROGRAMS OPERATED BY THE DEPARTMENT OF COMMERCE General Provisions § 8b.5...

Induction of Epstein-Barr Virus Oncoprotein LMP1 by Transcription Factors AP-2 and Early B Cell Factor

PubMed Central

Noda, Chieko; Narita, Yohei; Watanabe, Takahiro; Yoshida, Masahiro; Ashio, Keiji; Sato, Yoshitaka; Goshima, Fumi; Kanda, Teru; Yoshiyama, Hironori; Tsurumi, Tatsuya; Kimura, Hiroshi

2016-01-01

ABSTRACT Latent membrane protein 1 (LMP1) is a major oncogene essential for primary B cell transformation by Epstein-Barr virus (EBV). Previous studies suggested that some transcription factors, such as PU.1, RBP-Jκ, NF-κB, and STAT, are involved in this expression, but the underlying mechanism is unclear. Here, we identified binding sites for PAX5, AP-2, and EBF in the proximal LMP1 promoter (ED-L1p). We first confirmed the significance of PU.1 and POU domain transcription factor binding for activation of the promoter in latency III. We then focused on the transcription factors AP-2 and early B cell factor (EBF). Interestingly, among the three AP-2-binding sites in the LMP1 promoter, two motifs were also bound by EBF. Overexpression, knockdown, and mutagenesis in the context of the viral genome indicated that AP-2 plays an important role in LMP1 expression in latency II in epithelial cells. In latency III B cells, on the other hand, the B cell-specific transcription factor EBF binds to the ED-L1p and activates LMP1 transcription from the promoter. IMPORTANCE Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is crucial for B cell transformation and oncogenesis of other EBV-related malignancies, such as nasopharyngeal carcinoma and T/NK lymphoma. Its expression is largely dependent on the cell type or condition, and some transcription factors have been implicated in its regulation. However, these previous reports evaluated the significance of specific factors mostly by reporter assay. In this study, we prepared point-mutated EBV at the binding sites of such transcription factors and confirmed the importance of AP-2, EBF, PU.1, and POU domain factors. Our results will provide insight into the transcriptional regulation of the major oncogene LMP1. PMID:26819314

New methods for B meson decay constants and form factors from lattice NRQCD

DOE PAGES

Hughes, C.; Davies, C. T.H.; Monahan, C. J.

2018-03-20

We determine the normalization of scalar and pseudoscalar current operators made from nonrelativistic b quarks and highly improved staggered light quarks in lattice quantum chromodynamics (QCD) through O(α s) and Λ QCD/m b. We use matrix elements of these operators to extract B meson decay constants and form factors, and then compare to those obtained using the standard vector and axial-vector operators. This provides a test of systematic errors in the lattice QCD determination of the B meson decay constants and form factors. We provide a new value for the B and B s meson decay constants from lattice QCDmore » calculations on ensembles that include u, d, s, and c quarks in the sea and those that have the u/d quark mass going down to its physical value. Our results are f B=0.196(6) GeV, f Bs=0.236(7) GeV, and f Bs/f B=1.207(7), agreeing well with earlier results using the temporal axial current. By combining with these previous results, we provide updated values of f B=0.190(4) GeV, f Bs=0.229(5) GeV, and f Bs/f B=1.206(5).« less

New methods for B meson decay constants and form factors from lattice NRQCD

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hughes, C.; Davies, C. T.H.; Monahan, C. J.

We determine the normalization of scalar and pseudoscalar current operators made from nonrelativistic b quarks and highly improved staggered light quarks in lattice quantum chromodynamics (QCD) through O(α s) and Λ QCD/m b. We use matrix elements of these operators to extract B meson decay constants and form factors, and then compare to those obtained using the standard vector and axial-vector operators. This provides a test of systematic errors in the lattice QCD determination of the B meson decay constants and form factors. We provide a new value for the B and B s meson decay constants from lattice QCDmore » calculations on ensembles that include u, d, s, and c quarks in the sea and those that have the u/d quark mass going down to its physical value. Our results are f B=0.196(6) GeV, f Bs=0.236(7) GeV, and f Bs/f B=1.207(7), agreeing well with earlier results using the temporal axial current. By combining with these previous results, we provide updated values of f B=0.190(4) GeV, f Bs=0.229(5) GeV, and f Bs/f B=1.206(5).« less

New methods for B meson decay constants and form factors from lattice NRQCD

NASA Astrophysics Data System (ADS)

Hughes, C.; Davies, C. T. H.; Monahan, C. J.; Hpqcd Collaboration

2018-03-01

We determine the normalization of scalar and pseudoscalar current operators made from nonrelativistic b quarks and highly improved staggered light quarks in lattice quantum chromodynamics (QCD) through O (αs) and ΛQCD/mb. We use matrix elements of these operators to extract B meson decay constants and form factors, and then compare to those obtained using the standard vector and axial-vector operators. This provides a test of systematic errors in the lattice QCD determination of the B meson decay constants and form factors. We provide a new value for the B and Bs meson decay constants from lattice QCD calculations on ensembles that include u , d , s , and c quarks in the sea and those that have the u /d quark mass going down to its physical value. Our results are fB=0.196 (6 ) GeV , fBs=0.236(7 ) GeV , and fB s/fB=1.207 (7 ), agreeing well with earlier results using the temporal axial current. By combining with these previous results, we provide updated values of fB=0.190 (4 ) GeV , fBs=0.229(5 ) GeV , and fB s/fB=1.206 (5 ).

17 CFR 260.10b-5 - Content.

Code of Federal Regulations, 2010 CFR

2000-04-01

... 17 Commodity and Securities Exchanges 3 2000-04-01 2000-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a) Each application for a stay of a trustee's duty to...

Large electroweak penguin contribution in B{yields}K{pi} and {pi}{pi} decay modes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mishima, Satoshi; Yoshikawa, Tadashi

2004-11-01

We discuss a possibility of large electroweak penguin contribution in B{yields}K{pi} and {pi}{pi} from recent experimental data. The experimental data may be suggesting that there are some discrepancies between the data and theoretical estimation in the branching ratios of them. In B{yields}K{pi} decays, to explain it, a large electroweak penguin contribution and large strong phase differences seem to be needed. The contributions should appear also in B{yields}{pi}{pi}. We show, as an example, a solution to solve the discrepancies in both B{yields}K{pi} and B{yields}{pi}{pi}. However the magnitude of the parameters and the strong phase estimated from experimental data are quite largemore » compared with the theoretical estimations. It may be suggesting some new physics effects are included in these processes. We will have to discuss about the dependence of the new physics. To explain both modes at once, we may need large electroweak penguin contribution with new weak phases and some SU(3) breaking effects by new physics in both QCD and electroweak penguin-type processes.« less

Nuclear factor-kappaB activation and postischemic inflammation are suppressed in CD36-null mice after middle cerebral artery occlusion.

PubMed

Kunz, Alexander; Abe, Takato; Hochrainer, Karin; Shimamura, Munehisa; Anrather, Josef; Racchumi, Gianfranco; Zhou, Ping; Iadecola, Costantino

2008-02-13

CD36, a class-B scavenger receptor involved in multiple functions, including inflammatory signaling, may also contribute to ischemic brain injury through yet unidentified mechanisms. We investigated whether CD36 participates in the molecular events underlying the inflammatory reaction that accompanies cerebral ischemia and may contribute to the tissue damage. We found that activation of nuclear factor-kappaB, a transcription factor that coordinates postischemic gene expression, is attenuated in CD36-null mice subjected to middle cerebral artery occlusion. The infiltration of neutrophils and the glial reaction induced by cerebral ischemia were suppressed. Treatment with an inhibitor of inducible nitric oxide synthase, an enzyme that contributes to the tissue damage, reduced ischemic brain injury in wild-type mice, but not in CD36 nulls. In contrast to cerebral ischemia, the molecular and cellular inflammatory changes induced by intracerebroventricular injection of interleukin-1beta were not attenuated in CD36-null mice. The findings unveil a novel role of CD36 in early molecular events leading to nuclear factor-kappaB activation and postischemic inflammation. Inhibition of CD36 signaling may be a valuable therapeutic approach to counteract the deleterious effects of postischemic inflammation.

Anatomy of Bs → PV decays and effects of next-to-leading order contributions in the perturbative QCD factorization approach

NASA Astrophysics Data System (ADS)

Yan, Da-Cheng; Yang, Ping; Liu, Xin; Xiao, Zhen-Jun

2018-06-01

In this paper, we will make systematic calculations for the branching ratios and the CP-violating asymmetries of the twenty one Bbars0 → PV decays by employing the perturbative QCD (PQCD) factorization approach. Besides the full leading-order (LO) contributions, all currently known next-to-leading order (NLO) contributions are taken into account. We found numerically that: (a) the NLO contributions can provide ∼ 40% enhancement to the LO PQCD predictions for B (Bbars0 →K0K bar * 0) and B (Bbars0 →K±K*∓), or a ∼ 37% reduction to B (Bbars0 →π-K*+); and we confirmed that the inclusion of the known NLO contributions can improve significantly the agreement between the theory and those currently available experimental measurements; (b) the total effects on the PQCD predictions for the relevant Bs0 → P transition form factors after the inclusion of the NLO twist-2 and twist-3 contributions is generally small in magnitude: less than 10% enhancement respect to the leading order result; (c) for the "tree" dominated decay Bbars0 →K+ρ- and the "color-suppressed-tree" decay Bbars0 →π0K*0, the big difference between the PQCD predictions for their branching ratios are induced by different topological structure and by interference effects among the decay amplitude AT,C and AP: constructive for the first decay but destructive for the second one; and (d) for Bbars0 → V (η ,η‧) decays, the complex pattern of the PQCD predictions for their branching ratios can be understood by rather different topological structures and the interference effects between the decay amplitude A (Vηq) and A (Vηs) due to the η-η‧ mixing.

Risk factors for osteoarthritis and contributing factors to current arthritic pain in South Korean older adults.

PubMed

Lee, Kyoung Min; Chung, Chin Youb; Sung, Ki Hyuk; Lee, Seung Yeol; Won, Sung Hun; Kim, Tae Gyun; Choi, Young; Kwon, Soon Sun; Kim, Yeon Ho; Park, Moon Seok

2015-01-01

Although previous studies have focused on risk factors for osteoarthritis, there is some debate on this issue. Furthermore, associated factors with arthritic symptom (arthralgia) have not been sufficiently investigated, despite its clinical importance in the management of osteoarthritis. This study was performed to examine the risk factors for osteoarthritis and the contributing factors to current arthritic pain in older adults. The Fourth Korean National Health and Nutrition Examination Surveys was conducted in 2009. Therein, 720 males and 1008 females aged 65 years and older were included. Comprehensive data on habitual, socioeconomic, medical, nutritional, and psychological factors were collected along with the presence of osteoarthritis and arthritic pain. After univariate analysis, binary logistic regression analysis was performed to identify risk factors for osteoarthritis and contributing factors to current arthritic pain. Age (p=0.005), female gender (p<0.001), higher body mass index (BMI) (p<0.001), and osteoporosis (p<0.001) were significant risk factors for osteoarthritis, while higher education level (p=0.025) was a protective factor for osteoarthritis. Higher BMI (p=0.047), lack of weekly moderate intensity activity (p<0.001), and unfavorable subjective health status (p<0.001) were significant factors contributing to current arthritic pain among subjects with osteoarthritis. Both osteoarthritis and current arthritic pain adversely affected health related quality of life. Higher BMI, lack of weekly moderate intensity activity, and unfavorable subjective health status were significant factors contributing to current arthritic pain. More attention needs to be paid to psychiatric effects on osteoarthritis and joint related pain.

17 CFR 260.10b-5 - Content.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a) Each application for a stay of a trustee's duty to...

17 CFR 260.10b-5 - Content.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a) Each application for a stay of a trustee's duty to...

17 CFR 260.10b-5 - Content.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a) Each application for a stay of a trustee's duty to...

NF-κB is required for dengue virus NS5-induced RANTES expression.

PubMed

Khunchai, Sasiprapa; Junking, Mutita; Suttitheptumrong, Aroonroong; Kooptiwut, Suwattanee; Haegeman, Guy; Limjindaporn, Thawornchai; Yenchitsomanus, Pa-Thai

2015-02-02

Dengue virus (DENV) infection associates with renal disorders. Patients with dengue hemorrhagic fever and acute kidney injury have a high mortality rate. Increased levels of cytokines may contribute to the pathogenesis of DENV-induced kidney injury. Currently, molecular mechanisms how DENV induces kidney cell injury has not been thoroughly investigated. Excessive cytokine production may be involved in this process. Using human cytokine RT(2) Profiler PCR array, 14 genes including IP-10, RANTES, IL-8, CXCL-9 and MIP-1β were up-regulated more than 2 folds in DENV-infected HEK 293 cells compared to that of mock-infected HEK 293 cells. In the present study, RANTES was suppressed by the NF-κB inhibitor, compound A (CpdA), in DENV-infected HEK 293 cells implying the role of NF-κB in RANTES expression. Chromatin immunoprecipitation (ChIP) assay showed that NF-κB binds more efficiently to its binding sites on the RANTES promoter in NS5-transfected HEK 293 cells than in HEK 293 cells expressing the vector lacking NS5 gene. To further examine whether the NS5-activated RANTES promoter is mediated through NF-κB, the two NF-κB binding sites on the RANTES promoter were mutated and this promoter was coupled to the luciferase cDNA. The result showed that when both binding sites of NF-κB in the RANTES promoter were mutated, the ability of NS5 to induce the luciferase activity was significantly decreased. Therefore, DENV NS5 activates RANTES production by increasing NF-κB binding to its binding sites on the RANTES promoter. Copyright © 2014 Elsevier B.V. All rights reserved.

Identification of a novel A20-binding inhibitor of nuclear factor-kappa B activation termed ABIN-2.

PubMed

Van Huffel, S; Delaei, F; Heyninck, K; De Valck, D; Beyaert, R

2001-08-10

The nuclear factor kappaB (NF-kappaB) plays a central role in the regulation of genes implicated in immune responses, inflammatory processes, and apoptotic cell death. The zinc finger protein A20 is a cellular inhibitor of NF-kappaB activation by various stimuli and plays a critical role in terminating NF-kappaB responses. The underlying mechanism for NF-kappaB inhibition by A20 is still unknown. A20 has been shown to interact with several proteins including tumor necrosis factor (TNF) receptor-associated factors 2 and 6, as well as the inhibitory protein of kappaB kinase (IKK) gamma protein. Here we report the cloning and characterization of ABIN-2, a previously unknown protein that binds to the COOH-terminal zinc finger domain of A20. NF-kappaB activation induced by TNF and interleukin-1 is inhibited by overexpression of ABIN-2. The latter also inhibits NF-kappaB activation induced by overexpression of receptor-interacting protein or TNF receptor-associated factor 2. In contrast, NF-kappaB activation by overexpression of IKKbeta or direct activators of the IKK complex, such as Tax, cannot be inhibited by ABIN-2. These results indicate that ABIN-2 interferes with NF-kappaB activation upstream of the IKK complex and that it might contribute to the NF-kappaB-inhibitory function of A20.

Gladiolus hybridus ABSCISIC ACID INSENSITIVE 5 (GhABI5) is an important transcription factor in ABA signaling that can enhance Gladiolus corm dormancy and Arabidopsis seed dormancy.

PubMed

Wu, Jian; Seng, Shanshan; Sui, Juanjuan; Vonapartis, Eliana; Luo, Xian; Gong, Benhe; Liu, Chen; Wu, Chenyu; Liu, Chao; Zhang, Fengqin; He, Junna; Yi, Mingfang

2015-01-01

The phytohormone abscisic acid (ABA) regulates plant development and is crucial for abiotic stress response. In this study, cold storage contributes to reducing endogenous ABA content, resulting in dormancy breaking of Gladiolus. The ABA inhibitor fluridone also promotes germination, suggesting that ABA is an important hormone that regulates corm dormancy. Here, we report the identification and functional characterization of the Gladiolus ABI5 homolog (GhABI5), which is a basic leucine zipper motif transcriptional factor (TF). GhABI5 is expressed in dormant vegetative organs (corm, cormel, and stolon) as well as in reproductive organs (stamen), and it is up-regulated by ABA or drought. Complementation analysis reveals that GhABI5 rescues the ABA insensitivity of abi5-3 during seed germination and induces the expression of downstream ABA response genes in Arabidopsis thaliana (EM1, EM6, and RD29B). Down-regulation of GhABI5 in dormant cormels via virus induced gene silence promotes sprouting and reduces the expression of downstream genes (GhLEA and GhRD29B). The results of this study reveal that GhABI5 regulates bud dormancy (vegetative organ) in Gladiolus in addition to its well-studied function in Arabidopsis seeds (reproductive organ).

Gladiolus hybridus ABSCISIC ACID INSENSITIVE 5 (GhABI5) is an important transcription factor in ABA signaling that can enhance Gladiolus corm dormancy and Arabidopsis seed dormancy

PubMed Central

Wu, Jian; Seng, Shanshan; Sui, Juanjuan; Vonapartis, Eliana; Luo, Xian; Gong, Benhe; Liu, Chen; Wu, Chenyu; Liu, Chao; Zhang, Fengqin; He, Junna; Yi, Mingfang

2015-01-01

The phytohormone abscisic acid (ABA) regulates plant development and is crucial for abiotic stress response. In this study, cold storage contributes to reducing endogenous ABA content, resulting in dormancy breaking of Gladiolus. The ABA inhibitor fluridone also promotes germination, suggesting that ABA is an important hormone that regulates corm dormancy. Here, we report the identification and functional characterization of the Gladiolus ABI5 homolog (GhABI5), which is a basic leucine zipper motif transcriptional factor (TF). GhABI5 is expressed in dormant vegetative organs (corm, cormel, and stolon) as well as in reproductive organs (stamen), and it is up-regulated by ABA or drought. Complementation analysis reveals that GhABI5 rescues the ABA insensitivity of abi5-3 during seed germination and induces the expression of downstream ABA response genes in Arabidopsis thaliana (EM1, EM6, and RD29B). Down-regulation of GhABI5 in dormant cormels via virus induced gene silence promotes sprouting and reduces the expression of downstream genes (GhLEA and GhRD29B). The results of this study reveal that GhABI5 regulates bud dormancy (vegetative organ) in Gladiolus in addition to its well-studied function in Arabidopsis seeds (reproductive organ). PMID:26579187

Robo4 maintains vessel integrity and inhibits angiogenesis by interacting with UNC5B.

PubMed

Koch, Alexander W; Mathivet, Thomas; Larrivée, Bruno; Tong, Raymond K; Kowalski, Joe; Pibouin-Fragner, Laurence; Bouvrée, Karine; Stawicki, Scott; Nicholes, Katrina; Rathore, Nisha; Scales, Suzie J; Luis, Elizabeth; del Toro, Raquel; Freitas, Catarina; Bréant, Christiane; Michaud, Annie; Corvol, Pierre; Thomas, Jean-Léon; Wu, Yan; Peale, Franklin; Watts, Ryan J; Tessier-Lavigne, Marc; Bagri, Anil; Eichmann, Anne

2011-01-18

Robo4 is an endothelial cell-specific member of the Roundabout axon guidance receptor family. To identify Robo4 binding partners, we performed a protein-protein interaction screen with the Robo4 extracellular domain. We find that Robo4 specifically binds to UNC5B, a vascular Netrin receptor, revealing unexpected interactions between two endothelial guidance receptors. We show that Robo4 maintains vessel integrity by activating UNC5B, which inhibits signaling downstream of vascular endothelial growth factor (VEGF). Function-blocking monoclonal antibodies against Robo4 and UNC5B increase angiogenesis and disrupt vessel integrity. Soluble Robo4 protein inhibits VEGF-induced vessel permeability and rescues barrier defects in Robo4(-/-) mice, but not in mice treated with anti-UNC5B. Thus, Robo4-UNC5B signaling maintains vascular integrity by counteracting VEGF signaling in endothelial cells, identifying a novel function of guidance receptor interactions in the vasculature. Copyright © 2011 Elsevier Inc. All rights reserved.

Highway safety : research continues on a variety of factors that contribute to motor vehicle crashes

DOT National Transportation Integrated Search

2003-03-31

Nearly 6.3 million motor vehicle crashes occurred in the United States in 2001, or one crash every 5 seconds. This study examined human, environmental, and vehicle factors that contribute to crashes. As requested, this report provides more recent inf...

Implementation and evaluation of PM2.5 source contribution ...

EPA Pesticide Factsheets

Source culpability assessments are useful for developing effective emissions control programs. The Integrated Source Apportionment Method (ISAM) has been implemented in the Community Multiscale Air Quality (CMAQ) model to track contributions from source groups and regions to ambient levels and deposited amounts of primary and secondary inorganic PM2.5. Confidence in this approach is established by comparing ISAM source contribution estimates to emissions zero-out simulations recognizing that these approaches are not always expected to provide the same answer. The comparisons are expected to be most similar for more linear processes such as those involving primary emissions of PM2.5 and most different for non-linear systems like ammonium nitrate formation. Primarily emitted PM2.5 (e.g. elemental carbon), sulfur dioxide, ammonia, and nitrogen oxide contribution estimates compare well to zero-out estimates for ambient concentration and deposition. PM2.5 sulfate ion relationships are strong, but nonlinearity is evident and shown to be related to aqueous phase oxidation reactions in the host model. ISAM and zero-out contribution estimates are less strongly related for PM2.5 ammonium nitrate, resulting from instances of non-linear chemistry and negative responses (increases in PM2.5 due to decreases in emissions). ISAM is demonstrated in the context of an annual simulation tracking well characterized emissions source sectors and boundary conditions shows source contri

Plant extracts of spices and coffee synergistically dampen nuclear factor-κB in U937 cells.

PubMed

Kolberg, Marit; Paur, Ingvild; Balstad, Trude R; Pedersen, Sigrid; Jacobs, David R; Blomhoff, Rune

2013-10-01

A large array of bioactive plant compounds (phytochemicals) has been identified and synergy among these compounds might contribute to the beneficial effects of plant foods. The transcription factor nuclear factor-κB (NF-κB) has been suggested as a target for many phytochemicals. Due to the complexity of mechanisms involved in NF-κB regulation, including numerous feedback loops, and the large number of phytochemicals which regulate NF-κB activity, we hypothesize that synergistic or antagonistic effects are involved. The objectives of our study were to develop a statistical methodology to evaluate the concept of synergy and antagonism and to use this methodology in a monocytic cell line (U937 expressing an NF-κB-luciferase reporter) treated with lipopolysaccharide and phytochemical-rich plant extracts. Both synergistic and antagonistic effects were clearly observed. Observed synergy was most pronounced for the combinations of oregano and coffee, and thyme and oregano. For oregano and coffee the synergistic effect was highest at 5 mg/mL with 13.9% (P < .001), and for thyme and oregano the highest synergistic effects was at 3 mg/mL with 13.7% (P < .001). Dose dependent synergistic and antagonistic effects were observed for all combinations tested. In conclusion, this work presents a methodological tool to define synergy in experimental studies. Our results support the hypothesis that phytochemical-rich plants may exert synergistic and antagonistic effects on NF-κB regulation. Such complex mechanistic interactions between phytochemicals are likely to underlie the protective effects of a plant-based diet on life-style related diseases. © 2013 Elsevier Inc. All rights reserved.

ATP5B and ETFB metabolic markers in children with congenital hydronephrosis.

PubMed

Zhao, Qi; Yang, Yi; Wang, Changlin; Hou, Ying; Chen, Hui

2016-12-01

Congenital obstructive nephropathy is the primary cause of chronic renal failure in children. Disorders of mitochondrial energy metabolism may be a primary factor underlying tubular cell apoptosis in hydronephrosis. The β-F1-ATPase (ATP5B) and electron transfer flavoprotein β subunit (ETFB) metabolic markers are involved in mitochondrial energy metabolism in other diseases. The aim of the present study was to evaluate whether ATP5B and ETFB are represented in the hydronephrotic kidney, and whether they are associated with the progression of hydronephrosis. The cohort examined consisted of 20 children with hydronephrosis, graded III and IV using the Society for Fetal Urology grading system, and a control group consisting of 20 patients with nephroblastoma. Reverse transcription‑quantitative polymerase chain reaction and immunoblot analyses were used to investigate the differential expression of genes and proteins in the two groups. The gene and protein expression levels of ATP5B and ETFB were upregulated in the hydronephrosis group. Correlation analyses revealed negative correlations between ATP5B, ETFB protein and split renal function (SRF). Receiver‑operator curve analysis found a diagnostic profile of the ETFB protein in identifying children with hydronephrosis with abnormal SRF (<45%). These results suggested that increasing levels of ATP5B and ETFB were associated with worsening renal injury. ATP5B and ETFB may be novel markers in hydronephrosis and require further detailed investigation.

ATP5B and ETFB metabolic markers in children with congenital hydronephrosis

PubMed Central

Zhao, Qi; Yang, Yi; Wang, Changlin; Hou, Ying; Chen, Hui

2016-01-01

Congenital obstructive nephropathy is the primary cause of chronic renal failure in children. Disorders of mitochondrial energy metabolism may be a primary factor underlying tubular cell apoptosis in hydronephrosis. The β-F1-ATPase (ATP5B) and electron transfer flavoprotein β subunit (ETFB) metabolic markers are involved in mitochondrial energy metabolism in other diseases. The aim of the present study was to evaluate whether ATP5B and ETFB are represented in the hydronephrotic kidney, and whether they are associated with the progression of hydronephrosis. The cohort examined consisted of 20 children with hydronephrosis, graded III and IV using the Society for Fetal Urology grading system, and a control group consisting of 20 patients with nephroblastoma. Reverse transcription-quantitative polymerase chain reaction and immunoblot analyses were used to investigate the differential expression of genes and proteins in the two groups. The gene and protein expression levels of ATP5B and ETFB were upregulated in the hydronephrosis group. Correlation analyses revealed negative correlations between ATP5B, ETFB protein and split renal function (SRF). Receiver-operator curve analysis found a diagnostic profile of the ETFB protein in identifying children with hydronephrosis with abnormal SRF (<45%). These results suggested that increasing levels of ATP5B and ETFB were associated with worsening renal injury. ATP5B and ETFB may be novel markers in hydronephrosis and require further detailed investigation. PMID:27840937

Factors contributing to poor sleep quality as perceived by heart transplant recipients in Taiwan.

PubMed

Tseng, P H; Shih, F Jong; Yang, F C; Shih, F Jin; Wang, S S

2014-04-01

The aims of this project were to explore the factors contributing to poor sleep quality at 1 to 3 years after heart transplantation (post-HT), and to explore economic problems and social support for HT recipients (HTRs). This study used a cross-sectional retrospective triangulation approach combining qualitative and quantitative research method designs. Quantitative data included data from the visual analog scale and the Taiwanese version of the World Health Organization Quality of Life questionnaire. Qualitative data were derived from questions that explored physiological, psychological, and economic factors contributing to poor sleep quality postprocedure for HTRs. Sixty-four subjects (81% male, 19% female) participated in this research. Their ages ranged from 20 to 70 (M = 46.88 ± 12.12) years old. Their post-HT timeframe ranged from 1 to 4.10 years; 33% received preoperative extracorporeal membrane oxygenation support. Sleeping disturbances were reported by 72.7% of subjects after HT. Poor sleeping quality at 2 to 3 years post-HT (P = .028) was a complaint, and was worse than at 1 to 2 years post-HT (P = .008). Six physiological (62.5%) and 3 psychological (37.5%) contributing factors were further identified in qualitative interviews. Physiological factors were the major causes affecting their sleep quality 2 to 3 years after HT, whereas psychological factors arose from various family roles, responsibilities, and economic-related pressures. Medical teams should find the causes that lead to sleep disturbances and use the findings to improve HTR sleep quality. When the family financial status is affected, these teams should offer assistance and suggestions for patients who are unable to work due to post-HT physical decline. Establishing and providing good family support systems or patient support groups may allow patients to obtain physical, psychological, and spiritual comfort. Copyright © 2014 Elsevier Inc. All rights reserved.

Source Apportionment and Influencing Factor Analysis of Residential Indoor PM2.5 in Beijing

PubMed Central

Yang, Yibing; Liu, Liu; Xu, Chunyu; Li, Na; Liu, Zhe; Wang, Qin; Xu, Dongqun

2018-01-01

In order to identify the sources of indoor PM2.5 and to check which factors influence the concentration of indoor PM2.5 and chemical elements, indoor concentrations of PM2.5 and its related elements in residential houses in Beijing were explored. Indoor and outdoor PM2.5 samples that were monitored continuously for one week were collected. Indoor and outdoor concentrations of PM2.5 and 15 elements (Al, As, Ca, Cd, Cu, Fe, K, Mg, Mn, Na, Pb, Se, Tl, V, Zn) were calculated and compared. The median indoor concentration of PM2.5 was 57.64 μg/m3. For elements in indoor PM2.5, Cd and As may be sensitive to indoor smoking, Zn, Ca and Al may be related to indoor sources other than smoking, Pb, V and Se may mainly come from outdoor. Five factors were extracted for indoor PM2.5 by factor analysis, explained 76.8% of total variance, outdoor sources contributed more than indoor sources. Multiple linear regression analysis for indoor PM2.5, Cd and Pb was performed. Indoor PM2.5 was influenced by factors including outdoor PM2.5, smoking during sampling, outdoor temperature and time of air conditioner use. Indoor Cd was affected by factors including smoking during sampling, outdoor Cd and building age. Indoor Pb concentration was associated with factors including outdoor Pb and time of window open per day, building age and RH. In conclusion, indoor PM2.5 mainly comes from outdoor sources, and the contributions of indoor sources also cannot be ignored. Factors associated indoor and outdoor air exchange can influence the concentrations of indoor PM2.5 and its constituents. PMID:29621164

Source Apportionment and Influencing Factor Analysis of Residential Indoor PM2.5 in Beijing.

PubMed

Yang, Yibing; Liu, Liu; Xu, Chunyu; Li, Na; Liu, Zhe; Wang, Qin; Xu, Dongqun

2018-04-05

In order to identify the sources of indoor PM 2.5 and to check which factors influence the concentration of indoor PM 2.5 and chemical elements, indoor concentrations of PM 2.5 and its related elements in residential houses in Beijing were explored. Indoor and outdoor PM 2.5 samples that were monitored continuously for one week were collected. Indoor and outdoor concentrations of PM 2.5 and 15 elements (Al, As, Ca, Cd, Cu, Fe, K, Mg, Mn, Na, Pb, Se, Tl, V, Zn) were calculated and compared. The median indoor concentration of PM 2.5 was 57.64 μg/m³. For elements in indoor PM 2.5 , Cd and As may be sensitive to indoor smoking, Zn, Ca and Al may be related to indoor sources other than smoking, Pb, V and Se may mainly come from outdoor. Five factors were extracted for indoor PM 2.5 by factor analysis, explained 76.8% of total variance, outdoor sources contributed more than indoor sources. Multiple linear regression analysis for indoor PM 2.5 , Cd and Pb was performed. Indoor PM 2.5 was influenced by factors including outdoor PM 2.5 , smoking during sampling, outdoor temperature and time of air conditioner use. Indoor Cd was affected by factors including smoking during sampling, outdoor Cd and building age. Indoor Pb concentration was associated with factors including outdoor Pb and time of window open per day, building age and RH. In conclusion, indoor PM 2.5 mainly comes from outdoor sources, and the contributions of indoor sources also cannot be ignored. Factors associated indoor and outdoor air exchange can influence the concentrations of indoor PM 2.5 and its constituents.

Tree-level contributions to the rare decays B+→π+νν¯, B+→K+νν¯, and B+→K*νν¯ in the Standard Model

NASA Astrophysics Data System (ADS)

Kamenik, Jernej F.; Smith, Christopher

2009-10-01

The tree-level contributions to the rare decays B+ →π+ ννbar, B+ →K+ ννbar, and B+ →K*+ ννbar are analyzed and compared to those occurring in K+ →π+ ννbar, D+ →π+ ννbar, and Ds+ →π+ ννbar. It is shown that these purely long-distance contributions, arising from the exchange of a charged lepton, can be significant in B+ decays for an intermediate τ, potentially blurring the distinction between the modes used to extract B+ →τ+ντ and those used to probe the genuine short-distance b → dννbar and b → sννbar FCNC transitions. Numerically, the tree-level contributions are found to account for 98%, 12% and 14% of the total B+ →π+ ννbar, B+ →K+ ννbar, and B+ →K*+ ννbar rates, respectively.

Rescattering contributions to rare B-meson decays

NASA Astrophysics Data System (ADS)

Gronau, Michael; London, David; Rosner, Jonathan L.

2013-02-01

Several B and Bs decays have been observed that have been cited as evidence for exchange (E), penguin annihilation (PA), and annihilation (A) processes, such as b¯d→u¯u, b¯s→u¯u, and b¯u→W*→c¯s, respectively. These amplitudes are normally thought to be suppressed, as they involve the spectator quark in the weak interaction and thus should be proportional to the B-meson decay constant fB. However, as pointed out a number of years ago, they can also be generated by rescattering from processes whose amplitudes do not involve fB, such as color-favored tree amplitudes. In this paper we investigate a number of processes such as B0→K+K-, Bs→π+π-, and B+→Ds+ϕ, and identify promising states from which they can be generated by rescattering. We find that E-and PA-type processes are characterized, respectively, by amplitudes ranging from 5% to 10% and from 15% to 20% with respect to the largest amplitude from which they can rescatter. Based on this regularity, using approximate flavor SU(3) symmetry in some cases and time-reversal invariance in others, we predict the branching fractions for a large number of as-yet-unseen B and Bs decays in an extensive range from order 10-9 to 10-4.

Fisetin Ameliorated Photodamage by Suppressing the Mitogen-Activated Protein Kinase/Matrix Metalloproteinase Pathway and Nuclear Factor-κB Pathways.

PubMed

Chiang, Hsiu-Mei; Chan, Shih-Yun; Chu, Yin; Wen, Kuo-Ching

2015-05-13

Ultraviolet (UV) irradiation is one of the most important extrinsic factors contributing to skin photodamage. After UV irradiation, a series of signal transductions in the skin will be activated, leading to inflammatory response and photoaged skin. In this study, fisetin, a flavonol that exists in fruits and vegetables, was investigated for its photoprotective effects. The results revealed that 5-25 μM fisetin inhibits cyclooxygenase-2 (COX-2) and matrix metalloproteinase (MMP)-1, MMP-3, MMP-9 expression induced by ultraviolet B (UVB) irradiation in human skin fibroblasts. In addition, fisetin suppressed UVB-induced collagen degradation. With regard to its effect on upper-stream signal transduction, we found that fisetin reduced the expression of ultraviolet (UV)-induced ERK, JNK, and p38 phosphorylation in the mitogen-activated protein kinase (MAP kinase) pathway. Furthermore, fisetin reduced inhibitor κB (IκB) degradation and increased the amount of p65, which is a major subunit of nuclear factor-κB (NF-κB), in cytoplasm. It also suppressed NF-κB translocated to the nucleus and inhibited cAMP response element-binding protein (CREB) Ser-133 phosphorylation level in the phosphoinositide 3-kinase/protein kinase B/CREB (PI3K/AKT/CREB) pathway. Finally, fisetin inhibited UV-induced intracellular reactive oxygen species (ROS), prostaglandin E2 (PGE2), and nitric oxide (NO) generation. The mentioned effects and mechanisms suggest that fisetin can be used in the development of photoprotective agents.

Insulin-like growth factor-binding protein-5 (IGFBP-5) inhibits TNF-{alpha}-induced NF-{kappa}B activity by binding to TNFR1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hwang, Jae Ryoung; Huh, Jae Ho; Lee, Yoonna

2011-02-25

Research highlights: {yields} Binding assays demonstrated that secreted- and cellular-IGFBP-5 interacted with TNFR1. {yields} The interaction between IGFBP-5 and TNFR1 was inhibited by TNF-{alpha} and was blocked TNF-{alpha}-activated NF-{kappa}B activity. {yields} IGFBP-5 interacted with TNFR1 through its N- and L-domains but the binding of L-domain to TNFR1 was blocked by TNF-{alpha}. {yields} Competition between the L-domain of IGFBP-5 and TNF-{alpha} blocked TNF-{alpha}-induced NF-{kappa}B activity. {yields} This study suggests that the L-domain of IGFBP-5 is a novel TNFR1 ligand that functions as a competitive TNF-{alpha} inhibitor. -- Abstract: IGFBP-5 is known to be involved in various cell phenomena such as proliferation,more » differentiation, and apoptosis. However, the exact mechanisms by which IGFBP-5 exerts its functions are unclear. In this study, we demonstrate for the first time that IGFBP-5 is a TNFR1-interacting protein. We found that ectopic expression of IGFBP-5 induced TNFR1 gene expression, and that IGFBP-5 interacted with TNFR1 in both an in vivo and an in vitro system. Secreted IGFBP-5 interacted with GST-TNFR1 and this interaction was blocked by TNF-{alpha}, demonstrating that IGFBP-5 might be a TNFR1 ligand. Furthermore, conditioned media containing secreted IGFBP-5 inhibited PMA-induced NF-{kappa}B activity and IL-6 expression in U-937 cells. Coimmunoprecipitation assays of TNFR1 and IGFBP-5 wild-type and truncation mutants revealed that IGFBP-5 interacts with TNFR1 through its N- and L-domains. However, only the interaction between the L-domain of IGFBP-5 and TNFR1 was blocked by TNF-{alpha} in a dose-dependent manner, suggesting that the L-domain of IGFBP-5 can function as a TNFR1 ligand. Competition between the L-domain of IGFBP-5 and TNF-{alpha} resulted in inhibition of TNF-{alpha}-induced NF-{kappa}{Beta} activity. Taken together, our results suggest that the L-domain of IGFBP-5 is a novel TNFR1 ligand that functions as a

Distinct circuits underlie the effects of 5-HT1B receptors on aggression and impulsivity

PubMed Central

Nautiyal, Katherine M.; Tanaka, Kenji F.; Barr, Mary M.; Tritschler, Laurent; Le Dantec, Yannick; David, Denis J.; Gardier, Alain M.; Blanco, Carlos; Hen, René; Ahmari, Susanne E.

2015-01-01

Summary Impulsive and aggressive behaviors are both modulated by serotonergic signaling, specifically through the serotonin 1B receptor (5-HT1BR). 5-HT1BR knockout mice show increased aggression and impulsivity, and 5-HT1BR polymorphisms are associated with aggression and drug addiction in humans. To dissect the mechanisms by which the 5-HT1BR affects these phenotypes, we developed a mouse model to spatially and temporally regulate 5-HT1BR expression. Our results demonstrate that forebrain 5-HT1B heteroreceptors expressed during an early postnatal period contribute to the development of the neural systems underlying adult aggression. However, distinct heteroreceptors acting during adulthood are involved in mediating impulsivity. Correlating with the impulsivity, dopamine in the nucleus accumbens is elevated in the absence of 5-HT1BRs, and normalized following adult rescue of the receptor. Overall, these data show that while adolescent expression of 5-HT1BRs influences aggressive behavior, a distinct set of 5-HT1B receptors modulate impulsive behavior during adulthood. PMID:25892302

Factors contributing to adolescent obesity.

PubMed

Al-Kloub, Manal I; Froelicher, Erika S

2009-06-01

Obesity in children is a significant public health concern. The prevalence of overweight and obesity in Jordanian children, and adolescents has increased in the last decade. The consequences of obesity to health in childhood and adulthood have both medical, and economic cost to individuals and society. This paper reviews the factors that contribute to adolescent obesity and emphasizes behavioral and environmental factors. An individual's behaviors such as increased consumption of high caloric foods, increased sedentary activity while decreasing physical activity has been identified as key issues in the development of obesity. Additionally, the current environment in homes, schools, and neighborhoods tend to discourage a healthy lifestyle. A comprehensive approach that involves the whole community is the best strategy for preventing adolescent obesity. Nurses are in a unique position to provide leadership in developing programs for healthier lifestyle choices for adolescents' and adoption of these goals into their daily lives.

45 CFR 5b.5 - Notification of or access to records.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 5b.5 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PRIVACY ACT... privacy if disclosed to someone other than the subject individual; or, (ii) He makes a request for access... minor or legal incompetent as authorized under § 5b.10 of this part shall verify his relationship to the...

45 CFR 5b.5 - Notification of or access to records.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 5b.5 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PRIVACY ACT... privacy if disclosed to someone other than the subject individual; or, (ii) He makes a request for access... minor or legal incompetent as authorized under § 5b.10 of this part shall verify his relationship to the...

Genetic modification of human B-cell development: B-cell development is inhibited by the dominant negative helix loop helix factor Id3.

PubMed

Jaleco, A C; Stegmann, A P; Heemskerk, M H; Couwenberg, F; Bakker, A Q; Weijer, K; Spits, H

1999-10-15

Transgenic and gene targeted mice have contributed greatly to our understanding of the mechanisms underlying B-cell development. We describe here a model system that allows us to apply molecular genetic techniques to the analysis of human B-cell development. We constructed a retroviral vector with a multiple cloning site connected to a gene encoding green fluorescent protein by an internal ribosomal entry site. Human CD34(+)CD38(-) fetal liver cells, cultured overnight in a combination of stem cell factor and interleukin-7 (IL-7), could be transduced with 30% efficiency. We ligated the gene encoding the dominant negative helix loop helix (HLH) factor Id3 that inhibits many enhancing basic HLH transcription factors into this vector. CD34(+)CD38(-) FL cells were transduced with Id3-IRES-GFP and cultured with the murine stromal cell line S17. In addition, we cultured the transduced cells in a reaggregate culture system with an SV-transformed human fibroblast cell line (SV19). It was observed that overexpression of Id3 inhibited development of B cells in both culture systems. B-cell development was arrested at a stage before expression of the IL-7Ralpha. The development of CD34(+)CD38(-) cells into CD14(+) myeloid cells in the S17 system was not inhibited by overexpression of Id3. Moreover, Id3(+) cells, although inhibited in their B-cell development, were still able to develop into natural killer (NK) cells when cultured in a combination of Flt-3L, IL-7, and IL-15. These findings confirm the essential role of bHLH factors in B-cell development and demonstrate the feasibility of retrovirus-mediated gene transfer as a tool to genetically modify human B-cell development.

Determination of Ensemble-Average Pairwise Root Mean-Square Deviation from Experimental B-Factors

PubMed Central

Kuzmanic, Antonija; Zagrovic, Bojan

2010-01-01

Abstract Root mean-square deviation (RMSD) after roto-translational least-squares fitting is a measure of global structural similarity of macromolecules used commonly. On the other hand, experimental x-ray B-factors are used frequently to study local structural heterogeneity and dynamics in macromolecules by providing direct information about root mean-square fluctuations (RMSF) that can also be calculated from molecular dynamics simulations. We provide a mathematical derivation showing that, given a set of conservative assumptions, a root mean-square ensemble-average of an all-against-all distribution of pairwise RMSD for a single molecular species, 1/2, is directly related to average B-factors (<B>) and 1/2. We show this relationship and explore its limits of validity on a heterogeneous ensemble of structures taken from molecular dynamics simulations of villin headpiece generated using distributed-computing techniques and the Folding@Home cluster. Our results provide a basis for quantifying global structural diversity of macromolecules in crystals directly from x-ray experiments, and we show this on a large set of structures taken from the Protein Data Bank. In particular, we show that the ensemble-average pairwise backbone RMSD for a microscopic ensemble underlying a typical protein x-ray structure is ∼1.1 Å, under the assumption that the principal contribution to experimental B-factors is conformational variability. PMID:20197040

Acquisition of complement inhibitor serine protease factor I and its cofactors C4b-binding protein and factor H by Prevotella intermedia.

PubMed

Malm, Sven; Jusko, Monika; Eick, Sigrun; Potempa, Jan; Riesbeck, Kristian; Blom, Anna M

2012-01-01

Infection with the Gram-negative pathogen Prevotella intermedia gives rise to periodontitis and a growing number of studies implies an association of P. intermedia with rheumatoid arthritis. The serine protease Factor I (FI) is the central inhibitor of complement degrading complement components C3b and C4b in the presence of cofactors such as C4b-binding protein (C4BP) and Factor H (FH). Yet, the significance of complement inhibitor acquisition in P. intermedia infection and FI binding by Gram-negative pathogens has not been addressed. Here we show that P. intermedia isolates bound purified FI as well as FI directly from heat-inactivated human serum. FI bound to bacteria retained its serine protease activity as shown in degradation experiments with (125)I-labeled C4b. Since FI requires cofactors for its activity we also investigated the binding of purified cofactors C4BP and FH and found acquisition of both proteins, which retained their activity in FI mediated degradation of C3b and C4b. We propose that FI binding by P. intermedia represents a new mechanism contributing to complement evasion by a Gram-negative bacterial pathogen associated with chronic diseases.

Ecto-5'-nucleotidase: a candidate virulence factor in Streptococcus sanguinis experimental endocarditis.

PubMed

Fan, Jingyuan; Zhang, Yongshu; Chuang-Smith, Olivia N; Frank, Kristi L; Guenther, Brian D; Kern, Marissa; Schlievert, Patrick M; Herzberg, Mark C

2012-01-01

Streptococcus sanguinis is the most common cause of infective endocarditis (IE). Since the molecular basis of virulence of this oral commensal bacterium remains unclear, we searched the genome of S. sanguinis for previously unidentified virulence factors. We identified a cell surface ecto-5'-nucleotidase (Nt5e), as a candidate virulence factor. By colorimetric phosphate assay, we showed that S. sanguinis Nt5e can hydrolyze extracellular adenosine triphosphate to generate adenosine. Moreover, a nt5e deletion mutant showed significantly shorter lag time (P<0.05) to onset of platelet aggregation than the wild-type strain, without affecting platelet-bacterial adhesion in vitro (P=0.98). In the absence of nt5e, S. sanguinis caused IE (4 d) in a rabbit model with significantly decreased mass of vegetations (P<0.01) and recovered bacterial loads (log(10)CFU, P=0.01), suggesting that Nt5e contributes to the virulence of S. sanguinis in vivo. As a virulence factor, Nt5e may function by (i) hydrolyzing ATP, a pro-inflammatory molecule, and generating adenosine, an immunosuppressive molecule to inhibit phagocytic monocytes/macrophages associated with valvular vegetations. (ii) Nt5e-mediated inhibition of platelet aggregation could also delay presentation of platelet microbicidal proteins to infecting bacteria on heart valves. Both plausible Nt5e-dependent mechanisms would promote survival of infecting S. sanguinis. In conclusion, we now show for the first time that streptococcal Nt5e modulates S. sanguinis-induced platelet aggregation and may contribute to the virulence of streptococci in experimental IE.

MicroRNA-20b-5p inhibits platelet-derived growth factor-induced proliferation of human fetal airway smooth muscle cells by targeting signal transducer and activator of transcription 3.

PubMed

Tang, Jin; Luo, Lingying

2018-06-01

Pediatric asthma is still a health threat to the pediatric population in recent years. The airway remodeling induced by abnormal airway smooth muscle (ASM) cell proliferation is an important cause of asthma. MicroRNAs (miRNAs) are important regulators of ASM cell proliferation. Numerous studies have reported that miR-20b-5p is a critical regulator for cell proliferation. However, whether miR-20b-5p is involved in regulating ASM cell proliferation remains unknown. In this study, we aimed to investigate the potential role of miR-20b-5p in regulating the proliferation of fetal ASM cell induced by platelet-derived growth factor (PDGF). Here, we showed that miR-20b-5p was significantly decreased in fetal ASM cells treated with PDGF. Biological experiments showed that the overexpression of miR-20b-5p inhibited the proliferation while miR-20b-5p inhibition markedly promoted the proliferation of fetal ASM cells. Bioinformatics analysis and luciferase reporter assay showed that miR-20b-5p directly targeted the 3'-UTR of signal transducer and activator of transcription 3 (STAT3). Further data showed that miR-20b-5p negatively regulated the expression of STAT3 in fetal ASM cells. Moreover, miR-20b-5p regulates the transcriptional activity of STAT3 in fetal ASM cells. Overexpression of STAT3 reversed the inhibitory effect of miR-20b-5p overexpression on fetal ASM cell proliferation while the knockdown of STAT3 abrogated the promoted effect of miR-20b-5p inhibition on fetal ASM cell proliferation. Overall, our results show that miR-20b-5p impedes PDGF-induced proliferation of fetal ASM cells through targeting STAT3. Our study suggests that miR-20b-5p may play an important role in airway remodeling during asthma and suggests that miR-20b-5p may serve as a potential therapeutic target for pediatric asthma. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

B cell helper factors. II. Synergy among three helper factors in the response of T cell- and macrophage-depleted B cells.

PubMed

Liebson, H J; Marrack, P; Kappler, J

1982-10-01

The concanavalin A- (Con A) stimulated supernatant of normal spleen cells (normal Con A SN) was shown to contain a set of helper factors sufficient to allow T cell- and macrophage- (M phi) depleted murine splenic B cells to produce a plaque-forming cell response to the antigen sheep red blood cells (SRBC). The activity of normal Con A SN could be reconstituted by a mixture of three helper factor preparations. The first was the interleukin 2- (IL 2) containing Con A SN of the T cell hybridoma, FS6-14.13. The second was a normal Con A SN depleted of IL 2 by extended culture with T cell blasts from which the 30,000 to 50,000 m.w. factors were isolated (interleukin X, IL X). The third was a SN either from the M phi tumor cell line P388D1 or from normal M phi taken from Corynebacterium parvum-immune mice. The combination of all three helper factor preparations was required to equal the activity of normal Con A SN; however, the M phi SN had the least overall effect. The M phi SN and IL 2 had to be added at the initiation of the culture period for a maximal effect, but the IL X preparation was most effective when added 24 hr after the initiation of culture. These results indicate that at least three nonspecific helper factors contribute to the helper activity in normal Con A SN.

Antithrombotic effects of factor Xa inhibition with DU-176b: Phase-I study of an oral, direct factor Xa inhibitor using an ex-vivo flow chamber.

PubMed

Zafar, Mohammad Urooj; Vorchheimer, David A; Gaztanaga, Juan; Velez, Mauricio; Yadegar, Daniel; Moreno, Pedro R; Kunitada, Satoshi; Pagan, Juan; Fuster, Valentin; Badimon, Juan J

2007-10-01

Direct and specific inhibition of factor Xa is an emerging therapeutic strategy for atherothrombotic disease. Parenteral factor Xa inhibitors promise efficacy comparable to standard therapies, which could be extended to ambulatory patients with oral agents. We evaluated the antithrombotic effect of the oral, direct factor Xa inhibitor DU-176b in a phase-I study. Healthy subjects (n = 12) received a single, 60 mg dose of DU-176b. Antithrombotic effects were assessed by comparing ex-vivo thrombus formation at 1.5, 5, and 12 hours post-dose versus baseline, along with factor Xa activity, thrombin generation and clotting parameters. Under venous flow after 1.5 and 5 hours, the thrombus was 28% and 21% smaller versus baseline, respectively (p < 0.05). Under arterial condition, the reduction was 26% and 17% (p < 0.05). Thrombin generation decreased by 28% at 1.5 hours and 10% at 5 hours. Changes in PT and INR correlated well with plasma drug concentrations (R2 = 0.79 and 0.78). Direct and specific inhibition of factor Xa by DU-176b significantly reduced ex-vivo thrombus formation at both venous and arterial rheologies, up to 5 hours post-dose. The effects mirrored changes in clotting parameters, suggesting their potential usefulness for monitoring in a clinical setting.

Gut Microbiota: A Contributing Factor to Obesity

PubMed Central

Harakeh, Steve M.; Khan, Imran; Kumosani, Taha; Barbour, Elie; Almasaudi, Saad B.; Bahijri, Suhad M.; Alfadul, Sulaiman M.; Ajabnoor, Ghada M. A.; Azhar, Esam I.

2016-01-01

Obesity, a global epidemic of the modern era, is a risk factor for cardiovascular diseases (CVD) and diabetes. The pervasiveness of obesity and overweight in both developed as well as developing populations is on the rise and placing a huge burden on health and economic resources. Consequently, research to control this emerging epidemic is of utmost importance. Recently, host interactions with their resident gut microbiota (GM) have been reported to be involved in the pathogenesis of many metabolic diseases, including obesity, diabetes, and CVD. Around 1014 microorganisms reside within the lower human intestine and many of these 1014 microorganisms have developed mutualistic or commensal associations with the host and actively involved in many physiological processes of the host. However, dysbiosis (altered gut microbial composition) with other predisposing genetic and environmental factors, may contribute to host metabolic disorders resulting in many ailments. Therefore, delineating the role of GM as a contributing factor to obesity is the main objective of this review. Obesity research, as a field is expanding rapidly due to major advances in nutrigenomics, metabolomics, RNA silencing, epigenetics, and other disciplines that may result in the emergence of new technologies and methods to better interpret causal relationships between microbiota and obesity. PMID:27625997

Measurement of the B ± Meson Nuclear Modification Factor in Pb-Pb Collisions at s N N = 5.02 TeV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sirunyan, A. M.; Tumasyan, A.; Adam, W.

The differential production cross sections of B± mesons are measured via the exclusive decay channels B ± → J/ψK ± → μ +μ -K ± as a function of transverse momentum in pp and Pb-Pb collisions at a center-of-mass energy √ sNN = 5.02 TeV per nucleon pair with the CMS detector at the LHC. The pp(Pb-Pb) data set used for this analysis corresponds to an integrated luminosity of 28.0 pb -1 (351 μb -1). The measurement is performed in the B ± meson transverse momentum range of 7 to 50 GeV/c, in the rapidity interval |y|<2.4. In this kinematicmore » range, a strong suppression of the production cross section by about a factor of 2 is observed in the Pb-Pb system in comparison to the expectation from pp reference data. Finally, these results are found to be roughly compatible with theoretical calculations incorporating beauty quark diffusion and energy loss in a quark-gluon plasma.« less

Measurement of the B ± Meson Nuclear Modification Factor in Pb-Pb Collisions at s N N = 5.02 TeV

DOE PAGES

Sirunyan, A. M.; Tumasyan, A.; Adam, W.; ...

2017-10-13

The differential production cross sections of B± mesons are measured via the exclusive decay channels B ± → J/ψK ± → μ +μ -K ± as a function of transverse momentum in pp and Pb-Pb collisions at a center-of-mass energy √ sNN = 5.02 TeV per nucleon pair with the CMS detector at the LHC. The pp(Pb-Pb) data set used for this analysis corresponds to an integrated luminosity of 28.0 pb -1 (351 μb -1). The measurement is performed in the B ± meson transverse momentum range of 7 to 50 GeV/c, in the rapidity interval |y|<2.4. In this kinematicmore » range, a strong suppression of the production cross section by about a factor of 2 is observed in the Pb-Pb system in comparison to the expectation from pp reference data. Finally, these results are found to be roughly compatible with theoretical calculations incorporating beauty quark diffusion and energy loss in a quark-gluon plasma.« less

Factors That Contribute to ePortfolio Persistence

ERIC Educational Resources Information Center

Thibodeaux, Tilisa; Cummings, Cynthia; Harapnuik, Dwayne

2017-01-01

This study examined factors that contributed to persistent use, or discontinued use, of ePortfolios beyond the program of study, as perceived by former educational technology students in a graduate program. The related literature points to contemporary research that choice, ownership, voice, and authentic learning are growing trends emerging as…

Aspirin Hydrolysis in Plasma Is a Variable Function of Butyrylcholinesterase and Platelet-activating Factor Acetylhydrolase 1b2 (PAFAH1b2)*

PubMed Central

Zhou, Gang; Marathe, Gopal K.; Hartiala, Jaana; Hazen, Stanley L.; Allayee, Hooman; Tang, W. H. Wilson; McIntyre, Thomas M.

2013-01-01

Aspirin is rapidly hydrolyzed within erythrocytes by a heterodimer of PAFAH1b2/PAFAH1b3 but also in plasma by an unidentified activity. Hydrolysis in both compartments was variable, with a 12-fold variation in plasma among 2226 Cleveland Clinic GeneBank patients. Platelet inhibition by aspirin was suppressed in plasma that rapidly hydrolyzed aspirin. Plasma aspirin hydrolysis was significantly higher in patients with coronary artery disease compared with control subjects (16.5 ± 4.4 versus 15.1 ± 3.7 nmol/ml/min; p = 3.4 × 10−8). A genome-wide association study of 2054 GeneBank subjects identified a single locus immediately adjacent to the BCHE (butyrylcholinesterase) gene associated with plasma aspirin hydrolytic activity (lead SNP, rs6445035; p = 9.1 × 10−17). However, its penetrance was low, and plasma from an individual with an inactivating mutation in BCHE still effectively hydrolyzed aspirin. A second aspirin hydrolase was identified in plasma, the purification of which showed it to be homomeric PAFAH1b2. This is distinct from the erythrocyte PAFAH1b2/PAFAH1b3 heterodimer. Inhibitors showed that both butyrylcholinesterase (BChE) and PAFAH1b2 contribute to aspirin hydrolysis in plasma, with variation primarily reflecting non-genetic variation of BChE activity. Therefore, aspirin is hydrolyzed in plasma by two enzymes, BChE and a new extracellular form of platelet-activating factor acetylhydrolase, PAFAH1b2. Hydrolytic effectiveness varies widely primarily from non-genetic variation of BChE activity that affects aspirin bioavailability in blood and the ability of aspirin to inhibit platelet aggregation. PMID:23508960

AAV5-Factor VIII Gene Transfer in Severe Hemophilia A.

PubMed

Rangarajan, Savita; Walsh, Liron; Lester, Will; Perry, David; Madan, Bella; Laffan, Michael; Yu, Hua; Vettermann, Christian; Pierce, Glenn F; Wong, Wing Y; Pasi, K John

2017-12-28

Patients with hemophilia A rely on exogenous factor VIII to prevent bleeding in joints, soft tissue, and the central nervous system. Although successful gene transfer has been reported in patients with hemophilia B, the large size of the factor VIII coding region has precluded improved outcomes with gene therapy in patients with hemophilia A. We infused a single intravenous dose of a codon-optimized adeno-associated virus serotype 5 (AAV5) vector encoding a B-domain-deleted human factor VIII (AAV5-hFVIII-SQ) in nine men with severe hemophilia A. Participants were enrolled sequentially into one of three dose cohorts (low dose [one participant], intermediate dose [one participant], and high dose [seven participants]) and were followed through 52 weeks. Factor VIII activity levels remained at 3 IU or less per deciliter in the recipients of the low or intermediate dose. In the high-dose cohort, the factor VIII activity level was more than 5 IU per deciliter between weeks 2 and 9 after gene transfer in all seven participants, and the level in six participants increased to a normal value (>50 IU per deciliter) that was maintained at 1 year after receipt of the dose. In the high-dose cohort, the median annualized bleeding rate among participants who had previously received prophylactic therapy decreased from 16 events before the study to 1 event after gene transfer, and factor VIII use for participant-reported bleeding ceased in all the participants in this cohort by week 22. The primary adverse event was an elevation in the serum alanine aminotransferase level to 1.5 times the upper limit of the normal range or less. Progression of preexisting chronic arthropathy in one participant was the only serious adverse event. No neutralizing antibodies to factor VIII were detected. The infusion of AAV5-hFVIII-SQ was associated with the sustained normalization of factor VIII activity level over a period of 1 year in six of seven participants who received a high dose, with

Akt/protein kinase B activation by adenovirus vectors contributes to NFkappaB-dependent CXCL10 expression.

PubMed

Liu, Qiang; White, Lindsay R; Clark, Sharon A; Heffner, Daniel J; Winston, Brent W; Tibbles, Lee Anne; Muruve, Daniel A

2005-12-01

In gene therapy, the innate immune system is a significant barrier to the effective application of adenovirus (Ad) vectors. In kidney epithelium-derived (REC) cells, serotype 5 Ad vectors induce the expression of the chemokine CXCL10 (IP-10), a response that is dependent on NFkappaB. Compared to the parental vector AdLuc, transduction with the RGD-deleted vector AdL.PB resulted in reduced CXCL10 activation despite increasing titers, implying that RGD-alpha(V) integrin interactions contribute to adenovirus induction of inflammatory genes. Akt, a downstream effector of integrin signaling, was activated within 10 min of transduction with Ad vectors in a dose-dependent manner. Akt activation was not present following transduction with AdL.PB, confirming the importance of capsid-alpha(V) integrin interactions in Ad vector Akt activation. Inhibition of the phosphoinositide-3-OH kinase/Akt pathway by Wortmannin or Ly294002 compounds decreased Ad vector induction of CXCL10 mRNA. Similarly, adenovirus-mediated overexpression of the dominant negative AktAAA decreased CXCL10 mRNA expression compared to the reporter vector AdLacZ alone. The effect of Akt on CXCL10 mRNA expression occurred via NFkappaB-dependent transcriptional activation, since AktAAA overexpression and Ly294002 both inhibited CXCL10 and NFkappaB promoter activation in luciferase reporter experiments. These results show that Akt plays a role in the Ad vector activation of NFkappaB and CXCL10 expression. Understanding the mechanism underlying the regulation of host immunomodulatory genes by adenovirus vectors will lead to strategies that will improve the efficacy and safety of these agents for clinical use.

B-cell transcription factors Pax-5, Oct-2, BOB.1, Bcl-6, and MUM1 are useful markers for the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma.

PubMed

Herbeck, Rosemarie; Teodorescu Brînzeu, D; Giubelan, Marioara; Lazăr, Elena; Dema, Alis; Ioniţă, Hortensia

2011-01-01

In some instances, the overlap in morphologic features and antigen expression between nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and classical Hodgkin lymphoma (cHL) can cause confusion in the diagnosis. In these cases, the transcription factors (TFs) B-cell specific activator protein (BSAP)/Pax-5, octamer binding protein-2 (Oct-2), B-lymphocyte-specific co-activator BOB.1/OBF.1, Bcl-6 protein and multiple myeloma-1/interferon regulatory factor-4 (MUM1/IRF-4) may aid in clarifying the diagnosis. Twenty-two cases of NLPHL were studied for the immunohistochemical expression of Pax-5, Oct-2, BOB.1, Bcl-6 protein and MUM1/IRF-4. Our results sustain the usefulness of the selected set of TFs to diagnose and distinguish NLPHL from cHL since Pax-5, Oct-2, BOB.1 and Bcl-6 are consistently expressed by lymphocyte predominant (LP) cells and reported by others to be often unexpressed in Hodgkin and Reed-Sternberg cells. By contrast, MUM1/IRF-4 protein scored negative in the majority of LP cells, but is reported to be expressed in almost all cases of cHL. Thus, although the expression of transcription factors is very heterogeneous, their simultaneous implementation for positive and differential diagnosis may be useful.

Factors Contributing to Urban Heat Island Development: A Global Perspective

NASA Astrophysics Data System (ADS)

Hertel, W.; Snyder, P. K.; Twine, T. E.

2012-12-01

Urban heat islands (UHIs) are the result of the urban core of a city encountering temperatures that are warmer than the surrounding rural areas. Temperature in the urban core can be 2-5°C warmer during the day and as much as 10°C warmer at night compared to outlying areas. This modification of the local climate can contribute to significant health-related impacts during heat waves, increased energy consumption, a decrease in air quality, deteriorating urban ecosystems, and enhancing the thermal pollution into urban water bodies. To understand the mechanisms contributing to the formation of UHIs and to identify sound mitigation strategies requires examining the UHIs of cities around the world to look for factors that enhance or minimize the heat island effect. Numerous factors influence the strength of the UHI, and vary from city to city. Population size and density influence the magnitude and spatial extent of the UHI. The ecosystem in which the city resides affects the rural climatology. Regional weather patterns can also influence the development of UHIs, with the frequency of certain types of weather conducive to the development of strong UHIs. Local geography such as proximity to water bodies and topography can influence UHI development. Cultural and regional influences such as the use of certain types of building materials, architecture, and the density of vegetation can all contribute towards the strength of a city's UHI. To better understand how UHIs develop and to understand the factors that influence them, we have undertaken the Islands in the Sun project, which includes an analysis of the UHIs of the largest cities in the world. In this study we examine how different factors have influenced the structure of the UHI and to identify factors that can mitigate and minimize their impact. Here we present a preliminary analysis of four metropolitan areas: Minneapolis-St. Paul, Buenos Aires, Riyadh, and Jakarta. In this study we investigate how various factors

Serum miR-338-5p, soluble B-cell-activating factor, allo-antibodies, and renal transplantation.

PubMed

Xu, H; Ma, X; He, X; Dong, P; Xue, D; Zhang, Y; Zhang, X

2015-03-01

The objective of the study was to explore the expression features of serum miR-338-5p and soluble B-cell-activating factor (sBAFF) in renal transplant recipients. Follow-up renal transplant recipients (n = 49) were enrolled in this study (male/female: 38/11). Healthy volunteers were controlled; 2 mL of peripheral blood from each subject was collected. Total RNA was extracted from serum by use of the miRNeasy Serum/Plasma Kit (QIAGEN), and miR-338-5p was amplified by means of quantitative real-time reverse transcriptase-polymerase chain reaction. sBAFF was detected by means of enzyme-linked immunoassay. LABScreen Mix (LSM12) (One Lambda) was used to test the level of anti-human leukocyte antigen (HLA) I antibody (Ab), anti-HLA II Ab, and anti-major histocompatibility complex class I chain-related A (MICA) Ab. All data are shown as mean ± SD and were analyzed by use of SPSS software 17.0. Compared with healthy volunteers, serum miR-338-5p in recipients was statistically downregulated (2.79 ± 2.5 versus 0.09 ± 0.12, P < .001); sBAFF in recipients was significantly upregulated (1321 ± 950 pg/mL versus 534 ± 327 pg/mL, P < .01); serum anti-HLAII Ab, anti-MICA Ab, and anti-HLA+MICA Abs all statistically increased in recipients (P < .05). Spearman correlation analysis showed that miR-338-5p was significantly negatively correlated with sBAFF (r = -0.51, P < .001) and anti-HLA II antibody with mean fluorescence intensity value >1000 (r = -0.322, P < .05). Analysis results also suggested that sBAFF was significantly negatively correlated with anti-MICA Ab, with mean fluorescence intensity value >1000 (r = -0.579, P < .05). miR-338-5p is closely correlated with the procedure of renal allograft antibody-mediated rejection. Copyright © 2015 Elsevier Inc. All rights reserved.

Contributing factors to performance of a medicine ball explosive power test: a comparison between jump and nonjump athletes.

PubMed

Stockbrugger, Barry A; Haennel, Robert G

2003-11-01

The present study examined the factors contributing to performance of a backward overhead medicine ball throw (B-MBT) across 2 types of athletes. Twenty male volleyball players (jump athletes) and 20 wrestlers (nonjump athletes) were evaluated on 4 measures of power, including B-MBT, chest medicine ball throw (C-MBT), countermovement vertical jump (CMJ), and power index (PI). The athletes also completed 3 measures of strength: a 1-repetition-maximum (1RM) bench press (BP), a 1RM leg press (LP), and combined BP + LP strength. Jump athletes demonstrated greater absolute scores for CMJ, C-MBT, and B-MBT (p < 0.05), whereas nonjump athletes demonstrated greater strength scores for BP and for BP + LP (p < 0.05). When performances were examined on a relative basis, jump athletes achieved superior scores for C-MBT (p < 0.05), whereas nonjump athletes had greater scores for BP, LP, and BP + LP (p < 0.05). For both groups, B-MBT had strong correlations with PI (r = 0.817 [jump] and 0.917 [nonjump]), whereas for C-MBT, only nonjump athletes demonstrated a strong correlation (r = 0.842). When expressed in relative terms, B-MBT was strongly correlated with C-MBT (r = 0.762 [jump] and 0.835 [nonjump]) and CMJ (r = 0.899 [jump] and 0.945 [nonjump]). Only nonjump athletes demonstrated strong correlations with strength for absolute LP (r = 0.801) and BP + LP (r = 0.810) strength. The interaction of upper- and lower-body strength and power in the performance of a B-MBT appears complex, with the contributing factors differing for athletes with divergent skill sets and performance demands.

Anti-Factor B and Anti-C3b Autoantibodies in C3 Glomerulopathy and Ig-Associated Membranoproliferative GN

PubMed Central

Marinozzi, Maria Chiara; Roumenina, Lubka T.; Chauvet, Sophie; Hertig, Alexandre; Bertrand, Dominique; Olagne, Jérome; Frimat, Marie; Ulinski, Tim; Deschênes, Georges; Burtey, Stephane; Delahousse, Michel; Moulin, Bruno; Legendre, Christophe

2017-01-01

In C3 glomerulopathy (C3G), the alternative pathway of complement is frequently overactivated by autoantibodies that stabilize the C3 convertase C3bBb. Anti-C3b and anti-factor B (anti-FB) IgG have been reported in three patients with C3G. We screened a cohort of 141 patients with C3G and Ig-associated membranoproliferative GN (Ig-MPGN) for anti-FB and anti-C3b autoantibodies using ELISA. We identified seven patients with anti-FB IgG, three patients with anti-C3b IgG, and five patients with anti-FB and anti-C3b IgG. Of these 15 patients, ten were diagnosed with Ig-MPGN. Among those patients with available data, 92% had a nephrotic syndrome, 64% had AKI, and 67% had a documented infection. Patients negative for anti-C3b and anti-FB IgG had much lower rates of infection (17 [25%] patients with C3G and one [10%] patient with Ig-MPGN). After 48 months, four of 15 (26%) positive patients had developed ESRD or died. All 15 patients had high plasma Bb levels, six (40%) patients had low levels of C3, and nine (60%) patients had high levels of soluble C5b9. In vitro, IgG purified from patients with anti-FB Abs selectively enhanced C3 convertase activity; IgG from patients with anti-C3b/anti-FB Abs enhanced C3 and C5 cleavage. IgG from patients with anti-C3b Abs stabilized C3bBb and perturbed C3b binding to complement receptor 1 but did not perturb binding to factor H. In conclusion, the prevalence of anti-C3b/anti-FB Abs and alternative pathway activation is similar in Ig-MPGN and C3G, suggesting similar pathogenic mechanisms. Identification of the underlying defect in Ig-MPGN could lead to improved treatment. PMID:28096309

5 CFR 842.805 - Withholding and contributions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Withholding and contributions. 842.805 Section 842.805 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-BASIC ANNUITY Law Enforcement Officers...

5 CFR 842.805 - Withholding and contributions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false Withholding and contributions. 842.805 Section 842.805 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-BASIC ANNUITY Law Enforcement Officers...

5 CFR 842.805 - Withholding and contributions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Withholding and contributions. 842.805 Section 842.805 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-BASIC ANNUITY Law Enforcement Officers...

5 CFR 842.805 - Withholding and contributions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Withholding and contributions. 842.805 Section 842.805 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-BASIC ANNUITY Law Enforcement Officers...

5 CFR 842.805 - Withholding and contributions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Withholding and contributions. 842.805 Section 842.805 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-BASIC ANNUITY Law Enforcement Officers...

An observational study of bullying as a contributing factor in youth suicide in Toronto.

PubMed

Sinyor, Mark; Schaffer, Ayal; Cheung, Amy H

2014-12-01

Bullying has been identified as a potential contributing factor in youth suicide. This issue has been highlighted in recent widely publicized media reports, worldwide, in which deceased youth were bullied. We report on an observational study conducted to determine the frequency of bullying as a contributing factor to youth suicide. Coroner records were reviewed for all suicide deaths in youth aged between 10 and 19 in the city of Toronto from 1998 to 2011. Data abstracted were recent stressors (including bullying), clinical variables, such as the presence of mental illness, demographics, and methods of suicide. Ninety-four youth suicides were included in the study. The mean age was 16.8 years, and 70.2% were male. Bullying was present in 6 deaths (6.4%), and there were no deaths where online or cyberbullying was detected. Bullying was the only identified contributing factor in fewer than 5 deaths. The most common stressors identified were conflict with parents (21.3%), romantic partner problems (17.0%), academic problems (10.6%), and criminal and (or) legal problems (10.6%). Any stressor or mental and (or) physical illness was detected in 78.7% of cases. Depression was detected in 40.4% of cases. Our study highlights the need to view suicide in youth as arising from a complex interplay of various biological, psychological, and social factors of which bullying is only one. It challenges simple cause-and-effect models that may suggest that suicide arises from anyone factor, such as bullying.

[Job burnout and contributing factors for nurses].

PubMed

Zhu, Wei; Wang, Zhi-ming; Wang, Mian-zhen; Lan, Ya-jia; Wu, Si-ying

2006-07-01

To investigate the degree of job burnout and contributing factors for nurses. A total of 495 nurses from three provincial hospitals were randomly selected. The MBI-GS, EPQ-RSC and OSI-R were administered to measure job burnout, personality traits and occupational stress, respectively. The medical and surgical nurses had significant greater scores of job burnout than others (P < 0.05). The poorer educational background was correlated with lower professional efficacy. The younger nurses had stronger feeling of job burnout. The scores of job burnout changed with different personality traits. The main contributing variables to exhaustion were overload, sense of responsibility, role insufficient and self-care (P < 0.05). The main contributing variables to cynicism were role insufficiency, role boundary, sense of responsibility and self-care (P < 0.05). The main contributing variables to professional inefficacy were role insufficiency, social support and rational/cognitive coping (P < 0.05). Job burnout for nurses can be prevented by reducing or keeping moderate professional duties and responsibility, making clearer job descriptions, promoting leisure activities, and enhancing self-care capabilities.

5 CFR 831.907 - Withholdings and contributions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Withholdings and contributions. 831.907 Section 831.907 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Law Enforcement Officers and Firefighters § 831.907 Withholdings and...

5 CFR 831.907 - Withholdings and contributions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Withholdings and contributions. 831.907 Section 831.907 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Law Enforcement Officers and Firefighters § 831.907 Withholdings and...

5 CFR 831.907 - Withholdings and contributions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Withholdings and contributions. 831.907 Section 831.907 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Law Enforcement Officers and Firefighters § 831.907 Withholdings and...

5 CFR 831.907 - Withholdings and contributions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Withholdings and contributions. 831.907 Section 831.907 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Law Enforcement Officers and Firefighters § 831.907 Withholdings and...

5 CFR 831.907 - Withholdings and contributions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false Withholdings and contributions. 831.907 Section 831.907 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Law Enforcement Officers and Firefighters § 831.907 Withholdings and...

How large B-factors can be in protein crystal structures.

PubMed

Carugo, Oliviero

2018-02-23

Protein crystal structures are potentially over-interpreted since they are routinely refined without any restraint on the upper limit of atomic B-factors. Consequently, some of their atoms, undetected in the electron density maps, are allowed to reach extremely large B-factors, even above 100 square Angstroms, and their final positions are purely speculative and not based on any experimental evidence. A strategy to define B-factors upper limits is described here, based on the analysis of protein crystal structures deposited in the Protein Data Bank prior 2008, when the tendency to allow B-factor to arbitrary inflate was limited. This B-factor upper limit (B_max) is determined by extrapolating the relationship between crystal structure average B-factor and percentage of crystal volume occupied by solvent (pcVol) to pcVol =100%, when, ab absurdo, the crystal contains only liquid solvent, the structure of which is, by definition, undetectable in electron density maps. It is thus possible to highlight structures with average B-factors larger than B_max, which should be considered with caution by the users of the information deposited in the Protein Data Bank, in order to avoid scientifically deleterious over-interpretations.

[Social-psychological factors contributing to male juvenile delinquency].

PubMed

Wei, Hong-Ping; Yang, Fang-Ru

2011-11-01

To study the major social-psychological factors contributing to male juvenile delinquency. One hundred and thirty-seven cases of male juvenile delinquents (delinquent group) and 145 aged-matched male students (control group) were enrolled in this case-control study. A questionnaire survey was conducted using the Adolescent Self-Rating Life Events Check List, the Coping Style Questionnaire, the Family Environment Scale-Chinese version, and the Social Support Rating Scale. The monovariate analysis showed that the total score and the scores of some factors of negative life events, the scores of immature coping styles and family conflicts, and the proportion of broken families in the delinquent group were significantly higher than those in the control group. In contrast, the scores of educational levels, study stress factor in the negative life events, mature coping styles, family environments and social supports were significantly lower in the delinquent group than those in the control group. The multivariate factors analysis showed that 7 variables were enrolled into the discriminatory equations, including negative life events (interpersonal relationship and healthy adaptation), self-condemn styles, family conflicts, subjective supports, objective supports, and utilization of social supports. The total accuracy of this equation was 92.2%. Negative life events in the interpersonal relationship and healthy adaptation, self-condemn styles, family conflicts, and weak social support system may be major social-psychological factors contributing to male juvenile delinquency.

IL-10 production by B cells expressing CD5 with the alternative exon 1B.

PubMed

Garaud, Soizic; Le Dantec, Christelle; de Mendoza, Agnès Revol; Mageed, Rizgar A; Youinou, Pierre; Renaudineau, Yves

2009-09-01

B lymphocytes are divided into two subpopulations, B1 and B2 cells based on expression of the T cell-associated protein CD5. Natural B1 cells are further divided into B1a cells that express CD5 on their membrane and B1b cells that do not but share most other biological characteristics of B1a cells. Recent studies from our laboratory have revealed, in humans, the existence of two alternative isoforms of the CD5 protein. A cell surface CD5 isoform which uses exon 1A (E1A) of the gene in B1a cells, and an intracellular isoform which uses exon 1B (E1B) mainly in human B1b cells. Indeed, the protein isoform encoded by transcripts containing E1B lack the leader peptide and is, thus, retained in the cytoplasm of B cells. The restriction of interleukin (IL)-10 to B1 lymphocytes in the mouse raises the possibility that the human CD5-E1B-expressing B cells produce IL-10. This prediction was confirmed in the CD5 negative Jok-1 B cells transfected with cDNA for either isoforms resulted in high level IL-10 production. Our data indicate that E1B-CD5-expressing B cells have the capacity to interfere with the immune response through their ability to produce high levels of IL-10.

Electrostatic redesign of the [myoglobin, cytochrome b5] interface to create a well-defined docked complex with rapid interprotein electron transfer.

PubMed

Xiong, Peng; Nocek, Judith M; Griffin, Amanda K K; Wang, Jingyun; Hoffman, Brian M

2009-05-27

Cyt b(5) is the electron-carrier "repair" protein that reduces met-Mb and met-Hb to their O(2)-carrying ferroheme forms. Studies of electron transfer (ET) between Mb and cyt b(5) revealed that they react on a "Dynamic Docking" (DD) energy landscape on which binding and reactivity are uncoupled: binding is weak and involves an ensemble of nearly isoenergetic configurations, only a few of which are reactive; those few contribute negligibly to binding. We set the task of redesigning the surface of Mb so that its reaction with cyt b(5) instead would occur on a conventional "simple docking" (SD) energy landscape, on which a complex exhibits a well-defined (set of) reactive binding configuration(s), with binding and reactivity thus no longer being decoupled. We prepared a myoglobin (Mb) triple mutant (D44K/D60K/E85K; Mb(+6)) substituted with Zn-deuteroporphyrin and monitored cytochrome b(5) (cyt b(5)) binding and electron transfer (ET) quenching of the (3)ZnMb(+6) triplet state. In contrast, to Mb(WT), the three charge reversals around the "front-face" heme edge of Mb(+6) have directed cyt b(5) to a surface area of Mb adjacent to its heme, created a well-defined, most-stable structure that supports good ET pathways, and apparently coupled binding and ET: both K(a) and k(et) are increased by the same factor of approximately 2 x 10(2), creating a complex that exhibits a large ET rate constant, k(et) = 10(6 1) s(-1), and is in slow exchange (k(off) < k(et)). In short, these mutations indeed appear to have created the sought-for conversion from DD to simple docking (SD) energy landscapes.

Biogenic contribution to PM-2.5 ambient aerosol from radiocarbon measurements

NASA Astrophysics Data System (ADS)

Lewis, C.; Klouda, G.; Ellenson, W.

2003-04-01

Knowledge of the relative contributions of biogenic versus anthropogenic sources to ambient aerosol is of great interest in the formulation of strategies to achieve nationally mandated air quality standards. Radiocarbon (14C) measurements provide a means to quantify the biogenic fraction of any carbon-containing sample of ambient aerosol. In the absence of an impact from biomass burning (e.g., during summertime) such measurements can provide an estimate of the contribution of biogenic secondary organic aerosol, from biogenic volatile organic compound precursors. Radiocarbon results for 11.5-h PM-2.5 samples collected near Nashville, Tennessee, USA, during summer 1999 will be presented. On average the measured biogenic fraction was surprisingly large (more than half), with the average biogenic fraction for night samples being only slightly smaller than for day samples. Discussion will include (a) description of the radiocarbon methodology, (b) use of radiocarbon measurements on local vegetation and fuel samples as calibration data, (c) concurrent measurements of organic carbon and elemental carbon ambient concentrations, (d) assessment of organic aerosol sampling artifact through use of organic vapor denuders, variable face velocities, and filter extraction, and (e) comparison with published radiocarbon results obtained in Houston, Texas in a similar study. Disclaimer: This work has been funded wholly or in part by the United States Environmental Protection Agency under Interagency Agreement No. 13937923 to the National Institute of Standards and Technology, and Contract No. 68-D5-0049 to ManTech Environmental Tecnology, Inc. It has been subjected to Agency review and approved for publication.

Differential phosphorylations of Spi-B and Spi-1 transcription factors.

PubMed

Mao, C; Ray-Gallet, D; Tavitian, A; Moreau-Gachelin, F

1996-02-15

Spi-1/PU-1 and Spi-B are hematopoietic transcription factors, which, in vitro, display similar affinities for DNA target sequences containing the consensus binding site 5'-GGAA-3'. While the role of Spi-1 in the transcriptional regulation of B cell and myeloid specific genes has been largely demonstrated, the biological function of Spi-B still remains to be elucidated. Since Spi-B and Spi-1 are very divergent in their transactivator domain, these domains might acquire functional specificity in vivo by interacting with different co-factors and/or by undergoing different phosphorylations. First, we observed that casein kinase II phosphorylates Spi-B as well as Spi-1, in vitro. Then, by affinity chromatographies and in vitro kinase assays with fusion proteins between glutathione-S-transferase and the transactivator domain of Spi-B, two kinases were identified on their ability to interact and phosphorylate this domain; the MAP kinase ERK1 and the stress activated protein kinase JNK1. The Threonine 56 was defined as the ERK1 phosphorylation site by using phosphoamino-acid analyses and a Spi-B mutant version with the substitution T56 to A56. Strikingly, ERK1 failed to phosphorylate Spi-1, in vitro, whereas JNK1, like CK II, phosphorylated Spi-B and Spi-1. In addition, other purified Spi-B-kinase activities, unidentified as yet, display similar specificity than ERK1 for Spi-B versus Spi-1. Furthermore, the evident interaction of pRb protein with the transactivator domain of Spi-B in an unphosphorylated state disappeared when this domain was first phosphorylated in vitro either by ERK1 or by the purified Spi-B-kinase activities. Our data revealed multiple phosphorylation sites within Spi-B whose some of them appeared specific for Spi-B versus Spi-1 and which may account for differential regulation of their activities.

Undernutrition among Kenyan children: contribution of child, maternal and household factors.

PubMed

Gewa, Constance A; Yandell, Nanette

2012-06-01

To examine the contribution of selected child-, maternal- and household-related factors to child undernutrition across two different age groups of Kenyan under-5s. Demographic and Health Survey data, multistage stratified cluster sampling methodology. Rural and urban areas of Kenya. A total of 1851 children between the ages of 0 and 24 months and 1942 children between the ages of 25 and 59 months in Kenya. Thirty per cent of the younger children were stunted, 13 % were underweight and 8 % were wasted. Forty per cent of the older children were stunted, 17 % were underweight and 4 % were wasted. Longer breast-feeding duration, small birth size, childhood diarrhoea and/or cough, poor maternal nutritional status and urban residence were associated with higher odds of at least one form of undernutrition, while female gender, large birth size, up-to-date immunization, higher maternal age at first birth, BMI and education level at the time of the survey and higher household wealth were each associated with lower odds of at least one form of undernutrition among Kenyan children. The more proximal child factors had the strongest impact on the younger group of children while the intermediate and more distal maternal and household factors had the strongest impact on child undernutrition among the older group of children. The present analysis identifies determinants of undernutrition among two age groups of Kenyan pre-school children and demonstrates that the contribution of child, maternal and household factors on children's nutritional status varies with children's age.

5 CFR 831.403 - Eligibility to make voluntary contributions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Eligibility to make voluntary contributions. 831.403 Section 831.403 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Voluntary Contributions § 831.403 Eligibility to make voluntary...

5 CFR 831.403 - Eligibility to make voluntary contributions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Eligibility to make voluntary contributions. 831.403 Section 831.403 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Voluntary Contributions § 831.403 Eligibility to make voluntary...

The current contribution of molecular factors to risk estimation in neuroblastoma patients.

PubMed

Berthold, F; Sahin, K; Hero, B; Christiansen, H; Gehring, M; Harms, D; Horz, S; Lampert, F; Schwab, M; Terpe, J

1997-10-01

The association of molecular characteristics with prognosis has been reported, but not their relationship with each other and their impact in the context of known clinical risk factors. In this study, data of 1249 consecutive intent-to-treat-neuroblastoma patients with more than 1 year follow-up were examined by multivariate analysis using loglinear and Cox proportional hazard regression models on a stage-related basis (stages 1-3: 600, 4S: 116, 4: 533). In a first step, risk factors were identified from 18 selected clinical variables, and risk groups defined. The second step investigated whether molecular characteristics (MYCN, LOH 1p, del 1p, CD44, N-ras, NGF-R, bcl-2, APO-1 (CD95)) contributed additional prognostic information to the model. The loglinear model demonstrated several interactions between clinical factors. By the Cox regression model, seven independent clinical risk factors were found for stages 1-3, seven for stage 4 and two for stage 4S. By subsequent introduction of all molecular variables, MYCN amplification only added significant prognostic information to the clinical factors in localised and stage 4 neuroblastoma. The models allowed the definition of risk groups for stages 1-3 patients by age (e beta = 5.09) and MYCN (e beta = 4.26), for stage 4 by MYCN (e beta = 2.78) and number of symptoms (e beta = 2.44) and for stage 4S by platelet count (e beta = 3.91) and general condition (e beta = 2.99). Molecular factors and in particular MYCN contribute significantly to risk estimation. In conjunction with clinical factors, they are powerful tools to define risk groups in neuroblastoma.

The alternative complement component factor B regulates UV-induced oedema, systemic suppression of contact and delayed hypersensitivity, and mast cell infiltration into the skin.

PubMed

Byrne, Scott N; Hammond, Kirsten J L; Chan, Carling Y-Y; Rogers, Linda J; Beaugie, Clare; Rana, Sabita; Marsh-Wakefield, Felix; Thurman, Joshua M; Halliday, Gary M

2015-04-01

Ultraviolet (UV) wavelengths in sunlight are the prime cause of skin cancer in humans with both the UVA and UVB wavebands making a contribution to photocarcinogenesis. UV has many different biological effects on the skin that contribute to carcinogenesis, including suppression of adaptive immunity, sunburn and altering the migration of mast cells into and away from irradiated skin. Many molecular mechanisms have been identified as contributing to skin responses to UV. Recently, using gene set enrichment analysis of microarray data, we identified the alternative complement pathway with a central role for factor B (fB) in UVA-induced immunosuppression. In the current study we used mice genetically deficient in fB (fB-/- mice) to study the functional role of the alternative complement pathway in skin responses to UV. We found that fB is required for not only UVA but also UVB-induced immunosuppression and solar-simulated UV induction of the oedemal component of sunburn. Factor B-/- mice had a larger number of resident skin mast cells than control mice, but unlike the controls did not respond to UV by increasing mast cell infiltration into the skin. This study provides evidence for a function role for fB in skin responses to UV radiation. Factor B regulates UVA and UVB induced immunosuppression, UV induced oedema and mast cell infiltration into the skin. The alternative complement pathway is therefore an important regulator of skin responses to UV.

Adipocyte-derived factors in age-related dementia and their contribution to vascular and Alzheimer pathology.

PubMed

Ishii, Makoto; Iadecola, Costantino

2016-05-01

Age-related dementia is increasingly recognized as having a mixed pathology, with contributions from both cerebrovascular factors and pathogenic factors associated with Alzheimer's disease (AD). Furthermore, there is accumulating evidence that vascular risk factors in midlife, e.g., obesity, diabetes, and hypertension, increase the risk of developing late-life dementia. Since obesity and changes in body weight/adiposity often drive diabetes and hypertension, understanding the relationship between adiposity and age-related dementia may reveal common underlying mechanisms. Here we offer a brief appraisal of how changes in body weight and adiposity are related to both AD and dementia on vascular basis, and examine the involvement of two key adipocyte-derived hormones: leptin and adiponectin. The evidence suggests that in midlife increased body weight/adiposity and subsequent changes in adipocyte-derived hormones may increase the long-term susceptibility to dementia. On the other hand, later in life, decreases in body weight/adiposity and related hormonal changes are early manifestations of disease that precede the onset of dementia and may promote AD and vascular pathology. Understanding the contribution of adiposity to age-related dementia may help identify the underlying pathological mechanisms common to both vascular dementia and AD, and provide new putative targets for early diagnosis and therapy. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.

BDB: databank of PDB files with consistent B-factors.

PubMed

Touw, Wouter G; Vriend, Gert

2014-11-01

Protein structures available from the PDB contain for each atom the coordinates, the occupancy and the B-factor that indicates the mobility of the atom. The values that should represent B-factors can relate to atomic motions in different ways. We present here a databank in which all B-factors have been converted to the one, homogeneous representation that is most useful for protein engineering applications. The Databank of PDB files with consistent B-factors (BDB) is freely available through http://www.cmbi.umcn.nl/bdb/. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Developing a contributing factor classification scheme for Rasmussen's AcciMap: Reliability and validity evaluation.

PubMed

Goode, N; Salmon, P M; Taylor, N Z; Lenné, M G; Finch, C F

2017-10-01

One factor potentially limiting the uptake of Rasmussen's (1997) Accimap method by practitioners is the lack of a contributing factor classification scheme to guide accident analyses. This article evaluates the intra- and inter-rater reliability and criterion-referenced validity of a classification scheme developed to support the use of Accimap by led outdoor activity (LOA) practitioners. The classification scheme has two levels: the system level describes the actors, artefacts and activity context in terms of 14 codes; the descriptor level breaks the system level codes down into 107 specific contributing factors. The study involved 11 LOA practitioners using the scheme on two separate occasions to code a pre-determined list of contributing factors identified from four incident reports. Criterion-referenced validity was assessed by comparing the codes selected by LOA practitioners to those selected by the method creators. Mean intra-rater reliability scores at the system (M = 83.6%) and descriptor (M = 74%) levels were acceptable. Mean inter-rater reliability scores were not consistently acceptable for both coding attempts at the system level (M T1  = 68.8%; M T2  = 73.9%), and were poor at the descriptor level (M T1  = 58.5%; M T2  = 64.1%). Mean criterion referenced validity scores at the system level were acceptable (M T1  = 73.9%; M T2  = 75.3%). However, they were not consistently acceptable at the descriptor level (M T1  = 67.6%; M T2  = 70.8%). Overall, the results indicate that the classification scheme does not currently satisfy reliability and validity requirements, and that further work is required. The implications for the design and development of contributing factors classification schemes are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

34 CFR 5b.9 - Disclosure of records.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Disclosure of records. 5b.9 Section 5b.9 Education Office of the Secretary, Department of Education PRIVACY ACT REGULATIONS § 5b.9 Disclosure of records. (a... school year, while the subject individual is out of the country, whenever the subject individual is...

5 CFR 831.404 - Procedure for making voluntary contributions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Procedure for making voluntary contributions. 831.404 Section 831.404 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL... voluntary contributions to the Office of Personnel Management, at the address designated for that purpose...

5 CFR 831.404 - Procedure for making voluntary contributions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Procedure for making voluntary contributions. 831.404 Section 831.404 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL... voluntary contributions to the Office of Personnel Management, at the address designated for that purpose...

5 CFR 838.612 - Distinguishing between annuities and contributions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Distinguishing between annuities and... Orders Affecting Employee Annuities or Refunds of Employee Contributions Identification of Benefits § 838.612 Distinguishing between annuities and contributions. (a) A court order using “annuities,” “pensions...

Arid5b facilitates chondrogenesis by recruiting the histone demethylase Phf2 to Sox9-regulated genes

NASA Astrophysics Data System (ADS)

Hata, Kenji; Takashima, Rikako; Amano, Katsuhiko; Ono, Koichiro; Nakanishi, Masako; Yoshida, Michiko; Wakabayashi, Makoto; Matsuda, Akio; Maeda, Yoshinobu; Suzuki, Yutaka; Sugano, Sumio; Whitson, Robert H.; Nishimura, Riko; Yoneda, Toshiyuki

2013-11-01

Histone modification, a critical step for epigenetic regulation, is an important modulator of biological events. Sox9 is a transcription factor critical for endochondral ossification; however, proof of its epigenetic regulation remains elusive. Here we identify AT-rich interactive domain 5b (Arid5b) as a transcriptional co-regulator of Sox9. Arid5b physically associates with Sox9 and synergistically induces chondrogenesis. Growth of Arid5b-/- mice is retarded with delayed endochondral ossification. Sox9-dependent chondrogenesis is attenuated in Arid5b-deficient cells. Arid5b recruits Phf2, a histone lysine demethylase, to the promoter region of Sox9 target genes and stimulates H3K9me2 demethylation of these genes. In the promoters of chondrogenic marker genes, H3K9me2 levels are increased in Arid5b-/- chondrocytes. Finally, we show that Phf2 knockdown inhibits Sox9-induced chondrocyte differentiation. Our findings establish an epigenomic mechanism of skeletal development, whereby Arid5b promotes chondrogenesis by facilitating Phf2-mediated histone demethylation of Sox9-regulated chondrogenic gene promoters.

Tumour Necrosis Factor-alpha and Nuclear Factor-kappa B Gene Variants in Sepsis.

PubMed

Acar, Leyla; Atalan, Nazan; Karagedik, E Hande; Ergen, Arzu

2018-01-20

The humoral system is activated and various cytokines are released due to infections in tissues and traumatic damage. Nuclear factor-kappa B dimers are encoded by nuclear factor-kappa B genes and regulate transcription of several crucial proteins of inflammation such as tumour necrosis factor-alpha. To investigate the possible effect of polymorphisms on tumour necrosis factor-alpha serum levels with clinical and prognostic parameters of sepsis by determining the nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A) gene polymorphisms and tumour necrosis factor-alpha serum levels. Case-control study. Seventy-two patients with sepsis and 104 healthy controls were included in the study. In order to determine the polymorphisms of nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A), polymerase chain reaction-restriction fragment length polymorphism analysis was performed and serum tumour necrosis factor-alpha levels were determined using an enzyme-linked immunosorbent assay. We observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p>0.05). Our results showed the AA genotype and the A allele of the tumour necrosis factor-alpha (-308 G/A) polymorphism may be used as a predictor of elevated tumour necrosis factor-alpha levels in patients with sepsis.

Risk factors for hepatitis B in an outbreak of hepatitis B and D among injection drug users.

PubMed

Bialek, Stephanie R; Bower, William A; Mottram, Karen; Purchase, Dave; Nakano, T; Nainan, Omana; Williams, Ian T; Bell, Beth P

2005-09-01

During January-April, 2000, 12 cases of acute hepatitis B were reported in Pierce County, Washington, compared with seven in all of 1999. Seven (58.3%) case patients were injection drug users (IDUs), three of whom were coinfected with hepatitis D virus (HDV) and died of fulminant hepatitis. Vaccination clinics were implemented at the local health department and needle exchange program to control the outbreak. We investigated this outbreak to determine risk factors for hepatitis B virus (HBV) transmission among IDUs. Hepatitis B cases were ascertained through routine surveillance and prevaccination testing at vaccination clinics. We conducted a case-control study comparing IDU case patients with HBV-susceptible IDUs identified at the vaccination clinics. Fifty-eight case patients were identified during January-December, 2000, 20 (34.5%) of whom were coinfected with HDV. Thirty-eight case patients (65.5%) reported current IDU. In the case-control study, the 17 case patients were more likely than the 141 controls to report having more than one sex partner [odds ratio (OR) =4.8, 95% confidence interval (CI) =1.5-15.0], injecting more than four times a day (OR = 4.5, 95% CI =1.2-15.6) and sharing drug cookers with more than two people (58.8% vs. 14.0%, OR =14.0, 95% CI =2.4-81.5). Results were similar after controlling for syringe sharing in multivariable analysis. IDUs should be vaccinated against hepatitis B and should be advised against sharing drug injection equipment.

Determination of ensemble-average pairwise root mean-square deviation from experimental B-factors.

PubMed

Kuzmanic, Antonija; Zagrovic, Bojan

2010-03-03

Root mean-square deviation (RMSD) after roto-translational least-squares fitting is a measure of global structural similarity of macromolecules used commonly. On the other hand, experimental x-ray B-factors are used frequently to study local structural heterogeneity and dynamics in macromolecules by providing direct information about root mean-square fluctuations (RMSF) that can also be calculated from molecular dynamics simulations. We provide a mathematical derivation showing that, given a set of conservative assumptions, a root mean-square ensemble-average of an all-against-all distribution of pairwise RMSD for a single molecular species, (1/2), is directly related to average B-factors (<B>) and (1/2). We show this relationship and explore its limits of validity on a heterogeneous ensemble of structures taken from molecular dynamics simulations of villin headpiece generated using distributed-computing techniques and the Folding@Home cluster. Our results provide a basis for quantifying global structural diversity of macromolecules in crystals directly from x-ray experiments, and we show this on a large set of structures taken from the Protein Data Bank. In particular, we show that the ensemble-average pairwise backbone RMSD for a microscopic ensemble underlying a typical protein x-ray structure is approximately 1.1 A, under the assumption that the principal contribution to experimental B-factors is conformational variability. 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Histatin 5 binds to Porphyromonas gingivalis hemagglutinin B (HagB) and alters HagB-induced chemokine responses

NASA Astrophysics Data System (ADS)

Borgwardt, Derek S.; Martin, Aaron D.; van Hemert, Jonathan R.; Yang, Jianyi; Fischer, Carol L.; Recker, Erica N.; Nair, Prashant R.; Vidva, Robinson; Chandrashekaraiah, Shwetha; Progulske-Fox, Ann; Drake, David; Cavanaugh, Joseph E.; Vali, Shireen; Zhang, Yang; Brogden, Kim A.

2014-01-01

Histatins are human salivary gland peptides with anti-microbial and anti-inflammatory activities. In this study, we hypothesized that histatin 5 binds to Porphyromonas gingivalis hemagglutinin B (HagB) and attenuates HagB-induced chemokine responses in human myeloid dendritic cells. Histatin 5 bound to immobilized HagB in a surface plasmon resonance (SPR) spectroscopy-based biosensor system. SPR spectroscopy kinetic and equilibrium analyses, protein microarray studies, and I-TASSER structural modeling studies all demonstrated two histatin 5 binding sites on HagB. One site had a stronger affinity with a KD1 of 1.9 μM and one site had a weaker affinity with a KD2 of 60.0 μM. Binding has biological implications and predictive modeling studies and exposure of dendritic cells both demonstrated that 20.0 μM histatin 5 attenuated (p < 0.05) 0.02 μM HagB-induced CCL3/MIP-1α, CCL4/MIP-1β, and TNFα responses. Thus histatin 5 is capable of attenuating chemokine responses, which may help control oral inflammation.

Overexpressed KDM5B is associated with the progression of glioma and promotes glioma cell growth via downregulating p21

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dai, Bin; Hu, Zhiqiang, E-mail: zhiqhutg@126.com; Huang, Hui

Highlights: • KDM5B is overexpressed in glioma samples. • KDM5B stimulated proliferation of glioma cells. • Inhibition of p21contributes to KDM5B-induced proliferation. - Abstract: Epigenetic alterations such as aberrant expression of histone-modifying enzymes have been implicated in tumorigenesis. Upregulation of lysine (K)-specific demethylase 5B (KDM5B) has been reported in a variety of malignant tumors. However, the impact of KDM5B in glioma remains unclear. The objective of this study was to investigate the expression and prognostic value of KDM5B in glioma. In clinical glioma samples, we found that KDM5B expression was significantly upregulated in cancer lesions compared with normal brain tissues.more » Kaplan–Meier analysis showed that patients with glioma and higher KDM5B expression tend to have shorter overall survival time. By silencing or overexpressing KDM5B in glioma cells, we found that KDM5B could promote cell growth both in vitro and in vivo. Moreover, we demonstrated that KDM5B promoted glioma proliferation partly via regulation of the expression of p21. Our study provided evidence that KDM5B functions as a novel tumor oncogene in glioma and may be a potential therapeutic target for glioma management.« less

Measurement of the B^{±} Meson Nuclear Modification Factor in Pb-Pb Collisions at sqrt[s_{NN}]=5.02  TeV.

PubMed

Sirunyan, A M; Tumasyan, A; Adam, W; Asilar, E; Bergauer, T; Brandstetter, J; Brondolin, E; Dragicevic, M; Erö, J; Flechl, M; Friedl, M; Frühwirth, R; Ghete, V M; Hörmann, N; Hrubec, J; Jeitler, M; König, A; Krätschmer, I; Liko, D; Matsushita, T; Mikulec, I; Rabady, D; Rad, N; Rohringer, H; Schieck, J; Strauss, J; Waltenberger, W; Wulz, C-E; Chekhovsky, V; Mossolov, V; Suarez Gonzalez, J; Shumeiko, N; Alderweireldt, S; De Wolf, E A; Janssen, X; Lauwers, J; Van De Klundert, M; Van Haevermaet, H; Van Mechelen, P; Van Remortel, N; Van Spilbeeck, A; Abu Zeid, S; Blekman, F; D'Hondt, J; De Bruyn, I; De Clercq, J; Deroover, K; Lowette, S; Moortgat, S; Moreels, L; Olbrechts, A; Python, Q; Skovpen, K; Tavernier, S; Van Doninck, W; Van Mulders, P; Van Parijs, I; Brun, H; Clerbaux, B; De Lentdecker, G; Delannoy, H; Fasanella, G; Favart, L; Goldouzian, R; Grebenyuk, A; Karapostoli, G; Lenzi, T; Luetic, J; Maerschalk, T; Marinov, A; Randle-Conde, A; Seva, T; Vander Velde, C; Vanlaer, P; Vannerom, D; Yonamine, R; Zenoni, F; Zhang, F; Cimmino, A; Cornelis, T; Dobur, D; Fagot, A; Gul, M; Khvastunov, I; Poyraz, D; Salva, S; Schöfbeck, R; Tytgat, M; Van Driessche, W; Verbeke, W; Zaganidis, N; Bakhshiansohi, H; Bondu, O; Brochet, S; Bruno, G; Caudron, A; De Visscher, S; Delaere, C; Delcourt, M; Francois, B; Giammanco, A; Jafari, A; Komm, M; Krintiras, G; Lemaitre, V; Magitteri, A; Mertens, A; Musich, M; Piotrzkowski, K; Quertenmont, L; Vidal Marono, M; Wertz, S; Beliy, N; Aldá Júnior, W L; Alves, F L; Alves, G A; Brito, L; Hensel, C; Moraes, A; Pol, M E; Rebello Teles, P; Belchior Batista Das Chagas, E; Carvalho, W; Chinellato, J; Custódio, A; Da Costa, E M; Da Silveira, G G; De Jesus Damiao, D; Fonseca De Souza, S; Huertas Guativa, L M; Malbouisson, H; Mora Herrera, C; Mundim, L; Nogima, H; Santoro, A; Sznajder, A; Tonelli Manganote, E J; Torres Da Silva De Araujo, F; Vilela Pereira, A; Ahuja, S; Bernardes, C A; Fernandez Perez Tomei, T R; Gregores, E M; Mercadante, P G; Moon, C S; Novaes, S F; Padula, Sandra S; Romero Abad, D; Ruiz Vargas, J C; Aleksandrov, A; Hadjiiska, R; Iaydjiev, P; Rodozov, M; Stoykova, S; Sultanov, G; Vutova, M; Dimitrov, A; Glushkov, I; Litov, L; Pavlov, B; Petkov, P; Fang, W; Gao, X; Ahmad, M; Bian, J G; Chen, G M; Chen, H S; Chen, M; Chen, Y; Jiang, C H; Leggat, D; Liu, Z; Romeo, F; Shaheen, S M; Spiezia, A; Tao, J; Wang, C; Wang, Z; Yazgan, E; Zhang, H; Zhao, J; Ban, Y; Chen, G; Li, Q; Liu, S; Mao, Y; Qian, S J; Wang, D; Xu, Z; Avila, C; Cabrera, A; Chaparro Sierra, L F; Florez, C; González Hernández, C F; Ruiz Alvarez, J D; Godinovic, N; Lelas, D; Puljak, I; Ribeiro Cipriano, P M; Sculac, T; Antunovic, Z; Kovac, M; Brigljevic, V; Ferencek, D; Kadija, K; Mesic, B; Susa, T; Ather, M W; Attikis, A; Mavromanolakis, G; Mousa, J; Nicolaou, C; Ptochos, F; Razis, P A; Rykaczewski, H; Finger, M; Finger, M; Carrera Jarrin, E; Assran, Y; Mahmoud, M A; Mahrous, A; Dewanjee, R K; Kadastik, M; Perrini, L; Raidal, M; Tiko, A; Veelken, C; Eerola, P; Pekkanen, J; Voutilainen, M; Härkönen, J; Järvinen, T; Karimäki, V; Kinnunen, R; Lampén, T; Lassila-Perini, K; Lehti, S; Lindén, T; Luukka, P; Tuominen, E; Tuominiemi, J; Tuovinen, E; Talvitie, J; Tuuva, T; Besancon, M; Couderc, F; Dejardin, M; Denegri, D; Faure, J L; Ferri, F; Ganjour, S; Ghosh, S; Givernaud, A; Gras, P; Hamel de Monchenault, G; Jarry, P; Kucher, I; Locci, E; Machet, M; Malcles, J; Rander, J; Rosowsky, A; Sahin, M Ö; Titov, M; Abdulsalam, A; Antropov, I; Baffioni, S; Beaudette, F; Busson, P; Cadamuro, L; Chapon, E; Charlot, C; Davignon, O; Granier de Cassagnac, R; Jo, M; Lisniak, S; Lobanov, A; Miné, P; Nguyen, M; Ochando, C; Ortona, G; Paganini, P; Pigard, P; Regnard, S; Salerno, R; Sirois, Y; Stahl Leiton, A G; Strebler, T; Yilmaz, Y; Zabi, A; Agram, J-L; Andrea, J; Bloch, D; Brom, J-M; Buttignol, M; Chabert, E C; Chanon, N; Collard, C; Conte, E; Coubez, X; Fontaine, J-C; Gelé, D; Goerlach, U; Le Bihan, A-C; Van Hove, P; Gadrat, S; Beauceron, S; Bernet, C; Boudoul, G; Chierici, R; Contardo, D; Courbon, B; Depasse, P; El Mamouni, H; Fay, J; Finco, L; Gascon, S; Gouzevitch, M; Grenier, G; Ille, B; Lagarde, F; Laktineh, I B; Lethuillier, M; Mirabito, L; Pequegnot, A L; Perries, S; Popov, A; Sordini, V; Vander Donckt, M; Viret, S; Khvedelidze, A; Tsamalaidze, Z; Autermann, C; Beranek, S; Feld, L; Kiesel, M K; Klein, K; Lipinski, M; Preuten, M; Schomakers, C; Schulz, J; Verlage, T; Albert, A; Brodski, M; Dietz-Laursonn, E; Duchardt, D; Endres, M; Erdmann, M; Erdweg, S; Esch, T; Fischer, R; Güth, A; Hamer, M; Hebbeker, T; Heidemann, C; Hoepfner, K; Knutzen, S; Merschmeyer, M; Meyer, A; Millet, P; Mukherjee, S; Olschewski, M; Padeken, K; Pook, T; Radziej, M; Reithler, H; Rieger, M; Scheuch, F; Sonnenschein, L; Teyssier, D; Thüer, S; Flügge, G; Kargoll, B; Kress, T; Künsken, A; Lingemann, J; Müller, T; Nehrkorn, A; Nowack, A; Pistone, C; Pooth, O; Stahl, A; Aldaya Martin, M; Arndt, T; Asawatangtrakuldee, C; Beernaert, K; Behnke, O; Behrens, U; Bin Anuar, A A; Borras, K; Botta, V; Campbell, A; Connor, P; Contreras-Campana, C; Costanza, F; Diez Pardos, C; Eckerlin, G; Eckstein, D; Eichhorn, T; Eren, E; Gallo, E; Garay Garcia, J; Geiser, A; Gizhko, A; Grados Luyando, J M; Grohsjean, A; Gunnellini, P; Harb, A; Hauk, J; Hempel, M; Jung, H; Kalogeropoulos, A; Kasemann, M; Keaveney, J; Kleinwort, C; Korol, I; Krücker, D; Lange, W; Lelek, A; Lenz, T; Leonard, J; Lipka, K; Lohmann, W; Mankel, R; Melzer-Pellmann, I-A; Meyer, A B; Mittag, G; Mnich, J; Mussgiller, A; Ntomari, E; Pitzl, D; Placakyte, R; Raspereza, A; Roland, B; Savitskyi, M; Saxena, P; Shevchenko, R; Spannagel, S; Stefaniuk, N; Van Onsem, G P; Walsh, R; Wen, Y; Wichmann, K; Wissing, C; Bein, S; Blobel, V; Centis Vignali, M; Draeger, A R; Dreyer, T; Garutti, E; Gonzalez, D; Haller, J; Hoffmann, M; Junkes, A; Klanner, R; Kogler, R; Kovalchuk, N; Kurz, S; Lapsien, T; Marchesini, I; Marconi, D; Meyer, M; Niedziela, M; Nowatschin, D; Pantaleo, F; Peiffer, T; Perieanu, A; Scharf, C; Schleper, P; Schmidt, A; Schumann, S; Schwandt, J; Sonneveld, J; Stadie, H; Steinbrück, G; Stober, F M; Stöver, M; Tholen, H; Troendle, D; Usai, E; Vanelderen, L; Vanhoefer, A; Vormwald, B; Akbiyik, M; Barth, C; Baur, S; Baus, C; Berger, J; Butz, E; Caspart, R; Chwalek, T; Colombo, F; De Boer, W; Dierlamm, A; Freund, B; Friese, R; Giffels, M; Gilbert, A; Haitz, D; Hartmann, F; Heindl, S M; Husemann, U; Kassel, F; Kudella, S; Mildner, H; Mozer, M U; Müller, Th; Plagge, M; Quast, G; Rabbertz, K; Schröder, M; Shvetsov, I; Sieber, G; Simonis, H J; Ulrich, R; Wayand, S; Weber, M; Weiler, T; Williamson, S; Wöhrmann, C; Wolf, R; Anagnostou, G; Daskalakis, G; Geralis, T; Giakoumopoulou, V A; Kyriakis, A; Loukas, D; Topsis-Giotis, I; Kesisoglou, S; Panagiotou, A; Saoulidou, N; Evangelou, I; Flouris, G; Foudas, C; Kokkas, P; Manthos, N; Papadopoulos, I; Paradas, E; Strologas, J; Triantis, F A; Csanad, M; Filipovic, N; Pasztor, G; Bencze, G; Hajdu, C; Horvath, D; Sikler, F; Veszpremi, V; Vesztergombi, G; Zsigmond, A J; Beni, N; Czellar, S; Karancsi, J; Makovec, A; Molnar, J; Szillasi, Z; Bartók, M; Raics, P; Trocsanyi, Z L; Ujvari, B; Choudhury, S; Komaragiri, J R; Bahinipati, S; Bhowmik, S; Mal, P; Mandal, K; Nayak, A; Sahoo, D K; Sahoo, N; Swain, S K; Bansal, S; Beri, S B; Bhatnagar, V; Chawla, R; Dhingra, N; Bhawandeep, U; Kalsi, A K; Kaur, A; Kaur, M; Kumar, R; Kumari, P; Mehta, A; Mittal, M; Singh, J B; Walia, G; Kumar, Ashok; Shah, Aashaq; Bhardwaj, A; Chauhan, S; Choudhary, B C; Garg, R B; Keshri, S; Malhotra, S; Naimuddin, M; Ranjan, K; Sharma, R; Sharma, V; Bhardwaj, R; Bhattacharya, R; Bhattacharya, S; Dey, S; Dutt, S; Dutta, S; Ghosh, S; Majumdar, N; Modak, A; Mondal, K; Mukhopadhyay, S; Nandan, S; Purohit, A; Roy, A; Roy, D; Roy Chowdhury, S; Sarkar, S; Sharan, M; Thakur, S; Behera, P K; Chudasama, R; Dutta, D; Jha, V; Kumar, V; Mohanty, A K; Netrakanti, P K; Pant, L M; Shukla, P; Topkar, A; Aziz, T; Dugad, S; Mahakud, B; Mitra, S; Mohanty, G B; Parida, B; Sur, N; Sutar, B; Banerjee, S; Bhattacharya, S; 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Castle, J; Khalil, S; Kropivnitskaya, A; Majumder, D; Mcbrayer, W; Murray, M; Royon, C; Sanders, S; Stringer, R; Tapia Takaki, J D; Wang, Q; Ivanov, A; Kaadze, K; Maravin, Y; Mohammadi, A; Saini, L K; Skhirtladze, N; Toda, S; Rebassoo, F; Wright, D; Anelli, C; Baden, A; Baron, O; Belloni, A; Calvert, B; Eno, S C; Ferraioli, C; Hadley, N J; Jabeen, S; Jeng, G Y; Kellogg, R G; Kunkle, J; Mignerey, A C; Ricci-Tam, F; Shin, Y H; Skuja, A; Tonwar, S C; Abercrombie, D; Allen, B; Azzolini, V; Barbieri, R; Baty, A; Bi, R; Bierwagen, K; Brandt, S; Busza, W; Cali, I A; D'Alfonso, M; Demiragli, Z; Gomez Ceballos, G; Goncharov, M; Hsu, D; Iiyama, Y; Innocenti, G M; Klute, M; Kovalskyi, D; Lai, Y S; Lee, Y-J; Levin, A; Luckey, P D; Maier, B; Marini, A C; Mcginn, C; Mironov, C; Narayanan, S; Niu, X; Paus, C; Roland, C; Roland, G; Salfeld-Nebgen, J; Stephans, G S F; Tatar, K; Turner, A; Velicanu, D; Wang, J; Wang, T W; Wyslouch, B; Benvenuti, A C; Chatterjee, R M; Evans, A; Hansen, P; Kalafut, S; Kao, S C; Kubota, Y; Lesko, Z; Mans, J; Nourbakhsh, S; Ruckstuhl, N; Rusack, R; Tambe, N; Turkewitz, J; Acosta, J G; Oliveros, S; Avdeeva, E; Bloom, K; Claes, D R; Fangmeier, C; Gonzalez Suarez, R; Kamalieddin, R; Kravchenko, I; Monroy, J; Siado, J E; Snow, G R; Stieger, B; Alyari, M; Dolen, J; Godshalk, A; Harrington, C; Iashvili, I; Kharchilava, A; Parker, A; Rappoccio, S; Roozbahani, B; Alverson, G; Barberis, E; Hortiangtham, A; Massironi, A; Morse, D M; Nash, D; Orimoto, T; Teixeira De Lima, R; Trocino, D; Wang, R-J; Wood, D; Bhattacharya, S; Charaf, O; Hahn, K A; Mucia, N; Odell, N; Pollack, B; Schmitt, M H; Sung, K; Trovato, M; Velasco, M; Dev, N; Hildreth, M; Hurtado Anampa, K; Jessop, C; Karmgard, D J; Kellams, N; Lannon, K; Loukas, N; Marinelli, N; Meng, F; Mueller, C; Musienko, Y; Planer, M; Reinsvold, A; Ruchti, R; Rupprecht, N; Smith, G; Taroni, S; Wayne, M; Wolf, M; Woodard, A; Alimena, J; Antonelli, L; Bylsma, B; Durkin, L S; Flowers, S; Francis, B; Hart, A; Hill, C; Ji, W; Liu, B; Luo, W; Puigh, D; Winer, B L; Wulsin, H W; Benaglia, A; Cooperstein, S; Driga, O; Elmer, P; Hardenbrook, J; Hebda, P; Lange, D; Luo, J; Marlow, D; Mei, K; Ojalvo, I; Olsen, J; Palmer, C; Piroué, P; Stickland, D; Svyatkovskiy, A; Tully, C; Malik, S; Norberg, S; Barker, A; Barnes, V E; Folgueras, S; Gutay, L; Jha, M K; Jones, M; Jung, A W; Khatiwada, A; Miller, D H; Neumeister, N; Schulte, J F; Sun, J; Wang, F; Xie, W; Cheng, T; Parashar, N; Stupak, J; Adair, A; Akgun, B; Chen, Z; Ecklund, K M; Geurts, F J M; Guilbaud, M; Li, W; Michlin, B; Northup, M; Padley, B P; Roberts, J; Rorie, J; Tu, Z; Zabel, J; Betchart, B; Bodek, A; de Barbaro, P; Demina, R; Duh, Y T; Ferbel, T; Galanti, M; Garcia-Bellido, A; Han, J; Hindrichs, O; Khukhunaishvili, A; Lo, K H; Tan, P; Verzetti, M; Ciesielski, R; Goulianos, K; Mesropian, C; Agapitos, A; Chou, J P; Gershtein, Y; Gómez Espinosa, T A; Halkiadakis, E; Heindl, M; Hughes, E; Kaplan, S; Kunnawalkam Elayavalli, R; Kyriacou, S; Lath, A; Montalvo, R; Nash, K; Osherson, M; Saka, H; Salur, S; Schnetzer, S; Sheffield, D; Somalwar, S; Stone, R; Thomas, S; Thomassen, P; Walker, M; Foerster, M; Heideman, J; Riley, G; Rose, K; Spanier, S; Thapa, K; Bouhali, O; Castaneda Hernandez, A; Celik, A; Dalchenko, M; De Mattia, M; Delgado, A; Dildick, S; Eusebi, R; Gilmore, J; Huang, T; Kamon, T; Mueller, R; Pakhotin, Y; Patel, R; Perloff, A; Perniè, L; Rathjens, D; Safonov, A; Tatarinov, A; Ulmer, K A; Akchurin, N; Damgov, J; De Guio, F; Dragoiu, C; Dudero, P R; Faulkner, J; Gurpinar, E; Kunori, S; Lamichhane, K; Lee, S W; Libeiro, T; Peltola, T; Undleeb, S; Volobouev, I; Wang, Z; Greene, S; Gurrola, A; Janjam, R; Johns, W; Maguire, C; Melo, A; Ni, H; Sheldon, P; Tuo, S; Velkovska, J; Xu, Q; Arenton, M W; Barria, P; Cox, B; Hirosky, R; Ledovskoy, A; Li, H; Neu, C; Sinthuprasith, T; Sun, X; Wang, Y; Wolfe, E; Xia, F; Clarke, C; Harr, R; Karchin, P E; Sturdy, J; Zaleski, S; Belknap, D A; Buchanan, J; Caillol, C; Dasu, S; Dodd, L; Duric, S; Gomber, B; Grothe, M; Herndon, M; Hervé, A; Hussain, U; Klabbers, P; Lanaro, A; Levine, A; Long, K; Loveless, R; Pierro, G A; Polese, G; Ruggles, T; Savin, A; Smith, N; Smith, W H; Taylor, D; Woods, N

2017-10-13

The differential production cross sections of B^{±} mesons are measured via the exclusive decay channels B^{±}→J/ψK^{±}→μ^{+}μ^{-}K^{±} as a function of transverse momentum in pp and Pb-Pb collisions at a center-of-mass energy sqrt[s_{NN}]=5.02  TeV per nucleon pair with the CMS detector at the LHC. The pp(Pb-Pb) data set used for this analysis corresponds to an integrated luminosity of 28.0  pb^{-1} (351  μb^{-1}). The measurement is performed in the B^{±} meson transverse momentum range of 7 to 50  GeV/c, in the rapidity interval |y|<2.4. In this kinematic range, a strong suppression of the production cross section by about a factor of 2 is observed in the Pb-Pb system in comparison to the expectation from pp reference data. These results are found to be roughly compatible with theoretical calculations incorporating beauty quark diffusion and energy loss in a quark-gluon plasma.

Transcription factor Etv5 is essential for the maintenance of alveolar type II cells.

PubMed

Zhang, Zhen; Newton, Kim; Kummerfeld, Sarah K; Webster, Joshua; Kirkpatrick, Donald S; Phu, Lilian; Eastham-Anderson, Jeffrey; Liu, Jinfeng; Lee, Wyne P; Wu, Jiansheng; Li, Hong; Junttila, Melissa R; Dixit, Vishva M

2017-04-11

Alveolar type II (AT2) cell dysfunction contributes to a number of significant human pathologies including respiratory distress syndrome, lung adenocarcinoma, and debilitating fibrotic diseases, but the critical transcription factors that maintain AT2 cell identity are unknown. Here we show that the E26 transformation-specific (ETS) family transcription factor Etv5 is essential to maintain AT2 cell identity. Deletion of Etv5 from AT2 cells produced gene and protein signatures characteristic of differentiated alveolar type I (AT1) cells. Consistent with a defect in the AT2 stem cell population, Etv5 deficiency markedly reduced recovery following bleomycin-induced lung injury. Lung tumorigenesis driven by mutant KrasG12D was also compromised by Etv5 deficiency. ERK activation downstream of Ras was found to stabilize Etv5 through inactivation of the cullin-RING ubiquitin ligase CRL4 COP1/DET1 that targets Etv5 for proteasomal degradation. These findings identify Etv5 as a critical output of Ras signaling in AT2 cells, contributing to both lung homeostasis and tumor initiation.

Stimulation of EphB2/ephrin-B1 signalling by tumour necrosis factor alpha in human dental pulp stem cells.

PubMed

Zhu, Lifang; Dissanayaka, Waruna Lakmal; Green, David William; Zhang, Chengfei

2015-04-01

The aim of this study was to investigate whether in vitro stimulation of dental pulp stem cells (DPSCs) by tumour necrosis factor alpha (TNF-α) would induce secretion of EphB2/ephrin-B1 signalling. Dental pulp stem cells isolated from human dental pulp were treated with TNF-α (5-100 ng/ml) over 2-48 h. EphB2/ephrin-B1 mRNA and protein levels were measured by real-time polymerase chain reaction (RT-PCR) and western blot analysis respectively. Additionally, DPSCs were pre-incubated with TNF-α receptor neutralizing antibodies or infected with nuclear factor-kappa B (NF-ĸB) inhibitor, p38 MAPK inhibitor, Jun N-terminal kinase (JNK) inhibitor and MEK inhibitor before TNF-α treatment. Results were analysed by one-way ANOVA. Tumour necrosis factor alpha increased EphB2 mRNA expression in DPSCs at concentrations up to 20 ng/ml and ephrin-B1 at concentrations up to 40 ng/ml (P < 0.05). Its mRNA expression reached maximum at 24 h when treated with TNF-α at 20 ng/ml (P < 0.05). EphB2/ephrin-B1 protein expression levels were high at 16 and 24 h as shown by western blotting. Neutralizing antibodies for TNFR1/2 receptors down-regulated EphB2/ephrin-B1 mRNA expression (P < 0.05) and ephrin-B1 protein expression, but not EphB2 protein expression. JNK-inhibitor inhibited EphB2 mRNA expression only (P < 0.05). EphB2/ephrin-B1 were invoked in DPSCs with TNF-α treatment via the JNK-dependent pathway, but not NF-ĸB, p38 MAPK or MEK signalling. © 2015 John Wiley & Sons Ltd.

Acquisition of Complement Inhibitor Serine Protease Factor I and Its Cofactors C4b-Binding Protein and Factor H by Prevotella intermedia

PubMed Central

Malm, Sven; Jusko, Monika; Eick, Sigrun; Potempa, Jan; Riesbeck, Kristian; Blom, Anna M.

2012-01-01

Infection with the Gram-negative pathogen Prevotella intermedia gives rise to periodontitis and a growing number of studies implies an association of P. intermedia with rheumatoid arthritis. The serine protease Factor I (FI) is the central inhibitor of complement degrading complement components C3b and C4b in the presence of cofactors such as C4b-binding protein (C4BP) and Factor H (FH). Yet, the significance of complement inhibitor acquisition in P. intermedia infection and FI binding by Gram-negative pathogens has not been addressed. Here we show that P. intermedia isolates bound purified FI as well as FI directly from heat-inactivated human serum. FI bound to bacteria retained its serine protease activity as shown in degradation experiments with 125I-labeled C4b. Since FI requires cofactors for its activity we also investigated the binding of purified cofactors C4BP and FH and found acquisition of both proteins, which retained their activity in FI mediated degradation of C3b and C4b. We propose that FI binding by P. intermedia represents a new mechanism contributing to complement evasion by a Gram-negative bacterial pathogen associated with chronic diseases. PMID:22514678

Protein–energy malnutrition increases activation of the transcription factor, nuclear factor κB, in the gerbil hippocampus following global ischemia☆

PubMed Central

Ji, Liang; Nazarali, Adil J.; Paterson, Phyllis G.

2013-01-01

Protein–energy malnutrition (PEM) exacerbates functional impairment caused by brain ischemia. This is correlated with reactive gliosis, which suggests an increased inflammatory response. The objective of the current study was to investigate if PEM increases hippocampal activation of nuclear factor κB (NFκB), a transcription factor that amplifies the inflammatory response involved in ischemic brain injury. Mongolian gerbils (11–12 weeks old) were randomly assigned to control diet (12.5% protein) or protein-deficient diet (2%) for 4 weeks. The 2% protein group had a 15% decrease in voluntary food intake (P<.001; unpaired t test), resulting in PEM. Body weight after 4 weeks was 20% lower in the PEM group (P<.001). Gerbils were then exposed to sham surgery or global ischemia induced by 5-min bilateral common carotid artery occlusion. PEM independently increased hippocampal NFκB activation detected by electrophoretic mobility shift assay at 6 h after surgery (P=.014; 2-factor ANOVA). Ischemia did not significantly affect NFκB activation nor was there interaction between diet and ischemia. Serum glucose and cortisol concentrations at 6 h postischemia were unaltered by diet or ischemia. A second experiment using gerbils of the same age and feeding paradigm demonstrated that PEM also increases hippocampal NFκB activation in the absence of surgery. These findings suggest that PEM, which exists in 16% of elderly patients at admission for stroke, may worsen outcome by increasing activation of NFκB. Since PEM increased NFκB activation independent of ischemia or surgery, the data also have implications for the inflammatory response of the many individuals affected globally by PEM. PMID:18430555

5 CFR 842.907 - Withholding and contributions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Section 842.907 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE... required under 5 U.S.C. 8422(a)(3) and submit that amount to OPM in accordance with payroll office... payroll office instructions issued by OPM. (c) If the correct withholding and/or Government contributions...

Surface expression of hippocampal NMDA GluN2B receptors regulated by fear conditioning determines its contribution to memory consolidation in adult rats.

PubMed

Sun, Yan-Yan; Cai, Wei; Yu, Jie; Liu, Shu-Su; Zhuo, Min; Li, Bao-Ming; Zhang, Xue-Han

2016-08-04

The number and subtype composition of N-methyl-d-aspartate receptor (NMDAR) at synapses determines their functional properties and role in learning and memory. Genetically increased or decreased amount of GluN2B affects hippocampus-dependent memory in the adult brain. But in some experimental conditions (e.g., memory elicited by a single conditioning trial (1 CS-US)), GluN2B is not a necessary factor, which indicates that the precise role of GluN2B in memory formation requires further exploration. Here, we examined the role of GluN2B in the consolidation of fear memory using two training paradigms. We found that GluN2B was only required for the consolidation of memory elicited by five conditioning trials (5 CS-US), not by 1 CS-US. Strikingly, the expression of membrane GluN2B in CA1was training-strength-dependently increased after conditioning, and that the amount of membrane GluN2B determined its involvement in memory consolidation. Additionally, we demonstrated the increases in the activities of cAMP, ERK, and CREB in the CA1 after conditioning, as well as the enhanced intrinsic excitability and synaptic efficacy in CA1 neurons. Up-regulation of membrane GluN2B contributed to these enhancements. These studies uncover a novel mechanism for the involvement of GluN2B in memory consolidation by its accumulation at the cell surface in response to behavioral training.

Early life risk factors that contribute to irritable bowel syndrome in adults: a systematic review.

PubMed

Chitkara, Denesh K; van Tilburg, Miranda A L; Blois-Martin, Nannette; Whitehead, William E

2008-03-01

Irritable bowel syndrome (IBS) is a common disorder that occurs in adults. The natural history of symptoms and risk factors that contribute to IBS may begin in childhood. The aim of this systematic review was to determine what early life factors contribute to the development of IBS in adolescents and adults. A computer-assisted search of the PubMed database from 1966 to 2007 was performed. The selection criteria were: (a) studies conducted in adolescents or adults with IBS that (b) investigate premorbid factors occurring specifically during the childhood period and are (c) associated with the outcomes of symptoms, quality of life, health-care utilization, and interferences with work or disability. Twenty-five articles met inclusion criteria. The studies were categorized into articles examining the persistence of childhood gastrointestinal symptoms into adulthood, affluent childhood socioeconomic status and adult IBS, infantile and childhood trauma associated with the development of adult IBS, and social learning of illness behavior as predictors of adult IBS. Pediatricians should be aware of potentially modifiable childhood risk factors and should consider interventions such as early symptom management of recurrent functional abdominal pain with cognitive therapies and parent education about social learning of illness behavior. Early treatment may have a long-term impact. Research examining the effect of affluent childhood socioeconomic status and early childhood trauma in the evolution of functional gastrointestinal disorders may help identify causative factors of IBS.

Mechanisms of B cell activation in patients with acquired immunodeficiency syndrome and related disorders. Contribution of antibody-producing B cells, of Epstein-Barr virus-infected B cells, and of immunoglobulin production induced by human T cell lymphotropic virus, type III/lymphadenopathy-associated virus.

PubMed Central

Yarchoan, R; Redfield, R R; Broder, S

1986-01-01

Patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) have hyperimmunoglobulinemia and increased numbers of circulating immunoglobulin-secreting cells. In this paper, we studied the basis for this B cell hyperactivity. Limiting dilution studies of B cells from seven patients with ARC and four with AIDS revealed that some B cells spontaneously produced antibodies to human T cell lymphotropic virus, type III/lymphadenopathy-associated virus (HTLV-III/LAV) (39:10(6) and 7:10(6) B cells, respectively), suggesting that chronic antigenic stimulation by HTLV-III/LAV was one contributing factor. The patients also had an increased number of spontaneously outgrowing B cells than did normals (6:10(6) vs. less than 2:10(6) B cells), suggesting that they had an increased number of Epstein-Barr virus (EBV)-infected B cells. However, fewer B cells from patients were immortalized by exogenously added EBV than were B cells from normals. In additional studies, HTLV-III/LAV induced immunoglobulin secretion (mean 2,860 ng/ml) by peripheral blood mononuclear cells from normals; this HTLV-III/LAV-induced immunoglobulin secretion required the presence of both B and T cells. Thus, antigenic stimulation by HTLV-III/LAV, increased numbers of EBV-infected B cells, and HTLV-III/LAV-induced T cell-dependent B cell activation all contribute to the B cell hyperactivity in patients with HTLV-III/LAV disease. PMID:3016028

An Observational Study of Bullying as a Contributing Factor in Youth Suicide in Toronto

PubMed Central

Sinyor, Mark; Schaffer, Ayal; Cheung, Amy H

2014-01-01

Objective Bullying has been identified as a potential contributing factor in youth suicide. This issue has been highlighted in recent widely publicized media reports, worldwide, in which deceased youth were bullied. We report on an observational study conducted to determine the frequency of bullying as a contributing factor to youth suicide. Method: Coroner records were reviewed for all suicide deaths in youth aged between 10 and 19 in the city of Toronto from 1998 to 2011. Data abstracted were recent stressors (including bullying), clinical variables, such as the presence of mental illness, demographics, and methods of suicide. Results: Ninety-four youth suicides were included in the study. The mean age was 16.8 years, and 70.2% were male. Bullying was present in 6 deaths (6.4%), and there were no deaths where online or cyberbullying was detected. Bullying was the only identified contributing factor in fewer than 5 deaths. The most common stressors identified were conflict with parents (21.3%), romantic partner problems (17.0%), academic problems (10.6%), and criminal and (or) legal problems (10.6%). Any stressor or mental and (or) physical illness was detected in 78.7% of cases. Depression was detected in 40.4% of cases. Conclusions: Our study highlights the need to view suicide in youth as arising from a complex interplay of various biological, psychological, and social factors of which bullying is only one. It challenges simple cause-and-effect models that may suggest that suicide arises from any one factor, such as bullying. PMID:25702362

Factors contributing to employment patterns after liver transplantation.

PubMed

Beal, Eliza W; Tumin, Dmitry; Mumtaz, Khalid; Nau, Michael; Tobias, Joseph D; Hayes, Don; Washburn, Kenneth; Black, Sylvester M

2017-06-01

Many liver transplant recipients return to work, but their patterns of employment are unclear. We examine patterns of employment 5 years after liver transplantation. First-time liver transplant recipients ages 18-60 years transplanted from 2002 to 2009 and surviving at least 5 years were identified in the United Network for Organ Sharing registry. Recipients' post-transplant employment status was classified as follows: (i) never employed; (ii) returned to work within 2 years and remained employed (continuous employment); (iii) returned to work within 2 years, but was subsequently unemployed (intermittent employment); or (iv) returned to work ≥3 years post-transplant (delayed employment). Of 28 306 liver recipients identified during the study period, 12 998 survived at least 5 years and contributed at least 1 follow-up of employment status. A minority of patients (4654; 36%) were never employed, while 3780 (29%) were continuously employed, 3027 (23%) were intermittently employed, and 1537 (12%) had delayed employment. In multivariable logistic regression analysis, predictors of intermittent and delayed employment included lower socioeconomic status, higher local unemployment rates, and post-transplant comorbidities or complications. Never, intermittent, and delayed employment are common after liver transplantation. Socioeconomic and labor market characteristics may add to clinical factors that limit liver transplant recipients' continuous employment. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ecto-5′-Nucleotidase: A Candidate Virulence Factor in Streptococcus sanguinis Experimental Endocarditis

PubMed Central

Fan, Jingyuan; Zhang, Yongshu; Chuang-Smith, Olivia N.; Frank, Kristi L.; Guenther, Brian D.; Kern, Marissa; Schlievert, Patrick M.; Herzberg, Mark C.

2012-01-01

Streptococcus sanguinis is the most common cause of infective endocarditis (IE). Since the molecular basis of virulence of this oral commensal bacterium remains unclear, we searched the genome of S. sanguinis for previously unidentified virulence factors. We identified a cell surface ecto-5′-nucleotidase (Nt5e), as a candidate virulence factor. By colorimetric phosphate assay, we showed that S. sanguinis Nt5e can hydrolyze extracellular adenosine triphosphate to generate adenosine. Moreover, a nt5e deletion mutant showed significantly shorter lag time (P<0.05) to onset of platelet aggregation than the wild-type strain, without affecting platelet-bacterial adhesion in vitro (P = 0.98). In the absence of nt5e, S. sanguinis caused IE (4 d) in a rabbit model with significantly decreased mass of vegetations (P<0.01) and recovered bacterial loads (log10CFU, P = 0.01), suggesting that Nt5e contributes to the virulence of S. sanguinis in vivo. As a virulence factor, Nt5e may function by (i) hydrolyzing ATP, a pro-inflammatory molecule, and generating adenosine, an immunosuppressive molecule to inhibit phagocytic monocytes/macrophages associated with valvular vegetations. (ii) Nt5e-mediated inhibition of platelet aggregation could also delay presentation of platelet microbicidal proteins to infecting bacteria on heart valves. Both plausible Nt5e-dependent mechanisms would promote survival of infecting S. sanguinis. In conclusion, we now show for the first time that streptococcal Nt5e modulates S. sanguinis-induced platelet aggregation and may contribute to the virulence of streptococci in experimental IE. PMID:22685551

Contribution of cytochrome P450 1B1 to hypertension and associated pathophysiology: a novel target for antihypertensive agents.

PubMed

Malik, Kafait U; Jennings, Brett L; Yaghini, Fariborz A; Sahan-Firat, Seyhan; Song, Chi Young; Estes, Anne M; Fang, Xiao R

2012-08-01

The aim of this review is to discuss the contribution of cytochrome P450 (CYP) 1B1 in vascular smooth muscle cell growth, hypertension, and associated pathophysiology. CYP1B1 is expressed in cardiovascular and renal tissues, and mediates angiotensin II (Ang II)-induced activation of NADPH oxidase and generation of reactive oxygen species (ROS), and vascular smooth muscle cell migration, proliferation, and hypertrophy. Moreover, CYP1B1 contributes to the development and/or maintenance of hypertension produced by Ang II-, deoxycorticosterone (DOCA)-salt-, and N(ω)-nitro-L-arginine methyl ester-induced hypertension and in spontaneously hypertensive rats. The pathophysiological changes, including cardiovascular hypertrophy, increased vascular reactivity, endothelial and renal dysfunction, injury and inflammation associated with Ang II- and/or DOCA-salt induced hypertension in rats, and Ang II-induced hypertension in mice are minimized by inhibition of CYP1B1 activity with 2,4,3',5'-tetramethoxystilbene or by Cyp1b1 gene disruption in mice. These pathophysiological changes appear to be mediated by increased production of ROS via CYP1B1-dependent NADPH oxidase activity and extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase, and c-Src. Copyright © 2011 Elsevier Inc. All rights reserved.

Contribution of Cytochrome P450 1B1 to Hypertension and Associated Pathophysiology: A Novel Target for Antihypertensive Agents

PubMed Central

Malik, Kafait U.; Jennings, Brett L.; Yaghini, Fariborz A.; Sahan-Firat, Seyhan; Song, Chi Young; Estes, Anne M.; Fang, Xiao R.

2012-01-01

The aim of this review is to discuss the contribution of cytochrome P450 (CYP) 1B1 in vascular smooth muscle cell growth, hypertension, and associated pathophysiology. CYP1B1 is expressed in cardiovascular and renal tissues, and mediates angiotensin II (Ang II)-induced activation of NADPH oxidase and generation of reactive oxygen species (ROS), and vascular smooth muscle cell migration, proliferation, and hypertrophy. Moreover, CYP1B1 contributes to the development and/or maintenance of hypertension produced by Ang II-, deoxycorticosterone Nω-nitro-(DOCA)-salt-, and L-arginine methyl ester-induced hypertension and in spontaneously hypertensive rats. The pathophysiological changes, including cardiovascular hypertrophy, increased vascular reactivity, endothelial and renal dysfunction, injury and inflammation associated with Ang II- and/or DOCA-salt induced hypertension in rats, and Ang II-induced hypertension in mice are minimized by inhibition of CYP1B1 activity with 2,4,3′,5′-tetramethoxystilbene or by Cyp1b1 gene disruption in mice. These pathophysiological changes appear to be mediated by increased production of ROS via CYP1B1-dependent NADPH oxidase activity and extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase, and c-Src. PMID:22210049

Perturbative corrections to B → D form factors in QCD

NASA Astrophysics Data System (ADS)

Wang, Yu-Ming; Wei, Yan-Bing; Shen, Yue-Long; Lü, Cai-Dian

2017-06-01

We compute perturbative QCD corrections to B → D form factors at leading power in Λ/ m b , at large hadronic recoil, from the light-cone sum rules (LCSR) with B-meson distribution amplitudes in HQET. QCD factorization for the vacuum-to- B-meson correlation function with an interpolating current for the D-meson is demonstrated explicitly at one loop with the power counting scheme {m}_c˜ O(√{Λ {m}_b}) . The jet functions encoding information of the hard-collinear dynamics in the above-mentioned correlation function are complicated by the appearance of an additional hard-collinear scale m c , compared to the counterparts entering the factorization formula of the vacuum-to- B-meson correction function for the construction of B → π from factors. Inspecting the next-to-leading-logarithmic sum rules for the form factors of B → Dℓν indicates that perturbative corrections to the hard-collinear functions are more profound than that for the hard functions, with the default theory inputs, in the physical kinematic region. We further compute the subleading power correction induced by the three-particle quark-gluon distribution amplitudes of the B-meson at tree level employing the background gluon field approach. The LCSR predictions for the semileptonic B → Dℓν form factors are then extrapolated to the entire kinematic region with the z-series parametrization. Phenomenological implications of our determinations for the form factors f BD +,0 ( q 2) are explored by investigating the (differential) branching fractions and the R( D) ratio of B → Dℓν and by determining the CKM matrix element |V cb | from the total decay rate of B → Dμν μ .

Peer Victimization in Dutch School Classes of Four- to Five-Year-Olds: Contributing Factors at the School Level

ERIC Educational Resources Information Center

Bonnet, Marielle; Goossens, Frits A.; Willemen, Agnes M.; Schuengel, Carlo

2009-01-01

This research was designed to examine how factors within young children's environment (e.g., school factors, neighborhood) contribute to explaining peer victimization. The sample comprised 2,003 children (between 4 and 5 years of age) from 98 classrooms in 23 elementary schools in the Netherlands. Teachers were asked to complete a questionnaire on…

Mercury-Bridged Cobaltacarborane Complexes Containing B-Hg-B Three-Center Bonds. Synthesis and Structure of mu, mu’-((n5-C5R5)Co(CH3)2C2B3H4)Hg, mu-(n(5)-C5R5)Co(CH3)2C2B3H4)HgCl, (R=H, CH3) and Related Compounds.

DTIC Science & Technology

1980-11-01

MERCURY-BRIDGED COBALTACARBORANE COMPLEXES CONTAINING B-HG-B TH--ETC(U) NOV 80 D C FINSTER . R N GRIMES N0 0 0 1 4-75-0305 UNCLASSXFIED TR󈧨 NL ILn...C5R5) Co 3)2C2B3 4 2 5 .- -C5R5 )Co(CH3)2C2B3H4 ]HgCl, (R=H, CH3 ) and Related Compounds, David C./ Finster -- Russell N./Grimes ( Department of Chemistry...Compounds 1 \\David C. Finster And Russell N. Grimes* Abstract. Reactions of the nid~p-cobaltacarborane anions 01CR )(C 3 )C BH and [n (H 1oC ihH~5n 5

Human factors and education: evolution and contributions.

PubMed

Stone, Nancy J

2008-06-01

The major contributions of human factors to education are highlighted. Over the past 50 years, the education of human factors specialists has evolved, as well as the application of human factors and ergonomic knowledge to education. Human factors and ergonomics professional documentation and literature were reviewed to identify major events relevant to human factors education or the application of human factors to education. Human factors education has evolved from training in experimental psychology to highly specialized accredited human factors programs and a number of undergraduate programs, leading to program accreditation and the certification of professionals. In addition, human factors specialists have applied their knowledge to human factors education and, more recently, to educational systems in general. The greatest focus has been on technology such as multimedia. Others have evaluated the design of the physical environment, focusing primarily on seating. The research also often targets undergraduate or graduate education. Therefore, it has been proposed that a greater focus is needed at the K-12 educational level, especially given the advancement and implementation of technology in the classroom. Human factors and ergonomic expertise can benefit the educational system. Yet, there is a need to constantly evaluate the benefits of new technology in the classroom as well as the environmental design aspects of the educational environment while considering learners of different age groups, ethnicities, and sexes. Better application of human factors and ergonomics to the learning environment could enhance the educational experience for all learners.

Salicylates inhibit flavivirus replication independently of blocking nuclear factor kappa B activation.

PubMed

Liao, C L; Lin, Y L; Wu, B C; Tsao, C H; Wang, M C; Liu, C I; Huang, Y L; Chen, J H; Wang, J P; Chen, L K

2001-09-01

Flaviviruses comprise a positive-sense RNA genome that replicates exclusively in the cytoplasm of infected cells. Whether flaviviruses require an activated nuclear factor(s) to complete their life cycle and trigger apoptosis in infected cells remains elusive. Flavivirus infections quickly activate nuclear factor kappa B (NF-kappaB), and salicylates have been shown to inhibit NF-kappaB activation. In this study, we investigated whether salicylates suppress flavivirus replication and virus-induced apoptosis in cultured cells. In a dose-dependent inhibition, we found salicylates within a range of 1 to 5 mM not only restricted flavivirus replication but also abrogated flavivirus-triggered apoptosis. However, flavivirus replication was not affected by a specific NF-kappaB peptide inhibitor, SN50, and a proteosome inhibitor, lactacystin. Flaviviruses also replicated and triggered apoptosis in cells stably expressing IkappaBalpha-DeltaN, a dominant-negative mutant that antagonizes NF-kappaB activation, as readily as in wild-type BHK-21 cells, suggesting that NF-kappaB activation is not essential for either flavivirus replication or flavivirus-induced apoptosis. Salicylates still diminished flavivirus replication and blocked apoptosis in the same IkappaBalpha-DeltaN cells. This inhibition of flaviviruses by salicylates could be partially reversed by a specific p38 mitogen-activated protein (MAP) kinase inhibitor, SB203580. Together, these results show that the mechanism by which salicylates suppress flavivirus infection may involve p38 MAP kinase activity but is independent of blocking the NF-kappaB pathway.

Adenoviral mediated interferon-alpha 2b gene therapy suppresses the pro-angiogenic effect of vascular endothelial growth factor in superficial bladder cancer.

PubMed

Adam, Liana; Black, Peter C; Kassouf, Wassim; Eve, Beryl; McConkey, David; Munsell, Mark F; Benedict, William F; Dinney, Colin P N

2007-05-01

Intravesical adenovirus mediated interferon-alpha gene transfer has a potent therapeutic effect against superficial human bladder carcinoma xenografts growing in the bladder of athymic nude mice. We determined whether the inhibition of angiogenesis might contribute to the antitumor effect. We treated several human urothelial carcinoma cells with adenovirus mediated interferon-alpha 2b and monitored its effects on the production of angiogenic factors using real-time reverse-transcription polymerase chain reaction, Western blotting, and immunohistochemical analysis and a gel shift based transcription factor array. To assess the role of adenovirus mediated interferon 2b in angiogenic activity we used in vitro invasion assays and evaluated the anti-angiogenic effects of adenovirus mediated interferon gene therapy in an orthotopic murine model of human superficial bladder cancer. In adenovirus mediated interferon-alpha infected 253J B-V cells vascular endothelial growth factor was decreased and anti-angiogenic interferon-gamma inducible protein 10 was up-regulated. In contrast, the addition of as much as 100,000 IU recombinant interferon had no apparent effect on vascular endothelial growth factor production. Conditioned medium derived from adenovirus mediated interferon 2b infected 253J B-V cells greatly decreased the invasive potential of human endothelial cells and down-regulated their matrix metalloproteinase 2 expression compared to controls. Furthermore, adenovirus mediated interferon 2b blocked pro-angiogenic nuclear signals, such as the transcription factors activating protein-1 and 2, stimulating protein-1, nuclear factor kappaB and c-myb. In vivo experiments revealed significant vascular endothelial growth factor down-regulation and decreased tumor vessel density in the adenovirus mediated interferon 2b treated group compared to controls. Treatment with adenovirus mediated interferon 2b increases the angiostatic activity of the bladder cancer microenvironment

The Metastasis Efficiency Modifier Ribosomal RNA Processing 1 Homolog B (RRP1B) Is a Chromatin-associated Factor*

PubMed Central

Crawford, Nigel P. S.; Yang, Hailiu; Mattaini, Katherine R.; Hunter, Kent W.

2009-01-01

There is accumulating evidence for a role of germ line variation in breast cancer metastasis. We have recently identified a novel metastasis susceptibility gene, Rrp1b (ribosomal RNA processing 1 homolog B). Overexpression of Rrp1b in a mouse mammary tumor cell line induces a gene expression signature that predicts survival in breast cancer. Here we extend the analysis of RRP1B function by demonstrating that the Rrp1b activation gene expression signature accurately predicted the outcome in three of four publicly available breast carcinoma gene expression data sets. In addition, we provide insights into the mechanism of RRP1B. Tandem affinity purification demonstrated that RRP1B physically interacts with many nucleosome binding factors, including histone H1X, poly(ADP-ribose) polymerase 1, TRIM28 (tripartite motif-containing 28), and CSDA (cold shock domain protein A). Co-immunofluorescence and co-immunoprecipitation confirmed these interactions and also interactions with heterochromatin protein-1α and acetyl-histone H4 lysine 5. Finally, we investigated the effects of ectopic expression of an RRP1B allelic variant previously associated with improved survival in breast cancer. Gene expression analyses demonstrate that, compared with ectopic expression of wild type RRP1B in HeLa cells, the variant RRP1B differentially modulates various transcription factors controlled by TRIM28 and CSDA. These data suggest that RRP1B, a tumor progression and metastasis susceptibility candidate gene, is potentially a dynamic modulator of transcription and chromatin structure. PMID:19710015

Prevalence and risk factors of hepatitis B in Spanish prostitutes.

PubMed Central

Requena Caballero, L.; Requena Caballero, C.; Requena Caballero, I.; Sánchez López, M.; Vázquez López, F.; Romero Guerrero, J.; Casado Jiménez, M.

1987-01-01

Eighty prostitutes were tested by solid-phase radioimmunoassay for serum markers of hepatitis B virus (HBV). Of 8 (10%) with hepatitis B surface antigen (HBsAg), 6 (75%) also had hepatitis Be antigen (HBeAg). Antibodies to HBsAg (anti-HBs) and to hepatitis B core antigen (anti-HBc) were found in 52 (65%). Antibodies to HBeAg (anti-HBe) were positive in 32 (40%). Anti-HBc alone was found in 5 (6%) and anti-HBs alone in 2 (2%). Sixty-seven (84%) were positive for at least one HBV marker and 13 (16%) were still susceptible to infection. Hepatitis B markers were more prevalent in prostitutes than in the normal Spanish population. Age, a history of sexually transmitted diseases (STD), drug abuse and promiscuity are factors which were highly related to hepatitis B markers. We concluded that screening prostitutes for the presence of markers and vaccinating those who are negative would be worth while. PMID:3428379

ARID5B, CEBPE and PIP4K2A Germline Genetic Polymorphisms and Risk of Childhood Acute Lymphoblastic Leukemia in Mexican Patients: A MIGICCL Study.

PubMed

Bekker-Méndez, Vilma Carolina; Núñez-Enríquez, Juan Carlos; Torres Escalante, José Luis; Alvarez-Olmos, Enrique; González-Montalvoc, Pablo Miguel; Jiménez-Hernández, Elva; Sansón, Aurora Medina; Leal, Yelda A; Ramos-Cervantes, María Teresa; Guerra-Castillo, Francisco Xavier; Ortiz-Maganda, Mónica Patricia; Flores-Lujano, Janet; Pérez-Saldivar, Maria Luisa; Velazquez-Aviña, Martha Margarita; Bolea-Murga, Victoria; Torres-Nava, José Refugio; Amador-Sanchez, Raquel; Solis-Labastida, Karina Anastacia; Rámirez-Bello, Julian; Fragoso, José Manuel; Mejía-Aranguré, Juan Manuel

2016-11-01

Childhood acute lymphoblastic leukemia (ALL) is the leading cause of childhood cancer-related deaths worldwide. Multiples studies have shown that ALL seems to be originated by an interaction between environmental and genetic susceptibility factors. The ARID5B polymorphisms are among the most reproducible ALL associated-risk alleles in different populations. The aim of the present study was to examine the contribution of ARID5B, CEBPE, and PIP4K2 risk alleles for the development of ALL in children from Mexico City and Yucatan, Mexico. A study was conducted with a total of 761 unrelated subjects. Two hundred eighty five ALL cases (111 from Yucatan and 174 from Mexico City) and 476 healthy subjects. Genotyping included the rs7088318 (PIP4K2A), rs10821936 (ARID5B), rs7089424 (ARID5B) and rs2239633 (CEBPE) polymorphisms. Associations between ALL and rs10821936 and rs7089424 ARID5B SNPs were found (OR = 1.9, 95% CI (1.5-2.4) and OR = 2.0, 95% CI (1.6-2.5), respectively). Moreover, a higher risk was observed in the homozygous risk genotypes of carriers from Mexico City (OR = 3.1, 95% CI (2.0-4.9) and OR 3.1, CI 95% (2.0-4.8), respectively). Otherwise, the rs7088318 (PIP4K2A) and rs2239633 (CEBPE) polymorphisms were not associated with ALL risk. Our analysis suggests that ARID5B confers risk for childhood ALL in a Mexican population. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

32 CFR 806b.5 - Personal notes.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Personal notes. 806b.5 Section 806b.5 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION PRIVACY ACT PROGRAM... notes on individuals used as memory aids. Personal notes may become Privacy Act records if they are...

β-Adrenergic Stimulation Induces Histone Deacetylase 5 (HDAC5) Nuclear Accumulation in Cardiomyocytes by B55α-PP2A-Mediated Dephosphorylation.

PubMed

Weeks, Kate L; Ranieri, Antonella; Karaś, Agnieszka; Bernardo, Bianca C; Ashcroft, Alexandra S; Molenaar, Chris; McMullen, Julie R; Avkiran, Metin

2017-03-25

Class IIa histone deacetylase (HDAC) isoforms such as HDAC5 are critical signal-responsive repressors of maladaptive cardiomyocyte hypertrophy, through nuclear interactions with transcription factors including myocyte enhancer factor-2. β-Adrenoceptor (β-AR) stimulation, a signal of fundamental importance in regulating cardiac function, has been proposed to induce both phosphorylation-independent nuclear export and phosphorylation-dependent nuclear accumulation of cardiomyocyte HDAC5. The relative importance of phosphorylation at Ser259/Ser498 versus Ser279 in HDAC5 regulation is also controversial. We aimed to determine the impact of β-AR stimulation on the phosphorylation, localization, and function of cardiomyocyte HDAC5 and delineate underlying molecular mechanisms. A novel 3-dimensional confocal microscopy method that objectively quantifies the whole-cell nuclear/cytoplasmic distribution of green fluorescent protein tagged HDAC5 revealed the β-AR agonist isoproterenol to induce β 1 -AR-mediated and protein kinase A-dependent HDAC5 nuclear accumulation in adult rat cardiomyocytes, which was accompanied by dephosphorylation at Ser259/279/498. Mutation of Ser259/Ser498 to Ala promoted HDAC5 nuclear accumulation and myocyte enhancer factor-2 inhibition, whereas Ser279 ablation had no such effect and did not block isoproterenol-induced nuclear accumulation. Inhibition of the Ser/Thr phosphatase PP2A blocked isoproterenol-induced HDAC5 dephosphorylation. Co-immunoprecipitation revealed a specific interaction of HDAC5 with the PP2A targeting subunit B55α, as well as catalytic and scaffolding subunits, which increased >3-fold with isoproterenol. Knockdown of B55α in neonatal cardiomyocytes attenuated isoproterenol-induced HDAC5 dephosphorylation. β-AR stimulation induces HDAC5 nuclear accumulation in cardiomyocytes by a mechanism that is protein kinase A-dependent but requires B55α-PP2A-mediated dephosphorylation of Ser259/Ser498 rather than protein kinase A

Complement factor C5a induces atherosclerotic plaque disruptions

PubMed Central

Wezel, Anouk; de Vries, Margreet R; Lagraauw, H Maxime; Foks, Amanda C; Kuiper, Johan; Quax, Paul HA; Bot, Ilze

2014-01-01

Complement factor C5a and its receptor C5aR are expressed in vulnerable atherosclerotic plaques; however, a causal relation between C5a and plaque rupture has not been established yet. Accelerated atherosclerosis was induced by placing vein grafts in male apoE−/− mice. After 24 days, when advanced plaques had developed, C5a or PBS was applied locally at the lesion site in a pluronic gel. Three days later mice were killed to examine the acute effect of C5a on late stage atherosclerosis. A significant increase in C5aR in the plaque was detectable in mice treated with C5a. Lesion size and plaque morphology did not differ between treatment groups, but interestingly, local treatment with C5a resulted in a striking increase in the amount of plaque disruptions with concomitant intraplaque haemorrhage. To identify the potential underlying mechanisms, smooth muscle cells and endothelial cells were treated in vitro with C5a. Both cell types revealed a marked increase in apoptosis after stimulation with C5a, which may contribute to lesion instability in vivo. Indeed, apoptosis within the plaque was seen to be significantly increased after C5a treatment. We here demonstrate a causal role for C5a in atherosclerotic plaque disruptions, probably by inducing apoptosis. Therefore, intervention in complement factor C5a signalling may be a promising target in the prevention of acute atherosclerotic complications. PMID:25124749

Species-Specific 5 mC and 5 hmC Genomic Landscapes Indicate Epigenetic Contribution to Human Brain Evolution

PubMed Central

Madrid, Andy; Chopra, Pankaj; Alisch, Reid S.

2018-01-01

Human evolution from non-human primates has seen substantial change in the central nervous system, with the molecular mechanisms underlying human brain evolution remaining largely unknown. Methylation of cytosine at the fifth carbon (5-methylcytosine; 5 mC) is an essential epigenetic mark linked to neurodevelopment, as well as neurological disease. The emergence of another modified form of cytosine (5-hydroxymethylcytosine; 5 hmC) that is enriched in the brain further substantiates a role for these epigenetic marks in neurodevelopment, yet little is known about the evolutionary importance of these marks in brain development. Here, human and monkey brain tissue were profiled, identifying 5,516 and 4,070 loci that were differentially methylated and hydroxymethylated, respectively, between the species. Annotation of these loci to the human genome revealed genes critical for the development of the nervous system and that are associated with intelligence and higher cognitive functioning, such as RELN and GNAS. Moreover, ontological analyses of these differentially methylated and hydroxymethylated genes revealed a significant enrichment of neuronal/immunological–related processes, including neurogenesis and axon development. Finally, the sequences flanking the differentially methylated/hydroxymethylated loci contained a significant enrichment of binding sites for neurodevelopmentally important transcription factors (e.g., OTX1 and PITX1), suggesting that DNA methylation may regulate gene expression by mediating transcription factor binding on these transcripts. Together, these data support dynamic species-specific epigenetic contributions in the evolution and development of the human brain from non-human primates. PMID:29491831

A first-principles study on the B{sub 5}O{sub 5}{sup +/0} and B{sub 5}O{sub 5}{sup −} clusters: The boron oxide analogs of C{sub 6}H{sub 5}{sup +/0} and CH{sub 3}Cl

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tian, Wen-Juan; You, Xue-Rui; Ou, Ting

2015-08-14

The concept of boronyl (BO) and the BO/H isolobal analogy build an interesting structural link between boron oxide clusters and hydrocarbons. Based upon global-minimum searches and first-principles electronic structural calculations, we present here the perfectly planar C{sub 2v} B{sub 5}O{sub 5}{sup +} (1, {sup 1}A{sub 1}), C{sub 2v} B{sub 5}O{sub 5} (2, {sup 2}A{sub 1}), and tetrahedral C{sub s} B{sub 5}O{sub 5}{sup −} (3, {sup 1}A′) clusters, which are the global minima of the systems. Structural and molecular orbital analyses indicate that C{sub 2v} B{sub 5}O{sub 5}{sup +} (1) [B{sub 3}O{sub 3}(BO){sub 2}{sup +}] and C{sub 2v} B{sub 5}O{sub 5}more » (2) [B{sub 3}O{sub 3}(BO){sub 2}] feature an aromatic six-membered boroxol (B{sub 3}O{sub 3}) ring as the core with two equivalent boronyl terminals, similar to the recently reported boronyl boroxine D{sub 3h} B{sub 6}O{sub 6} [B{sub 3}O{sub 3}(BO){sub 3}]; whereas C{sub s} B{sub 5}O{sub 5}{sup −} (3) [B(BO){sub 3}(OBO){sup −}] is characterized with a tetrahedral B{sup −} center, terminated with three BO groups and one OBO unit, similar to the previously predicted boronyl methane T{sub d} B{sub 5}O{sub 4}{sup −} [B(BO){sub 4}{sup −}]. Alternatively, the 1–3 clusters can be viewed as the boron oxide analogs of phenyl cation C{sub 6}H{sub 5}{sup +}, phenyl radical C{sub 6}H{sub 5}, and chloromethane CH{sub 3}Cl, respectively. Chemical bonding analyses also reveal a dual three-center four-electron (3c-4e) π hyperbond in C{sub s} B{sub 5}O{sub 5}{sup −} (3). The infrared absorption spectra of B{sub 5}O{sub 5}{sup +} (1), B{sub 5}O{sub 5} (2), and B{sub 5}O{sub 5}{sup −} (3) and anion photoelectron spectrum of B{sub 5}O{sub 5}{sup −} (3) are predicted to facilitate their forthcoming experimental characterizations. The present work completes the B{sub n}O{sub n}{sup +/0/−} series for n = 1–6 and enriches the analogous relationship between boron oxides and hydrocarbons.« less

The Murine Factor H-Related Protein FHR-B Promotes Complement Activation.

PubMed

Cserhalmi, Marcell; Csincsi, Ádám I; Mezei, Zoltán; Kopp, Anne; Hebecker, Mario; Uzonyi, Barbara; Józsi, Mihály

2017-01-01

Factor H-related (FHR) proteins consist of varying number of complement control protein domains that display various degrees of sequence identity to respective domains of the alternative pathway complement inhibitor factor H (FH). While such FHR proteins are described in several species, only human FHRs were functionally investigated. Their biological role is still poorly understood and in part controversial. Recent studies on some of the human FHRs strongly suggest a role for FHRs in enhancing complement activation via competing with FH for binding to certain ligands and surfaces. The aim of the current study was the functional characterization of a murine FHR, FHR-B. To this end, FHR-B was expressed in recombinant form. Recombinant FHR-B bound to human C3b and was able to compete with human FH for C3b binding. FHR-B supported the assembly of functionally active C3bBb alternative pathway C3 convertase via its interaction with C3b. This activity was confirmed by demonstrating C3 activation in murine serum. In addition, FHR-B bound to murine pentraxin 3 (PTX3), and this interaction resulted in murine C3 fragment deposition due to enhanced complement activation in mouse serum. FHR-B also induced C3 deposition on C-reactive protein, the extracellular matrix (ECM) extract Matrigel, and endothelial cell-derived ECM when exposed to mouse serum. Moreover, mouse C3 deposition was strongly enhanced on necrotic Jurkat T cells and the mouse B cell line A20 by FHR-B. FHR-B also induced lysis of sheep erythrocytes when incubated in mouse serum with FHR-B added in excess. Altogether, these data demonstrate that, similar to human FHR-1 and FHR-5, mouse FHR-B modulates complement activity by promoting complement activation via interaction with C3b and via competition with murine FH.

18 CFR 3b.5 - Legal guardians.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Legal guardians. 3b.5... INFORMATION General § 3b.5 Legal guardians. For the purposes of this part, the parent of any minor, or the legal guardian of any individual who has been declared to be incompetent due to physical or mental...

18 CFR 3b.5 - Legal guardians.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Legal guardians. 3b.5... INFORMATION General § 3b.5 Legal guardians. For the purposes of this part, the parent of any minor, or the legal guardian of any individual who has been declared to be incompetent due to physical or mental...

18 CFR 3b.5 - Legal guardians.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Legal guardians. 3b.5... INFORMATION General § 3b.5 Legal guardians. For the purposes of this part, the parent of any minor, or the legal guardian of any individual who has been declared to be incompetent due to physical or mental...

18 CFR 3b.5 - Legal guardians.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Legal guardians. 3b.5... INFORMATION General § 3b.5 Legal guardians. For the purposes of this part, the parent of any minor, or the legal guardian of any individual who has been declared to be incompetent due to physical or mental...

18 CFR 3b.5 - Legal guardians.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Legal guardians. 3b.5... INFORMATION General § 3b.5 Legal guardians. For the purposes of this part, the parent of any minor, or the legal guardian of any individual who has been declared to be incompetent due to physical or mental...

29 CFR 2530.200b-5 - Seasonal industries. [Reserved

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 9 2014-07-01 2014-07-01 false Seasonal industries. [Reserved] 2530.200b-5 Section 2530.200b-5 Labor Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION... and General Provisions § 2530.200b-5 Seasonal industries. [Reserved] ...

29 CFR 2530.200b-5 - Seasonal industries. [Reserved

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 9 2010-07-01 2010-07-01 false Seasonal industries. [Reserved] 2530.200b-5 Section 2530.200b-5 Labor Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION... and General Provisions § 2530.200b-5 Seasonal industries. [Reserved] ...

29 CFR 2530.200b-5 - Seasonal industries. [Reserved

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 9 2012-07-01 2012-07-01 false Seasonal industries. [Reserved] 2530.200b-5 Section 2530.200b-5 Labor Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION... and General Provisions § 2530.200b-5 Seasonal industries. [Reserved] ...

29 CFR 2530.200b-5 - Seasonal industries. [Reserved

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 9 2013-07-01 2013-07-01 false Seasonal industries. [Reserved] 2530.200b-5 Section 2530.200b-5 Labor Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION... and General Provisions § 2530.200b-5 Seasonal industries. [Reserved] ...

29 CFR 2530.200b-5 - Seasonal industries. [Reserved

Code of Federal Regulations, 2011 CFR

2011-07-01