Adoptive cell therapy for lymphoma with CD4 T cells depleted of CD137-expressing regulatory T cells.

PubMed

Goldstein, Matthew J; Kohrt, Holbrook E; Houot, Roch; Varghese, Bindu; Lin, Jack T; Swanson, Erica; Levy, Ronald

2012-03-01

Adoptive immunotherapy with antitumor T cells is a promising novel approach for the treatment of cancer. However, T-cell therapy may be limited by the cotransfer of regulatory T cells (T(reg)). Here, we explored this hypothesis by using 2 cell surface markers, CD44 and CD137, to isolate antitumor CD4 T cells while excluding T(regs). In a murine model of B-cell lymphoma, only CD137(neg)CD44(hi) CD4 T cells infiltrated tumor sites and provided protection. Conversely, the population of CD137(pos)CD44hi CD4 T cells consisted primarily of activated T(regs). Notably, this CD137(pos) T(reg) population persisted following adoptive transfer and maintained expression of FoxP3 as well as CD137. Moreover, in vitro these CD137(pos) cells suppressed the proliferation of effector cells in a contact-dependent manner, and in vivo adding the CD137(pos)CD44(hi) CD4 cells to CD137(neg)CD44(hi) CD4 cells suppressed the antitumor immune response. Thus, CD137 expression on CD4 T cells defined a population of activated T(regs) that greatly limited antitumor immune responses. Consistent with observations in the murine model, human lymphoma biopsies also contained a population of CD137(pos) CD4 T cells that were predominantly CD25(pos)FoxP3(pos) T(regs). In conclusion, our findings identify 2 surface markers that can be used to facilitate the enrichment of antitumor CD4 T cells while depleting an inhibitory T(reg) population.

FOXP3 Expression in GARP-Transduced Helper T Cells Is Not Associated with FOXP3 TSDR Demethylation.

PubMed

Kehrmann, Jan; Zeschnigk, Michael; Buer, Jan; Probst-Kepper, Michael

2011-10-01

AIM: Glycoprotein A repetitions predominant (GARP or LRRC32) represents a human regulatory CD4+ CD25(hi) FOXP3+ T (T(reg)) cell-specific receptor that controls FOXP3. Ectopic expression of GARP in helper T (T(h)) cells has been shown to be sufficient for the induction of FOXP3 and generation of a stable regulatory phenotype. Since expression of FOXP3 in Treg cells is epigenetically controlled by a conserved motif, the so-called T(reg)-specific demethylated region (TSDR), we asked whether GARP-mediated upregulation of FOXP3 in Th cells is similarly accompanied by demethylation of the TSDR. METHODS: DNA methylation of the FOXP3 TSDR was analyzed by direct sequencing of polymerase chain reaction (PCR) products from bisulfite-treated genomic DNA. RESULTS: Although GARP-transduced T(h) cells exhibit constitutive FOXP3 expression and a regulatory phenotype, the FOXP3 TSDR is completely methylated as in naive T(h) cells. GARP-mediated FOXP3 upregulation in T(h) cells is not associated with T(reg)-specific demethylation of the FOXP3 TSDR. CONCLUSION: Although GARP-engineered T(h) cells exhibit stable FOXP3 expression and a phenotypic reprogramming towards T(reg) cells in vitro, these cells do not completely mimic the epigenotype of natural T(reg) cells. Thus, concepts based on the genetic modification of T(h) cells as cellular therapies to treat autoimmune diseases or to control transplantation tolerance should be critically tested before any clinical application.

Immunomodulation by adoptive regulatory T-cell transfer improves Coxsackievirus B3-induced myocarditis.

PubMed

Pappritz, Kathleen; Savvatis, Konstantinos; Miteva, Kapka; Kerim, Bahtiyar; Dong, Fengquan; Fechner, Henry; Müller, Irene; Brandt, Christine; Lopez, Begoña; González, Arantxa; Ravassa, Susana; Klingel, Karin; Diez, Javier; Reinke, Petra; Volk, Hans-Dieter; Van Linthout, Sophie; Tschöpe, Carsten

2018-06-04

Regulatory T (T reg ) cells offer new therapeutic options for controlling undesired systemic and local immune responses. The aim of the current study was to determine the impact of therapeutic T reg administration on systemic and cardiac inflammation and remodeling in coxsackievirus B3 (CVB3) -induced myocarditis. Therefore, syngeneic T reg cells were applied intravenously in CVB3-infected mice 3 d after infection. Compared with CVB3 + PBS mice, CVB3 + T reg mice exhibited lower left ventricular (LV) chemokine expression, accompanied by reduced cardiac presence of proinflammatory Ly6C high CCR2 high Cx3Cr1 low monocytes and higher retention of proinflammatory Ly6C mid CCR2 high Cx3Cr1 low monocytes in the spleen. In addition, splenic myelopoiesis was reduced in CVB3 + T reg compared with CVB3 + PBS mice. Coculture of T reg cells with splenocytes isolated from mice 3 d post-CVB3 infection further demonstrated the ability of T reg cells to modulate monocyte differentiation in favor of the anti-inflammatory Ly6C low CCR2 low Cx3Cr1 high subset. T reg -mediated immunomodulation was paralleled by lower collagen 1 protein expression and decreased levels of soluble and insoluble collagen in LV of CVB3 + T reg compared with CVB3 + PBS mice. In agreement with these findings, LV systolic and diastolic function was improved in CVB3 + T reg mice compared with CVB3 + PBS mice. In summary, adoptive T reg transfer in the inflammatory phase of viral-induced myocarditis protects the heart against inflammatory damage and fibrosis via modulation of monocyte subsets.-Pappritz, K., Savvatis, K., Miteva, K., Kerim, B., Dong, F., Fechner, H., Müller, I., Brandt, C., Lopez, B., González, A., Ravassa, S., Klingel, K., Diez, J., Reinke, P., Volk, H.-D., Van Linthout, S., Tschöpe, C. Immunomodulation by adoptive regulatory T-cell transfer improves Coxsackievirus B3-induced myocarditis.

Decreased frequencies and impaired functions of the CD31+ subpopulation in Treg cells associated with decreased FoxP3 expression and enhanced Treg cell defects in patients with coronary heart disease.

PubMed

Huang, L; Zheng, Y; Yuan, X; Ma, Y; Xie, G; Wang, W; Chen, H; Shen, L

2017-03-01

Coronary heart disease (CHD) is one of the most common types of organ lesions caused by atherosclerosis, in which CD4 + CD25 + forkhead box protein 3 (FoxP3 + ) regulatory T cells (T reg ) play an atheroprotective role. However, T reg cell numbers are decreased and their functions are impaired in atherosclerosis; the underlying mechanisms remain unclear. CD31 plays an important part in T cell response and contributes to maintaining T cell tolerance. The immunomodulatory effects of CD31 are also implicated in atherosclerosis. In this study, we found that decreased frequencies of the CD31 + subpopulation in T reg cells (CD31 + Tr cells) correlated positively with decreased FoxP3 expression in CHD patients. Cell culture in vitro demonstrated CD31 + Tr cells maintaining stable FoxP3 expression after activation and exhibited enhanced proliferation and immunosuppression compared with the CD31 - subpopulation in T reg cells (CD31 - Tr cells). We also confirmed impaired secretion of transforming growth factor (TGF)-β1 and interleukin (IL)-10 in CD31 + Tr cells of CHD patients. Further analysis revealed reduced phospho-SHP2 (associated with CD31 activation) and phospho-signal transducer and activator of transcription-5 (STAT-5) (associated with FoxP3 transcription) levels in CD31 + Tr cells of CHD patients, suggesting that decreased FoxP3 expression in CD31 + Tr cells might be because of attenuated SHP2 and STAT-5 activation. These data indicate that decreased frequencies and impaired functions of the CD31 + Tr subpopulation associated with decreased FoxP3 expression give rise, at least in part, to T reg cell defects in CHD patients. Our findings emphasize the important role of the CD31 + Tr subpopulation in maintaining T reg cell normal function and may provide a novel explanation for impaired immunoregulation of T reg cells in CHD. © 2016 British Society for Immunology.

The Global Redox Responding RegB/RegA Signal Transduction System Regulates the Genes Involved in Ferrous Iron and Inorganic Sulfur Compound Oxidation of the Acidophilic Acidithiobacillus ferrooxidans

PubMed Central

Moinier, Danielle; Byrne, Deborah; Amouric, Agnès; Bonnefoy, Violaine

2017-01-01

The chemical attack of ore by ferric iron and/or sulfuric acid releases valuable metals. The products of these reactions are recycled by iron and sulfur oxidizing microorganisms. These acidophilic chemolithotrophic prokaryotes, among which Acidithiobacillus ferrooxidans, grow at the expense of the energy released from the oxidation of ferrous iron and/or inorganic sulfur compounds (ISCs). In At. ferrooxidans, it has been shown that the expression of the genes encoding the proteins involved in these respiratory pathways is dependent on the electron donor and that the genes involved in iron oxidation are expressed before those responsible for ISCs oxidation when both iron and sulfur are present. Since the redox potential increases during iron oxidation but remains stable during sulfur oxidation, we have put forward the hypothesis that the global redox responding two components system RegB/RegA is involved in this regulation. To understand the mechanism of this system and its role in the regulation of the aerobic respiratory pathways in At. ferrooxidans, the binding of different forms of RegA (DNA binding domain, wild-type, unphosphorylated and phosphorylated-like forms of RegA) on the regulatory region of different genes/operons involved in ferrous iron and ISC oxidation has been analyzed. We have shown that the four RegA forms are able to bind specifically the upstream region of these genes. Interestingly, the phosphorylation of RegA did not change its affinity for its cognate DNA. The transcriptional start site of these genes/operons has been determined. In most cases, the RegA binding site(s) was (were) located upstream from the −35 (or −24) box suggesting that RegA does not interfere with the RNA polymerase binding. Based on the results presented in this report, the role of the RegB/RegA system in the regulation of the ferrous iron and ISC oxidation pathways in At. ferrooxidans is discussed. PMID:28747899

Reg proteins and their roles in inflammation and cancer of the human digestive system.

PubMed

Zhao, Jie; Wang, Jingyu; Wang, Hao; Lai, Maode

2013-01-01

The regenerating gene (Reg) family is a group of small molecules that includes four members found in various species, although only three are found in human tissues. Their expression is stimulated by certain growth factors or cytokines. The Reg family plays different roles in proliferation, migration, and anti-apoptosis through activating different signaling pathways. Their dysexpression is closely associated with a number of human conditions and diseases such as inflammation and cancer, especially in the human digestive system. Clinically, upregulation of Reg proteins is usually demonstrated in histological sections and sera from cancer patients. Therefore, Reg proteins can predict the progression and prognosis of cancers, especially those of the digestive tract, and can also act as diagnostic markers and therapeutic targets.

Crosstalk between bone marrow-derived mesenchymal stem cells and regulatory T cells through a glucocorticoid-induced leucine zipper/developmental endothelial locus-1-dependent mechanism.

PubMed

Yang, Nianlan; Baban, Babak; Isales, Carlos M; Shi, Xing-Ming

2015-09-01

Bone marrow is a reservoir for regulatory T (T(reg)) cells, but how T(reg) cells are regulated in that environment remains poorly understood. We show that expression of glucocorticoid (GC)-induced leucine zipper (GILZ) in bone marrow mesenchymal lineage cells or bone marrow-derived mesenchymal stem cells (BMSCs) increases the production of T(reg) cells via a mechanism involving the up-regulation of developmental endothelial locus-1 (Del-1), an endogenous leukocyte-endothelial adhesion inhibitor. We found that the expression of Del-1 is increased ∼4-fold in the bone tissues of GILZ transgenic (Tg) mice, and this increase is coupled with a significant increase in the production of IL-10 (2.80 vs. 0.83) and decrease in the production of IL-6 (0.80 vs. 2.33) and IL-12 (0.25 vs. 1.67). We also show that GILZ-expressing BMSCs present antigen in a way that favors T(reg) cells. These results indicate that GILZ plays a critical role mediating the crosstalk between BMSCs and T(reg) in the bone marrow microenvironment. These data, together with our previous findings that overexpression of GILZ in BMSCs antagonizes TNF-α-elicited inflammatory responses, suggest that GILZ plays important roles in bone-immune cell communication and BMSC immune suppressive functions. © FASEB.

Symbiotic Bacteria Direct Expression of an Intestinal Bactericidal Lectin

PubMed Central

Cash, Heather L.; Whitham, Cecilia V.; Behrendt, Cassie L.; Hooper, Lora V.

2009-01-01

The mammalian intestine harbors complex societies of beneficial bacteria that are maintained in the lumen with minimal penetration of mucosal surfaces. Microbial colonization of germ-free mice triggers epithelial expression of RegIIIγ, a secreted C-type lectin. RegIIIγ binds intestinal bacteria but lacks the complement recruitment domains present in other microbe-binding mammalian C-type lectins. We show that RegIIIγ and its human counterpart, HIP/PAP, are directly antimicrobial proteins that bind their bacterial targets via interactions with peptidoglycan carbohydrate. We propose that these proteins represent an evolutionarily primitive form of lectin-mediated innate immunity, and that they reveal intestinal strategies for maintaining symbiotic host-microbial relationships. PMID:16931762

HaploReg v4: systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease.

PubMed

Ward, Lucas D; Kellis, Manolis

2016-01-04

More than 90% of common variants associated with complex traits do not affect proteins directly, but instead the circuits that control gene expression. This has increased the urgency of understanding the regulatory genome as a key component for translating genetic results into mechanistic insights and ultimately therapeutics. To address this challenge, we developed HaploReg (http://compbio.mit.edu/HaploReg) to aid the functional dissection of genome-wide association study (GWAS) results, the prediction of putative causal variants in haplotype blocks, the prediction of likely cell types of action, and the prediction of candidate target genes by systematic mining of comparative, epigenomic and regulatory annotations. Since first launching the website in 2011, we have greatly expanded HaploReg, increasing the number of chromatin state maps to 127 reference epigenomes from ENCODE 2012 and Roadmap Epigenomics, incorporating regulator binding data, expanding regulatory motif disruption annotations, and integrating expression quantitative trait locus (eQTL) variants and their tissue-specific target genes from GTEx, Geuvadis, and other recent studies. We present these updates as HaploReg v4, and illustrate a use case of HaploReg for attention deficit hyperactivity disorder (ADHD)-associated SNPs with putative brain regulatory mechanisms. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti–CTLA-4 therapy against melanoma

PubMed Central

Simpson, Tyler R.; Li, Fubin; Montalvo-Ortiz, Welby; Sepulveda, Manuel A.; Bergerhoff, Katharina; Arce, Frederick; Roddie, Claire; Henry, Jake Y.; Yagita, Hideo; Wolchok, Jedd D.; Peggs, Karl S.; Ravetch, Jeffrey V.

2013-01-01

Treatment with monoclonal antibody specific for cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), an inhibitory receptor expressed by T lymphocytes, has emerged as an effective therapy for the treatment of metastatic melanoma. Although subject to debate, current models favor a mechanism of activity involving blockade of the inhibitory activity of CTLA-4 on both effector (T eff) and regulatory (T reg) T cells, resulting in enhanced antitumor effector T cell activity capable of inducing tumor regression. We demonstrate, however, that the activity of anti–CTLA-4 antibody on the T reg cell compartment is mediated via selective depletion of T reg cells within tumor lesions. Importantly, T reg cell depletion is dependent on the presence of Fcγ receptor–expressing macrophages within the tumor microenvironment, indicating that T reg cells are depleted in trans in a context-dependent manner. Our results reveal further mechanistic insight into the activity of anti-CTLA-4–based cancer immunotherapy, and illustrate the importance of specific features of the local tumor environment on the final outcome of antibody-based immunomodulatory therapies. PMID:23897981

Design Considerations for IAP Charts: Approach Course Track and Communication Frequencies

DTIC Science & Technology

1991-08-01

Text Rotated 2m4 Amdt 8KINSTONIEASTERN REG JETPORT AT STALLINGS FLO) ( ISO ) ND B RWY 4 ML-=oUM) KINSTON. NORTH CAROLINA [ EYMOUR .10KSGX AMx COM KISTON...TOWNER 125.6 (CTAF) 238.0 GNUD CONl 121 8 UICOM I 223.8 109.6 ISO ~- 2100 02n33 STS -41 FA;LV.J-*TON CLEY 94 y8IV7 6mac ST LOUF bdd 12 A 2 S4700-11314...Text Un rotated 2U4 AmntBKINSTONIEASTERN REG JETPORT AT STAUWHGS RDO ( ISO ) NOB FlWY 4 VI~~t ~STOUJ. NORTH ALAI 3EYLOURJOHSOXAPP COXE 119.7m.. 123.6 (CTAF

Perspectives on Regulatory T Cell Therapies.

PubMed

Probst-Kepper, Michael; Kröger, Andrea; Garritsen, Henk S P; Buer, Jan

2009-01-01

Adoptive transfer in animal models clearly indicate an essential role of CD4+ CD25+ FOXP3+ regulatory T (T(reg)) cells in prevention and treatment of autoimmune and graft-versus-host disease. Thus, T(reg) cell therapies and development of drugs that specifically enhance T(reg) cell function and development represent promising tools to establish dominant tolerance. So far, lack of specific markers to differentiate human T(reg) cells from activated CD4+ CD25+ effector T cells, which also express FOXP3 at different levels, hampered such an approach. Recent identification of the orphan receptor glycoprotein-A repetitions predominant (GARP or LRRC32) as T(reg) cell-specific key molecule that dominantly controls FOXP3 via a positive feedback loop opens up new perspectives for molecular and cellular therapies. This brief review focuses on the role of GARP as a safeguard of a complex regulatory network of human T(reg) cells and its implications for regulatory T cell therapies in autoimmunity and graft-versus-host disease.

Global changes in the proteome of Cupriavidus necator H16 during poly-(3-hydroxybutyrate) synthesis from various biodiesel by-product substrates.

PubMed

Sharma, Parveen K; Fu, Jilagamazhi; Spicer, Victor; Krokhin, Oleg V; Cicek, Nazim; Sparling, Richard; Levin, David B

2016-12-01

Synthesis of poly-[3-hydroxybutyrate] (PHB) by Cupriavidus necator H16 in batch cultures was evaluated using three biodiesel-derived by-products as the sole carbon sources: waste glycerol (REG-80, refined to 80 % purity with negligible free fatty acids); glycerol bottom (REG-GB, with up to 65 % glycerol and 35 % free fatty acids), and free fatty acids (REG-FFA, with up to 75 % FFA and no glycerol). All the three substrates supported growth and PHB production by C. necator, with polymer accumulation ranging from 9 to 84 % cell dry weight (cdw), depending on the carbon source. To help understand these differences, proteomic analysis indicated that although C. necator H16 was able to accumulate PHB during growth on all three biodiesel by-products, no changes in the levels of PHB synthesis enzymes were observed. However, significant changes in the levels of expression were observed for two Phasin proteins involved with PHB accumulation, and for a number of gene products in the fatty acid β-oxidation pathway, the Glyoxylate Shunt, and the hydrogen (H2) synthesis pathways in C. necator cells cultured with different substrates. The glycerol transport protein (GlpF) was induced in REG-GB and REG-80 glycerol cultures only. Cupriavidus necator cells cultured with REG-GB and REG-FFA showed up-regulation of β-oxidation and Glyoxylate Shunt pathways proteins at 24 h pi, but H2 synthesis pathways enzymes were significantly down-regulated, compared with cells cultured with waste glycerol. Our data confirmed earlier observations of constitutive expression of PHB synthesis proteins, but further suggested that C. necator H16 cells growing on biodiesel-derived glycerol were under oxidative stress.

76 FR 2596 - Suspension of Community Eligibility

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-14

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76 FR 56117 - Suspension of Community Eligibility

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-12

..., Susp. Frederic, Village of, Polk 550334 March 24, 1975, ......do Do. County. Emerg; September 1, 1986..., Town of, 050412 March 23, 1976, ......do Do. Sharp County. Emerg; November 1, 1985, Reg; September 16...; September 16, 2011, Susp. Region IV Alabama: Albertville, City of, 010366 October 13, 1976, ......do Do...

Dendritic cells induce antigen-specific regulatory T cells that prevent graft versus host disease and persist in mice

PubMed Central

Olds, Peter; Park, Andrew; Schlesinger, Sarah J.

2011-01-01

Foxp3+ regulatory T cells (T reg cells) effectively suppress immunity, but it is not determined if antigen-induced T reg cells (iT reg cells) are able to persist under conditions of inflammation and to stably express the transcription factor Foxp3. We used spleen cells to stimulate the mixed leukocyte reaction (MLR) in the presence of transforming growth factor β (TGF-β) and retinoic acid. We found that the CD11chigh dendritic cell fraction was the most potent at inducing high numbers of alloreactive Foxp3+ cells. The induced CD4+CD25+Foxp3+ cells appeared after extensive proliferation. When purified from the MLR, iT reg cells suppressed both primary and secondary MLR in vitro in an antigen-specific manner. After transfer into allogeneic mice, iT reg cells persisted for 6 mo and prevented graft versus host disease (GVHD) caused by co-transferred CD45RBhi T cells. Similar findings were made when iT reg cells were transferred after onset of GVHD. The CNS2 intronic sequence of the Foxp3 gene in the persisting iT reg cells was as demethylated as the corresponding sequence of naturally occurring T reg cells. These results indicate that induced Foxp3+ T reg cells, after proliferating and differentiating into antigen-specific suppressive T cells, can persist for long periods while suppressing a powerful inflammatory disease. PMID:22084406

Gene selection in cancer classification using sparse logistic regression with Bayesian regularization.

PubMed

Cawley, Gavin C; Talbot, Nicola L C

2006-10-01

Gene selection algorithms for cancer classification, based on the expression of a small number of biomarker genes, have been the subject of considerable research in recent years. Shevade and Keerthi propose a gene selection algorithm based on sparse logistic regression (SLogReg) incorporating a Laplace prior to promote sparsity in the model parameters, and provide a simple but efficient training procedure. The degree of sparsity obtained is determined by the value of a regularization parameter, which must be carefully tuned in order to optimize performance. This normally involves a model selection stage, based on a computationally intensive search for the minimizer of the cross-validation error. In this paper, we demonstrate that a simple Bayesian approach can be taken to eliminate this regularization parameter entirely, by integrating it out analytically using an uninformative Jeffrey's prior. The improved algorithm (BLogReg) is then typically two or three orders of magnitude faster than the original algorithm, as there is no longer a need for a model selection step. The BLogReg algorithm is also free from selection bias in performance estimation, a common pitfall in the application of machine learning algorithms in cancer classification. The SLogReg, BLogReg and Relevance Vector Machine (RVM) gene selection algorithms are evaluated over the well-studied colon cancer and leukaemia benchmark datasets. The leave-one-out estimates of the probability of test error and cross-entropy of the BLogReg and SLogReg algorithms are very similar, however the BlogReg algorithm is found to be considerably faster than the original SLogReg algorithm. Using nested cross-validation to avoid selection bias, performance estimation for SLogReg on the leukaemia dataset takes almost 48 h, whereas the corresponding result for BLogReg is obtained in only 1 min 24 s, making BLogReg by far the more practical algorithm. BLogReg also demonstrates better estimates of conditional probability than the RVM, which are of great importance in medical applications, with similar computational expense. A MATLAB implementation of the sparse logistic regression algorithm with Bayesian regularization (BLogReg) is available from http://theoval.cmp.uea.ac.uk/~gcc/cbl/blogreg/

Mycobacterium tuberculosis PhoY Proteins Promote Persister Formation by Mediating Pst/SenX3-RegX3 Phosphate Sensing.

PubMed

Namugenyi, Sarah B; Aagesen, Alisha M; Elliott, Sarah R; Tischler, Anna D

2017-07-11

The Mycobacterium tuberculosis phosphate-specific transport (Pst) system controls gene expression in response to phosphate availability by inhibiting the activation of the SenX3-RegX3 two-component system under phosphate-rich conditions, but the mechanism of communication between these systems is unknown. In Escherichia coli , inhibition of the two-component system PhoR-PhoB under phosphate-rich conditions requires both the Pst system and PhoU, a putative adaptor protein. E. coli PhoU is also involved in the formation of persisters, a subpopulation of phenotypically antibiotic-tolerant bacteria. M. tuberculosis encodes two PhoU orthologs, PhoY1 and PhoY2. We generated phoY single- and double-deletion mutants and examined the expression of RegX3-regulated genes by quantitative reverse transcription-PCR (qRT-PCR). Gene expression was increased only in the Δ phoY1 Δ phoY2 double mutant and could be restored to the wild-type level by complementation with either phoY1 or phoY2 or by deletion of regX3 These data suggest that the PhoY proteins function redundantly to inhibit SenX3-RegX3 activation. We analyzed the frequencies of antibiotic-tolerant persister variants in the phoY mutants using several antibiotic combinations. Persister frequency was decreased at least 40-fold in the Δ phoY1 Δ phoY2 mutant compared to the frequency in the wild type, and this phenotype was RegX3 dependent. A Δ pstA1 mutant lacking a Pst system transmembrane component exhibited a similar RegX3-dependent decrease in persister frequency. In aerosol-infected mice, the Δ phoY1 Δ phoY2 and Δ pstA1 mutants were more susceptible to treatment with rifampin but not isoniazid. Our data demonstrate that disrupting phosphate sensing mediated by the PhoY proteins and the Pst system enhances the susceptibility of M. tuberculosis to antibiotics both in vitro and during infection. IMPORTANCE Persister variants, subpopulations of bacteria that are phenotypically antibiotic tolerant, contribute to the lengthy treatment times required to cure Mycobacterium tuberculosis infection, but the molecular mechanisms governing their formation and maintenance are poorly characterized. Here, we demonstrate that a phosphate-sensing signal transduction system, comprising the Pst phosphate transporter, the two-component system SenX3-RegX3, and functionally redundant PhoY proteins that mediate signaling between Pst and SenX3-RegX3, influences persister formation. Activation of RegX3 by deletion of the phoY genes or a Pst system component resulted in decreased persister formation in vitro Activated RegX3 also limited persister formation during growth under phosphate-limiting conditions. Importantly, increased susceptibility to the front-line drug rifampin was also observed in a mouse infection model. Thus, the M. tuberculosis phosphate-sensing signal transduction system contributes to antibiotic tolerance and is a potential target for the development of novel therapeutics that may shorten the duration of tuberculosis treatment. Copyright © 2017 Namugenyi et al.

Profiling of human epigenetic regulators using a semi-automated real-time qPCR platform validated by next generation sequencing

PubMed Central

Dudakovic, Amel; Gluscevic, Martina; Paradise, Christopher R.; Dudakovic, Halil; Khani, Farzaneh; Thaler, Roman; Ahmed, Farah S.; Li, Xiaodong; Dietz, Allan B.; Stein, Gary S.; Montecino, Martin A.; Deyle, David R.; Westendorf, Jennifer J.; van Wijnen, Andre J.

2017-01-01

Epigenetic mechanisms control phenotypic commitment of mesenchymal stromal/stem cells (MSCs) into osteogenic, chondrogenic or adipogenic lineages. To investigate enzymes and chromatin binding proteins controlling the epigenome, we developed a hybrid expression screening strategy that combines semi-automatic real-time qPCR (RT-qPCR), next generation RNA sequencing (RNA-seq), and a novel data management application (FileMerge). This strategy was used to interrogate expression of a large cohort (n>300) of human epigenetic regulators (EpiRegs) that generate, interpret and/or edit the histone code. We find that EpiRegs with similar enzymatic functions are variably expressed and specific isoforms dominate over others in human MSCs. This principle is exemplified by analysis of key histone acetyl transferases (HATs) and deacetylases (HDACs), H3 lysine methyl transferases (e.g., EHMTs) and demethylases (KDMs), as well as bromodomain (BRDs) and chromobox (CBX) proteins. Our results show gender-specific expression of H3 lysine 9 [H3K9] demethylases (e.g., KDM5D and UTY) as expected and upregulation of distinct EpiRegs (n>30) during osteogenic differentiation of MSCs (e.g., HDAC5 and HDAC7). The functional significance of HDACs in osteogenic lineage commitment of MSCs was functionally validated using panobinostat (LBH-589). This pan-deacetylase inhibitor suppresses osteoblastic differentiation as evidenced by reductions in bone-specific mRNA markers (e.g., ALPL), alkaline phosphatase activity and calcium deposition (i.e., Alizarin Red staining). Thus, our RT-qPCR platform identifies candidate EpiRegs by expression screening, predicts biological outcomes of their corresponding inhibitors, and enables manipulation of the human epigenome using molecular or pharmacological approaches to control stem cell differentiation. PMID:28132772

CoryneRegNet 4.0 – A reference database for corynebacterial gene regulatory networks

PubMed Central

Baumbach, Jan

2007-01-01

Background Detailed information on DNA-binding transcription factors (the key players in the regulation of gene expression) and on transcriptional regulatory interactions of microorganisms deduced from literature-derived knowledge, computer predictions and global DNA microarray hybridization experiments, has opened the way for the genome-wide analysis of transcriptional regulatory networks. The large-scale reconstruction of these networks allows the in silico analysis of cell behavior in response to changing environmental conditions. We previously published CoryneRegNet, an ontology-based data warehouse of corynebacterial transcription factors and regulatory networks. Initially, it was designed to provide methods for the analysis and visualization of the gene regulatory network of Corynebacterium glutamicum. Results Now we introduce CoryneRegNet release 4.0, which integrates data on the gene regulatory networks of 4 corynebacteria, 2 mycobacteria and the model organism Escherichia coli K12. As the previous versions, CoryneRegNet provides a web-based user interface to access the database content, to allow various queries, and to support the reconstruction, analysis and visualization of regulatory networks at different hierarchical levels. In this article, we present the further improved database content of CoryneRegNet along with novel analysis features. The network visualization feature GraphVis now allows the inter-species comparisons of reconstructed gene regulatory networks and the projection of gene expression levels onto that networks. Therefore, we added stimulon data directly into the database, but also provide Web Service access to the DNA microarray analysis platform EMMA. Additionally, CoryneRegNet now provides a SOAP based Web Service server, which can easily be consumed by other bioinformatics software systems. Stimulons (imported from the database, or uploaded by the user) can be analyzed in the context of known transcriptional regulatory networks to predict putative contradictions or further gene regulatory interactions. Furthermore, it integrates protein clusters by means of heuristically solving the weighted graph cluster editing problem. In addition, it provides Web Service based access to up to date gene annotation data from GenDB. Conclusion The release 4.0 of CoryneRegNet is a comprehensive system for the integrated analysis of procaryotic gene regulatory networks. It is a versatile systems biology platform to support the efficient and large-scale analysis of transcriptional regulation of gene expression in microorganisms. It is publicly available at . PMID:17986320

Inducible Intestine-specific Deletion Of Krüppel-Like Factor 5 Is Characterized By A Regenerative Response In Adult Mouse Colon

PubMed Central

Nandan, Mandayam O.; Ghaleb, Amr M.; Liu, Yang; Bialkowska, Agnieszka B.; McConnell, Beth B.; Shroyer, Kenneth R.; Robine, Sylvie

2014-01-01

Krüppel-like factor 5 (KLF5) is a pro-proliferative transcriptional regulator primarily expressed in the intestinal crypt epithelial cells. Constitutive intestine-specific deletion of Klf5 is neonatal lethal suggesting a crucial role for KLF5 in intestinal development and homeostasis. We have previously shown Klf5 to play an active role regulating intestinal tumorigenesis. Here we examine the effect of inducible intestine-specific deletion of Klf5 in adult mice. Klf5 is lost from the intestine beginning at day 3 after the start of a 5-day treatment with the inducer tamoxifen. Although the mice have no significant weight loss or lethality, the colonic tissue shows signs of epithelial distress starting at day 3 following induction. Accompanying the morphological changes is a significant loss of proliferative crypt epithelial cells as revealed by BrdU or Ki67 staining at days 3 & 5 after start of tamoxifen. We also observed a loss of goblet cells from the colon and Paneth cells from the small intestine upon induced deletion of Klf5. In addition, loss of Klf5 from the colonic epithelium is accompanied by a regenerative response that coincides with an expansion in the zone of Sox9 expression along the crypt axis. At day 11, both proliferation and Sox9 expression return to baseline levels. Microarray and quantitative PCR analyses reveal an upregulation of several regeneration-associated genes (Reg1A, Reg3G and Reg3B) and down-regulation of many Klf5 targets (Ki-67, cyclin B, Cdc2 and cyclin D1). Sox9 and Reg1A protein levels are also increased upon Klf5 loss. Lentiviral-mediated knockdown of KLF5 and exogenous expression of KLF5 in colorectal cancer cell lines confirm that Sox9 expression is negatively regulated by KLF5. Furthermore, ChIP assays reveal a direct association of KLF5 with both the Sox9 and Reg1A promoters. We have shown that disruption of epithelial homeostasis due to Klf5 loss from the adult colon is followed by a regenerative response led by Sox9 and the Reg family of proteins. Our study demonstrates that adult mouse colonic tissue undergoes acute physiological changes to accommodate the loss of Klf5 withstanding epithelial damage further signifying importance of Klf5 in colonic homeostasis. PMID:24440658

Reduction of regulatory T cells in skin lesions but not in peripheral blood of patients with systemic scleroderma.

PubMed

Klein, S; Kretz, C C; Ruland, V; Stumpf, C; Haust, M; Hartschuh, W; Hartmann, M; Enk, A; Suri-Payer, E; Oberle, N; Krammer, P H; Kuhn, A

2011-08-01

To determine the frequency and suppressive capacity of regulatory T cells (T(reg)) and their association with clinical parameters in patients with systemic scleroderma (SSc). Peripheral blood from 25 patients with SSc, 15 patients with localised scleroderma (LS) and 29 healthy controls (HC) was studied. Analysis of CD4(+) forkhead box P3 (Foxp3)(+) and CD4(+)CD25(++)Foxp3(+) T(reg) subpopulations was carried out by flow cytometry and cell proliferation was quantified by (3)H-thymidine incorporation. Quantitative analysis of T(reg) was further performed in skin biopsies from 17 patients with SSc and 21 patients with LS using anti-CD4 and anti-Foxp3 monoclonal antibodies for immunohistochemistry. The frequency of CD4(+)Foxp3(+) and CD4(+)CD25(++)Foxp3(+) T(reg) in peripheral blood from patients with SSc was not significantly different from that of patients with LS or HC. The suppressive capacity of CD4(+)CD25(++) T(reg) in SSc was also found to be similar to that of HC. Phenotypic and functional data revealed no significant difference between the limited or diffuse form of SSc. Moreover, therapy with bosentan showed no significant effect on the frequency of T(reg) during the course of the disease. However, the frequency of T(reg) in skin lesions from patients with SSc or LS, determined as the percentage of CD4(+) cells expressing Foxp3 in the inflammatory infiltrate, was significantly reduced compared with other inflammatory skin diseases. These results indicate that although the authors found no defect in the frequency or function of peripheral T(reg) subpopulations, the reduction of CD4(+)Foxp3(+) T(reg) in the skin of patients with SSc may be important in the pathogenesis of the disease.

36 CFR 1200.7 - What are NARA logos and how are they used?

Code of Federal Regulations, 2011 CFR

2011-07-01

... business cards; (2) On all NARA web and social media sites (intranet and internet), whether hosted...) Regulations.gov and FedReg.gov Web sites. ER11MY04.008 (iii) Federal Register paper edition. ER11MY04.009 (iv...) NARA Web sites (Intranet and Internet); (4) Officially approved internal and external publications; and...

76 FR 71089 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-16

... Receipts/SPDRs (``SPY''); (ii) the PowerShares QQQ Trust (``QQQ'') [reg]; (iii) Apple, Inc. (``AAPL''); (iv... initially filed a proposed rule change \\6\\ to pay a different Customer Complex Order Rebate to Add Liquidity... the Exchange from continuing to increase its order flow. Currently, the Exchange pays a Customer...

Diets enriched with cranberry beans alter the microbiota and mitigate colitis severity and associated inflammation.

PubMed

Monk, Jennifer M; Lepp, Dion; Zhang, Claire P; Wu, Wenqing; Zarepoor, Leila; Lu, Jenifer T; Pauls, K Peter; Tsao, Rong; Wood, Geoffrey A; Robinson, Lindsay E; Power, Krista A

2016-02-01

Common beans are rich in phenolic compounds and nondigestible fermentable components, which may help alleviate intestinal diseases. We assessed the gut health priming effect of a 20% cranberry bean flour diet from two bean varieties with differing profiles of phenolic compounds [darkening (DC) and nondarkening (NDC) cranberry beans vs. basal diet control (BD)] on critical aspects of gut health in unchallenged mice, and during dextran sodium sulfate (DSS)-induced colitis (2% DSS wt/vol, 7 days). In unchallenged mice, NDC and DC increased (i) cecal short-chain fatty acids, (ii) colon crypt height, (iii) crypt goblet cell number and mucus content and (iv) Muc1, Klf4, Relmβ and Reg3γ gene expression vs. BD, indicative of enhanced microbial activity and gut barrier function. Fecal 16S rRNA sequencing determined that beans reduced abundance of the Lactobacillaceae (Ruminococcus gnavus), Clostridiaceae (Clostridium perfringens), Peptococcaceae, Peptostreptococcaceae, Rikenellaceae and Pophyromonadaceae families, and increased abundance of S24-7 and Prevotellaceae. During colitis, beans reduced (i) disease severity and colonic histological damage, (ii) increased gene expression of barrier function promoting genes (Muc1-3, Relmβ, and Reg3γ) and (iii) reduced colonic and circulating inflammatory cytokines (IL-1β, IL-6, IFNγ and TNFα). Therefore, prior to disease induction, bean supplementation enhanced multiple concurrent gut health promoting parameters that translated into reduced colitis severity. Moreover, both bean diets exerted similar effects, indicating that differing phenolic content did not influence the endpoints assessed. These data demonstrate a proof-of-concept regarding the gut-priming potential of beans in colitis, which could be extended to mitigate the severity of other gut barrier-associated pathologies. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Tumor evasion of the immune system by converting CD4+CD25- T cells into CD4+CD25+ T regulatory cells: role of tumor-derived TGF-beta.

PubMed

Liu, Victoria C; Wong, Larry Y; Jang, Thomas; Shah, Ali H; Park, Irwin; Yang, Ximing; Zhang, Qiang; Lonning, Scott; Teicher, Beverly A; Lee, Chung

2007-03-01

CD4+CD25+ T regulatory (T(reg)) cells were initially described for their ability to suppress autoimmune diseases in animal models. An emerging interest is the potential role of T(reg) cells in cancer development and progression because they have been shown to suppress antitumor immunity. In this study, CD4+CD25- T cells cultured in conditioned medium (CM) derived from tumor cells, RENCA or TRAMP-C2, possess similar characteristics as those of naturally occurring T(reg) cells, including expression of Foxp3, a crucial transcription factor of T(reg) cells, production of low levels of IL-2, high levels of IL-10 and TGF-beta, and the ability to suppress CD4+CD25- T cell proliferation. Further investigation revealed a critical role of tumor-derived TGF-beta in converting CD4+CD25- T cells into T(reg) cells because a neutralizing Ab against TGF-beta, 1D11, completely abrogated the induction of T(reg) cells. CM from a nontumorigenic cell line, NRP-152, or irradiated tumor cells did not convert CD4+CD25- T cells to T(reg) cells because they produce low levels of TGF-beta in CM. Finally, we observed a reduced tumor burden in animals receiving 1D11. The reduction in tumor burden correlated with a decrease in tumor-derived TGF-beta. Treatment of 1D11 also reduced the conversion of CD4+ T cells into T(reg) cells and subsequent T(reg) cell-mediated suppression of antitumor immunity. In summary, we have demonstrated that tumor cells directly convert CD4+CD25- T cells to T(reg) cells through production of high levels of TGF-beta, suggesting a possible mechanism through which tumor cells evade the immune system.

FOXP3+ regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer.

PubMed

Davidsson, Sabina; Andren, Ove; Ohlson, Anna-Lena; Carlsson, Jessica; Andersson, Swen-Olof; Giunchi, Francesca; Rider, Jennifer R; Fiorentino, Michelangelo

2018-01-01

The tumor promoting or counteracting effects of the immune response to cancer development are thought to be mediated to some extent by the infiltration of regulatory T cells (T regs ). In the present study we evaluated the prevalence of T reg populations in stromal and epithelial compartments of normal, post atrophic hyperplasia (PAH), prostatic intraepithelial neoplasia (PIN), and tumor lesions in men with and without prostate cancer. Study subjects were 102 men consecutively diagnosed with localized prostate cancer undergoing radical prostatectomy and 38 men diagnosed with bladder cancer undergoing cystoprostatectomy without prostate cancer at the pathological examination. Whole mount sections from all patients were evaluated for the epithelial and stromal expression of CD4 + T regs and CD8 + T regs in normal, PAH, PIN, and tumor lesions. A Friedmańs test was used to investigate differences in the mean number of T regs across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area. In men with prostate cancer, similarly high numbers of stromal CD4 + T regs were identified in PAH and tumor, but CD4 + T regs were less common in PIN. Greater numbers of epithelial CD4+ T regs in normal prostatic tissue were positively associated with both Gleason score and pT-stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4 + T regs in the normal prostatic tissue counterpart. Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4 + T regs and indicate that transformation of the anti-tumor immune response may be initiated even before the primary tumor is established. © 2017 The Authors. The Prostate Published by Wiley Periodicals Inc.

Bicarbonate-mediated transcriptional activation of divergent operons by the virulence regulatory protein, RegA, from Citrobacter rodentium.

PubMed

Yang, Ji; Hart, Emily; Tauschek, Marija; Price, G Dean; Hartland, Elizabeth L; Strugnell, Richard A; Robins-Browne, Roy M

2008-04-01

Regulation of virulence gene expression plays a central role in the pathogenesis of enteric bacteria as they encounter diverse environmental conditions in the gastrointestinal tract of their hosts. In this study, we investigated environmental regulation of two putative virulence determinants adcA and kfc by RegA, an AraC/XylS-like regulator, from Citrobacter rodentium, and identified bicarbonate as the environmental signal which induced transcription of adcA and kfc through RegA. Primer extension experiments showed that adcA and kfc were divergently transcribed from sigma(70) promoters. In vivo and in vitro experiments demonstrated that bicarbonate facilitated and stabilized the binding of RegA to an operator located between the two promoters. The interaction of RegA with its DNA target resulted in the formation of a nucleosome-like structure, which evidently displaced the histone-like proteins, H-NS and StpA, from the adcA and kfc promoter regions, leading to transcriptional derepression. In addition, our results indicated that RegA also behaved as a Class I activator by directly stimulating transcription initiation by RNA polymerase. This is the first report to describe the molecular mechanism by which an environmental chemical stimulates transcription of virulence-associated genes of an enteric pathogen through an AraC/XlyS-like activator.

Disarming Bacterial Virulence through Chemical Inhibition of the DNA Binding Domain of an AraC-like Transcriptional Activator Protein*

PubMed Central

Yang, Ji; Hocking, Dianna M.; Cheng, Catherine; Dogovski, Con; Perugini, Matthew A.; Holien, Jessica K.; Parker, Michael W.; Hartland, Elizabeth L.; Tauschek, Marija; Robins-Browne, Roy M.

2013-01-01

The misuse of antibiotics during past decades has led to pervasive antibiotic resistance in bacteria. Hence, there is an urgent need for the development of new and alternative approaches to combat bacterial infections. In most bacterial pathogens the expression of virulence is tightly regulated at the transcriptional level. Therefore, targeting pathogens with drugs that interfere with virulence gene expression offers an effective alternative to conventional antimicrobial chemotherapy. Many Gram-negative intestinal pathogens produce AraC-like proteins that control the expression of genes required for infection. In this study we investigated the prototypical AraC-like virulence regulator, RegA, from the mouse attaching and effacing pathogen, Citrobacter rodentium, as a potential drug target. By screening a small molecule chemical library and chemical optimization, we identified two compounds that specifically inhibited the ability of RegA to activate its target promoters and thus reduced expression of a number of proteins required for virulence. Biophysical, biochemical, genetic, and computational analyses indicated that the more potent of these two compounds, which we named regacin, disrupts the DNA binding capacity of RegA by interacting with amino acid residues within a conserved region of the DNA binding domain. Oral administration of regacin to mice, commencing 15 min before or 12 h after oral inoculation with C. rodentium, caused highly significant attenuation of intestinal colonization by the mouse pathogen comparable to that of an isogenic regA-deletion mutant. These findings demonstrate that chemical inhibition of the DNA binding domains of transcriptional regulators is a viable strategy for the development of antimicrobial agents that target bacterial pathogens. PMID:24019519

Where's Wally: the influence of visual salience on referring expression generation.

PubMed

Clarke, Alasdair D F; Elsner, Micha; Rohde, Hannah

2013-01-01

REFERRING EXPRESSION GENERATION (REG) PRESENTS THE CONVERSE PROBLEM TO VISUAL SEARCH: given a scene and a specified target, how does one generate a description which would allow somebody else to quickly and accurately locate the target?Previous work in psycholinguistics and natural language processing has failed to find an important and integrated role for vision in this task. That previous work, which relies largely on simple scenes, tends to treat vision as a pre-process for extracting feature categories that are relevant to disambiguation. However, the visual search literature suggests that some descriptions are better than others at enabling listeners to search efficiently within complex stimuli. This paper presents a study testing whether participants are sensitive to visual features that allow them to compose such "good" descriptions. Our results show that visual properties (salience, clutter, area, and distance) influence REG for targets embedded in images from the Where's Wally? books. Referring expressions for large targets are shorter than those for smaller targets, and expressions about targets in highly cluttered scenes use more words. We also find that participants are more likely to mention non-target landmarks that are large, salient, and in close proximity to the target. These findings identify a key role for visual salience in language production decisions and highlight the importance of scene complexity for REG.

12 CFR 210.4 - Sending items to Reserve Banks.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 2 2013-01-01 2013-01-01 false Sending items to Reserve Banks. 210.4 Section... Reserve Bank); and (iv) Another Reserve Bank, if any, that receives the item from a Reserve Bank. (2) A... par. The Reserve Banks shall receive cash items and other checks at par. [Reg. J, 77 FR 21858, Apr. 12...

12 CFR 210.4 - Sending items to Reserve Banks.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 2 2014-01-01 2014-01-01 false Sending items to Reserve Banks. 210.4 Section... Reserve Bank); and (iv) Another Reserve Bank, if any, that receives the item from a Reserve Bank. (2) A... par. The Reserve Banks shall receive cash items and other checks at par. [Reg. J, 77 FR 21858, Apr. 12...

RegA Plays a Key Role in Oxygen-Dependent Establishment of Persistence and in Isocitrate Lyase Activity, a Critical Determinant of In vivo Brucella suis Pathogenicity

PubMed Central

Abdou, Elias; Jiménez de Bagüés, María P.; Martínez-Abadía, Ignacio; Ouahrani-Bettache, Safia; Pantesco, Véronique; Occhialini, Alessandra; Al Dahouk, Sascha; Köhler, Stephan; Jubier-Maurin, Véronique

2017-01-01

For aerobic human pathogens, adaptation to hypoxia is a critical factor for the establishment of persistent infections, as oxygen availability is low inside the host. The two-component system RegB/A of Brucella suis plays a central role in the control of respiratory systems adapted to oxygen deficiency, and in persistence in vivo. Using an original “in vitro model of persistence” consisting in gradual oxygen depletion, we compared transcriptomes and proteomes of wild-type and ΔregA strains to identify the RegA-regulon potentially involved in the set-up of persistence. Consecutive to oxygen consumption resulting in growth arrest, 12% of the genes in B. suis were potentially controlled directly or indirectly by RegA, among which numerous transcriptional regulators were up-regulated. In contrast, genes or proteins involved in envelope biogenesis and in cellular division were repressed, suggesting a possible role for RegA in the set-up of a non-proliferative persistence state. Importantly, the greatest number of the RegA-repressed genes and proteins, including aceA encoding the functional IsoCitrate Lyase (ICL), were involved in energy production. A potential consequence of this RegA impact may be the slowing-down of the central metabolism as B. suis progressively enters into persistence. Moreover, ICL is an essential determinant of pathogenesis and long-term interactions with the host, as demonstrated by the strict dependence of B. suis on ICL activity for multiplication and persistence during in vivo infection. RegA regulates gene or protein expression of all functional groups, which is why RegA is a key regulator of B. suis in adaptation to oxygen depletion. This function may contribute to the constraint of bacterial growth, typical of chronic infection. Oxygen-dependent activation of two-component systems that control persistence regulons, shared by several aerobic human pathogens, has not been studied in Brucella sp. before. This work therefore contributes significantly to the unraveling of persistence mechanisms in this important zoonotic pathogen. PMID:28573107

c-MAF-dependent regulatory T cells mediate immunological tolerance to a gut pathobiont.

PubMed

Xu, Mo; Pokrovskii, Maria; Ding, Yi; Yi, Ren; Au, Christy; Harrison, Oliver J; Galan, Carolina; Belkaid, Yasmine; Bonneau, Richard; Littman, Dan R

2018-02-15

Both microbial and host genetic factors contribute to the pathogenesis of autoimmune diseases. There is accumulating evidence that microbial species that potentiate chronic inflammation, as in inflammatory bowel disease, often also colonize healthy individuals. These microorganisms, including the Helicobacter species, can induce pathogenic T cells and are collectively referred to as pathobionts. However, how such T cells are constrained in healthy individuals is not yet understood. Here we report that host tolerance to a potentially pathogenic bacterium, Helicobacter hepaticus, is mediated by the induction of RORγt + FOXP3 + regulatory T (iT reg ) cells that selectively restrain pro-inflammatory T helper 17 (T H 17) cells and whose function is dependent on the transcription factor c-MAF. Whereas colonization of wild-type mice by H. hepaticus promoted differentiation of RORγt-expressing microorganism-specific iT reg cells in the large intestine, in disease-susceptible IL-10-deficient mice, there was instead expansion of colitogenic T H 17 cells. Inactivation of c-MAF in the T reg cell compartment impaired differentiation and function, including IL-10 production, of bacteria-specific iT reg cells, and resulted in the accumulation of H. hepaticus-specific inflammatory T H 17 cells and spontaneous colitis. By contrast, RORγt inactivation in T reg cells had only a minor effect on the bacteria-specific T reg and T H 17 cell balance, and did not result in inflammation. Our results suggest that pathobiont-dependent inflammatory bowel disease is driven by microbiota-reactive T cells that have escaped this c-MAF-dependent mechanism of iT reg -T H 17 homeostasis.

Reduced TCR signaling potential impairs negative selection but does not result in autoimmune disease

PubMed Central

Hwang, SuJin; Song, Ki-Duk; Lesourne, Renaud; Lee, Jan; Pinkhasov, Julia; Li, LiQi; El-Khoury, Dalal

2012-01-01

Negative selection and regulatory T (T reg) cell development are two thymus-dependent processes necessary for the enforcement of self-tolerance, and both require high-affinity interactions between the T cell receptor (TCR) and self-ligands. However, it remains unclear if they are similarly impacted by alterations in TCR signaling potential. We generated a knock-in allele (6F) of the TCR ζ chain gene encoding a mutant protein lacking signaling capability whose expression is controlled by endogenous ζ regulatory sequences. Although negative selection was defective in 6F/6F mice, leading to the survival of autoreactive T cells, 6F/6F mice did not develop autoimmune disease. We found that 6F/6F mice generated increased numbers of thymus-derived T reg cells. We show that attenuation of TCR signaling potential selectively impacts downstream signaling responses and that this differential effect favors Foxp3 expression and T reg cell lineage commitment. These results identify a potential compensatory pathway for the enforcement of immune tolerance in response to defective negative selection caused by reduced TCR signaling capability. PMID:22945921

FOXP3 and GARP (LRRC32): the master and its minion.

PubMed

Probst-Kepper, Michael; Buer, Jan

2010-02-05

The transcription factor FOXP3 is essential for the development and function of CD4+CD25hiFOXP3+ regulatory T (T(reg)) cells, but also expressed in activated human helper T cells without acquisition of a regulatory phenotype. This comment focuses on glycoprotein-A repetitions predominant (GARP or LRRC32) recently identified as specific marker of activated human T(reg) cells, which may provide the missing link toward a better molecular definition of the regulatory phenotype.

GARP: a key receptor controlling FOXP3 in human regulatory T cells.

PubMed

Probst-Kepper, M; Geffers, R; Kröger, A; Viegas, N; Erck, C; Hecht, H-J; Lünsdorf, H; Roubin, R; Moharregh-Khiabani, D; Wagner, K; Ocklenburg, F; Jeron, A; Garritsen, H; Arstila, T P; Kekäläinen, E; Balling, R; Hauser, H; Buer, J; Weiss, S

2009-09-01

Recent evidence suggests that regulatory pathways might control sustained high levels of FOXP3 in regulatory CD4(+)CD25(hi) T (T(reg)) cells. Based on transcriptional profiling of ex vivo activated T(reg) and helper CD4(+)CD25(-) T (T(h)) cells we have identified GARP (glycoprotein-A repetitions predominant), LGALS3 (lectin, galactoside-binding, soluble, 3) and LGMN (legumain) as novel genes implicated in human T(reg) cell function, which are induced upon T-cell receptor stimulation. Retroviral overexpression of GARP in antigen-specific T(h) cells leads to an efficient and stable re-programming of an effector T cell towards a regulatory T cell, which involves up-regulation of FOXP3, LGALS3, LGMN and other T(reg)-associated markers. In contrast, overexpression of LGALS3 and LGMN enhance FOXP3 and GARP expression, but only partially induced a regulatory phenotype. Lentiviral down-regulation of GARP in T(reg) cells significantly impaired the suppressor function and was associated with down-regulation of FOXP3. Moreover, down-regulation of FOXP3 resulted in similar phenotypic changes and down-regulation of GARP. This provides compelling evidence for a GARP-FOXP3 positive feedback loop and provides a rational molecular basis for the known difference between natural and transforming growth factor-beta induced T(reg) cells as we show here that the latter do not up-regulate GARP. In summary, we have identified GARP as a key receptor controlling FOXP3 in T(reg) cells following T-cell activation in a positive feedback loop assisted by LGALS3 and LGMN, which represents a promising new system for the therapeutic manipulation of T cells in human disease.

Eosinophils from eosinophilic oesophagitis patients have T cell suppressive capacity and express FOXP3.

PubMed

Lingblom, C; Wallander, J; Ingelsten, M; Bergquist, H; Bove, M; Saalman, R; Welin, A; Wennerås, C

2017-03-01

Eosinophilic esophagitis (EoE) is an antigen-driven T cell-mediated chronic inflammatory disease where food and environmental antigens are thought to have a role. Human eosinophils express the immunoregulatory protein galectin-10 and have T cell suppressive capacity similar to regulatory T cells (T regs ). We hypothesized that one function of eosinophils in EoE might be to regulate the T cell-driven inflammation in the oesophagus. This was tested by evaluating the suppressive capacity of eosinophils isolated from the blood of adult EoE patients in a mixed lymphocyte reaction. In addition, eosinophilic expression of forkhead box protein 3 (FOXP3), the canonical transcription factor of T regs , was determined by conventional and imaging flow cytometry, quantitative polymerase chain reaction (qPCR), confocal microscopy and immunoblotting. It was found that blood eosinophils from EoE patients had T cell suppressive capacity, and that a fraction of the eosinophils expressed FOXP3. A comparison of EoE eosinophils with healthy control eosinophils indicated that the patients' eosinophils had inferior suppressive capacity. Furthermore, a higher percentage of the EoE eosinophils expressed FOXP3 protein compared with the healthy eosinophils, and they also had higher FOXP3 protein and mRNA levels. FOXP3 was found in the cytosol and nucleus of the eosinophils from both the patients and healthy individuals, contrasting with the strict nuclear localization of FOXP3 in T regs . To conclude, these findings suggest that the immunoregulatory function of eosinophils may be impaired in EoE. © 2016 British Society for Immunology.

CoryneRegNet: an ontology-based data warehouse of corynebacterial transcription factors and regulatory networks.

PubMed

Baumbach, Jan; Brinkrolf, Karina; Czaja, Lisa F; Rahmann, Sven; Tauch, Andreas

2006-02-14

The application of DNA microarray technology in post-genomic analysis of bacterial genome sequences has allowed the generation of huge amounts of data related to regulatory networks. This data along with literature-derived knowledge on regulation of gene expression has opened the way for genome-wide reconstruction of transcriptional regulatory networks. These large-scale reconstructions can be converted into in silico models of bacterial cells that allow a systematic analysis of network behavior in response to changing environmental conditions. CoryneRegNet was designed to facilitate the genome-wide reconstruction of transcriptional regulatory networks of corynebacteria relevant in biotechnology and human medicine. During the import and integration process of data derived from experimental studies or literature knowledge CoryneRegNet generates links to genome annotations, to identified transcription factors and to the corresponding cis-regulatory elements. CoryneRegNet is based on a multi-layered, hierarchical and modular concept of transcriptional regulation and was implemented by using the relational database management system MySQL and an ontology-based data structure. Reconstructed regulatory networks can be visualized by using the yFiles JAVA graph library. As an application example of CoryneRegNet, we have reconstructed the global transcriptional regulation of a cellular module involved in SOS and stress response of corynebacteria. CoryneRegNet is an ontology-based data warehouse that allows a pertinent data management of regulatory interactions along with the genome-scale reconstruction of transcriptional regulatory networks. These models can further be combined with metabolic networks to build integrated models of cellular function including both metabolism and its transcriptional regulation.

RegNetwork: an integrated database of transcriptional and post-transcriptional regulatory networks in human and mouse

PubMed Central

Liu, Zhi-Ping; Wu, Canglin; Miao, Hongyu; Wu, Hulin

2015-01-01

Transcriptional and post-transcriptional regulation of gene expression is of fundamental importance to numerous biological processes. Nowadays, an increasing amount of gene regulatory relationships have been documented in various databases and literature. However, to more efficiently exploit such knowledge for biomedical research and applications, it is necessary to construct a genome-wide regulatory network database to integrate the information on gene regulatory relationships that are widely scattered in many different places. Therefore, in this work, we build a knowledge-based database, named ‘RegNetwork’, of gene regulatory networks for human and mouse by collecting and integrating the documented regulatory interactions among transcription factors (TFs), microRNAs (miRNAs) and target genes from 25 selected databases. Moreover, we also inferred and incorporated potential regulatory relationships based on transcription factor binding site (TFBS) motifs into RegNetwork. As a result, RegNetwork contains a comprehensive set of experimentally observed or predicted transcriptional and post-transcriptional regulatory relationships, and the database framework is flexibly designed for potential extensions to include gene regulatory networks for other organisms in the future. Based on RegNetwork, we characterized the statistical and topological properties of genome-wide regulatory networks for human and mouse, we also extracted and interpreted simple yet important network motifs that involve the interplays between TF-miRNA and their targets. In summary, RegNetwork provides an integrated resource on the prior information for gene regulatory relationships, and it enables us to further investigate context-specific transcriptional and post-transcriptional regulatory interactions based on domain-specific experimental data. Database URL: http://www.regnetworkweb.org PMID:26424082

Central nervous system demyelinating disease protection by the human commensal Bacteroides fragilis depends on polysaccharide A expression.

PubMed

Ochoa-Repáraz, Javier; Mielcarz, Daniel W; Ditrio, Lauren E; Burroughs, Ashley R; Begum-Haque, Sakhina; Dasgupta, Suryasarathi; Kasper, Dennis L; Kasper, Lloyd H

2010-10-01

The importance of gut commensal bacteria in maintaining immune homeostasis is increasingly understood. We recently described that alteration of the gut microflora can affect a population of Foxp3(+)T(reg) cells that regulate demyelination in experimental autoimmune encephalomyelitis (EAE), the experimental model of human multiple sclerosis. We now extend our previous observations on the role of commensal bacteria in CNS demyelination, and we demonstrate that Bacteroides fragilis producing a bacterial capsular polysaccharide Ag can protect against EAE. Recolonization with wild type B. fragilis maintained resistance to EAE, whereas reconstitution with polysaccharide A-deficient B. fragilis restored EAE susceptibility. Enhanced numbers of Foxp3(+)T(reg) cells in the cervical lymph nodes were observed after intestinal recolonization with either strain of B. fragilis. Ex vivo, CD4(+)T cells obtained from mice reconstituted with wild type B. fragilis had significantly enhanced rates of conversion into IL-10-producing Foxp3(+)T(reg) cells and offered greater protection against disease. Our results suggest an important role for commensal bacterial Ags, in particular B. fragilis expressing polysaccharide A, in protecting against CNS demyelination in EAE and perhaps human multiple sclerosis.

A PC Program to Calculate the One-Sided Lower Tolerance Limit for Total Ionizing Dose Radiation Data

DTIC Science & Technology

1991-08-01

include <graphics .h> #define VEDIO OxlO #define ESC 27 1* Decelerations * FILE *pfile; FILE *outf; FILE *inf; mnt n; mnt un; float max scale...regs.h.ah=2; regs .h.dh=y; regs .h.dl=x; regs .h.bh=O; int86( VEDIO , ®s, ®s); char attribute(char blink, char back-color,char intensity, char...set lint mode) union REGS regs; regs.h.ah=O; regs h a l-mode; int86( VEDIO , ®s, ®s); void str-color (char x, char y, char *str, char blink, char

A Saccharomyces cerevisiae mitochondrial DNA fragment activates Reg1p-dependent glucose-repressible transcription in the nucleus.

PubMed

Santangelo, G M; Tornow, J

1997-12-01

As part of an effort to identify random carbon-source-regulated promoters in the Saccharomyces cerevisiae genome, we discovered that a mitochondrial DNA fragment is capable of directing glucose-repressible expression of a reporter gene. This fragment (CR24) originated from the mitochondrial genome adjacent to a transcription initiation site. Mutational analyses identified a GC cluster within the fragment that is required for transcriptional induction. Repression of nuclear CR24-driven transcription required Reg1p, indicating that this mitochondrially derived promoter is a member of a large group of glucose-repressible nuclear promoters that are similarly regulated by Reg1p. In vivo and in vitro binding assays indicated the presence of factors, located within the nucleus and the mitochondria, that bind to the GC cluster. One or more of these factors may provide a regulatory link between the nucleus and mitochondria.

Pulmonary Th17 anti-fungal immunity is regulated by the gut microbiome12

PubMed Central

McAleer, Jeremy P.; Nguyen, Nikki L.H.; Chen, Kong; Kumar, Pawan; Ricks, David M.; Binnie, Matthew; Armentrout, Rachel A.; Pociask, Derek A.; Hein, Aaron; Yu, Amy; Vikram, Amit; Bibby, Kyle; Umesaki, Yoshinori; Rivera, Amariliz; Sheppard, Dean; Ouyang, Wenjun; Hooper, Lora V.; Kolls, Jay K.

2016-01-01

Commensal microbiota are critical for the development of local immune responses. Here, we show that gut microbiota can regulate CD4 T cell polarization during pulmonary fungal infections. Vancomycin drinking water significantly decreased lung Th17 cell numbers during acute infection, demonstrating that Gram-positive commensals contribute to systemic inflammation. We next tested a role for RegIIIγ, an IL-22 inducible anti-microbial protein with specificity for Gram-positive bacteria. Following infection, increased accumulation of Th17 cells in the lungs of RegIIIγ−/− and Il22−/− mice was associated with intestinal segmented filamentous bacteria (SFB) colonization. Although gastrointestinal delivery of recombinant RegIIIγ decreased lung inflammatory gene expression and protected Il22−/− mice from weight-loss during infection, RegIIIγ had no direct effect on SFB colonization, fungal clearance or lung Th17 immunity. We further show that vancomycin only decreased lung IL-17 production in mice colonized with SFB. To determine the link between gut microbiota and lung immunity, serum transfer experiments revealed that IL-1 receptor ligands increase the accumulation of lung Th17 cells. These data suggest that intestinal microbiota including SFB can regulate pulmonary adaptive immune responses. PMID:27217583

CoryneRegNet: An ontology-based data warehouse of corynebacterial transcription factors and regulatory networks

PubMed Central

Baumbach, Jan; Brinkrolf, Karina; Czaja, Lisa F; Rahmann, Sven; Tauch, Andreas

2006-01-01

Background The application of DNA microarray technology in post-genomic analysis of bacterial genome sequences has allowed the generation of huge amounts of data related to regulatory networks. This data along with literature-derived knowledge on regulation of gene expression has opened the way for genome-wide reconstruction of transcriptional regulatory networks. These large-scale reconstructions can be converted into in silico models of bacterial cells that allow a systematic analysis of network behavior in response to changing environmental conditions. Description CoryneRegNet was designed to facilitate the genome-wide reconstruction of transcriptional regulatory networks of corynebacteria relevant in biotechnology and human medicine. During the import and integration process of data derived from experimental studies or literature knowledge CoryneRegNet generates links to genome annotations, to identified transcription factors and to the corresponding cis-regulatory elements. CoryneRegNet is based on a multi-layered, hierarchical and modular concept of transcriptional regulation and was implemented by using the relational database management system MySQL and an ontology-based data structure. Reconstructed regulatory networks can be visualized by using the yFiles JAVA graph library. As an application example of CoryneRegNet, we have reconstructed the global transcriptional regulation of a cellular module involved in SOS and stress response of corynebacteria. Conclusion CoryneRegNet is an ontology-based data warehouse that allows a pertinent data management of regulatory interactions along with the genome-scale reconstruction of transcriptional regulatory networks. These models can further be combined with metabolic networks to build integrated models of cellular function including both metabolism and its transcriptional regulation. PMID:16478536

The 1986 ARI Survey of U.S. Army Recruits: Codebook for Active Army Survey Respondents

DTIC Science & Technology

1987-04-01

VIEWING NBA - REG SEASON GAMES 0562 153S Y067 REG TV VIEWING NBA PLAYOFFS 0563 153T Y068 REG TV VIEWING NEWHART 0564 153U Y069 REG TV VIEWING WHO’S THE...BSKTBL-REG SEASON 0560 Y065 53Q REG TV VIEWING NCAA BSKTBL PLAYOFFS 0561 YO66 53R REG TV VIEWING NBA - REG SEASON GAMES 0562 Y067 53S REG TV VIEWING... NBA PLAYOFFS 0563 YO68 53T REG TV VIEWING NEWHART 0564 Y069 53U REG TV VIEWING WHO’S THE BOSS 0565 Y070 53V REG TV VIEWING THE COSBY SHOW 0566

Bioabsorbable poly-L/D-lactide (96/4) scaffold arthroplasty (RegJoint™) for trapeziometacarpal osteoarthritis: a 3-year follow-up study.

PubMed

Mattila, Simo; Ainola, Mari; Waris, Eero

2018-05-01

The poly-L/D-lactide joint scaffold (RegJoint™) has recently been associated with adverse tissue reactions and osteolysis after partial trapeziectomy for trapeziometacarpal osteoarthritis. Twenty-two of 23 patients previously operated on with this scaffold were re-examined at a mean follow-up of 3.3 years (range 36-53 months). Overall, the results showed an unacceptably high rate of adverse tissue reactions related to the degradation process of the implant, resulting in a revision procedure in three patients. At final follow-up, at which point the implant had completely degraded, there were no signs of ongoing adverse tissue reactions. There was a significant decrease in pain, increase in strength and subjective improvement in function at final follow-up compared with the pre-operative results in patients who had not undergone revision surgery. However, owing to the high incidence of adverse tissue reactions, the use of the implant has been discontinued in the treatment of trapeziometacarpal osteoarthritis. IV.

Foxp3-positive macrophages display immunosuppressive properties and promote tumor growth

PubMed Central

Zorro Manrique, Soraya; Duque Correa, Maria Adelaida; Hoelzinger, Dominique B.; Dominguez, Ana Lucia; Mirza, Noweeda; Lin, Hsi-Hsien; Stein-Streilein, Joan; Gordon, Siamon

2011-01-01

Regulatory T cells (T reg cells) are characterized by the expression of the forkhead lineage-specific transcription factor Foxp3, and their main function is to suppress T cells. While evaluating T reg cells, we identified a population of Foxp3-positive cells that were CD11b+F4/80+CD68+, indicating macrophage origin. These cells were observed in spleen, lymph nodes, bone marrow, thymus, liver, and other tissues of naive animals. To characterize this subpopulation of macrophages, we devised a strategy to purify CD11b+F4/80+Foxp3+ macrophages using Foxp3-GFP mice. Analysis of CD11b+F4/80+Foxp3+ macrophage function indicated that these cells inhibited the proliferation of T cells, whereas Foxp3− macrophages did not. Suppression of T cell proliferation was mediated through soluble factors. Foxp3− macrophages acquired Foxp3 expression after activation, which conferred inhibitory properties that were indistinguishable from natural Foxp3+ macrophages. The cytokine and transcriptional profiles of Foxp3+ macrophages were distinct from those of Foxp3− macrophages, indicating that these cells have different biological functions. Functional in vivo analyses indicated that CD11b+F4/80+Foxp3+ macrophages are important in tumor promotion and the induction of T reg cell conversion. For the first time, these studies demonstrate the existence of a distinct subpopulation of naturally occurring macrophage regulatory cells in which expression of Foxp3 correlates with suppressive function. PMID:21670203

Exosomes from heat-stressed tumour cells inhibit tumour growth by converting regulatory T cells to Th17 cells via IL-6.

PubMed

Guo, Danfeng; Chen, Yinghu; Wang, Shoujie; Yu, Lei; Shen, Yingying; Zhong, Haijun; Yang, Yunshan

2018-05-01

Exosomes derived from heat-stressed tumour cells (HS-TEXs), which contain abundant heat shock protein (HSP) 70, strongly induce antitumour immune responses. HSP70-induced interleukin (IL)-6 promotes IL-17 expression and causes rejection of established prostate tumours. However, it remains unclear whether HS-TEXs exhibit antitumour effects by converting regulatory T cells (T regs ) into T helper type 17 (Th17) cells. In this study, we found that compared with TEXs, HS-TEXs were more potent in stimulating secretion of IL-6 from dendritic cells. In vitro, IL-6 blocked tumour cell-derived transforming growth factor beta 1-induced T reg differentiation and promoted Th17 cell differentiation. HS-TEXs exerted strong antitumour effects, converting T regs into Th17 cells with high efficiency, a process that was entirely dependent upon IL-6. Neutralization of IL-17 completely abolished the antitumour effect of TEXs, but only partially inhibited that of HS-TEXs. In addition, we found higher levels of IL-6 and IL-17 in serum from tumour patients treated with hyperthermia, and an increase in Th17 cells and a decrease in T regs was detected in peripheral blood mononuclear cells isolated from these patients after hyperthermia. Therefore, our results demonstrate that HS-TEXs possess a powerful capacity to convert immunosuppressive T regs into Th17 cells via IL-6, which contributes to their potent antitumour effect. © 2017 John Wiley & Sons Ltd.

A Bone Anabolic Effect of RANKL in a Murine Model of Osteoporosis mediated through FoxP3+ CD8 T-cells

PubMed Central

Buchwald, Zachary S.; Yang, Chang; Nellore, Suman; Shashkova, Elena V.; Davis, Jennifer L.; Cline, Anna; Ko, Je; Novack, Deborah V.; DiPaolo, Richard; Aurora, Rajeev

2015-01-01

TNFα and IL-17 secreted by proinflammatory T-cells (TEFF) promote bone erosion by activating osteoclasts. We previously demonstrated that in addition to bone resorption, osteoclasts act as antigen presenting cells to induce FoxP3 in CD8 T-cells (TcREG). The osteoclast-induced regulatory CD8 T-cells limit bone resorption in ovariectomized mice (a murine model of postmenopausal osteoporosis). Here we show that while low-dose RANKL maximally induces TcREG via Notch signaling pathway to limit bone resorption, high-dose RANKL promotes bone resorption. In vitro, both TNFα and IL-17, cytokines that are abundant in ovariectomized animals, suppress TcREG induction by osteoclasts by repressing Notch ligand expression in osteoclasts but this effect can be counteracted by addition of RANKL. Ovariectomized mice treated with low-dose RANKL induced TcREG that suppressed bone resorption, decreased TEFF levels and increased bone formation. High dose RANKL had the expected osteolytic effect. Low dose RANKL administration in ovariectomized mice lacking CD8 T-cells was also osteolytic, confirming that TcREG mediate this bone anabolic effect. Our results show that while RANKL directly stimulates osteoclasts to resorb bone, it also controls the osteoclasts’ ability to induce regulatory T-cells, engaging an important negative feedback loop. In addition to the conceivable clinical relevance to treatment of osteoporosis, these observations have potential relevance to induction of tolerance and autoimmune diseases. PMID:25656537

Registration of eight six-rowed feed barley germplasm lines resistant to both Russian wheat aphid and greenbug

USDA-ARS?s Scientific Manuscript database

STARS 1006B (Reg. No. GP- , PI 659760), STARS 1007B (Reg. No. GP- , PI 659761), STARS 1008B (Reg. No. GP- , PI 659762), STARS 1009B (Reg. No. GP- , PI 659763), STARS 1010B (Reg. No. GP- , PI 659764), STARS 1011B (Reg. No. GP- , PI 659765), STARS 1012B (Reg. No. GP- , PI 659766), and STARS 1013B (Reg...

Regulators of nonsulfur purple phototrophic bacteria and the interactive control of CO2 assimilation, nitrogen fixation, hydrogen metabolism and energy generation.

PubMed

Dubbs, James M; Tabita, F Robert

2004-06-01

For the metabolically diverse nonsulfur purple phototrophic bacteria, maintaining redox homeostasis requires balancing the activities of energy supplying and energy-utilizing pathways, often in the face of drastic changes in environmental conditions. These organisms, members of the class Alphaproteobacteria, primarily use CO2 as an electron sink to achieve redox homeostasis. After noting the consequences of inactivating the capacity for CO2 reduction through the Calvin-Benson-Bassham (CBB) pathway, it was shown that the molecular control of many additional important biological processes catalyzed by nonsulfur purple bacteria is linked to expression of the CBB genes. Several regulator proteins are involved, with the two component Reg/Prr regulatory system playing a major role in maintaining redox poise in these organisms. Reg/Prr was shown to be a global regulator involved in the coordinate control of a number of metabolic processes including CO2 assimilation, nitrogen fixation, hydrogen metabolism and energy-generation pathways. Accumulating evidence suggests that the Reg/Prr system senses the oxidation/reduction state of the cell by monitoring a signal associated with electron transport. The response regulator RegA/PrrA activates or represses gene expression through direct interaction with target gene promoters where it often works in concert with other regulators that can be either global or specific. For the key CO2 reduction pathway, which clearly triggers whether other redox balancing mechanisms are employed, the ability to activate or inactivate the specific regulator CbbR is of paramount importance. From these studies, it is apparent that a detailed understanding of how diverse regulatory elements integrate and control metabolism will eventually be achieved.

76 FR 80332 - Foreign-Trade Zone 7-Mayaguez, PR, Expansion of Manufacturing Authority; Amgen Manufacturing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-23

... approved by the Board in 2008 for the manufacture of epogen[reg] (epoetin alfa), neupogen[reg] (filgrastim), aransep[reg] (darbepoetin alfa), enbrel[reg] (etanercept), kineret[reg] (anakinra), and neulasta[reg...

T cell PPARγ is required for the anti-inflammatory efficacy of abscisic acid against experimental IBD.

PubMed

Guri, Amir J; Evans, Nicholas P; Hontecillas, Raquel; Bassaganya-Riera, Josep

2011-09-01

The phytohormone abscisic acid (ABA) has been shown to be effective in ameliorating chronic and acute inflammation. The objective of this study was to investigate whether ABA's anti-inflammatory efficacy in the gut is dependent on peroxisome proliferator-activated receptor γ (PPARγ) in T cells. PPARγ-expressing and T cell-specific PPARγ null mice were fed diets with or without ABA (100 mg/kg) for 35 days prior to challenge with 2.5% dextran sodium sulfate. The severity of clinical disease was assessed daily, and mice were euthanized on Day 7 of the dextran sodium sulfate challenge. Colonic inflammation was assessed through macroscopic and histopathological examination of inflammatory lesions and real-time quantitative RT-PCR-based quantification of inflammatory genes. Flow cytometry was used to phenotypically characterize leukocyte populations in the blood and mesenteric lymph nodes. Colonic sections were stained immunohistochemically to determine the effect of ABA on colonic regulatory T (T(reg)) cells. ABA's beneficial effects on disease activity were completely abrogated in T cell-specific PPARγ null mice. Additionally, ABA improved colon histopathology, reduced blood F4/80(+)CD11b(+) monocytes, increased the percentage of CD4(+) T cells expressing the inhibitory molecule cytotoxic T lymphocyte antigen 4 in blood and enhanced the number of T(reg) cells in the mesenteric lymph nodes and colons of PPARγ-expressing but not T cell-specific PPARγ null mice. We conclude that dietary ABA ameliorates experimental inflammatory bowel disease by enhancing T(reg) cell accumulation in the colonic lamina propria through a PPARγ-dependent mechanism. Copyright © 2011 Elsevier Inc. All rights reserved.

Regadenoson pharmacologic stress for myocardial perfusion imaging: a three-way comparison between regadenoson administered at peak exercise, during walk recovery, or no-exercise.

PubMed

Thompson, Randall C; Patil, Harshal; Thompson, Elaine C; Thomas, Gregory S; Al-Amoodi, Mohammed; Kennedy, Kevin F; Bybee, Kevin A; Iain McGhie, A; O'Keefe, James H; Oakes, Lisa; Bateman, Timothy M

2013-04-01

Regadenoson (Reg) is being administered with increasing frequency either at peak exercise (ExPeak-Reg) or during a slow-down/walking recovery state (ExRec-Reg) rather than at rest (Rest-Reg). The aim of this study was to compare the clinical response of ExPeak-Reg, ExRec-Reg, and Rest-Reg. We compared 531 patients divided equally between Rest-Reg, ExPeak-Reg, and ExRec-Reg matched for age, sex, and BMI. The average systolic blood pressure (SBP) rise following Reg was modest, but there was considerable heterogeneity and the ExPeak-Reg group had a higher percentage of patients who had a SBP rise of 40 mm Hg or a fall of 20 mm Hg than either the ExRec-Reg or the Rest-Reg groups (≥40 mm Hg rise 6.8%, 1.7%, and 1.7%, respectively) (P < .02) (≥20 mm Hg fall 15.8%, 13.0%, and 7.3%, respectively) (P < .05). Chest discomfort, nausea, dizziness, and interfering abdominal radiotracer activity were less common in both exercise Reg groups compared to Rest-Reg (P < .05). Regadenoson injected at peak of symptom-limited exercise was generally well tolerated, but some patients had a significant rise or drop in SBP. There is no apparent advantage of administering regadenoson at peak exercise rather than during walk recovery, and the latter approach may have a greater safety margin.

Regulatory T cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to intravenous immunoglobulin therapy.

PubMed

Maddur, Mohan S; Stephen-Victor, Emmanuel; Das, Mrinmoy; Prakhar, Praveen; Sharma, Varun K; Singh, Vikas; Rabin, Magalie; Trinath, Jamma; Balaji, Kithiganahalli N; Bolgert, Francis; Vallat, Jean-Michel; Magy, Laurent; Kaveri, Srini V; Bayry, Jagadeesh

2017-03-20

Intravenous immunoglobulin (IVIG) is a polyspecific pooled immunoglobulin G preparation and one of the commonly used therapeutics for autoimmune diseases including those of neurological origin. A recent report in murine model proposed that IVIG expands regulatory T (T reg ) cells via induction of interleukin 33 (IL-33). However, translational insight on these observations is lacking. Ten newly diagnosed Guillain-Barré syndrome (GBS) patients were treated with IVIG at the rate of 0.4 g/kg for three to five consecutive days. Clinical evaluation for muscular weakness was performed by Medical Research Council (MRC) and modified Rankin scoring (MRS) system. Heparinized blood samples were collected before and 1, 2, and 4-5 weeks post-IVIG therapy. Peripheral blood mononuclear cells were stained for surface CD4 and intracellular Foxp3, IFN-γ, and tumor necrosis factor alpha (TNF-α) and were analyzed by flow cytometry. IL-33 and prostaglandin E2 in the plasma were measured by ELISA. The fold changes in plasma IL-33 at week 1 showed no correlation with the MRC and MRS scores at weeks 1, 2, and ≥4 post-IVIG therapy. Clinical recovery following IVIG therapy appears to be associated with T reg cell response. Contrary to murine study, there was no association between the fold changes in IL-33 at week 1 and T reg cell frequency at weeks 1, 2, and ≥4 post-IVIG therapy. T reg cell-mediated clinical response to IVIG therapy in GBS patients was associated with reciprocal regulation of effector T cells-expressing TNF-α. T reg cell expansion by IVIG in patients with autoimmune diseases lack correlation with IL-33. T reg cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to IVIG therapy.

The residual and direct effects of reduced-risk and conventional miticides on twospotted spider mites, Tetranychus urticae (Acari: Tetranychidae) and predatory mites (Acari: Phytoseiidae)

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

Liburd, O.E.; White, J.C.; Rhodes, E.M.

2007-03-15

The residual effects of several reduced-risk and conventional miticides were evaluated in strawberries (Fragaria z ananassa Duchesne) on the twospotted spider mite (TSSM), Tetranychus urticae Koch (Acari: Tetranychidae) and on 2 predatory mites, Neoseiulus californicus McGregor and Phytoseiulus persimilis Athias-Henriot (Acari: Phytoseiidae). Experiments were conducted in the laboratory and greenhouse. The greenhouse experiments also tested the direct effects of the miticides on TSSM. The efficacy of conventional and reduced-risk miticides was evaluated on strawberry leaf discs and on whole plants for control of TSSM. Furthermore, the residual effects of these miticides were evaluated on whole strawberry plants against selective predatorymore » mites. For TSSM, 5 treatments were evaluated: a conventional miticide; fenbutatin-oxide (Vendex[reg]) and 3 reduced-risk miticides; binfenazate (Acramite 50WP[reg]), activated garlic extract (Repel[reg]), sesame seed and castor oil (Wipeout[reg]), and a water-treated control. For predatory mites, the residual effects of only Acramite[reg] and Vendex[reg] were evaluated. Acramite[reg] was the most effective acaricide in reducing TSSM populations in both the laboratory and greenhouse experiments. Vendex[reg] and Wipeout[reg] were also effective in the laboratory, but did not cause significant reduction of TSSM in the greenhouse. Repel[reg] was the least effective of the 4 pesticides evaluated. Neither Acramite[reg] nor Vendex[reg] had a significant effect on either predatory mite species. However, there appeared to be more predatory mites on the Vendex[reg]-treated plants than on the Acramite[reg]-treated plants. There were significantly more predatory mites of both species on the cue plants, which were inoculated with TSSM versus the non-cue plants, which were not inoculated. (author) [Spanish] Los efectos residuales en poblaciones de la 'arana roja', Tetranychus urticae Koch (Acari: Tetranichidae) y de los acaros predadores Neoseiulus californicus McGregor y Phytoseilus persimilis Athias-Henriot (Acari: Phytoseiidae) causados por varios acaricidas convencionales y de riesgo-reducido fueron evaluados en fresas (Fragaria x ananassa Duchense). Los experimentos fueron realizados en laboratorio e invernadero. Los experimentos en el invernadero evaluaron tambien el efecto directo de los acaricidas en la 'arana roja'. La eficacia para controlar la 'arana roja' de los acaricidas convencionales y de riesgo-reducido fue evaluada en discos de las hojas y en plantas de fresa, y los efectos residuales de los acaricidas en los acaros predadores fueron evaluados en plantas completas. Para la 'arana roja' se evaluaron cinco tratamientos: el acaricida convencional fenbutatin-oxido (Vendex[reg]), 3 acaricidas de riesgo-reducido binfenazate (Acaramite 50WP[reg]), extracto de ajo activado (Repel[reg]), aceite de semillas de ajonjoli y ricino (Wipeout[reg]) y un control tratado con agua. Para los acaros predadores solamente los efectos de Acaramite[reg] y Vendex[reg] fueron evaluados. Acaramite[reg] fue el tratamiento mas efectivo para la 'arana roja' en el laboratorio y el invernadero. Vendex[reg] y Wipeout[reg] fueron tambien efectivos en el laboratorio, pero no causaron una reduccion significativa de 'aranas rojas' en el invernadero. Repel[reg] fue el tratamiento evaluado menos eficaz. Ni Acaramite[reg] ni Vendex[reg] redujeron significativamente las poblaciones de acaros predadores. Sin embargo, aparentemente hay mas acaros predadores en Vendex[reg] que en Acaramite[reg]. Tambien se encontraron significativamente mas acaros predadores en plantas inoculadas que en plantas no inoculadas. (author)« less

Sensitivity of simulated South America Climate to the Land Surface Schemes in RegCM4

NASA Astrophysics Data System (ADS)

Llopart, Marta; da Rocha, Rosmeri; Reboita, Michelle; Cuadra, Santiago

2017-04-01

This work evaluates the impact of two land surface parameterizations on the simulated climate and its variability over South America (SA). Two numerical experiments using RegCM4 coupled with Biosphere-Atmosphere Transfer Scheme (RegBATS) and Community Land Model version 3.5 (RegCLM) land surface schemes are compared. For the period 1979-2008, RegCM4 simulations used 50 km horizontal grid spacing and the ERA-Interim reanalysis as initial and boundary conditions. For the period studied, both simulations represent the main observed spatial patterns of rainfall, air temperature and low level circulation over SA. However, concerning the precipitation intensity, RegCLM values are closer to the observations than RegBATS (it is in general, wetter) over most of SA. RegCLM also provides smaller biases for air temperature. Over the Amazon basin, the amplitudes of the annual cycles of the soil moisture, evapotranspiration and sensible heat flux are higher in RegBATS than in RegCLM. This indicates that RegBATS provides large amounts of water vapor to the atmosphere and has more available energy to increase the boundary layer and make it reach the level of free convection (higher sensible heat flux values) resulting in higher precipitation rates and a large wet bias. RegCLM is closer to the observations than RegBATS, presenting smaller wet and warm biases over the Amazon basin. On an interannual scale, the magnitudes of the anomalies of the precipitation and air temperature simulated by RegCLM are closer to the observations. In general, RegBATS simulates higher magnitude for the interannual variability signal.

Registration of six grain sorghum pollinator (R) lines

USDA-ARS?s Scientific Manuscript database

Six sorghum [Sorghum bicolor (L.) Moench] pollinators [KS142R (Reg. No. PI XXXX), KS143R (Reg. No. PI XXXX), KS144R (Reg.No. PI XXXX), KS145R (Reg. No. PI XXXX), KS146R (Reg. No. PI XXXX) and KS147R (Reg. No. PI XXXX) were developed from random mating using a recurrent selection followed by pedigree...

Sensitivity of simulated South America climate to the land surface schemes in RegCM4

NASA Astrophysics Data System (ADS)

Llopart, Marta; da Rocha, Rosmeri P.; Reboita, Michelle; Cuadra, Santiago

2017-12-01

This work evaluates the impact of two land surface parameterizations on the simulated climate and its variability over South America (SA). Two numerical experiments using RegCM4 coupled with the Biosphere-Atmosphere Transfer Scheme (RegBATS) and the Community Land Model version 3.5 (RegCLM) land surface schemes are compared. For the period 1979-2008, RegCM4 simulations used 50 km horizontal grid spacing and the ERA-Interim reanalysis as initial and boundary conditions. For the period studied, both simulations represent the main observed spatial patterns of rainfall, air temperature and low level circulation over SA. However, with regard to the precipitation intensity, RegCLM values are closer to the observations than RegBATS (it is wetter in general) over most of SA. RegCLM also produces smaller biases for air temperature. Over the Amazon basin, the amplitudes of the annual cycles of the soil moisture, evapotranspiration and sensible heat flux are higher in RegBATS than in RegCLM. This indicates that RegBATS provides large amounts of water vapor to the atmosphere and has more available energy to increase the boundary layer thickness and cause it to reach the level of free convection (higher sensible heat flux values) resulting in higher precipitation rates and a large wet bias. RegCLM is closer to the observations than RegBATS, presenting smaller wet and warm biases over the Amazon basin. On an interannual scale, the magnitudes of the anomalies of the precipitation and air temperature simulated by RegCLM are closer to the observations. In general, RegBATS simulates higher magnitude for the interannual variability signal.

Effect of systemic administration of lipopolysaccharides derived from Porphyromonas gingivalis on gene expression in mice kidney.

PubMed

Harada, Fumiya; Uehara, Osamu; Morikawa, Tetsuro; Hiraki, Daichi; Onishi, Aya; Toraya, Seiko; Adhikari, Bhoj Raj; Takai, Rie; Yoshida, Koki; Sato, Jun; Nishimura, Michiko; Chiba, Itsuo; Wu, Ching Zong; Abiko, Yoshihiro

2018-01-31

Although an association between periodontitis and chronic kidney disease (CKD) has been suggested, the mechanism involved remains unclear. Herein, we examined the global gene expression profile in a mouse model that showed no acute inflammation in the kidney following stimulation with lipopolysaccharides (LPS) derived from Porphyromonas gingivalis (PG-LPS). The mice were injected with PG-LPS at a concentration of 5 mg/kg intraperitoneally, every 3 days, for 1 month. Microarray analysis was used to identify 10 genes with the highest expression levels in the kidney stimulated with PG-LPS. Among them, the functions of five genes (Saa3, Ticam2, Reg3b, Ocxt2a, and Xcr1) were known. The upregulation of these genes was confirmed by quantitative polymerase chain reaction assay. Furthermore, we examined whether the expression of these upregulated genes were altered in endothelial cells derived from the kidney, in vitro. The mRNA expression levels of all five genes were significantly higher in the experimental group than in the controls (no LPS stimulation; *p < 0.05). In conclusion, the responses noted in the kidney may have arisen mainly from the endothelial cells. Moreover, upregulation of the expression levels of Saa3, Ticam2, Reg3b, Ocxt2a, and Xcr1 may be associated with the pathogenesis of CKD.

Interferon-γ Drives Treg Fragility to Promote Anti-tumor Immunity.

PubMed

Overacre-Delgoffe, Abigail E; Chikina, Maria; Dadey, Rebekah E; Yano, Hiroshi; Brunazzi, Erin A; Shayan, Gulidanna; Horne, William; Moskovitz, Jessica M; Kolls, Jay K; Sander, Cindy; Shuai, Yongli; Normolle, Daniel P; Kirkwood, John M; Ferris, Robert L; Delgoffe, Greg M; Bruno, Tullia C; Workman, Creg J; Vignali, Dario A A

2017-06-01

Regulatory T cells (T regs ) are a barrier to anti-tumor immunity. Neuropilin-1 (Nrp1) is required to maintain intratumoral T reg stability and function but is dispensable for peripheral immune tolerance. T reg -restricted Nrp1 deletion results in profound tumor resistance due to T reg functional fragility. Thus, identifying the basis for Nrp1 dependency and the key drivers of T reg fragility could help to improve immunotherapy for human cancer. We show that a high percentage of intratumoral NRP1 + T regs correlates with poor prognosis in melanoma and head and neck squamous cell carcinoma. Using a mouse model of melanoma where Nrp1-deficient (Nrp1 -/- ) and wild-type (Nrp1 +/+ ) T regs can be assessed in a competitive environment, we find that a high proportion of intratumoral Nrp1 -/- T regs produce interferon-γ (IFNγ), which drives the fragility of surrounding wild-type T regs , boosts anti-tumor immunity, and facilitates tumor clearance. We also show that IFNγ-induced T reg fragility is required for response to anti-PD1, suggesting that cancer therapies promoting T reg fragility may be efficacious. Copyright © 2017 Elsevier Inc. All rights reserved.

T-cell expression of AhR inhibits the maintenance of pTreg cells in the gastrointestinal tract in acute GVHD.

PubMed

Dant, Trisha A; Lin, Kaifeng L; Bruce, Danny W; Montgomery, Stephanie A; Kolupaev, Oleg V; Bommiasamy, Hemamalini; Bixby, Lisa M; Woosley, John T; McKinnon, Karen P; Gonzalez, Frank J; Blazar, Bruce R; Vincent, Benjamin G; Coghill, James M; Serody, Jonathan S

2017-07-20

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that affects the function and development of immune cells. Here, we show that recipient mice receiving AhR -/- T cells have improved survival and decreased acute graft-versus-host disease (aGVHD) in 2 different murine allogeneic bone marrow transplant (BMT) models. We also show that CD4 + T cells lacking AhR demonstrate reduced accumulation in secondary lymphoid tissue because of low levels of proliferation 4 days after BMT. Additionally, we found a significant increase in the quantity of peripherally induced regulatory donor T (pT reg ) cells in the colon of recipients transplanted with AhR -/- T cells 14 days after transplant. Blockade of AhR using a clinically available AhR antagonist greatly enhanced the in vitro generation of inducible T reg (iT reg ) cells from naïve CD4 + human T cells. We have identified AhR as a novel target on donor T cells that is critical to the pathogenesis of aGVHD.

Registration of N619 to N640 grain sorghum lines with waxy or wild-type endosperm

USDA-ARS?s Scientific Manuscript database

Sorghum [Sorghum bicolor (L.) Moench] lines A N619 to A N636 (Reg. No. GS-XXX, PI 670134 to Reg. No. GS-XXX, PI 670151); B N619 to B N636 (Reg. No. GS-XXX, PI 671777 to Reg. No. GS-XXX, PI 671794); and R N637 to R N640 (Reg. No. GS-XXX, PI 670152 to Reg. No. GS-XXX, PI 670155) comprise nine pairs of...

Pregnancy-associated diseases are characterized by the composition of the systemic regulatory T cell (Treg) pool with distinct subsets of Tregs.

PubMed

Steinborn, A; Schmitt, E; Kisielewicz, A; Rechenberg, S; Seissler, N; Mahnke, K; Schaier, M; Zeier, M; Sohn, C

2012-01-01

Dysregulations concerning the composition and function of regulatory T cells (T(regs)) are assumed to be involved in the pathophysiology of complicated pregnancies. We used six-colour flow cytometric analysis to demonstrate that the total CD4(+) CD127(low+/-) CD25(+) forkhead box protein 3 (FoxP3)(+) T(reg) cell pool contains four distinct T(reg) subsets: DR(high+) CD45RA(-), DR(low+) CD45RA(-), DR(-) CD45RA(-) T(regs) and naive DR(-) CD45RA(+) T(regs). During the normal course of pregnancy, the most prominent changes in the composition of the total T(reg) cell pool were observed between the 10th and 20th weeks of gestation, with a clear decrease in the percentage of DR(high+) CD45RA(-) and DR(low+) CD45RA(-) T(regs) and a clear increase in the percentage of naive DR(-) CD45RA(+) T(regs). After that time, the composition of the total T(reg) cell pool did not change significantly. Its suppressive activity remained stable during normally progressing pregnancy, but decreased significantly at term. Compared to healthy pregnancies the composition of the total T(reg) cell pool changed in the way that its percentage of naive DR(-) CD45RA(+) T(regs) was reduced significantly in the presence of pre-eclampsia and in the presence of preterm labour necessitating preterm delivery (PL). Interestingly, its percentage of DR(high+) CD45RA(-) and DR(low+) CD45RA(-) T(regs) was increased significantly in pregnancies affected by pre-eclampsia, while PL was accompanied by a significantly increased percentage of DR(-) CD45RA(-) and DR(low+) CD45RA(-) T(regs). The suppressive activity of the total T(reg) cell pool was diminished in both patient collectives. Hence, our findings propose that pre-eclampsia and PL are characterized by homeostatic changes in the composition of the total T(reg) pool with distinct T(reg) subsets that were accompanied by a significant decrease of its suppressive activity. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival.

PubMed

Curiel, Tyler J; Coukos, George; Zou, Linhua; Alvarez, Xavier; Cheng, Pui; Mottram, Peter; Evdemon-Hogan, Melina; Conejo-Garcia, Jose R; Zhang, Lin; Burow, Matthew; Zhu, Yun; Wei, Shuang; Kryczek, Ilona; Daniel, Ben; Gordon, Alan; Myers, Leann; Lackner, Andrew; Disis, Mary L; Knutson, Keith L; Chen, Lieping; Zou, Weiping

2004-09-01

Regulatory T (T(reg)) cells mediate homeostatic peripheral tolerance by suppressing autoreactive T cells. Failure of host antitumor immunity may be caused by exaggerated suppression of tumor-associated antigen-reactive lymphocytes mediated by T(reg) cells; however, definitive evidence that T(reg) cells have an immunopathological role in human cancer is lacking. Here we show, in detailed studies of CD4(+)CD25(+)FOXP3(+) T(reg) cells in 104 individuals affected with ovarian carcinoma, that human tumor T(reg) cells suppress tumor-specific T cell immunity and contribute to growth of human tumors in vivo. We also show that tumor T(reg) cells are associated with a high death hazard and reduced survival. Human T(reg) cells preferentially move to and accumulate in tumors and ascites, but rarely enter draining lymph nodes in later cancer stages. Tumor cells and microenvironmental macrophages produce the chemokine CCL22, which mediates trafficking of T(reg) cells to the tumor. This specific recruitment of T(reg) cells represents a mechanism by which tumors may foster immune privilege. Thus, blocking T(reg) cell migration or function may help to defeat human cancer.

Assessment of two versions of regional climate model in simulating the Indian Summer Monsoon over South Asia CORDEX domain

NASA Astrophysics Data System (ADS)

Pattnayak, K. C.; Panda, S. K.; Saraswat, Vaishali; Dash, S. K.

2018-04-01

This study assess the performance of two versions of Regional Climate Model (RegCM) in simulating the Indian summer monsoon over South Asia for the period 1998 to 2003 with an aim of conducting future climate change simulations. Two sets of experiments were carried out with two different versions of RegCM (viz. RegCM4.2 and RegCM4.3) with the lateral boundary forcings provided from European Center for Medium Range Weather Forecast Reanalysis (ERA-interim) at 50 km horizontal resolution. The major updates in RegCM4.3 in comparison to the older version RegCM4.2 are the inclusion of measured solar irradiance in place of hardcoded solar constant and additional layers in the stratosphere. The analysis shows that the Indian summer monsoon rainfall, moisture flux and surface net downward shortwave flux are better represented in RegCM4.3 than that in the RegCM4.2 simulations. Excessive moisture flux in the RegCM4.2 simulation over the northern Arabian Sea and Peninsular India resulted in an overestimation of rainfall over the Western Ghats, Peninsular region as a result of which the all India rainfall has been overestimated. RegCM4.3 has performed well over India as a whole as well as its four rainfall homogenous zones in reproducing the mean monsoon rainfall and inter-annual variation of rainfall. Further, the monsoon onset, low-level Somali Jet and the upper level tropical easterly jet are better represented in the RegCM4.3 than RegCM4.2. Thus, RegCM4.3 has performed better in simulating the mean summer monsoon circulation over the South Asia. Hence, RegCM4.3 may be used to study the future climate change over the South Asia.

Intestinal lamina propria dendritic cells maintain T cell homeostasis but do not affect commensalism

PubMed Central

Welty, Nathan E.; Staley, Christopher; Ghilardi, Nico; Sadowsky, Michael J.; Igyártó, Botond Z.

2013-01-01

Dendritic cells (DCs) in the intestinal lamina propria (LP) are composed of two CD103+ subsets that differ in CD11b expression. We report here that Langerin is expressed by human LP DCs and that transgenic human langerin drives expression in CD103+CD11b+ LP DCs in mice. This subset was ablated in huLangerin-DTA mice, resulting in reduced LP Th17 cells without affecting Th1 or T reg cells. Notably, cognate DC–T cell interactions were not required for Th17 development, as this response was intact in huLangerin-Cre I-Aβfl/fl mice. In contrast, responses to intestinal infection or flagellin administration were unaffected by the absence of CD103+CD11b+ DCs. huLangerin-DTA x BatF3−/− mice lacked both CD103+ LP DC subsets, resulting in defective gut homing and fewer LP T reg cells. Despite these defects in LP DCs and resident T cells, we did not observe alterations of intestinal microbial communities. Thus, CD103+ LP DC subsets control T cell homeostasis through both nonredundant and overlapping mechanisms. PMID:24019552

How do you make me feel better? Social cognitive emotion regulation and the default mode network.

PubMed

Xie, Xiyao; Mulej Bratec, Satja; Schmid, Gabriele; Meng, Chun; Doll, Anselm; Wohlschläger, Afra; Finke, Kathrin; Förstl, Hans; Zimmer, Claus; Pekrun, Reinhard; Schilbach, Leonhard; Riedl, Valentin; Sorg, Christian

2016-07-01

Socially-induced cognitive emotion regulation (Social-Reg) is crucial for emotional well-being and social functioning; however, its brain mechanisms remain poorly understood. Given that both social cognition and cognitive emotion regulation engage key regions of the default-mode network (DMN), we hypothesized that Social-Reg would rely on the DMN, and that its effectiveness would be associated with social functioning. During functional MRI, negative emotions were elicited by pictures, and - via short instructions - a psychotherapist either down-regulated participants' emotions by employing reappraisal (Reg), or asked them to simply look at the pictures (Look). Adult Attachment Scale was used to measure social functioning. Contrasting Reg versus Look, aversive emotions were successfully reduced during Social-Reg, with increased activations in the prefrontal and parietal cortices, precuneus and the left temporo-parietal junction. These activations covered key nodes of the DMN and were associated with Social-Reg success. Furthermore, participants' attachment security was positively correlated with both Social-Reg success and orbitofrontal cortex involvement during Social-Reg. In addition, specificity of the neural correlates of Social-Reg was confirmed by comparisons with participants' DMN activity at rest and their brain activations during a typical emotional self-regulation task based on the same experimental paradigm without a psychotherapist. Our results provide first evidence for the specific involvement of the DMN in Social-Reg, and the association of Social-Reg with individual differences in attachment security. The findings suggest that DMN dysfunction, found in many neuropsychiatric disorders, may impair the ability to benefit from Social-Reg. Copyright © 2016 Elsevier Inc. All rights reserved.

75 FR 48965 - Ameren Services Company; Notice of Petition for Declaratory Order

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-12

..., Promoting Transmission Investment Through Pricing Reform, Order No. 679, 2006-2007 FERC Stats. & Regs., Regs. Preambles ] 31,222, order on reh'g, Order No. 679-A, 2006-2007 FERC Stats. & Regs., Regs. Preambles ] 31,236...

In situ cytokine expression in pulmonary granulomas of cattle experimentally infected by aerosolized Mycobacterium bovis

USDA-ARS?s Scientific Manuscript database

Mycobacterium bovis is the cause of tuberculosis in most animal species, including cattle and is a serious zoonotic pathogen. In humans, M. bovis infection can result in disease clinically indistinguishable from that caused by Mycobacterium tuberculosis, the cause of most tuberculosis in humans. Reg...

Registration of five upland cotton mutant germplasm lines with superior fiber length, strength, and uniformity

USDA-ARS?s Scientific Manuscript database

Mutant germplasm lines MD 15-Mut 13 (Reg. No. GP-1025, PI 681706), MD 15-Mut 31 (Reg. No. GP-1026, PI 681707), MD 15-Mut 61 (Reg. No. GP-1027, PI 681708), MD 15-Mut 89 (Reg. No. GP-1028, PI 681709), and MD 15-Mut 138 (Reg. No. GP-1029, PI 681710) are unique genotypes of upland cotton (Gossypium hirs...

Coupling of Community Land Model with RegCM4 for Indian Summer Monsoon Simulation

NASA Astrophysics Data System (ADS)

Maurya, R. K. S.; Sinha, P.; Mohanty, M. R.; Mohanty, U. C.

2017-11-01

Three land surface schemes available in the regional climate model RegCM4 have been examined to understand the coupling between land and atmosphere for simulation of the Indian summer monsoon rainfall. The RegCM4 is coupled with biosphere-atmosphere transfer scheme (BATS) and the National Center for Atmospheric Research (NCAR) Community Land Model versions 3.5, and 4.5 (CLM3.5 and CLM4.5, respectively) and model performance is evaluated for recent drought (2009) and normal (2011) monsoon years. The CLM4.5 has a more distinct category of surface and it is capable of representing better the land surface characteristics. National Centers for Environmental Prediction (NCEP) and Department of Energy (DOE) reanalysis version 2 (NNRP2) datasets are considered as driving force to conduct the experiments for the Indian monsoon region (30°E-120°E; 30°S-50°N). The NNRP2 and India Meteorological Department (IMD) gridded precipitation data are used for verification analysis. The results indicate that RegCM4 simulations with CLM4.5 (RegCM4-CLM4.5) and CLM3.5 (RegCM4-CLM3.5) surface temperature (at 2 ms) have very low warm biases ( 1 °C), while with BATS (RegCM4-BATS) has a cold bias of about 1-3 °C in peninsular India and some parts of central India. Warm bias in the RegCM4-BATS is observed over the Indo-Gangetic plain and northwest India and the bias is more for the deficit year as compared to the normal year. However, the warm (cold) bias is less in RegCM4-CLM4.5 than other schemes for both the deficit and normal years. The model-simulated maximum (minimum) surface temperature and sensible heat flux at the surface are positively (negatively) biased in all the schemes; however, the bias is higher in RegCM4-BATS and lower in RegCM4-CLM4.5 over India. All the land surface schemes overestimated the precipitation in peninsular India and underestimated in central parts of India for both the years; however, the biases are less in RegCM4-CLM4.5 and more in RegCM4-CLM3.5 and RegCM4-BATS. During both the years, BATS scheme in RegCM4 failed to represent low precipitation over the leeward than windward side of the Western Ghats, while CLM schemes (both versions) in the RegCM4 are able to depict this feature. In the topographic regions, such as the Western Ghats, northeast India and state of Jammu and Kashmir, RegCM4-BATS overestimates the rainfall amount with higher bias. Statistical analysis using anomaly correlation coefficient, root mean square error, equitable threat score, and critical success index confirms that RegCM4-CLM performs better than RegCM4-BATS in the simulation of the Indian summer monsoon.

Essiac? and Flor-Essence? herbal tonics stimulate the in vitro growth of human breast cancer cells

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

Kulp, K S; Montgomery, J L; McLimans, B

People diagnosed with cancer often self-administer complementary and alternative medicines (CAMs) to supplement their conventional treatments, improve health, or prevent recurrence. Flor-Essence{reg_sign} and Essiac{reg_sign} Herbal Tonics are commercially available complex mixtures of herbal extracts sold as dietary supplements and used by cancer patients based on anecdotal evidence that they can treat or prevent disease. In this study, we evaluated Flor-Essence{reg_sign} and Essiac{reg_sign} for their effects on the growth of human tumor cells in culture. The effect of Flor-Essence{reg_sign} and Essiac{reg_sign} herbal tonics on cell proliferation was tested in MCF-7, MDA-MB-436, MDA-MB-231, and T47D cancer cells isolated from human breast tumors.more » Estrogen receptor (ER) dependent activation of a luciferase reporter construct was tested in MCF-7 cells. Specific binding to the ER was tested using an ICI 182,780 competition assay. Flor-Essence{reg_sign} and Essiac{reg_sign} herbal tonics at 1%, 2%, 4% and 8% stimulated cell proliferation relative to untreated controls and activated ER dependent luciferase activity in MCF-7 cells. A 10{sup -7} M concentration of ICI 870,780 inhibited the induction of ER dependent luciferase activity by Flor-Essence{reg_sign} and Essiac{reg_sign}, but did not affect cell proliferation. Flor-Essence{reg_sign} and Essiac{reg_sign} Herbal Tonics can stimulate the growth of human breast cancer cells through ER mediated as well as ER independent mechanisms of action. Cancer patients and health care providers can use this information to make informed decisions about the use of these CAMs.« less

76 FR 1153 - Atlantic Grid Operations A LLC, Atlantic Grid Operations B LLC, Atlantic Grid Operations C LLC...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-07

...\\ Promoting Transmission Investment through Pricing Reform, Order No. 679, 2006-2007 FERC Stats. & Regs., Regs. Preambles ] 31,222, order on reh'g, Order No. 679-A, 2006-2007 FERC Stats. & Regs., Regs. Preambles ] 31,236...

CatReg Software for Categorical Regression Analysis (May 2016)

EPA Science Inventory

CatReg 3.0 is a Microsoft Windows enhanced version of the Agency’s categorical regression analysis (CatReg) program. CatReg complements EPA’s existing Benchmark Dose Software (BMDS) by greatly enhancing a risk assessor’s ability to determine whether data from separate toxicologic...

Springing into Action: Reg2 Negatively Regulates Snf1 Protein Kinase and Facilitates Recovery from Prolonged Glucose Starvation in Saccharomyces cerevisiae.

PubMed

Maziarz, Marcin; Shevade, Aishwarya; Barrett, LaKisha; Kuchin, Sergei

2016-07-01

Glucose is the preferred carbon source for the yeast Saccharomyces cerevisiae Glucose limitation activates Snf1 protein kinase, a key regulator of energy homeostasis that promotes utilization of alternative carbon sources and enforces energy conservation. Snf1 activation requires phosphorylation of its T-loop threonine (Thr210) by upstream kinases. When glucose is abundant, Snf1 is inhibited by Thr210 dephosphorylation. This involves the function of the type 1 protein phosphatase Glc7, which is targeted to Snf1 by a regulatory subunit, Reg1. The reg1 mutation causes increased Snf1 activity and mimics various aspects of glucose limitation, including slower growth. Reg2 is another Glc7 regulatory subunit encoded by a paralogous gene, REG2 Previous evidence indicated that the reg2 mutation exacerbates the Snf1-dependent slow-growth phenotype caused by reg1, suggesting a link between Reg2 and Snf1. Here, we explore this link in more detail and present evidence that Reg2 contributes to Snf1 Thr210 dephosphorylation. Consistent with this role, Reg2 interacts with wild-type Snf1 but not with nonphosphorylatable Snf1-T210A. Reg2 accumulation increases in a Snf1-dependent manner during prolonged glucose deprivation, and glucose-starved cells lacking Reg2 exhibit delayed Snf1 Thr210 dephosphorylation and slower growth recovery upon glucose replenishment. Accordingly, cells lacking Reg2 are outcompeted by wild-type cells in the course of several glucose starvation/replenishment cycles. Collectively, our results support a model in which Reg2-Glc7 contributes to the negative control of Snf1 in response to glucose refeeding after prolonged starvation. The competitive growth advantage provided by Reg2 underscores the evolutionary significance of this paralog for S. cerevisiae The ability of microorganisms to respond to stress is essential for their survival. However, rapid recovery from stress could be equally crucial in competitive environments. Therefore, a wise stress response program should prepare cells for quick recovery upon reexposure to favorable conditions. Glucose is the preferred carbon source for the yeast S. cerevisiae Glucose depletion activates the stress response protein kinase Snf1, which functions to limit energy-consuming processes, such as growth. We show that prolonged glucose deprivation also leads to Snf1-dependent accumulation of Reg2 and that this protein helps to inhibit Snf1 and to accelerate growth recovery upon glucose replenishment. Cells lacking Reg2 are readily outcompeted by wild-type cells during glucose depletion/replenishment cycles. Thus, while prolonged glucose deprivation might seem to put yeast cells "on their knees," concomitant accumulation of Reg2 helps configure the cells into a "sprinter's crouch start position" to spring into action once glucose becomes available. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Springing into Action: Reg2 Negatively Regulates Snf1 Protein Kinase and Facilitates Recovery from Prolonged Glucose Starvation in Saccharomyces cerevisiae

PubMed Central

Maziarz, Marcin; Shevade, Aishwarya; Barrett, LaKisha

2016-01-01

ABSTRACT Glucose is the preferred carbon source for the yeast Saccharomyces cerevisiae. Glucose limitation activates Snf1 protein kinase, a key regulator of energy homeostasis that promotes utilization of alternative carbon sources and enforces energy conservation. Snf1 activation requires phosphorylation of its T-loop threonine (Thr210) by upstream kinases. When glucose is abundant, Snf1 is inhibited by Thr210 dephosphorylation. This involves the function of the type 1 protein phosphatase Glc7, which is targeted to Snf1 by a regulatory subunit, Reg1. The reg1 mutation causes increased Snf1 activity and mimics various aspects of glucose limitation, including slower growth. Reg2 is another Glc7 regulatory subunit encoded by a paralogous gene, REG2. Previous evidence indicated that the reg2 mutation exacerbates the Snf1-dependent slow-growth phenotype caused by reg1, suggesting a link between Reg2 and Snf1. Here, we explore this link in more detail and present evidence that Reg2 contributes to Snf1 Thr210 dephosphorylation. Consistent with this role, Reg2 interacts with wild-type Snf1 but not with nonphosphorylatable Snf1-T210A. Reg2 accumulation increases in a Snf1-dependent manner during prolonged glucose deprivation, and glucose-starved cells lacking Reg2 exhibit delayed Snf1 Thr210 dephosphorylation and slower growth recovery upon glucose replenishment. Accordingly, cells lacking Reg2 are outcompeted by wild-type cells in the course of several glucose starvation/replenishment cycles. Collectively, our results support a model in which Reg2-Glc7 contributes to the negative control of Snf1 in response to glucose refeeding after prolonged starvation. The competitive growth advantage provided by Reg2 underscores the evolutionary significance of this paralog for S. cerevisiae. IMPORTANCE The ability of microorganisms to respond to stress is essential for their survival. However, rapid recovery from stress could be equally crucial in competitive environments. Therefore, a wise stress response program should prepare cells for quick recovery upon reexposure to favorable conditions. Glucose is the preferred carbon source for the yeast S. cerevisiae. Glucose depletion activates the stress response protein kinase Snf1, which functions to limit energy-consuming processes, such as growth. We show that prolonged glucose deprivation also leads to Snf1-dependent accumulation of Reg2 and that this protein helps to inhibit Snf1 and to accelerate growth recovery upon glucose replenishment. Cells lacking Reg2 are readily outcompeted by wild-type cells during glucose depletion/replenishment cycles. Thus, while prolonged glucose deprivation might seem to put yeast cells “on their knees,” concomitant accumulation of Reg2 helps configure the cells into a “sprinter's crouch start position” to spring into action once glucose becomes available. PMID:27107116

Cell-penetrable mouse forkhead box protein 3 alleviates experimental arthritis in mice by up-regulating regulatory T cells.

PubMed

Liu, Xia; Ji, Baoju; Sun, Mengyi; Wu, Weijiang; Huang, Lili; Sun, Aihua; Zong, Yangyong; Xia, Sheng; Shi, Liyun; Qian, Hui; Xu, Wenrong; Shao, Qixiang

2015-07-01

Regulatory T cells (T(regs)) have potential applications in clinical disease therapy, such as autoimmune diseases and transplant rejection. However, their numbers are limited. Forkhead box protein 3 (FoxP3) is a key transcription factor that controls T(reg) development and function. Here, we generated a cell-permeable fusion protein, protein transduction domain (PTD)-conjugated mouse FoxP3 protein (PTD-mFoxP3), and evaluated whether PTD-mFoxp3 can alleviate rheumatoid arthritis (RA) in the collagen-induced arthritis (CIA) mouse model. As expected, PTD-mFoxP3 was transduced into cells effectively, and inhibited T cell activation and attenuated the cell proliferation. It decreased interleukin (IL) 2 and interferon (IFN)-γ expression, and increased IL-10 expression in activated CD4(+)CD25(-) T cells. PTD-mFoxP3-transduced CD4(+)CD25(-) T cells attenuated proliferation of activated CD4(+)CD25(-) T cells. In addition, PTD-mFoxP3 blocked the Th17 differentiation programme in vitro and down-regulated IL-17 production from T cells by modulating induction and levels of retinoid-related orphan receptor gamma t (RORγt). Intra-articular delivery of PTD-mFoxP3 delayed disease incidence remarkably and alleviated autoimmune symptoms of CIA mice. Moreover, protective effects of PTD-mFoxP3 were associated with regulating the balance of T helper type 17 (Th17) and T(regs). These results suggest that PTD-mFoxP3 may be a candidate for RA therapy. © 2015 British Society for Immunology.

21 CFR 186.1551 - Hydrogenated fish oil.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Hydrogenated fish oil. 186.1551 Section 186.1551... as GRAS § 186.1551 Hydrogenated fish oil. (a) Hydrogenated fish oil (CAS Reg. No. 91078-95-4) is a class of oils produced by partial hydrogenation of oils expressed from fish, primarily menhaden, and...

Resistin-like molecule β regulates innate colonic function: Barrier integrity and inflammation susceptibility

PubMed Central

Hogan, Simon P.; Seidu, Luqman; Blanchard, Carine; Groschwitz, Katherine; Mishra, Anil; Karow, Margaret L.; Ahrens, Richard; Artis, David; Murphy, Andrew J.; Valenzuela, David M.; Yancopoulos, George D.; Rothenberg, Marc E.

2007-01-01

Background: Resistin-like molecule (RELM) β is a cysteine-rich cytokine expressed in the gastrointestinal tract and implicated in insulin resistance and gastrointestinal nematode immunity; however, its function primarily remains an enigma. Objective: We sought to elucidate the function of RELM-β in the gastrointestinal tract. Methods: We generated RELM-β gene-targeted mice and examined colonic epithelial barrier function, gene expression profiles, and susceptibility to acute colonic inflammation. Results: We show that RELM-β is constitutively expressed in the colon by goblet cells and enterocytes and has a role in homeostasis, as assessed by alterations in colon mRNA transcripts and epithelial barrier function in the absence of RELM-β. Using acute colonic inflammatory models, we demonstrate that RELM-β has a central role in the regulation of susceptibility to colonic inflammation. Mechanistic studies identify that RELM-β regulates expression of type III regenerating gene (REG) (REG3β and γ), molecules known to influence nuclear factor κB signaling. Conclusions: These data define a critical role for RELM-β in the maintenance of colonic barrier function and gastrointestinal innate immunity. Clinical implications: These findings identify RELM-β as an important molecule in homeostatic gastrointestinal function and colonic inflammation, and as such, these results have implications for a variety of human inflammatory gastrointestinal conditions, including allergic gastroenteropathies. PMID:16815164

Assessment of the simulated climate in two versions of the RegT-Band

NASA Astrophysics Data System (ADS)

da Rocha, Rosmeri; Reboita, Michelle; Llopart, Marta

2017-04-01

This study evaluates two simulations carried out with the tropical band version of the Regional Climate Model (RegT-Band). The purpose was to compare the performance of the RegCM 4.4.5 and 4.6 versions (RegT4.4.5 and RegT4.6). The domain used in the simulations extends from 45° S to 45° N and covers all tropical longitudes, with grid spacing of 39 km, 18 sigma-pressure vertical levels. The initial and boundary conditions for the simulations were provided by ERA-Interim reanalysis and the analyzed period is from January 2005 to December 2008. Regarding the physical parameterizations schemes were used the Emanuel scheme to solve cumulus convection and Community Land Model version 4.5 (CLM4.5) to surface-atmosphere interactions. Seasonal simulated precipitation was compared with Global Precipitation Climatology Project (GPCP) while 2 meters air temperature with ERA-Interim reanalysis. The main results of this study are that RegT4.6 reduces the wet bias over the oceans and the cold bias over the continents compared with RegT4.4.5. In austral summer, RegT4.6 improves the simulation reducing the precipitation amounts mainly over Indian Ocean, Indonesia and eastern northeastern Brazil. However, both versions underestimate the precipitation over the South America Convergence Zone (SACZ). During the austral winter, RegT4.6 simulates the precipitation similar to GPCP over India and it reduces the cold bias over this country compared with RegT4.4.5. However, over the South of Africa, Australia and central-southeast South America, RegT4.6 simulates a strong warm bias.

Initial Gut Microbial Composition as a Key Factor Driving Host Response to Antibiotic Treatment, as Exemplified by the Presence or Absence of Commensal Escherichia coli

PubMed Central

Ju, Tingting; Shoblak, Yasmeen; Gao, Yanhua; Yang, Kaiyuan; Fouhse, Janelle; Finlay, B. Brett; So, Yee Wing; Stothard, Paul

2017-01-01

ABSTRACT Antibiotics are important for treating bacterial infection; however, efficacies and side effects of antibiotics vary in medicine and experimental models. A few studies have correlated microbiota composition variations with health outcomes in response to antibiotics; however, no study has demonstrated causality. We had noted variation in colonic expression of C-type lectins, regenerating islet-derived protein 3β (Reg3β) and Reg3γ, after metronidazole treatment in a mouse model. To investigate the effects of specific variations in the preexisting microbiome on host response to antibiotics, mice harboring a normal microbiota were allocated to 4 treatments in a 2-by-2 factorial arrangement with or without commensal Escherichia coli and with or without metronidazole in drinking water. E. coli colonized readily without causing a notable shift in the microbiota or host response. Metronidazole administration reduced microbiota biodiversity, indicated by decreased Chao1 and Shannon index values, and altered microbiota composition. However, the presence of E. coli strongly affected metronidazole-induced microbiota shifts. Remarkably, this single commensal bacterium in the context of a complex population led to variations in host responses to metronidazole treatment, including increased expression of antimicrobial peptides Reg3β and Reg3γ and intestinal inflammation indicated by tumor necrosis factor alpha levels. Similar results were obtained from 2-week antibiotic exposure and with additional E. coli isolates. The results of this proof-of-concept study indicate that even minor variations in initial commensal microbiota can drive shifts in microbial composition and host response after antibiotic administration. As well as providing an explanation for variability in animal models using antibiotics, the findings encourage the development of personalized medication in antibiotic therapies. IMPORTANCE This work provides an understanding of variability in studies where antibiotics are used to alter the gut microbiota to generate a host response. Furthermore, although providing evidence only for the one antibiotic, the study demonstrated that initial gut microbial composition is a key factor driving host response to antibiotic administration, creating a compelling argument for considering personalized medication based on individual variations in gut microbiota. PMID:28667114

Initial Gut Microbial Composition as a Key Factor Driving Host Response to Antibiotic Treatment, as Exemplified by the Presence or Absence of Commensal Escherichia coli.

PubMed

Ju, Tingting; Shoblak, Yasmeen; Gao, Yanhua; Yang, Kaiyuan; Fouhse, Janelle; Finlay, B Brett; So, Yee Wing; Stothard, Paul; Willing, Benjamin P

2017-09-01

Antibiotics are important for treating bacterial infection; however, efficacies and side effects of antibiotics vary in medicine and experimental models. A few studies have correlated microbiota composition variations with health outcomes in response to antibiotics; however, no study has demonstrated causality. We had noted variation in colonic expression of C-type lectins, regenerating islet-derived protein 3β (Reg3β) and Reg3γ, after metronidazole treatment in a mouse model. To investigate the effects of specific variations in the preexisting microbiome on host response to antibiotics, mice harboring a normal microbiota were allocated to 4 treatments in a 2-by-2 factorial arrangement with or without commensal Escherichia coli and with or without metronidazole in drinking water. E. coli colonized readily without causing a notable shift in the microbiota or host response. Metronidazole administration reduced microbiota biodiversity, indicated by decreased Chao1 and Shannon index values, and altered microbiota composition. However, the presence of E. coli strongly affected metronidazole-induced microbiota shifts. Remarkably, this single commensal bacterium in the context of a complex population led to variations in host responses to metronidazole treatment, including increased expression of antimicrobial peptides Reg3β and Reg3γ and intestinal inflammation indicated by tumor necrosis factor alpha levels. Similar results were obtained from 2-week antibiotic exposure and with additional E. coli isolates. The results of this proof-of-concept study indicate that even minor variations in initial commensal microbiota can drive shifts in microbial composition and host response after antibiotic administration. As well as providing an explanation for variability in animal models using antibiotics, the findings encourage the development of personalized medication in antibiotic therapies. IMPORTANCE This work provides an understanding of variability in studies where antibiotics are used to alter the gut microbiota to generate a host response. Furthermore, although providing evidence only for the one antibiotic, the study demonstrated that initial gut microbial composition is a key factor driving host response to antibiotic administration, creating a compelling argument for considering personalized medication based on individual variations in gut microbiota. Copyright © 2017 American Society for Microbiology.

The induction of autoimmune hepatitis in the human leucocyte antigen-DR4 non-obese diabetic mice autoimmune hepatitis mouse model.

PubMed

Yuksel, M; Xiao, X; Tai, N; Vijay, G M; Gülden, E; Beland, K; Lapierre, P; Alvarez, F; Hu, Z; Colle, I; Ma, Y; Wen, L

2016-11-01

Autoimmune hepatitis (AIH) is a chronic liver disease characterized by progressive inflammation, female preponderance and seropositivity for autoantibodies such as anti-smooth muscle actin and/or anti-nuclear, anti-liver kidney microsomal type 1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1) in more than 80% of cases. AIH is linked strongly to several major histocompatibility complex (MHC) alleles, including human leucocyte antigen (HLA)-DR3, -DR7 and -DR13. HLA-DR4 has the second strongest association with adult AIH, after HLA-DR3. We investigated the role of HLA-DR4 in the development of AIH by immunization of HLA-DR4 (DR4) transgenic non-obese diabetic (NOD) mice with DNA coding for human CYP2D6/FTCD fusion autoantigen. Immunization of DR4 mice leads to sustained mild liver injury, as assessed biochemically by elevated alanine aminotransferase, histologically by interface hepatitis, plasma cell infiltration and mild fibrosis and immunologically by the development of anti-LKM1/anti-LC1 antibodies. In addition, livers from DR4 mice had fewer regulatory T cells (T regs ), which had decreased programmed death (PD)-1 expression. Splenic T regs from these mice also showed impaired inhibitory capacity. Furthermore, DR4 expression enhanced the activation status of CD8 + T cells, macrophages and dendritic cells in naive DR4 mice compared to naive wild-type (WT) NOD mice. Our results demonstrate that HLA-DR4 is a susceptibility factor for the development of AIH. Impaired suppressive function of T regs and reduced PD-1 expression may result in spontaneous activation of key immune cell subsets, such as antigen-presenting cells and CD8 + T effectors, facilitating the induction of AIH and persistent liver damage. © 2016 British Society for Immunology.

Lactobacillus salivarius reverse diabetes-induced intestinal defense impairment in mice through non-defensin protein.

PubMed

Chung, Pei-Hsuan; Wu, Ying-Ying; Chen, Pei-Hsuan; Fung, Chang-Phone; Hsu, Ching-Mei; Chen, Lee-Wei

2016-09-01

Altered intestinal microbiota and subsequent endotoxemia play pathogenic roles in diabetes. We aimed to study the mechanisms of intestinal defense impairment in type 1 diabetes and the effects of Lactobacillus salivarius as well as fructooligosaccharides (FOS) supplementation on diabetes-induced bacterial translocation. Alterations in the enteric microbiome, expression of mucosal antibacterial proteins and bacteria-killing activity of the intestinal mucosa in streptozotocin (STZ)-induced diabetic mice and Ins2(Akita) mice were investigated. The effects of dead L. salivarius (2×10(8)CFU/ml) and FOS (250 mg per day) supplementation for 1 week on endotoxin levels and Klebsiella pneumoniae translocation were also examined. Finally, germ-free mice were cohoused with wild-type or Ins2(Akita) mice for 2 weeks to examine the contribution of microbiota on the antibacterial protein expression. STZ-induced diabetic mice developed intestinal defense impairment as demonstrated by decreased mucosal bacteria-killing activity; reduction of non-defensin family proteins, such as Reg3β, Reg3γ, CRP-ductin and RELMβ, but not the defensin family proteins; and increased bacterial translocation. Intestinal bacteria overgrowth, enteric dysbiosis and increased intestinal bacterial translocation, particularly pathogenic K. pneumoniae in STZ-induced diabetic mice and Ins2(Akita) mice, were noted. Treating diabetic mice with dead L. salivarius or FOS reversed enteric dysbiosis, restored mucosal antibacterial protein and lessened endotoxin levels as well as K. pneumoniae translocation. Moreover, germ-free mice cohoused with wild-type mice demonstrated more intestinal Reg3β and RELMβ expression than those cohoused with Ins2(Akita) mice. These results indicate that hyperglycemia induces enteric dysbiosis, reduction of non-defensin proteins as well as bacteria-killing activity of the intestinal mucosa and intestinal defense impairment. Reversal of enteric dysbiosis with dead L. salivarius or FOS supplementation decreases diabetes-induced K. pneumoniae translocation and endotoxin levels through the induction of non-defensin proteins. Copyright © 2016 Elsevier Inc. All rights reserved.

Registration of four post-flowering drought tolerant grain sorghum lines with early season cold tolerance

USDA-ARS?s Scientific Manuscript database

Four sorghum (Sorghum bicolor L.) germplasm lines— PSLS-SGCTB01 (Reg. No.), PSLS-SGCTR02 (Reg. No.), PSLS-SGCTB03 (Reg. No.) and PSLS-SGCTB04 (Reg. No.) — were developed by the USDA-ARS in Lubbock TX, in 2017. The primary purpose for the release of these lines is to provide an alternative germplasm ...

Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy.

PubMed

Chen, Jiahuan; Ganguly, Anutosh; Mucsi, Ashley D; Meng, Junchen; Yan, Jiacong; Detampel, Pascal; Munro, Fay; Zhang, Zongde; Wu, Mei; Hari, Aswin; Stenner, Melanie D; Zheng, Wencheng; Kubes, Paul; Xia, Tie; Amrein, Matthias W; Qi, Hai; Shi, Yan

2017-02-01

Dendritic cells are targeted by regulatory T (T reg) cells, in a manner that operates as an indirect mode of T cell suppression. In this study, using a combination of single-cell force spectroscopy and structured illumination microscopy, we analyze individual T reg cell-DC interaction events and show that T reg cells exhibit strong intrinsic adhesiveness to DCs. This increased DC adhesion reduces the ability of contacted DCs to engage other antigen-specific cells. We show that this unusually strong LFA-1-dependent adhesiveness of T reg cells is caused in part by their low calpain activities, which normally release integrin-cytoskeleton linkage, and thereby reduce adhesion. Super resolution imaging reveals that such T reg cell adhesion causes sequestration of Fascin-1, an actin-bundling protein essential for immunological synapse formation, and skews Fascin-1-dependent actin polarization in DCs toward the T reg cell adhesion zone. Although it is reversible upon T reg cell disengagement, this sequestration of essential cytoskeletal components causes a lethargic state of DCs, leading to reduced T cell priming. Our results reveal a dynamic cytoskeletal component underlying T reg cell-mediated DC suppression in a contact-dependent manner. © 2017 Chen et al.

Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy

PubMed Central

Mucsi, Ashley D.; Meng, Junchen; Yan, Jiacong; Zhang, Zongde; Wu, Mei; Hari, Aswin; Stenner, Melanie D.; Zheng, Wencheng; Kubes, Paul; Xia, Tie; Amrein, Matthias W.

2017-01-01

Dendritic cells are targeted by regulatory T (T reg) cells, in a manner that operates as an indirect mode of T cell suppression. In this study, using a combination of single-cell force spectroscopy and structured illumination microscopy, we analyze individual T reg cell–DC interaction events and show that T reg cells exhibit strong intrinsic adhesiveness to DCs. This increased DC adhesion reduces the ability of contacted DCs to engage other antigen-specific cells. We show that this unusually strong LFA-1–dependent adhesiveness of T reg cells is caused in part by their low calpain activities, which normally release integrin–cytoskeleton linkage, and thereby reduce adhesion. Super resolution imaging reveals that such T reg cell adhesion causes sequestration of Fascin-1, an actin-bundling protein essential for immunological synapse formation, and skews Fascin-1–dependent actin polarization in DCs toward the T reg cell adhesion zone. Although it is reversible upon T reg cell disengagement, this sequestration of essential cytoskeletal components causes a lethargic state of DCs, leading to reduced T cell priming. Our results reveal a dynamic cytoskeletal component underlying T reg cell–mediated DC suppression in a contact-dependent manner. PMID:28082358

Registration of ‘CP 06-2425’, ‘CP 06-2495’, ‘CP 06-2964’, ‘CP 06-3103’, and ‘CP 07-1313’ Sugarcane for Sand Soils in Florida

USDA-ARS?s Scientific Manuscript database

‘CP 06-2425’ (Reg. No. CV-172; PI 678574), ‘CP 06-2495’ (Reg. No. CV-173; PI 678575), ‘CP 06-2964’ (Reg. No. CV-174; PI 678576), ‘CP 06-3103’ (Reg. No. CV-175; PI 678577), and ‘CP 07-1313’ (Reg. No. CV-176; PI 678578) sugarcane (a complex hybrid of Saccharum spp.) were released in June 2015 to be cu...

Development of Thixomolded{reg_sign} magnesium products

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

Ghosh, D.; Fan, R.; Kang, K.

1995-10-01

Thixomolding{reg_sign} is a racial new process which merges the technologies of die-casting and plastic injection molding for the net shape molding of magnesium based alloys. Properties of Thixomolded{reg_sign} magnesium alloys are discussed and compared with those of traditional die casting. Magnesium alloys are of great interest to automobile manufacturers because of the potential weight savings and corresponding energy savings due to increased fuel economy. For this reason, one of the first target markets for Thixomolded{reg_sign} products is the automotive industry. The use of Thixomolding{reg_sign} in the production of an automobile part is examined.

Toll-Like Receptor Stimulation Induces Nondefensin Protein Expression and Reverses Antibiotic-Induced Gut Defense Impairment

PubMed Central

Wu, Ying-Ying; Hsu, Ching-Mei; Chen, Pei-Hsuan; Fung, Chang-Phone

2014-01-01

Prior antibiotic exposure is associated with increased mortality in Gram-negative bacteria-induced sepsis. However, how antibiotic-mediated changes of commensal bacteria promote the spread of enteric pathogenic bacteria in patients remains unclear. In this study, the effects of systemic antibiotic treatment with or without Toll-like receptor (TLR) stimulation on bacterium-killing activity, antibacterial protein expression in the intestinal mucosa, and bacterial translocation were examined in mice receiving antibiotics with or without oral supplementation of dead Escherichia coli or Staphylococcus aureus. We developed a systemic ampicillin, vancomycin, and metronidazole treatment protocol to simulate the clinical use of antibiotics. Antibiotic treatment decreased the total number of bacteria, including aerobic bacteria belonging to the family Enterobacteriaceae and the genus Enterococcus as well as organisms of the anaerobic genera Lactococcus and Bifidobacterium in the intestinal mucosa and lumen. Antibiotic treatment significantly decreased the bacterium-killing activity of the intestinal mucosa and the expression of non-defensin-family proteins, such as RegIIIβ, RegIIIγ, C-reactive protein-ductin, and RELMβ, but not the defensin-family proteins, and increased Klebsiella pneumoniae translocation. TLR stimulation after antibiotic treatment increased NF-κB DNA binding activity, nondefensin protein expression, and bacterium-killing activity in the intestinal mucosa and decreased K. pneumoniae translocation. Moreover, germfree mice showed a significant decrease in nondefensin proteins as well as intestinal defense against pathogen translocation. Since TLR stimulation induced NF-κB DNA binding activity, TLR4 expression, and mucosal bacterium-killing activity in germfree mice, we conclude that the commensal microflora is critical in maintaining intestinal nondefensin protein expression and the intestinal barrier. In turn, we suggest that TLR stimulation induces nondefensin protein expression and reverses antibiotic-induced gut defense impairment. PMID:24595141

Toll-like receptor stimulation induces nondefensin protein expression and reverses antibiotic-induced gut defense impairment.

PubMed

Wu, Ying-Ying; Hsu, Ching-Mei; Chen, Pei-Hsuan; Fung, Chang-Phone; Chen, Lee-Wei

2014-05-01

Prior antibiotic exposure is associated with increased mortality in Gram-negative bacteria-induced sepsis. However, how antibiotic-mediated changes of commensal bacteria promote the spread of enteric pathogenic bacteria in patients remains unclear. In this study, the effects of systemic antibiotic treatment with or without Toll-like receptor (TLR) stimulation on bacterium-killing activity, antibacterial protein expression in the intestinal mucosa, and bacterial translocation were examined in mice receiving antibiotics with or without oral supplementation of dead Escherichia coli or Staphylococcus aureus. We developed a systemic ampicillin, vancomycin, and metronidazole treatment protocol to simulate the clinical use of antibiotics. Antibiotic treatment decreased the total number of bacteria, including aerobic bacteria belonging to the family Enterobacteriaceae and the genus Enterococcus as well as organisms of the anaerobic genera Lactococcus and Bifidobacterium in the intestinal mucosa and lumen. Antibiotic treatment significantly decreased the bacterium-killing activity of the intestinal mucosa and the expression of non-defensin-family proteins, such as RegIIIβ, RegIIIγ, C-reactive protein-ductin, and RELMβ, but not the defensin-family proteins, and increased Klebsiella pneumoniae translocation. TLR stimulation after antibiotic treatment increased NF-κB DNA binding activity, nondefensin protein expression, and bacterium-killing activity in the intestinal mucosa and decreased K. pneumoniae translocation. Moreover, germfree mice showed a significant decrease in nondefensin proteins as well as intestinal defense against pathogen translocation. Since TLR stimulation induced NF-κB DNA binding activity, TLR4 expression, and mucosal bacterium-killing activity in germfree mice, we conclude that the commensal microflora is critical in maintaining intestinal nondefensin protein expression and the intestinal barrier. In turn, we suggest that TLR stimulation induces nondefensin protein expression and reverses antibiotic-induced gut defense impairment.

Differentially expressed drought-responsive genes in Malus sieversii roots may contribute to this species' adaptation to arid environments

USDA-ARS?s Scientific Manuscript database

Understanding naturally evolved adaptation to arid climates may be a key factor in developing crops that can thrive during extreme climate fluctuations. Malus sieversii (Ledeb.) M. Roem. is a wild apple species that has adapted to harsh environments in Kazakhstan, including extreme cold and dry reg...

Deformable image registration for adaptive radiotherapy with guaranteed local rigidity constraints.

PubMed

König, Lars; Derksen, Alexander; Papenberg, Nils; Haas, Benjamin

2016-09-20

Deformable image registration (DIR) is a key component in many radiotherapy applications. However, often resulting deformations are not satisfying, since varying deformation properties of different anatomical regions are not considered. To improve the plausibility of DIR in adaptive radiotherapy in the male pelvic area, this work integrates a local rigidity deformation model into a DIR algorithm. A DIR framework is extended by constraints, enforcing locally rigid deformation behavior for arbitrary delineated structures. The approach restricts those structures to rigid deformations, while surrounding tissue is still allowed to deform elastically. The algorithm is tested on ten CT/CBCT male pelvis datasets with active rigidity constraints on bones and prostate and compared to the Varian SmartAdapt deformable registration (VSA) on delineations of bladder, prostate and bones. The approach with no rigid structures (REG0) obtains an average dice similarity coefficient (DSC) of 0.87 ± 0.06 and a Hausdorff-Distance (HD) of 8.74 ± 5.95 mm. The new approach with rigid bones (REG1) yields a DSC of 0.87 ± 0.07, HD 8.91 ± 5.89 mm. Rigid deformation of bones and prostate (REG2) obtains 0.87 ± 0.06, HD 8.73 ± 6.01 mm, while VSA yields a DSC of 0.86 ± 0.07, HD 10.22 ± 6.62 mm. No deformation grid foldings are observed for REG0 and REG1 in 7 of 10 cases; for REG2 in 8 of 10 cases, with no grid foldings in prostate, an average of 0.08 % in bladder (REG2: no foldings) and 0.01 % inside the body contour. VSA exhibits grid foldings in each case, with an average percentage of 1.81 % for prostate, 1.74 % for bladder and 0.12 % for the body contour. While REG1 and REG2 keep bones rigid, elastic bone deformations are observed with REG0 and VSA. An average runtime of 26.2 s was achieved with REG1; 31.1 s with REG2, compared to 10.5 s with REG0 and 10.7 s with VMS. With accuracy in the range of VSA, the new approach with constraints delivers physically more plausible deformations in the pelvic area with guaranteed rigidity of arbitrary structures. Although the algorithm uses an advanced deformation model, clinically feasible runtimes are achieved.

40 CFR 52.170 - Identification of plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Chapter 14—CAIR NO X Ozone Season Trading Program General Provisions Reg. 19.1401 Adoption of Regulations 07/15/07 09/26/07 (72 FR 54556) Reg. 19.1402 State Trading Budget 07/15/07 09/26/07 (72 FR 54556) Reg... Offsets 07/03/06 04/12/07 (72 FR 18394) Reg. 31.305 Zones Targeted for Economic Development 07/03/06 04/12...

Use of Regional Climate Model Output for Hydrologic Simulations

NASA Astrophysics Data System (ADS)

Hay, L. E.; Clark, M. P.; Wilby, R. L.; Gutowski, W. J.; Leavesley, G. H.; Pan, Z.; Arritt, R. W.; Takle, E. S.

2001-12-01

Daily precipitation and maximum and minimum temperature time series from a Regional Climate Model (RegCM2) were used as input to a distributed hydrologic model for a rainfall-dominated basin (Alapaha River at Statenville, Georgia) and three snowmelt-dominated basins (Animas River at Durango, Colorado; East Fork of the Carson River near Gardnerville, Nevada; and Cle Elum River near Roslyn, Washington). For comparison purposes, spatially averaged daily data sets of precipitation and maximum and minimum temperature were developed from measured data. These datasets included precipitation and temperature data for all stations that are located within the area of the RegCM2 model output used for each basin, but excluded station data used to calibrate the hydrologic model. Both the RegCM2 output and station data capture the gross aspects of the seasonal cycles of precipitation and temperature. However, in all four basins, the RegCM2- and station-based simulations of runoff show little skill on a daily basis (Nash-Sutcliffe (NS) values ranging from 0.05-0.37 for RegCM2 and -0.08-0.65 for station). When the precipitation and temperature biases are corrected in the RegCM2 output and station data sets (Bias-RegCM2 and Bias-station, respectively) the accuracy of the daily runoff simulations improve dramatically for the snowmelt-dominated basins. In the rainfall-dominated basin, runoff simulations based on the Bias-RegCM2 output show no skill (NS value of 0.09) whereas Bias-All simulated runoff improves (NS value improved from -0.08 to 0.72). These results indicate that the resolution of the RegCM2 output is appropriate for basin-scale modeling, but RegCM2 model output does not contain the day-to-day variability needed for basin-scale modeling in rainfall-dominated basins. Future work is warranted to identify the causes for systematic biases in RegCM2 simulations, develop methods to remove the biases, and improve RegCM2 simulations of daily variability in local climate.

Hes1 promotes the IL-22-mediated antimicrobial response by enhancing STAT3-dependent transcription in human intestinal epithelial cells

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

Murano, Tatsuro; Okamoto, Ryuichi, E-mail: rokamoto.gast@tmd.ac.jp; Department of Advanced GI Therapeutics, Graduate School, Tokyo Medical and Dental University, Tokyo

Highlights: •Hes1 enhances IL-22-STAT3 signaling in human intestinal epithelial cells. •Hes1 enhances REG family gene induction by IL-22-STAT3 signaling. •Protein level of Hes1 restricts the response to IL-22. •Present regulation of a cytokine signal represents a new mode of Hes1 function. -- Abstract: Notch signaling plays an essential role in the proliferation and differentiation of intestinal epithelial cells (IECs). We have previously shown that Notch signaling is up-regulated in the inflamed mucosa of ulcerative colitis (UC) and thereby plays an indispensable role in tissue regeneration. Here we show that in addition to Notch signaling, STAT3 signaling is highly activated inmore » the inflamed mucosa of UC. Forced expression of the Notch target gene Hes1 dramatically enhanced the IL-22-mediated STAT3-dependent transcription in human IECs. This enhancement of STAT3-dependent transcription was achieved by the extended phosphorylation of STAT3 by Hes1. Microarray analysis revealed that Hes1-mediated enhancement of IL-22-STAT3 signaling significantly increased the induction of genes encoding antimicrobial peptides, such as REG1A, REG3A and REG3G, in human IECs. Conversely, the reduction of Hes1 protein levels with a γ-secretase inhibitor significantly down-regulated the induction of those genes in IECs, resulting in a markedly poor response to IL-22. Our present findings identify a new role for the molecular function of Hes1 in which the protein can interact with cytokine signals and regulate the immune response of IECs.« less

21 CFR 177.1632 - Poly (phenyl-enetereph-thala-mide) resins.

Code of Federal Regulations, 2010 CFR

2010-04-01

...). Poly(oxyethylene) sorbitol monolaurate tetraoleate (CAS Reg. No. 71243-28-2). Poly(oxyethylene) sorbitol hexaoleate (CAS Reg. No. 57171-56-9). 4,4′-Butylidenebis (6-tert-butyl-m-cresol) (CAS Reg. No. 85...

Use of regional climate model output for hydrologic simulations

USGS Publications Warehouse

Hay, L.E.; Clark, M.P.; Wilby, R.L.; Gutowski, W.J.; Leavesley, G.H.; Pan, Z.; Arritt, R.W.; Takle, E.S.

2002-01-01

Daily precipitation and maximum and minimum temperature time series from a regional climate model (RegCM2) configured using the continental United States as a domain and run on a 52-km (approximately) spatial resolution were used as input to a distributed hydrologic model for one rainfall-dominated basin (Alapaha River at Statenville, Georgia) and three snowmelt-dominated basins (Animas River at Durango. Colorado; east fork of the Carson River near Gardnerville, Nevada: and Cle Elum River near Roslyn, Washington). For comparison purposes, spatially averaged daily datasets of precipitation and maximum and minimum temperature were developed from measured data for each basin. These datasets included precipitation and temperature data for all stations (hereafter, All-Sta) located within the area of the RegCM2 output used for each basin, but excluded station data used to calibrate the hydrologic model. Both the RegCM2 output and All-Sta data capture the gross aspects of the seasonal cycles of precipitation and temperature. However, in all four basins, the RegCM2- and All-Sta-based simulations of runoff show little skill on a daily basis [Nash-Sutcliffe (NS) values range from 0.05 to 0.37 for RegCM2 and -0.08 to 0.65 for All-Sta]. When the precipitation and temperature biases are corrected in the RegCM2 output and All-Sta data (Bias-RegCM2 and Bias-All, respectively) the accuracy of the daily runoff simulations improve dramatically for the snowmelt-dominated basins (NS values range from 0.41 to 0.66 for RegCM2 and 0.60 to 0.76 for All-Sta). In the rainfall-dominated basin, runoff simulations based on the Bias-RegCM2 output show no skill (NS value of 0.09) whereas Bias-All simulated runoff improves (NS value improved from - 0.08 to 0.72). These results indicate that measured data at the coarse resolution of the RegCM2 output can be made appropriate for basin-scale modeling through bias correction (essentially a magnitude correction). However, RegCM2 output, even when bias corrected, does not contain the day-to-day variability present in the All-Sta dataset that is necessary for basin-scale modeling. Future work is warranted to identify the causes for systematic biases in RegCM2 simulations, develop methods to remove the biases, and improve RegCM2 simulations of daily variability in local climate.

Analysis of cytokine mRNA expression using a novel chromogenic in situ hybridization method in pulmonary granulomas of cattle experimentally infected by aerosolized Mycobacterium bovis

USDA-ARS?s Scientific Manuscript database

Mycobacterium bovis is the cause of tuberculosis in most animal species, including cattle and is a serious zoonotic pathogen. In humans, M. bovis infection can result in disease clinically indistinguishable from that caused by Mycobacterium tuberculosis, the cause of most tuberculosis in humans. Reg...

xdamp Version 6 : an IDL-based data and image manipulation program.

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

Ballard, William Parker

2012-04-01

The original DAMP (DAta Manipulation Program) was written by Mark Hedemann of Sandia National Laboratories and used the CA-DISSPLA{trademark} (available from Computer Associates International, Inc., Garden City, NY) graphics package as its engine. It was used to plot, modify, and otherwise manipulate the one-dimensional data waveforms (data vs. time) from a wide variety of accelerators. With the waning of CA-DISSPLA and the increasing popularity of Unix(reg sign)-based workstations, a replacement was needed. This package uses the IDL(reg sign) software, available from Research Systems Incorporated, a Xerox company, in Boulder, Colorado, as the engine, and creates a set of widgets tomore » manipulate the data in a manner similar to the original DAMP and earlier versions of xdamp. IDL is currently supported on a wide variety of Unix platforms such as IBM(reg sign) workstations, Hewlett Packard workstations, SUN(reg sign) workstations, Microsoft(reg sign) Windows{trademark} computers, Macintosh(reg sign) computers and Digital Equipment Corporation VMS(reg sign) and Alpha(reg sign) systems. Thus, xdamp is portable across many platforms. We have verified operation, albeit with some minor IDL bugs, on personal computers using Windows 7 and Windows Vista; Unix platforms; and Macintosh computers. Version 6 is an update that uses the IDL Virtual Machine to resolve the need for licensing IDL.« less

Molecular pathology of gastric cancer: research and practice.

PubMed

Yasui, Wataru; Sentani, Kazuhiro; Sakamoto, Naoya; Anami, Katsuhiro; Naito, Yutaka; Oue, Naohide

2011-10-15

Recent advances in the understanding of molecular stomach carcinogenesis are reviewed. As to molecular events in individual mucin phenotypes of gastric cancer, the CDX2-Reg IV-SOX9 pathway is associated with the intestinal mucin phenotype, while OLFM4 and CLDN18 are novel markers for the gastric phenotype. microRNAs play an important role in epigenetic deregulation in gastric cancer. Many microRNAs are up-regulated and down-regulated, and some of these are associated with histological differentiation and cancer progression. Reduced miR-200 may participate in the genesis of diffuse type gastric cancer by reducing E-cadherin expression. Genetic polymorphism is a crucial endogenous cause and a fundamental factor of cancer risk. PSCA polymorphism alters the susceptibility to diffuse type gastric cancer through modulation of cell proliferation activity. Cancer stem cells possess the capacity for self-renewal and cause the heterogeneous lineages of cancer cells. Cancer stem cells also show resistance to anti-tumor chemotherapy. Only a minor population of gastric cancer cells reveals the properties of cancer stem cells, and CD44 is one of the markers for gastric cancer stem cells. The origin of gastric cancer stem cells remains to be elucidated. Copyright © 2011 Elsevier GmbH. All rights reserved.

Evaluation of natural regulatory T cells in subjects with selective IgA deficiency: from senior idea to novel opportunities.

PubMed

Soheili, Habib; Abolhassani, Hassan; Arandi, Narges; Khazaei, Hossein Ali; Shahinpour, Shervin; Hirbod-Mobarakeh, Armin; Rezaei, Nima; Aghamohammadi, Asghar

2013-01-01

Selective IgA deficiency (SIgAD) is the most common primary immunodeficiency disorder, which is characterized by significantly decreased serum levels of IgA. Abnormalities of CD4+CD25(high)forkhead box P3 (FoxP3)+ regulatory T cells (T(reg)) have been shown in association with autoimmune and inflammatory disorders. In order to evaluate the relationship between autoimmunity and T(reg) in SIgAD, we studied 26 IgA-deficient patients (aged 4-17 years) with serum IgA levels <7 mg/dl, 26 age- and sex-matched healthy controls and 26 age- and sex matched idiopathic thrombocytopenic purpura cases with normal immune system. T(reg) were determined by flow cytometry using T(reg) markers, including CD4, CD25 and FoxP3. The mean percentage of CD4, CD25+FoxP3+ T(reg) from all CD4+ cells was 4.08 ± 0.86 in healthy controls, which was significantly higher than in SIgAD patients (2.93 ± 1.3; p = 0.003). We set a cutoff point (2.36%) for T(reg), which was two standard deviations lower than the mean of normal controls. According to this cutoff point and in order to assess the role of T(reg) in clinical SIgAD manifestation, we classified patients into two groups: 16 patients in G1 with T(reg) <2.36% and 10 patients in G2 with T(reg) >2.36%. Autoimmunity was recorded in 9 patients (53.3%) of G1 and only 1 patient of G2, respectively (p = 0.034). Although a defect in class switching recombination was observed in 40% of the patients in G1, none of the G2 patients had such a defect (p = 0.028). This study showed decreased proportions of T(reg) in SIgAD patients, particularly in those with signs of chronic inflammation. Copyright © 2012 S. Karger AG, Basel.

GPU-based stochastic-gradient optimization for non-rigid medical image registration in time-critical applications

NASA Astrophysics Data System (ADS)

Bhosale, Parag; Staring, Marius; Al-Ars, Zaid; Berendsen, Floris F.

2018-03-01

Currently, non-rigid image registration algorithms are too computationally intensive to use in time-critical applications. Existing implementations that focus on speed typically address this by either parallelization on GPU-hardware, or by introducing methodically novel techniques into CPU-oriented algorithms. Stochastic gradient descent (SGD) optimization and variations thereof have proven to drastically reduce the computational burden for CPU-based image registration, but have not been successfully applied in GPU hardware due to its stochastic nature. This paper proposes 1) NiftyRegSGD, a SGD optimization for the GPU-based image registration tool NiftyReg, 2) random chunk sampler, a new random sampling strategy that better utilizes the memory bandwidth of GPU hardware. Experiments have been performed on 3D lung CT data of 19 patients, which compared NiftyRegSGD (with and without random chunk sampler) with CPU-based elastix Fast Adaptive SGD (FASGD) and NiftyReg. The registration runtime was 21.5s, 4.4s and 2.8s for elastix-FASGD, NiftyRegSGD without, and NiftyRegSGD with random chunk sampling, respectively, while similar accuracy was obtained. Our method is publicly available at https://github.com/SuperElastix/NiftyRegSGD.

CD4+ CD25+ CD127low Regulatory T Cells as Indicator of Rheumatoid Arthritis Disease Activity.

PubMed

Khattab, Sahar S; El-Saied, Amany M; Mohammed, Rehab A; Mohamed, Eman E

2016-06-01

Rheumatoid arthritis (RA) is an autoimmune disease characterized by disturbed immune regulation, inducing a progressive cartilage and bone destruction. Despite enrichment of T regulatory cell (T-regs) in synovial fluid, conflicting results are reported concerning T-regs in peripheral blood (PB) of RA patients. To determine possible correlation between the frequency of PB CD4+ CD25+CD127low (T-regs) with RA disease activity. Forty females with RA, classified according to the Disease Activity Score 28 (DAS-28), as highly active, mild-moderate or low disease activity; and 20 age and sex matched healthy controls, were enrolled to study CD4+ CD25+ CD127low T- regs in PB by flow cytometry. Active RA patients had lower frequency of the CD4+ CD25+ CD127low T- regs compared to those with mild-moderate or low disease activity (P <0.001). The frequencies of the T- regs showed negative correlation with the DAS-28 (P<0.01). In conclusion, CD4+ CD25+ CD127low T-regs is significantly lower in highly active RA patients compared to patients with lower activity or controls. Copyright© by the Egyptian Association of Immunologists.

Registration of cytoplasmic male-sterile oilseed sunflower genetic stocks CMS GIG2 and CMS GIG2-RV, and fertility restoration lines RF GIG2-MAX 1631 and RF GIG2-MAX 1631-RV

USDA-ARS?s Scientific Manuscript database

Two cytoplasmic male-sterile (CMS) oilseed sunflower (Helianthus annuus L.) genetic stocks, CMS GIG2 (Reg. No. xxx, PI xxxx), and CMS GIG2-RV (Reg. No. xxx, PI xxxx), and corresponding fertility restoration lines RF GIG2-MAX 1631 (Reg. No. xxx, PI xxxx) and RF GIG2-MAX 1631-RV (Reg. No. xxx, PI xxx...

Gut REG3γ-Associated Lactobacillus Induces Anti-inflammatory Macrophages to Maintain Adipose Tissue Homeostasis

PubMed Central

Huang, Yugang; Qi, HouBao; Zhang, Zhiqian; Wang, Enlin; Yun, Huan; Yan, Hui; Su, Xiaomin; Liu, Yingquan; Tang, Zenzen; Gao, Yunhuan; Shang, Wencong; Zhou, Jiang; Wang, Tianze; Che, Yongzhe; Zhang, Yuan; Yang, Rongcun

2017-01-01

Gut microbiota may not only affect composition of local immune cells but also affect systemic immune cells. However, it is not completely clear how gut microbiota modulate these immune systems. Here, we found that there exist expanded macrophage pools in huREG3γtgIEC mice. REG3γ-associated Lactobacillus, which is homology to Lactobacillus Taiwanese, could enlarge macrophage pools not only in the small intestinal lamina propria but also in the spleen and adipose tissues. STAT3-mediated signal(s) was a critical factor in the Lactobacillus-mediated anti-inflammatory macrophages. We also offered evidence for critical cellular links among REG3γ-associated Lactobacillus, tissue macrophages, and obesity diseases. Anti-inflammatory macrophages in the lamina propria, which are induced by REG3γ-associated Lactobacillus, may migrate into adipose tissues and are involved in resistance against high-fat diet-mediated obesity. Thus, REG3γ-associated Lactobacillus-induced anti-inflammatory macrophages in gut tissues may play a role in adipose tissue homeostasis. PMID:28928739

75 FR 66429 - Proposed Collection; Comment Request for Regulation Project REG-104924-98

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... DEPARTMENT OF THE TREASURY Internal Revenue Service [REG-104924-98] Proposed Collection; Comment Request for Regulation Project REG- 104924-98 AGENCY: Internal Revenue Service (IRS), Treasury. ACTION... Christophe, (202) 622-3179, or at Internal Revenue Service, Room 6129, 1111 Constitution Avenue, NW...

Pinto common bean cultivars Blackfoot, Nez Perce, and Twin Falls

USDA-ARS?s Scientific Manuscript database

Pinto common bean cultivars Blackfoot (Reg. No. -----,), Nez Perce (Reg. No. -----, PI), and Twin Falls (Reg. No. -----,) were developed at the University of Idaho-Kimberly Research and Extension Center in collaboration with researchers in Colorado, Nebraska, and Washington State. Twin Falls is a fu...

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Body map of regional vs. whole body sweating rate and sweat electrolyte concentrations in men and women during moderate exercise-heat stress.

PubMed

Baker, Lindsay B; Ungaro, Corey T; Sopeña, Bridget C; Nuccio, Ryan P; Reimel, Adam J; Carter, James M; Stofan, John R; Barnes, Kelly A

2018-05-01

This study determined the relations between regional (REG) and whole body (WB) sweating rate (RSR and WBSR, respectively) as well as REG and WB sweat Na + concentration ([Na + ]) during exercise. Twenty-six recreational athletes (17 men, 9 women) cycled for 90 min while WB sweat [Na + ] was measured using the washdown technique. RSR and REG sweat [Na + ] were measured from nine regions using absorbent patches. RSR and REG sweat [Na + ] from all regions were significantly ( P < 0.05) correlated with WBSR ( r = 0.58-0.83) and WB sweat [Na + ] ( r = 0.74-0.88), respectively. However, the slope and y-intercept of the regression lines for most models were significantly different than 1 and 0, respectively. The coefficients of determination ( r 2 ) were 0.44-0.69 for RSR predicting WBSR [best predictors: dorsal forearm ( r 2  = 0.62) and triceps ( r 2  = 0.69)] and 0.55-0.77 for REG predicting WB sweat [Na + ] [best predictors: ventral forearm ( r 2  = 0.73) and thigh ( r 2  = 0.77)]. There was a significant ( P < 0.05) effect of day-to-day variability on the regression model predicting WBSR from RSR at most regions but no effect on predictions of WB sweat [Na + ] from REG. Results suggest that REG cannot be used as a direct surrogate for WB sweating responses. Nonetheless, the use of regression equations to predict WB sweat [Na + ] from REG can provide an estimation of WB sweat [Na + ] with an acceptable level of accuracy, especially using the forearm or thigh. However, the best practice for measuring WBSR remains conventional WB mass balance calculations since prediction of WBSR from RSR using absorbent patches does not meet the accuracy or reliability required to inform fluid intake recommendations. NEW & NOTEWORTHY This study developed a body map of regional sweating rate and regional (REG) sweat electrolyte concentrations and determined the effect of within-subject (bilateral and day-to-day) and between-subject (sex) factors on the relations between REG and the whole body (WB). Regression equations can be used to predict WB sweat Na + concentration from REG, especially using the forearm or thigh. However, prediction of WB sweating rate from REG sweating rate using absorbent patches does not reach the accuracy or reliability required to inform fluid intake recommendations.

Regulatory Dendritic Cells.

PubMed

Sato, Katsuaki; Uto, Tomofumi; Fukaya, Tomohiro; Takagi, Hideaki

2017-01-01

Dendritic cells (DCs) comprise heterogeneous subsets, functionally classified into conventional DCs (cDCs) and plasmacytoid DCs (pDCs). DCs are considered to be essential antigen (Ag)-presenting cells (APCs) that play crucial roles in activation and fine-tuning of innate and adaptive immunity under inflammatory conditions, as well as induction of immune tolerance to maintain immune homeostasis under steady-state conditions. Furthermore, DC functions can be modified and influenced by stimulation with various extrinsic factors, such as ligands for pattern-recognition receptors (PRRs) and cytokines. On the other hand, treatment of DCs with certain immunosuppressive drugs and molecules leads to the generation of tolerogenic DCs that show downregulation of both the major histocompatibility complex (MHC) and costimulatory molecules, and not only show defective T-cell activation, but also possess tolerogenic properties including the induction of anergic T-cells and regulatory T (T reg ) cells. To develop an effective strategy for Ag-specific intervention of T-cell-mediated immune disorders, we have previously established the modified DCs with moderately high levels of MHC molecules that are defective in the expression of costimulatory molecules that had a greater immunoregulatory property than classical tolerogenic DCs, which we therefore designated as regulatory DCs (DC reg ). Herein, we integrate the current understanding of the role of DCs in the control of immune responses, and further provide new information of the characteristics of tolerogenic DCs and DC reg , as well as their regulation of immune responses and disorders.

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CatReg Software for Categorical Regression Analysis (Jul 2012)

EPA Science Inventory

CatReg is a computer program, written in the R (http://cran.r-project.org) programming language, to support the conduct of exposure-response analyses by toxicologists and health scientists. CatReg can be used to perform categorical regressi...

CatReg Software for Categorical Regression Analysis (Nov 2006)

EPA Science Inventory

CatReg is a computer program, written in the R (http://cran.r-project.org) programming language, to support the conduct of exposure-response analyses by toxicologists and health scientists. CatReg can be used to perform categorical regressi...

CatReg Software for Categorical Regression Analysis (Feb 2011)

EPA Science Inventory

CatReg is a computer program, written in the R (http://cran.r-project.org) programming language, to support the conduct of exposure-response analyses by toxicologists and health scientists. CatReg can be used to perform categorical regressi...

21 CFR 178.1010 - Sanitizing solutions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... permanganate (CAS Reg. No. 7722-64-7). Magnesium oxide (CAS Reg. No. 1309-48-4) and potassium bromide (CAS Reg... permanganate. (ii) The solution identified in paragraph (b)(37) of this section with potassium bromide shall... potassium permanganate. (iii) Magnesium oxide when used in paragraph (c)(32) (i) or (ii) of this section...

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EVALUATION OF GLOVEBOX GLOVES FOR EFFECTIVE PERMEATION CONTROL

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

Korinko, P.

A research and development task was undertaken to determine the permeabilities of hydrogen and dry air through different polymeric glove materials that are used to maintain the integrity of glovebox secondary containment. Fifteen different glove samples were obtained from four different manufacturers and samples cut from these gloves were tested. The gloves included baseline butyl rubber, Viton{reg_sign}, Dupont{reg_sign} Hypalon{reg_sign}, polyurethane, as well as composite gloves. The testing indicated that all of the vendor's butyl rubber gloves and the Jung Viton{reg_sign} gloves performed comparably in both gases.

Elevated Cyclic AMP Levels in T Lymphocytes Transformed by Human T-Cell Lymphotropic Virus Type 1▿

PubMed Central

Kress, Andrea K.; Schneider, Grit; Pichler, Klemens; Kalmer, Martina; Fleckenstein, Bernhard; Grassmann, Ralph

2010-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1), the cause of adult T-cell leukemia/lymphoma (ATLL), transforms CD4+ T cells to permanent growth through its transactivator Tax. HTLV-1-transformed cells share phenotypic properties with memory and regulatory T cells (T-reg). Murine T-reg-mediated suppression employs elevated cyclic AMP (cAMP) levels as a key regulator. This led us to determine cAMP levels in HTLV-1-transformed cells. We found elevated cAMP concentrations as a consistent feature of all HTLV-1-transformed cell lines, including in vitro-HTLV-1-transformed, Tax-transformed, and patient-derived cells. In transformed cells with conditional Tax expression, high cAMP levels coincided with the presence of Tax but were lost without it. However, transient ectopic expression of Tax alone was not sufficient to induce cAMP. We found specific downregulation of the cAMP-degrading phosphodiesterase 3B (PDE3B) in HTLV-1-transformed cells, which was independent of Tax in transient expression experiments. This is in line with the notion that PDE3B transcripts and cAMP levels are inversely correlated. Overexpression of PDE3B led to a decrease of cAMP in HTLV-1-transformed cells. Decreased expression of PDE3B was associated with inhibitory histone modifications at the PDE3B promoter and the PDE3B locus. In summary, Tax transformation and its continuous expression contribute to elevated cAMP levels, which may be regulated through PDE3B suppression. This shows that HTLV-1-transformed cells assume biological features of long-lived T-cell populations that potentially contribute to viral persistence. PMID:20573814

On the ability of RegCM4 regional climate model to simulate surface solar radiation patterns over Europe: an assessment using satellite-based observations

NASA Astrophysics Data System (ADS)

Alexandri, G.; Georgoulias, A. K.; Zanis, P.; Katragkou, E.; Tsikerdekis, A.; Kourtidis, K.; Meleti, C.

2015-11-01

In this work, we assess the ability of RegCM4 regional climate model to simulate surface solar radiation (SSR) patterns over Europe. A decadal RegCM4 run (2000-2009) was implemented and evaluated against satellite-based observations from the Satellite Application Facility on Climate Monitoring (CM SAF), showing that the model simulates adequately the SSR patterns over the region. The SSR bias between RegCM4 and CM SAF is +1.5 % for MFG (Meteosat First Generation) and +3.3 % for MSG (Meteosat Second Generation) observations. The relative contribution of parameters that determine the transmission of solar radiation within the atmosphere to the deviation appearing between RegCM4 and CM SAF SSR is also examined. Cloud macrophysical and microphysical properties such as cloud fractional cover (CFC), cloud optical thickness (COT) and cloud effective radius (Re) from RegCM4 are evaluated against data from CM SAF. Generally, RegCM4 underestimates CFC by 24.3 % and Re for liquid/ice clouds by 36.1 %/28.3 % and overestimates COT by 4.3 %. The same procedure is repeated for aerosol optical properties such as aerosol optical depth (AOD), asymmetry factor (ASY) and single-scattering albedo (SSA), as well as other parameters, including surface broadband albedo (ALB) and water vapor amount (WV), using data from MACv1 aerosol climatology, from CERES satellite sensors and from ERA-Interim reanalysis. It is shown here that the good agreement between RegCM4 and satellite-based SSR observations can be partially attributed to counteracting effects among the above mentioned parameters. The potential contribution of each parameter to the RegCM4-CM SAF SSR deviations is estimated with the combined use of the aforementioned data and a~radiative transfer model (SBDART). CFC, COT and AOD are the major determinants of these deviations on a monthly basis; however, the other parameters also play an important role for specific regions and seasons. Overall, for the European domain, CFC, COT and AOD are the most important factors, since their underestimations and overestimations by RegCM4 cause an annual RegCM4-CM SAF SSR absolute deviation of 8.4, 3.8 and 4.5 %, respectively.

Differential expression of basement membrane type IV collagen α2 and α6 chains as a prognostic factor in patients with extrahepatic bile duct carcinoma.

PubMed

Hirashima, Kotaro; Iyama, Ken-Ichi; Baba, Yoshifumi; Honda, Yumi; Sado, Yoshikazu; Ninomiya, Yoshifumi; Watanabe, Masayuki; Takamori, Hiroshi; Beppu, Toru; Baba, Hideo

2013-03-01

The destruction of the basement membrane (BM) is the first step in cancer invasion and metastasis. Type IV collagen is a major component of the BM, and is composed of six genetically distinct α(IV) chains; α1(IV) to α6(IV). The loss of α5(IV) and α6(IV) chains from the epithelial BM at the early stage of cancer invasion has been reported in several types of cancers. However, the expression of α5(IV) and α6(IV) chains in extrahepatic bile duct carcinoma (EBDC) remains unclear. We examined the expression of α(IV) chains by immunohistochemistry using 71 resected EBDC specimens. Prognostic significance of α(IV) chains was examined by Cox regression and Kaplan-Meier analyses. In the invasive cancer, the expression of α6(IV) chain in the BM was lost partially or completely preceded by the loss of α2(IV) chain. The loss of α6(IV) chain in the BM of the invasive cancer was related to the tumor classification, TNM stages, and the expression of α2(IV) chain. The patients with α2(IV)-negative and α6(IV)-negative chains had significantly poorer prognosis than those with α2(IV)-positive and α6(IV)-positive/negative chains (P = 0.04). The loss of α2(IV) and α6(IV) chains might be a useful prognostic factor in patients with EBDC. Copyright © 2012 Wiley Periodicals, Inc.

Survival from breast, colon, lung, ovarian and rectal cancer by geographical remoteness in New South Wales, Australia, 2000-2008.

PubMed

Chen, Tina Y T; Morrell, Stephen; Thomson, Wendy; Baker, Deborah F; Walton, Richard; Aranda, Sanchia; Currow, David C

2015-02-01

This study aims to compare survival from breast, colon, lung, ovarian and rectal cancer by geographical remoteness in New South Wales (NSW). Retrospective population-wide registry study. NSW, Australia. A total of 107 060 NSW residents, who were diagnosed with any of the five cancers between 01 January 2000 and 31 December 2008. Kaplan-Meier survival curves and proportional hazards regression were used to compare survival by geographical remoteness of residence at diagnosis, controlling for gender, age and extent of disease at diagnosis. Remoteness was classified using standard definitions: major city, inner regional (InnReg), outer regional (OutReg) and remote (including very remote). Significant differences in survival (likelihood of death) were identified in all five cancers: breast (adjusted hazard ratio(HR) = 1.22 (95% confidence interval (CI), 1.001-1.48) in regionalised and HR = 1.30 (1.02-1.64) in metastatic disease for OutReg areas); colon (HR = 1.14 (1.01-1.29) for OutReg areas in metastatic disease); lung (HR range = 1.08-1.35 (1.01-1.48) for most non-metropolitan areas in all stages of disease excepting regionalised); ovarian (HR = 1.32 (1.06-1.65) for OutReg areas in metastatic disease, HR = 1.40 (1.04-1.90) for InnReg areas and HR = 1.68 (1.02-2.77) for OutReg areas in unknown stage of disease) and rectal (HR = 1.37 (1.05-1.78) for OutReg areas in localised and HR = 1.14 (1.002-1.30) for InnReg areas in regionalised disease). Where significant differences were found, major cities tended to show the best survival, whereas OutReg areas tended to show the worst. Although no definitive interpretation could be made regarding remote areas due to small patient numbers, their survival appeared relatively favourable. Reasons that contribute to the differences observed and the disparate results between cancer types need to be further explored in order to facilitate targeted solutions in reducing survival inequality between NSW regions. © 2015 National Rural Health Alliance Inc.

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

Cozzi, A; Cora Berry, C; Michael Bronikowski, M

The decontaminated salt solution waste stream from the Modular Caustic Side Solvent Extraction Unit and the Salt Waste Processing Facility is anticipated to contain entrained extraction solvent. The decontaminated salt solution is scheduled to be processed through Tank 50 into the Saltstone Production Facility. This study, among others, has been undertaken because the solvent concentration in the decontaminated salt solution may cause flammability issues within the Saltstone Disposal Facility that may need to be addressed prior to operation. Previous work at the Savannah River National Laboratory determined the release of Isopar{reg_sign} L from saltstone prepared with a simulated DSS withmore » Isopar{reg_sign} L concentrations ranging from 50 to 200 {micro}g/g in the salt fraction and with test temperatures ranging from ambient to 95 C. The results from the curing of the saltstone showed that the Isopar{reg_sign} L release data can be treated as a percentage of initial concentration in the concentration range studied. The majority of the Isopar{reg_sign} L that was released over the test duration was released in the first few days. The release of Isopar{reg_sign} L begins immediately and the rate of release decreases over time. At higher temperatures the immediate release is larger than at lower temperatures. In this study, saltstone was prepared using a simulated decontaminated salt solution containing Isopar{reg_sign} L concentrations of 50 {micro}L/L (30 {micro}g/g) and 100 {micro}L/L (61 {micro}g/g) and cured at 55 C. The headspace of each sample was purged and the Isopar{reg_sign} L was trapped on a coconut shell carbon tube. The amount of Isopar{reg_sign} L captured was determined using NIOSH Method 1501. The percentage of Isopar{reg_sign} L released after 20 days was 1.4 - 3.7% for saltstone containing 50 {micro}L/L concentration and 2.1 - 4.3% for saltstone containing 100 {micro}L/L concentration. Given the measurement uncertainties in this work there is no clearly discernible relationship between percentage release and initial Isopar{reg_sign} L concentration.« less

Exacerbation of spontaneous autoimmune nephritis following regulatory T cell depletion in B cell lymphoma 2-interacting mediator knock-out mice.

PubMed

Wang, Y M; Zhang, G Y; Wang, Y; Hu, M; Zhou, J J; Sawyer, A; Cao, Q; Wang, Y; Zheng, G; Lee, V W S; Harris, D C H; Alexander, S I

2017-05-01

Regulatory T cells (T regs ) have been recognized as central mediators for maintaining peripheral tolerance and limiting autoimmune diseases. The loss of T regs or their function has been associated with exacerbation of autoimmune disease. However, the temporary loss of T regs in the chronic spontaneous disease model has not been investigated. In this study, we evaluated the role of T regs in a novel chronic spontaneous glomerulonephritis model of B cell lymphoma 2-interacting mediator (Bim) knock-out mice by transient depleting T regs . Bim is a pro-apoptotic member of the B cell lymphoma 2 (Bcl-2) family. Bim knock-out (Bim -/- ) mice fail to delete autoreactive T cells in thymus, leading to chronic spontaneous autoimmune kidney disease. We found that T reg depletion in Bim -/- mice exacerbated the kidney injury with increased proteinuria, impaired kidney function, weight loss and greater histological injury compared with wild-type mice. There was a significant increase in interstitial infiltrate of inflammatory cells, antibody deposition and tubular damage. Furthermore, the serum levels of cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17α, interferon (IFN)-γ and tumour necrosis factor (TNF)-α were increased significantly after T reg depletion in Bim -/- mice. This study demonstrates that transient depletion of T regs leads to enhanced self-reactive T effector cell function followed by exacerbation of kidney disease in the chronic spontaneous kidney disease model of Bim-deficient mice. © 2017 British Society for Immunology.

Predicting Summer Dryness Under a Warmer Climate: Modeling Land Surface Processes in the Midwestern United States

NASA Astrophysics Data System (ADS)

Winter, J. M.; Eltahir, E. A.

2009-12-01

One of the most significant impacts of climate change is the potential alteration of local hydrologic cycles over agriculturally productive areas. As the world’s food supply continues to be taxed by its burgeoning population, a greater percentage of arable land will need to be utilized and land currently producing food must become more efficient. This study seeks to quantify the effects of climate change on soil moisture in the American Midwest. A series of 24-year numerical experiments were conducted to assess the ability of Regional Climate Model Version 3 coupled to Integrated Biosphere Simulator (RegCM3-IBIS) and Biosphere-Atmosphere Transfer Scheme 1e (RegCM3-BATS1e) to simulate the observed hydroclimatology of the midwestern United States. Model results were evaluated using NASA Surface Radiation Budget, NASA Earth Radiation Budget Experiment, Illinois State Water Survey, Climate Research Unit Time Series 2.1, Global Soil Moisture Data Bank, and regional-scale estimations of evapotranspiration. The response of RegCM3-IBIS and RegCM3-BATS1e to a surrogate climate change scenario, a warming of 3oC at the boundaries and doubling of CO2, was explored. Precipitation increased significantly during the spring and summer in both RegCM3-IBIS and RegCM3-BATS1e, leading to additional runoff. In contrast, enhancement of evapotranspiration and shortwave radiation were modest. Soil moisture remained relatively unchanged in RegCM3-IBIS, while RegCM3-BATS1e exhibited some fall and winter wetting.

75 FR 47893 - Proposed Collection; Comment Request for REG-111583-07, (T.D. 9405) (Final)

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...-111583-07, (T.D. 9405) (Final) AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and... comments concerning temporary and final regulations (REG-111583-07) (T.D. 9405), Employment Tax Adjustments... Adjustments. OMB Number: 1545-2097. Form Number: REG-111583-07 (T.D. 9405) (final). Abstract: This document...

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21 CFR 175.320 - Resinous and polymeric coatings for polyolefin films.

Code of Federal Regulations, 2010 CFR

2010-04-01

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21 CFR 175.320 - Resinous and polymeric coatings for polyolefin films.

Code of Federal Regulations, 2011 CFR

2011-04-01

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T-Reg Comparator: an analysis tool for the comparison of position weight matrices

PubMed Central

Roepcke, Stefan; Grossmann, Steffen; Rahmann, Sven; Vingron, Martin

2005-01-01

T-Reg Comparator is a novel software tool designed to support research into transcriptional regulation. Sequence motifs representing transcription factor binding sites are usually encoded as position weight matrices. The user inputs a set of such weight matrices or binding site sequences and our program matches them against the T-Reg database, which is presently built on data from the Transfac [E. Wingender (2004) In Silico Biol., 4, 55–61] and Jaspar [A. Sandelin, W. Alkema, P. Engstrom, W. W. Wasserman and B. Lenhard (2004) Nucleic Acids Res., 32, D91–D94]. Our tool delivers a detailed report on similarities between user-supplied motifs and motifs in the database. Apart from simple one-to-one relationships, T-Reg Comparator is also able to detect similarities between submatrices. In addition, we provide a user interface to a program for sequence scanning with weight matrices. Typical areas of application for T-Reg Comparator are motif and regulatory module finding and annotation of regulatory genomic regions. T-Reg Comparator is available at . PMID:15980506

T-Reg Comparator: an analysis tool for the comparison of position weight matrices.

PubMed

Roepcke, Stefan; Grossmann, Steffen; Rahmann, Sven; Vingron, Martin

2005-07-01

T-Reg Comparator is a novel software tool designed to support research into transcriptional regulation. Sequence motifs representing transcription factor binding sites are usually encoded as position weight matrices. The user inputs a set of such weight matrices or binding site sequences and our program matches them against the T-Reg database, which is presently built on data from the Transfac [E. Wingender (2004) In Silico Biol., 4, 55-61] and Jaspar [A. Sandelin, W. Alkema, P. Engstrom, W. W. Wasserman and B. Lenhard (2004) Nucleic Acids Res., 32, D91-D94]. Our tool delivers a detailed report on similarities between user-supplied motifs and motifs in the database. Apart from simple one-to-one relationships, T-Reg Comparator is also able to detect similarities between submatrices. In addition, we provide a user interface to a program for sequence scanning with weight matrices. Typical areas of application for T-Reg Comparator are motif and regulatory module finding and annotation of regulatory genomic regions. T-Reg Comparator is available at http://treg.molgen.mpg.de.

Rheoencephalographic and electroencephalographic measures of cognitive workload: analytical procedures.

PubMed

Montgomery, L D; Montgomery, R W; Guisado, R

1995-05-01

This investigation demonstrates the feasibility of mental workload assessment by rheoencephalographic (REG) and multichannel electroencephalographic (EEG) monitoring. During the performance of this research, unique testing, analytical and display procedures were developed for REG and EEG monitoring that extend the current state of the art and provide valuable tools for the study of cerebral circulatory and neural activity during cognition. REG records are analyzed to provide indices of the right and left hemisphere hemodynamic changes that take place during each test sequence. The EEG data are modeled using regression techniques and mathematically transformed to provide energy-density distributions of the scalp electrostatic field. These procedures permit concurrent REG/EEG cognitive testing not possible with current techniques. The introduction of a system for recording and analysis of cognitive REG/EEG test sequences facilitates the study of learning and memory disorders, dementia and other encephalopathies.

Rheoencephalographic and electroencephalographic measures of cognitive workload: analytical procedures

NASA Technical Reports Server (NTRS)

Montgomery, L. D.; Montgomery, R. W.; Guisado, R.

1995-01-01

This investigation demonstrates the feasibility of mental workload assessment by rheoencephalographic (REG) and multichannel electroencephalographic (EEG) monitoring. During the performance of this research, unique testing, analytical and display procedures were developed for REG and EEG monitoring that extend the current state of the art and provide valuable tools for the study of cerebral circulatory and neural activity during cognition. REG records are analyzed to provide indices of the right and left hemisphere hemodynamic changes that take place during each test sequence. The EEG data are modeled using regression techniques and mathematically transformed to provide energy-density distributions of the scalp electrostatic field. These procedures permit concurrent REG/EEG cognitive testing not possible with current techniques. The introduction of a system for recording and analysis of cognitive REG/EEG test sequences facilitates the study of learning and memory disorders, dementia and other encephalopathies.

Transfer of the α5(IV) Collagen Chain Gene to Smooth Muscle Restores in Vivo Expression of the α6(IV) Collagen Chain in a Canine Model of Alport Syndrome

PubMed Central

Harvey, Scott J.; Zheng, Keqin; Jefferson, Barbara; Moak, Peter; Sado, Yoshikazu; Naito, Ichiro; Ninomiya, Yoshifumi; Jacobs, Robert; Thorner, Paul S.

2003-01-01

X-linked Alport syndrome is a progressive renal disease caused by mutations in the COL4A5 gene, which encodes the α5(IV) collagen chain. As an initial step toward gene therapy for Alport syndrome, we report on the expression of recombinant α5(IV) collagen in vitro and in vivo. A full-length cDNA-encoding canine α5(IV) collagen was cloned and expressed in vitro by transfection of HEK293 cells that synthesize the α1(IV) and α2(IV), but not the α3(IV) to α6(IV) collagen chains. By Northern blotting, an α5(IV) mRNA transcript of 5.2 kb was expressed and the recombinant protein was detected by immunocytochemistry. The chain was secreted into the medium as a 190-kd monomer; no triple helical species were detected. Transfected cells synthesized an extracellular matrix containing the α1(IV) and α2(IV) chains but the recombinant α5(IV) chain was not incorporated. These findings are consistent with the concept that the α5(IV) chain requires one or more of the α3(IV), α4(IV), or α6(IV) chains for triple helical assembly. In vivo studies were performed in dogs with X-linked Alport syndrome. An adenoviral vector containing the α5(IV) transgene was injected into bladder smooth muscle that lacks both the α5(IV) and α6(IV) chains in these animals. At 5 weeks after injection, there was expression of both the α5(IV) and α6(IV) chains by smooth muscle cells at the injection site in a basement membrane distribution. Thus, this recombinant α5(IV) chain is capable of restoring expression of a second α(IV) chain that requires the presence of the α5(IV) chain for incorporation into collagen trimers. This vector will serve as a useful tool to further explore gene therapy for Alport syndrome. PMID:12598321

Collagen type IV at the fetal-maternal interface.

PubMed

Oefner, C M; Sharkey, A; Gardner, L; Critchley, H; Oyen, M; Moffett, A

2015-01-01

Extracellular matrix proteins play a crucial role in influencing the invasion of trophoblast cells. However the role of collagens and collagen type IV (col-IV) in particular at the implantation site is not clear. Immunohistochemistry was used to determine the distribution of collagen types I, III, IV and VI in endometrium and decidua during the menstrual cycle and the first trimester of pregnancy. Expression of col-IV alpha chains during the reproductive cycle was determined by qPCR and protein localisation by immunohistochemistry. The structure of col-IV in placenta was examined using transmission electron microscopy. Finally, the expression of col-IV alpha chain NC1 domains and collagen receptors was localised by immunohistochemistry. Col-IV alpha chains were selectively up-regulated during the menstrual cycle and decidualisation. Primary extravillous trophoblast cells express collagen receptors and secrete col-IV in vitro and in vivo, resulting in the increased levels found in decidua basalis compared to decidua parietalis. A novel expression pattern of col-IV in the mesenchyme of placental villi, as a three-dimensional network, was found. NC1 domains of col-IV alpha chains are known to regulate tumour cell migration and the selective expression of these domains in decidua basalis compared to decidua parietalis was determined. Col-IV is expressed as novel forms in the placenta. These findings suggest that col-IV not only represents a structural protein providing tissue integrity but also influences the invasive behaviour of trophoblast cells at the implantation site. Copyright © 2014 Elsevier Ltd. All rights reserved.

Inhibition of human UDP-glucuronosyltransferase enzymes by lapatinib, pazopanib, regorafenib and sorafenib: Implications for hyperbilirubinemia.

PubMed

Miners, John O; Chau, Nuy; Rowland, Andrew; Burns, Kushari; McKinnon, Ross A; Mackenzie, Peter I; Tucker, Geoffrey T; Knights, Kathleen M; Kichenadasse, Ganessan

2017-04-01

Kinase inhibitors (KIs) are a rapidly expanding class of drugs used primarily for the treatment of cancer. Data relating to the inhibition of UDP-glucuronosyltransferase (UGT) enzymes by KIs is sparse. However, lapatinib (LAP), pazopanib (PAZ), regorafenib (REG) and sorafenib (SOR) have been implicated in the development of hyperbilirubinemia in patients. This study aimed to characterise the role of UGT1A1 inhibition in hyperbilirubinemia and assess the broader potential of these drugs to perpetrate drug-drug interactions arising from UGT enzyme inhibition. Twelve recombinant human UGTs from subfamilies 1A and 2B were screened for inhibition by LAP, PAZ, REG and SOR. IC 50 values for the inhibition of all UGT1A enzymes, except UGT1A3 and UGT1A4, by the four KIs were <10μM. LAP, PAZ, REG and SOR inhibited UGT1A1-catalysed bilirubin glucuronidation with mean IC 50 values ranging from 34nM (REG) to 3734nM (PAZ). Subsequent kinetic experiments confirmed that REG and SOR were very potent inhibitors of human liver microsomal β-estradiol glucuronidation, an established surrogate for bilirubin glucuronidation, with mean K i values of 20 and 33nM, respectively. K i values for LAP and PAZ were approximately 1- and 2-orders of magnitude higher than those for REG and SOR. REG and SOR were equipotent inhibitors of human liver microsomal UGT1A9 (mean K i 678nM). REG and SOR are the most potent inhibitors of a human UGT enzyme identified to date. In vitro-in vivo extrapolation indicates that inhibition of UGT1A1 contributes significantly to the hyperbilirubinemia observed in patients treated with REG and SOR, but not with LAP and PAZ. Inhibition of other UGT1A1 substrates in vivo is likely. Copyright © 2017 Elsevier Inc. All rights reserved.

Resetting microbiota by Lactobacillus reuteri inhibits T reg deficiency–induced autoimmunity via adenosine A2A receptors

PubMed Central

Hoang, Thomas K.; Tian, Xiangjun; Luo, Meng; Zhou, Jain; Tatevian, Nina; Molina, Jose G.; Blackburn, Michael R.; Gomez, Thomas H.

2017-01-01

Regulatory T (T reg) cell deficiency causes lethal, CD4+ T cell–driven autoimmune diseases. Stem cell transplantation is used to treat these diseases, but this procedure is limited by the availability of a suitable donor. The intestinal microbiota drives host immune homeostasis by regulating the differentiation and expansion of T reg, Th1, and Th2 cells. It is currently unclear if T reg cell deficiency–mediated autoimmune disorders can be treated by targeting the enteric microbiota. Here, we demonstrate that Foxp3+ T reg cell deficiency results in gut microbial dysbiosis and autoimmunity over the lifespan of scurfy (SF) mouse. Remodeling microbiota with Lactobacillus reuteri prolonged survival and reduced multiorgan inflammation in SF mice. L. reuteri changed the metabolomic profile disrupted by T reg cell deficiency, and a major effect was to restore levels of the purine metabolite inosine. Feeding inosine itself prolonged life and inhibited multiorgan inflammation by reducing Th1/Th2 cells and their associated cytokines. Mechanistically, the inhibition of inosine on the differentiation of Th1 and Th2 cells in vitro depended on adenosine A2A receptors, which were also required for the efficacy of inosine and of L. reuteri in vivo. These results reveal that the microbiota–inosine–A2A receptor axis might represent a potential avenue for combatting autoimmune diseases mediated by T reg cell dysfunction. PMID:27994068

Multidecadal simulation of coastal fog with a regional climate model

NASA Astrophysics Data System (ADS)

O'Brien, Travis A.; Sloan, Lisa C.; Chuang, Patrick Y.; Faloona, Ian C.; Johnstone, James A.

2013-06-01

In order to model stratocumulus clouds and coastal fog, we have coupled the University of Washington boundary layer model to the regional climate model, RegCM (RegCM-UW). By comparing fog occurrences observed at various coastal airports in the western United States, we show that RegCM-UW has success at modeling the spatial and temporal (diurnal, seasonal, and interannual) climatology of northern California coastal fog. The quality of the modeled fog estimate depends on whether coast-adjacent ocean or land grid cells are used; for the model runs shown here, the oceanic grid cells seem to be most appropriate. The interannual variability of oceanic northern California summertime fog, from a multi-decadal simulation, has a high and statistically significant correlation with the observed interannual variability ( r = 0.72), which indicates that RegCM-UW is capable of investigating the response of fog to long-term climatological forcing. While RegCM-UW has a number of aspects that would benefit from further investigation and development, RegCM-UW is a new tool for investigating the climatology of coastal fog and the physical processes that govern it. We expect that with appropriate physical parameterizations and moderate horizontal resolution, other climate models should be capable of simulating coastal fog. The source code for RegCM-UW is publicly available, under the GNU license, through the International Centre for Theoretical Physics.

Limited tumor infiltration by activated T effector cells restricts the therapeutic activity of regulatory T cell depletion against established melanoma

PubMed Central

Quezada, Sergio A.; Peggs, Karl S.; Simpson, Tyler R.; Shen, Yuelei; Littman, Dan R.; Allison, James P.

2008-01-01

Interference with inhibitory immunological checkpoints controlling T cell activation provides new opportunities to augment cancer immunotherapies. Whereas cytotoxic T lymphocyte–associated antigen-4 blockade has shown promising preclinical and clinical results, therapeutic CD4+CD25+ T reg cell depletion has failed to consistently enhance immune-based therapies. Using B16/BL6, a transplantable murine melanoma model, we show a dichotomy between the effects of T reg cell depletion on tumor rejection dependent on whether depletion occurs before (prophylactic) or after (therapeutic) tumor engraftment. Failure to promote rejection with therapeutic depletion is not related to lack of T reg cell depletion, to elimination of CD25+ effector T cells, or to a failure to enhance systemic antitumor T cell responses, but correlates with failure of effector cells to infiltrate the tumor and increase the intratumor ratio of effector T cell/T reg cell. Finally, systemic antitumor responses generated upon therapeutic T reg cell depletion are significantly stronger than those generated in the presence of T reg cells, and are capable of eliciting rejection of established tumors after transfer into immunoablated recipients receiving combination immunotherapy. The data demonstrate a dissociation between measurable systemic responses and tumor rejection during CD25-directed T reg cell depletion, and suggest an alternative, clinically applicable strategy for the treatment of established tumors. PMID:18725522

Three Molecular Subtypes of Gastric Adenocarcinoma Have Distinct Histochemical Features Reflecting Epstein-Barr Virus Infection Status and Neuroendocrine Differentiation.

PubMed

Speck, Olga; Tang, Weihua; Morgan, Douglas R; Kuan, Pei Fen; Meyers, Michael O; Dominguez, Ricardo L; Martinez, Enrique; Gulley, Margaret L

2015-10-01

Current histopathologic classification schemes for gastric adenocarcinoma have limited clinical utility and are difficult to apply due to tumor heterogeneity. Elucidation of molecular subtypes of gastric cancer may contribute to our understanding of gastric cancer biology and to the development of new molecular markers that may lead to improved diagnosis, therapy, or prognosis. We previously demonstrated that Epstein-Barr virus (EBV)-infected gastric cancers have a distinct human gene expression profile compared with uninfected cancers. We now examine the histopathologic features characterizing infected (n=14) and uninfected (n=89) cancers; the latter of which are now further divided into 2 major molecular subtypes based on expression patterns of 93 RNAs. One uninfected gastric cancer subtype was distinguished by upregulation of 3 genes with neuroendocrine (NE) function (CHGA, GAST, and REG4 encoding chromogranin, gastrin, and the secreted peptide REG4 involved in epithelial cell regeneration), implicating hormonal factors in the pathogenesis of a major class of gastric adenocarcinomas. Evidence of NE differentiation (molecular, immunohistochemical, or morphologic) was mutually exclusive of EBV infection. EBV-infected tumors tended to have solid-type morphology with lymphoid stroma. This study reveals novel molecular subtypes of gastric cancer and their associated morphologies that demonstrate divergent NE features.

Treatment and prevention of experimental autoimmune myocarditis with CD28 superagonists.

PubMed

Wang, Shu; Liu, Jing; Wang, Min; Zhang, Jinghui; Wang, Zhaohui

2010-01-01

Experimental autoimmune myocarditis (EAM), a rodent model of human dilated cardiomyopathy (DCM), is mediated by an autoimmune mechanism. We investigated whether a CD28 superagonistic antibody selectively targeting CD4+CD25+ regulatory T cells (T(regs)) provides effective therapy for EAM. Four groups of 5 rats were used. The normal control group was immunized with PBS. The EAM group was immunized with porcine myosin. The experimental group was immunized with myosin and superagonistic CD28 antibody JJ316. The final group was immunized with myosin and an unrelated rat IgG. Autoantibody and IL-10 production, CD4+CD25+ cell levels, Foxp3 expression and cardiac histology were analyzed. Anti-myosin autoantibody levels were higher in the EAM and isotype control groups than the normal control group (p < 0.05), and reduced in the CD28-JJ316 group (p < 0.05). The levels of CD25+CD4+ cells, IL-10 and splenocyte Foxp3 expression were significantly lower in the EAM and isotype control groups versus the CD28-JJ316 group (p < 0.05). Infiltration of inflammatory cells was observed in the EAM and isotype control groups, whereas CD28-JJ316 ameliorated myocarditis. CD28 superagonists could be effective in EAM treatment by up-regulating Foxp3 expression and contributing to CD4+CD25+ T(reg) activation and expansion. The enhancement in IL-10 by CD28 superagonists also ameliorated the disease.

21 CFR 176.300 - Slimicides.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) cyclohexanone 1,2-Bis(monobromoacetoxy) ethane [CA Reg. No. 3785-34-0] At a maximum level of 0.10 pound per ton... Methylenebisbutanethiolsulfonate Methylenebisthiocyanate 2-Nitrobutyl bromoacetate [CA Reg. No. 32815-96-6] At a maximum level of 0...)phosphonium sulfate (CAS Reg. No. 55566-30-8) Maximum use level of 84 mg/kg in the pulp slurry. The additive...

21 CFR 176.300 - Slimicides.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) cyclohexanone 1,2-Bis(monobromoacetoxy) ethane [CA Reg. No. 3785-34-0] At a maximum level of 0.10 pound per ton... Methylenebisbutanethiolsulfonate Methylenebisthiocyanate 2-Nitrobutyl bromoacetate [CA Reg. No. 32815-96-6] At a maximum level of 0...)phosphonium sulfate (CAS Reg. No. 55566-30-8) Maximum use level of 84 mg/kg in the pulp slurry. The additive...

40 CFR 180.920 - Inert ingredients used pre-harvest; exemptions from the requirement of a tolerance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Defoamer γ-Butyrolactone Solvent C.I. Pigment Blue #15 (CAS Reg. No. 147-14-8; containing no more than 50... Surfactants, related adjuvants of surfactants Aluminum sulfate Safener adjuvant Ammonium chloride (CAS Reg. No... herbicides Ammonium polyphosphate (CAS Reg. No. 68333-79-9) Sequestrant, buffer, or surfactant Barium sulfate...

40 CFR 180.930 - Inert ingredients applied to animals; exemptions from the requirement of a tolerance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... clay Solid diluent, carrier Barium sulfate (CAS Reg. No. 7727-43-7) Carrier, density control agent...-Difluoroethane (CAS Reg. No. 75-37-6) For aerosol pesticide formulations used for insect control in food- and... tris-12-hydroxystearate Flow control agent Graphite Solid diluent, carrier n-Hexyl alcohol (CAS Reg. No...

RegCM4-HadGEM2-ES simulated cyclone climatology (1979-2005) over the Southwestern South Atlantic Ocean

NASA Astrophysics Data System (ADS)

Porfírio da Rocha, Rosmeri; Simões Reboita, Michelle

2015-04-01

Cyclones over the Southwestern South Atlantic Ocean (SAO) are a subject of great interest once they modify the weather and control the climate near east coast of South America (SA). In this study we compare the cyclones climatology in the period 1979-2005 simulated by Regional Climate Model version 4 (RegCM4) with that from ERA-Interim reanalysis (ECMWF). RegCM4 was nested in HadGEM2-ES output and the simulation used the SA domain of CORDEX project, with a horizontal grid of 50 km and 18 sigma-pressure levels in the vertical. The RegCM4 simulation used the land surface Biosphere-Atmosphere Transfer Scheme (BATS) and the mixed convection Emanuel-Grell scheme configurations. This simulation is part of the CREMA (CORDEX REgCM4 hyper-MAtrix) experiment. The cyclones were identified using an automated tracking scheme based on minima (cyclonic in Southern Hemisphere) of relative vorticity from the wind at 925 hPa. The threshold of -1.5 x 10-5s-1 was used in the algorithm. All cyclones in RegCM4 and ERA-Interim with relative vorticity lower than this threshold and with lifetime higher or equal 24 hours were included in the climatology. ERA-Interim shows three main cyclogenetic regions near east coast of SA. In general, RegCM4 simulated these same regions but with an underestimation of the number of cyclones. In each of these regions, there is a different season of higher cyclones frequency. Over extreme south of southern Brazil and Uruguay the higher frequency of cyclones occurs in winter, while southeastern Brazil and southeastern Argentina cyclones are most frequent during summer. RegCM4 is able to simulate this observed seasonality.

CD4+/CD25+ regulatory cells inhibit activation of tumor-primed CD4+ T cells with IFN-gamma-dependent antiangiogenic activity, as well as long-lasting tumor immunity elicited by peptide vaccination.

PubMed

Casares, Noelia; Arribillaga, Laura; Sarobe, Pablo; Dotor, Javier; Lopez-Diaz de Cerio, Ascensión; Melero, Ignacio; Prieto, Jesús; Borrás-Cuesta, Francisco; Lasarte, Juan J

2003-12-01

CD25(+) regulatory T (T reg) cells suppress the activation/proliferation of other CD4(+) or CD8(+) T cells in vitro. Also, down-regulation of CD25(+) T reg cells enhance antitumor immune responses. In this study, we show that depletion of CD25(+) T reg cells allows the host to induce both CD4(+) and CD8(+) antitumoral responses following tumor challenge. Simultaneous depletion of CD25(+) and CD8(+) cells, as well as adoptive transfer experiments, revealed that tumor-specific CD4(+) T cells, which emerged in the absence of CD25(+) T reg cells, were able to reject CT26 colon cancer cells, a MHC class II-negative tumor. The antitumoral effect mediated by CD4(+) T cells was dependent on IFN-gamma production, which exerted a potent antiangiogenic activity. The capacity of the host to mount this antitumor response is lost once the number of CD25(+) T reg cells is restored over time. However, CD25(+) T reg cell depletion before immunization with AH1 (a cytotoxic T cell determinant from CT26 tumor cells) permits the induction of a long-lasting antitumoral immune response, not observed if immunization is conducted in the presence of regulatory cells. A study of the effect of different levels of depletion of CD25(+) T reg cells before immunization with the peptide AH1 alone, or in combination with a Th determinant, unraveled that Th cells play an important role in overcoming the suppressive effect of CD25(+) T reg on the induction of long-lasting cellular immune responses.

On the ability of RegCM4 regional climate model to simulate surface solar radiation patterns over Europe: an assessment using satellite-based observations

NASA Astrophysics Data System (ADS)

Alexandri, G.; Georgoulias, A. K.; Zanis, P.; Katragkou, E.; Tsikerdekis, A.; Kourtidis, K.; Meleti, C.

2015-07-01

In this work, we assess the ability of RegCM4 regional climate model to simulate surface solar radiation (SSR) patterns over Europe. A decadal RegCM4 run (2000-2009) was implemented and evaluated against satellite-based observations from the Satellite Application Facility on Climate Monitoring (CM SAF) showing that the model simulates adequately the SSR patterns over the region. The bias between RegCM4 and CM SAF is +1.54 % for MFG (Meteosat First Generation) and +3.34 % for MSG (Meteosat Second Generation) observations. The relative contribution of parameters that determine the transmission of solar radiation within the atmosphere to the deviation appearing between RegCM4 and CM SAF SSR is also examined. Cloud macrophysical and microphysical properties such as cloud fractional cover (CFC), cloud optical thickness (COT) and cloud effective radius (Re) from RegCM4 are evaluated against data from CM SAF. The same procedure is repeated for aerosol optical properties such as aerosol optical depth (AOD), asymmetry factor (ASY) and single scattering albedo (SSA), as well as other parameters including surface broadband albedo (ALB) and water vapor amount (WV) using data from MACv1 aerosol climatology, from CERES satellite sensors and from ERA-Interim reanalysis. It is shown here that the good agreement between RegCM4 and satellite-based SSR observations can be partially attributed to counteracting effects among the above mentioned parameters. The contribution of each parameter to the RegCM4-CM SAF SSR deviations is estimated with the combined use of the aforementioned data and a radiative transfer model (SBDART). CFC, COT and AOD are the major determinants of these deviations; however, the other parameters also play an important role for specific regions and seasons.

REG1B as a predictor of childhood stunting in Bangladesh and Peru123

PubMed Central

Peterson, Kristine M; Buss, Janice; Easley, Rebecca; Yang, Zhengyu; Korpe, Poonum S; Niu, Feiyang; Ma, Jennie Z; Olortegui, Maribel Paredes; Haque, Rashidul; Kosek, Margaret N; Petri, William A

2013-01-01

Background: Undernutrition remains a significant problem worldwide, with environmental enteropathy implicated as a contributing factor. An understanding of the pathogenesis and identification of children at risk are critical to the design of more-effective interventions. Objective: The stool regenerating gene 1β (REG1B) protein, which is a putative measure of intestinal injury and repair, was tested as a noninvasive biomarker of future childhood stunting. Design: A total of 222 children from Bangladesh and 97 children from Peru, who were from impoverished communities, were followed from birth through 24 mo of age with anthropometric measures obtained every 3 mo. Stool REG1B protein concentrations were obtained by using an REG1B polyclonal-polyclonal ELISA at 3 mo of age. We tested for the ability of REG1B to forecast future anthropometric shortfalls, independent of known predictors of undernutrition of family income and baseline height and weight. Results: In the Bangladesh cohort of 222 children, higher REG1B concentrations at month 3 were significantly and independently associated with a growth shortfall in a linear regression analysis at months 9, 12, 18, 21, and 24 and, in the Peru cohort, at months 12, 15, 18, 21, and 24. With the use of a mixed model for repeated measurements, higher stool REG1B concentrations at 3 mo were also independently predictive of a lower future length-for-age z score through 24 mo of age (Bangladesh P = 0.006; Peru P = 0.058). Conclusion: The ability of fecal REG1B to predict growth shortfall in independent cohorts of impoverished children from the developing world offers promise as a malnutrition biomarker and supports a role for environmental enteropathy in the pathogenesis of growth shortfall. PMID:23553156

TOXPERT: An Expert System for Risk Assessment

PubMed Central

Soto, R. J.; Osimitz, T. G.; Oleson, A.

1988-01-01

TOXPERT is an artificial intelligence based system used to model product safety, toxicology (TOX) and regulatory (REG) decision processes. An expert system shell uses backward chaining rule control to link “marketing approval” goals to the type of product, REG agency, exposure conditions and TOX. Marketing risks are primarily a function of the TOX, hazards and exposure potential. The method employed differentiates between REG requirements in goal seeking control for various types of products. This is accomplished by controlling rule execution by defining frames for each REG agency. In addition, TOXPERT produces classifications of TOX ratings and suggested product labeling. This production rule system uses principles of TOX, REGs, corporate guidelines and internal “rules of thumb.” TOXPERT acts as an advisor for this narrow domain. Advantages are that it can make routine decisions freeing professional's time for more complex problem solving, provide backup and training.

76 FR 81928 - Kansas City, KS, Board of Public Utilities; Notice of Petition for Waiver

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-29

.... \\1\\ Open Access Same-Time Information System and Standards of Conduct, Order No. 889, FERC Stats. & Regs. ] 31,035 (1996), order on reh'g, Order No. 889-A, FERC Stats. & Regs. ] 31,049 (1997), reh'g... Providers, Order No. 2004, FERC Stats. & Regs. ] 31,155 (2003), order on reh'g, Order No. 2004-A, FERC Stats...

78 FR 25434 - Minnesota Municipal Power Agency; Notice of Filing

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-01

..., 61 FR 21,737, FERC Stats. & Regs. ] 31,035 (1996), order on reh'g, Order No. 889-A, 62 FR 12,484, FERC Stats. & Regs. ] 31,049 (1997) (Order No. 889-A), reh'g denied, Order No. 889-B, 81 FERC ] 61,253.... Cir. 2000). \\2\\ Standards of Conduct for Transmission Providers, Order No. 2004, FERC Stats. & Regs...

40 CFR 180.910 - Inert ingredients used pre- and post-harvest; exemptions from the requirement of a tolerance.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) Solvent Kaolinite-type clay Solid diluent, carrier Lactic acid Solvent Lactic acid, 2-ethylhexyl ester (CAS Reg. No. 6283-86-9) Solvent Lactic acid, 2-ethylhexyl ester, (2S)- (CAS Reg. No. 186817-80-1) Solvent Lactic acid, n-propyl ester, (S); (CAS Reg. No. 53651-69-7) Solvent Lauryl alcohol Surfactant...

40 CFR 180.910 - Inert ingredients used pre- and post-harvest; exemptions from the requirement of a tolerance.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., carrier Lactic acid Solvent Lactic acid, 2-ethylhexyl ester (CAS Reg. No. 6283-86-9) Solvent Lactic acid, 2-ethylhexyl ester, (2S)- (CAS Reg. No. 186817-80-1) Solvent Lactic acid, n-propyl ester, (S); (CAS... agent Thiosulfuric acid, disodium salt, pentahydrate. (CAS Reg. No. 10102-17-7) Do. d-Alpha tocopherol...

In vivo cerebral blood flow autoregulation studies using rheoencephalography

NASA Astrophysics Data System (ADS)

Bodo, M.; Pearce, F.; Garcia, A.; Van Albert, S.; Settle, T.; Szebeni, J.; Baranyi, L.; Hartings, J.; Armonda, R.

2010-04-01

Acute management of patients with traumatic brain/blast injury is a challenge. To minimize secondary injury and improve outcome, it is critical to detect neurological deterioration early, when it is potentially reversible. One potential monitoring method is cerebral electrical impedance (rheoencephalography-REG) because of its non-invasiveness and good time resolution. Reported here are the results of cerebral blood flow (CBF) manipulations comparing electroencephalogram (EEG) with REG (both intra-cerebral) and measuring with surface and skull REG electrodes. Our hypothesis was that REG would reflect spreading depression and CBF autoregulation. Animal experiments were performed using one rat (four trials with intracerebral electrodes), monkeys (n=8, with surface electrodes) and pigs (n = 24 pigs with skull electrodes; 57 trials, 19 types of liposomes). Challenges included intracranial pressure (ICP) elevation, liposome infusion, and hemorrhage. Data were stored on a PC and evaluated off line. CBF autoregulation was evaluated both by visual inspection and by a Matlab script. These studies confirmed that REG reflects CBF autoregulation and that REG is useful for detecting spreading depression (SD), vasospasm and the lower limit of CBF autoregulation. These findings have clinical relevance for use in noninvasive neuro-monitoring in the neurosurgery intensive care and during transportation of patients with brain injury.

Interleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to intestinal helminths.

PubMed

Pelly, Victoria S; Coomes, Stephanie M; Kannan, Yashaswini; Gialitakis, Manolis; Entwistle, Lewis J; Perez-Lloret, Jimena; Czieso, Stephanie; Okoye, Isobel S; Rückerl, Dominik; Allen, Judith E; Brombacher, Frank; Wilson, Mark S

2017-06-05

Immunity to intestinal helminth infections requires the rapid activation of T helper 2 cells (Th2 cells). However, simultaneous expansion of CD4 + Foxp3 + regulatory T cells (T reg cells) impedes protective responses, resulting in chronic infections. The ratio between T reg and effector T cells can therefore determine the outcome of infection. The redifferentiation of T reg cells into Th cells has been identified in hyperinflammatory diseases. In this study, we asked whether ex-T reg Th2 cells develop and contribute to type-2 immunity. Using multigene reporter and fate-reporter systems, we demonstrate that a significant proportion of Th2 cells derive from Foxp3 + cells after Heligmosomoides polygyrus infection and airway allergy. Ex-Foxp3 Th2 cells exhibit characteristic Th2 effector functions and provide immunity to H. polygyrus Through selective deletion of Il4ra on Foxp3 + cells, we further demonstrate IL-4 is required for the development of ex-Foxp3 Th2 cells. Collectively, our findings indicate that converting T reg cells into Th2 cells could concomitantly enhance Th2 cells and limit T reg cell-mediated suppression. © 2017 Pelly et al.

Interleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to intestinal helminths

PubMed Central

Coomes, Stephanie M.; Kannan, Yashaswini; Entwistle, Lewis J.; Perez-Lloret, Jimena; Czieso, Stephanie

2017-01-01

Immunity to intestinal helminth infections requires the rapid activation of T helper 2 cells (Th2 cells). However, simultaneous expansion of CD4+Foxp3+ regulatory T cells (T reg cells) impedes protective responses, resulting in chronic infections. The ratio between T reg and effector T cells can therefore determine the outcome of infection. The redifferentiation of T reg cells into Th cells has been identified in hyperinflammatory diseases. In this study, we asked whether ex–T reg Th2 cells develop and contribute to type-2 immunity. Using multigene reporter and fate-reporter systems, we demonstrate that a significant proportion of Th2 cells derive from Foxp3+ cells after Heligmosomoides polygyrus infection and airway allergy. Ex-Foxp3 Th2 cells exhibit characteristic Th2 effector functions and provide immunity to H. polygyrus. Through selective deletion of Il4ra on Foxp3+ cells, we further demonstrate IL-4 is required for the development of ex-Foxp3 Th2 cells. Collectively, our findings indicate that converting T reg cells into Th2 cells could concomitantly enhance Th2 cells and limit T reg cell–mediated suppression. PMID:28507062

"Boldness" in the domestic dog differs among breeds and breed groups.

PubMed

Starling, Melissa J; Branson, Nicholas; Thomson, Peter C; McGreevy, Paul D

2013-07-01

"Boldness" in dogs is believed to be one end of the shy-bold axis, representing a super-trait. Several personality traits fall under the influence of this super-trait. Previous studies on boldness in dogs have found differences among breeds, but grouping breeds on the basis of behavioural similarities has been elusive. This study investigated differences in the expression of boldness among dog breeds, kennel club breed groups, and sub-groups of kennel club breed groups by way of a survey on dog personality circulated among Australian dog-training clubs and internet forums and lists. Breed had a significant effect on boldness (F=1.63, numDF=111, denDF=272, p<0.001), as did breed group (F=10.66, numDF=8, denDF=772, p<0.001). Herding and gundog groups were broken into sub-groups based on historic breed purpose. Retrievers were significantly bolder than flushing and pointing breeds (Reg. Coef.=2.148; S.E.=0.593; p<0.001), and tending and loose-eyed herding breeds were bolder than heading and cattle-herding breeds (Reg. Coef.=1.744; S.E.=0.866; p=0.045 and Reg. Coef.=1.842; S.E.=0.693; p=0.0084, respectively). This study supports the existence of the shy-bold continuum in dogs. Differences in boldness among groups and sub-groups suggest that behavioural tendencies may be influenced by historical purpose regardless of whether that purpose still factors in selective breeding. Copyright © 2013 Elsevier B.V. All rights reserved.

Pivotal roles of CD4+ effector T cells in mediating agonistic anti-GITR mAb-induced-immune activation and tumor immunity in CT26 tumors.

PubMed

Zhou, Pengfei; L'italien, Lawrence; Hodges, Douglas; Schebye, Xiao Min

2007-12-01

Glucocorticoid-induced TNF receptor family related protein (GITR) is a member of the TNFR superfamily. Previous studies have shown that in vivo administration of a GITR agonistic Ab (DTA-1) is able to overcome tolerance and induce tumor rejection in several murine syngeneic tumor models. However, little is known about the in vivo targets and the mechanisms of how this tolerance is overcome in a tumor-bearing host, nor is much known about how the immune network is regulated to achieve this antitumor response. In this study, we demonstrate that the in vivo ligation of GITR on CD4(+) effector T cells renders them refractory to suppression by regulatory T (T(reg)) cells in the CT26 tumor-bearing mouse. GITR engagement on T(reg) cells does not appear to directly abrogate their suppressive function; rather, it increases the expansion of T(reg) cells and promotes IL-10 production, a cytokine important for their suppressive function. Moreover, CD4(+) effector T cells play a crucial role in mediating DTA-1-induced immune activation and expansion of CD8(+), NK, and B cells in the tumor-draining lymph nodes. This includes increased CD69 expression on all of these subsets. In addition, NK and tumor-specific CD8(+) T cells are generated that are cytolytic, which show increased intracellular IFN-gamma production and CD107a mobilization, the latter a hallmark of cytolytic activities that lead to tumor killing.

Analysis of gut microbial regulation of host gene expression along the length of the gut and regulation of gut microbial ecology through MyD88.

PubMed

Larsson, Erik; Tremaroli, Valentina; Lee, Ying Shiuan; Koren, Omry; Nookaew, Intawat; Fricker, Ashwana; Nielsen, Jens; Ley, Ruth E; Bäckhed, Fredrik

2012-08-01

The gut microbiota has profound effects on host physiology but local host-microbial interactions in the gut are only poorly characterised and are likely to vary from the sparsely colonised duodenum to the densely colonised colon. Microorganisms are recognised by pattern recognition receptors such as Toll-like receptors, which signal through the adaptor molecule MyD88. To identify host responses induced by gut microbiota along the length of the gut and whether these required MyD88, transcriptional profiles of duodenum, jejunum, ileum and colon were compared from germ-free and conventionally raised wild-type and Myd88-/- mice. The gut microbial ecology was assessed by 454-based pyrosequencing and viruses were analysed by PCR. The gut microbiota modulated the expression of a large set of genes in the small intestine and fewer genes in the colon but surprisingly few microbiota-regulated genes required MyD88 signalling. However, MyD88 was essential for microbiota-induced colonic expression of the antimicrobial genes Reg3β and Reg3γ in the epithelium, and Myd88 deficiency was associated with both a shift in bacterial diversity and a greater proportion of segmented filamentous bacteria in the small intestine. In addition, conventionally raised Myd88-/- mice had increased expression of antiviral genes in the colon, which correlated with norovirus infection in the colonic epithelium. This study provides a detailed description of tissue-specific host transcriptional responses to the normal gut microbiota along the length of the gut and demonstrates that the absence of MyD88 alters gut microbial ecology.

Registration of F1025, F1026, and F1027 sugarbeet germplasm with low concentrations of sodium, potassium, or amino-nitrogen

USDA-ARS?s Scientific Manuscript database

F1025 (Reg. No. GP-xxx, PI xxxxxx), F1026 (Reg. No. GP-xxx, PI xxxxxx), and F1027 (Reg. No. GP-xxx, PI xxxxxx) sugarbeet (Beta vulgaris L.) germplasm lines, selected for low concentrations of sodium, potassium, and amino-nitrogen, respectively, in the roots, were released by the USDA-ARS and the Nor...

Safety assessment of immunomodulatory biologics: the promise and challenges of regulatory T-cell modulation.

PubMed

Ponce, Rafael A

2011-01-01

Regulatory T-cell (T(reg)) modulation is developing as an important therapeutic opportunity for the treatment of a number of important diseases, including cancer, autoimmunity, infection, and organ transplant rejection. However, as demonstrated with IL-2 and TGN-1412, our understanding of the complex immunological interactions that occur with T(reg) modulation in both non-clinical models and in patients remains limited and appears highly contextual. This lack of understanding will challenge our ability to identify the patient population who might derive the highest benefit from T(reg) modulation and creates special challenges as we transition these therapeutics from non-clinical models into humans. Thus, in vivo testing in the most representative animal model systems, with careful progress in the clinic, will remain critical in developing therapeutics targeting T(reg) and understanding their clinical utility. Moreover, toxicology models can inform some of the potential liabilities associated with T(reg) modulation, but not all, suggesting a continued need to explore and validate predictive models.

Intestinal REG3 Lectins Protect Against Alcoholic Steatohepatitis by Reducing Mucosa-Associated Microbiota and Preventing Bacterial Translocation

PubMed Central

Wang, Lirui; Fouts, Derrick E.; Stärkel, Peter; Hartmann, Phillipp; Chen, Peng; Llorente, Cristina; DePew, Jessica; Moncera, Kelvin; Ho, Samuel B.; Brenner, David A.; Hooper, Lora V.; Schnabl, Bernd

2016-01-01

Summary Approximately half of all deaths from liver cirrhosis, the 10th leading cause of mortality in the United States, are related to alcohol use. Chronic alcohol consumption is accompanied by intestinal dysbiosis and bacterial overgrowth, yet little is known about the factors that alter the microbial composition or their contribution to liver disease. We previously associated chronic alcohol consumption with lower intestinal levels of the antimicrobial-regenerating islet-derived (REG)-3 lectins. Here, we demonstrate that intestinal deficiency in REG3B or REG3G increases numbers of mucosa-associated bacteria and enhances bacterial translocation to the mesenteric lymph nodes and liver, promoting the progression of ethanol-induced fatty liver disease toward steatohepatitis. Overexpression of Reg3g in intestinal epithelial cells restricts bacterial colonization of mucosal surfaces, reduces bacterial translocation, and protects mice from alcohol-induced steatohepatitis. Thus, alcohol appears to impair control of the mucosa-associated microbiota, and subsequent breach of the mucosal barrier facilitates progression of alcoholic liver disease. PMID:26867181

Computer-guided design of optimal microbial consortia for immune system modulation.

PubMed

Stein, Richard R; Tanoue, Takeshi; Szabady, Rose L; Bhattarai, Shakti K; Olle, Bernat; Norman, Jason M; Suda, Wataru; Oshima, Kenshiro; Hattori, Masahira; Gerber, Georg K; Sander, Chris; Honda, Kenya; Bucci, Vanni

2018-04-17

Manipulation of the gut microbiota holds great promise for the treatment of diseases. However, a major challenge is the identification of therapeutically potent microbial consortia that colonize the host effectively while maximizing immunologic outcome. Here, we propose a novel workflow to select optimal immune-inducing consortia from microbiome compositicon and immune effectors measurements. Using published and newly generated microbial and regulatory T-cell (T reg ) data from germ-free mice, we estimate the contributions of twelve Clostridia strains with known immune-modulating effect to T reg induction. Combining this with a longitudinal data-constrained ecological model, we predict the ability of every attainable and ecologically stable subconsortium in promoting T reg activation and rank them by the T reg Induction Score (TrIS). Experimental validation of selected consortia indicates a strong and statistically significant correlation between predicted TrIS and measured T reg . We argue that computational indexes, such as the TrIS, are valuable tools for the systematic selection of immune-modulating bacteriotherapeutics. © 2018, Stein et al.

TNF-alpha and IL-6 inhibit apolipoprotein A-IV production induced by linoleic acid in human intestinal Caco2 cells.

PubMed

Li, Xiaoming; Xu, Min; Liu, Min; Ji, Yong; Li, Zongfang

2015-01-01

Apolipoprotein A-IV (apoA-IV) is a protein mainly synthesized by enterocytes in the intestine. Its gene expression is suppressed during fasting and stimulated during active fat absorption. Chronic feeding of a high-fat (HF) diet abolishes the differential expression between fasting and fat-feeding and therefore may contribute to diet-induced obesity since apoA-IV is a potent satiety factor. It is well established that the circulating pro-inflammatory cytokines TNF-α and IL-6 are increased by HF feeding. To determine whether pro-inflammatory cytokines are involved in the diminished response of apoA-IV gene expression to fat-feeding, different concentrations of linoleic acid (LA), an important dietary fatty acid, was used to stimulate apoA-IV expression in human intestinal Caco2 cells. Cells were pre-treated with or without human recombinant TNF-α, IL-6 or their combination before the addition of LA. Real-time PCR and ELISA were used to detect and quantify RNA transcripts and proteins of apoA-IV and the cytokines. LA stimulated gene and protein expression of apoA-IV in a dose and time dependent manner. Pre-treatment with the cytokines for 72 h significantly inhibited the increased expression of apoA-IV gene and protein induced by LA. Furthermore, the cytokines, especially TNF-α, also positively up-regulate the cytokine themselves in Caco2 cells. Our data indicate that the pro-inflammatory cytokines may be responsible for the reduced apoA-IV production in response to fat feeding. Because of apoA-IV's role in satiety, we propose the inhibitory effect of circulating pro-inflammatory cytokines on apoA-IV production contributes to diet-induced obesity.

In-vitro generation of interleukin-10 secreting B-regulatory cells from donor adipose tissue derived mesenchymal stem cells and recipient peripheral blood mononuclear cells for potential cell therapy.

PubMed

Gupte, Kunal S; Vanikar, Aruna V; Trivedi, Hargovind L; Patel, Chetan N; Patel, Jignesh V

2017-02-01

Interleukin-10 secreting B-cells are a major subset of B-regulatory cells (B-regs), commonly recognized as CD19 + /38 hi /24 hi /IL10 + . They carry out immunomodulation by release of specific cytokines and/or cell-to-cell contact. We have generated B-regs in-vitro from donor adipose tissue derived mesenchymal stem cells (AD-MSC) and renal allograft recipient (RAR) peripheral blood mononuclear cells (PBMC) for potential cell therapy. Mononuclear cells separated by density gradient centrifugation from 50 ml anti-coagulated blood of 15-RAR and respective donors were analysed for baseline B-regs using appropriate antibodies. Equal amount (20 × 10 6  cells/ml) of stimulator (irradiated at 7.45 Gy/min for 10 min) and responder (non-irradiated) cells were co-cultured with in-vitro generated AD-MSC (1 × 10 6  cells/ml) in proliferation medium containing lipopolysaccharide from E. coli K12 strain at 37 °C with 5% CO 2 . Cells were harvested on day-7 and analyzed for viability, sterility, quantity, morphology and phenotyping. In-vitro generated B-reg levels were compared with baseline B-regs. In-vitro generated B-reg count increased to 16.75% from baseline count of 3.35%. B-regs can be successfully generated in-vitro from donor AD-MSC and RAR PBMC for potential cell therapy. Copyright © 2017 Chang Gung University. Published by Elsevier B.V. All rights reserved.

The effect of interleukin (IL)-21 and CD4+ CD25++ T cells on cytokine production of CD4+ responder T cells in patients with myasthenia gravis.

PubMed

Alahgholi-Hajibehzad, M; Durmuş, H; Aysal, F; Gülşen-Parman, Y; Oflazer, P; Deymeer, F; Saruhan-Direskeneli, G

2017-11-01

Impairment of the suppressive function of regulatory T (T reg ) cells has been reported in myasthenia gravis (MG). In this study, cytokine-related mechanisms that may lead to the defect of T reg were investigated in patients with anti-acetylcholine receptor antibody-positive MG (AChR + MG). Proliferation and cytokine production of responder T (T resp ) cells in response to polyclonal activation were measured in a suppression assay. The effect of interleukin (IL)-21 on suppression was evaluated in vitro in co-culture. IL-21 increased the proliferation of T resp cells in T resp /T reg co-cultures. T resp cells from patients with MG secreted significantly lower levels of IL-2. In patients with MG, IL-2 levels did not change with the addition of T reg to cultures, whereas it decreased significantly in controls. In T resp /T reg co-cultures, IL-4, IL-6 and IL-10 production increased in the presence of T reg in patients. Interferon (IFN)-γ was decreased, whereas IL-17A was increased in both patient and control groups. IL-21 inhibited the secretion of IL-4 in MG and healthy controls (HC), and IL-17A in HC only. The results demonstrated that IL-21 enhances the proliferation of T resp cells in the presence of T reg . An effect of IL-21 mainly on T resp cells through IL-2 is implicated. © 2017 British Society for Immunology.

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients.

PubMed

Saison, J; Ferry, T; Demaret, J; Maucort Boulch, D; Venet, F; Perpoint, T; Ader, F; Icard, V; Chidiac, C; Monneret, G

2014-06-01

The mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active anti-retroviral therapy (HAART) remain elusive. Immune activation, regulatory T cells (T(regs)) or very low-level viraemia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. We performed a cross-sectional study in HIV-infected aviraemic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters associated independently with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39), depending on the CD4(+) T cell count (> or < 500/mm(3)). Clinical and virological data (including very low-level viraemia) were collected. In parallel, immunophenotyping of CD4(+) lymphocytes, including T(reg) subsets, and CD8(+) T cells was performed. Percentages of activated CD4(+) T cells, T(regs), effector T(regs) and terminal effector T(regs) were found to be significantly elevated in iIR. Neither the percentage of activated CD8(+) T cells nor VLLV were found to be associated with iIR. In the multivariate analysis, nadir of CD4(+) T cell count and percentage of T(regs) were the only two parameters associated independently with iIR [odds ratio (OR) = 2·339, P = 0·001, and OR = 0·803, P = 0·041]. We present here the largest study investigating simultaneously the immune response to long-term HAART, activation of CD4(+) and CD8(+) T cells, T(reg) percentages and very low-level viraemia. Causative interactions between T(regs) and CD4(+) T cells should now be explored prospectively in a large patients cohort. © 2014 British Society for Immunology.

The nature of electron acceptor (MnIV/NO3) triggers differential expression of genes associated with stress and ammonium limitation responses in Shewanella algae C6G3.

PubMed

Aigle, Axel; Bonin, Patricia; -Nunez, Nicolas Fernandez; Loriod, Béatrice; Guasco, Sophie; Bergon, Aurélie; Armougom, Fabrice; Iobbi-Nivol, Chantal; Imbert, Jean; Michotey, Valérie

2018-03-16

Shewanella algae C6G3 can reduce dissimilatively nitrate into ammonium and manganese-oxide (MnIV) into MnII. It has the unusual ability to produce anaerobically nitrite from ammonium in the presence of MnIV. To gain insight into their metabolic capabilities, global mRNA expression patterns were investigated by RNA-seq and qRT-PCR in cells growing with lactate and ammonium as carbon and nitrogen sources and with either MnIV or nitrate as electron acceptors. Gene exhibiting higher expression levels in the presence of MnIV belonged to functional categories of carbohydrate, coenzyme, lipid metabolisms and inorganic ion transport. Comparative transcriptomic pattern between MnIV and NO3 revealed that the strain presented an ammonium limitation status with MnIV, despite the presence of non-limiting concentration of ammonium under both culture conditions. In addition, in presence of MnIV, ntrB/nrtC regulators, ammonium channel, nitrogen regulatory protein P-II, glutamine synthetase and asparagine synthetase glutamine dependent genes were over-represented. Under nitrate condition, the expression of genes involved in the synthesis of several amino acids was increased. Finally, expression level of genes associated with the general stress response was also amplified and among them, katE, a putative catalase/peroxidase present on several Shewanella genomes, was highly expressed with a relative median value higher in MnIV condition.

Production of extended release mini-tablets using directly compressible grades of HPMC.

PubMed

Mohamed, Faiezah A A; Roberts, Matthew; Seton, Linda; Ford, James L; Levina, Marina; Rajabi-Siahboomi, Ali R

2013-11-01

Hypromellose (HPMC) has been previously used to control drug release from mini-tablets. However, owing to poor flow, production of mini-tablets containing high HPMC levels is challenging. Directly compressible (DC) HPMC grades have been developed by Dow Chemical Company. To compare the properties of HPMC DC (METHOCEL™ K4M and K100M) with regular (REG) HPMC grades. Particle size distribution and flowability of HPMC REG and DC were evaluated. 3 mm mini-tablets, containing hydrocortisone or theophylline as model drugs and 40% w/w HPMC DC or REG were produced. Mini-tablets containing HPMC DC grades were manufactured using a rotary press simulator at forces between 2-4 kN and speeds of 5, 10, 15 or 20 rpm. Mini-tablets containing HPMC REG were produced manually. The improved flowability of HPMC DC grades, which have a narrower particle size distribution and larger particle sizes, meant that simulated large scale production of mini-tablets with good weight uniformity (CV 1.79-4.65%) was feasible. It was not possible to automatically manufacture mini-tablets containing HPMC REG due to the poor flowability of the formulations. Drug release from mini-tablets comprising HPMC DC and REG were comparable. Mini-tablets containing HPMC DC illustrated a higher tensile strength compared to mini-tablets made with HPMC REG. Mini-tablets produced with HPMC DC at different compression speeds had similar drug release profiles. Production of extended release mini-tablets was successfully achieved when HPMC DC was used. Drug release rate was not influenced by the different HPMC DC grades (K4M or K100M) or production speed.

The accumulation of regulatory T cells in the hepatic hilar lymph nodes in biliary atresia.

PubMed

Sakamoto, Naoya; Muraji, Toshihiro; Ohtani, Haruo; Masumoto, Kouji

2017-10-01

A proposed etiopathogenesis of biliary atresia (BA) involves T-cell-mediated inflammatory bile duct damage and progressive hepatic fibrosis. Pediatric surgeons often observe swelling of the hepatic hilar lymph nodes during the Kasai procedure. Given the importance of regulatory mechanisms in immune responses, the present study was designed to analyze the quantitative changes of regulatory T cells (T reg cells) in the hepatic hilar lymph nodes (hepatic hilar LNs) and peripheral blood (PB) in BA. The hepatic hilar LNs and PB obtained during the Kasai procedure were analyzed by flow cytometry. The ratios of total and active Tregs to the total CD4 + cells in the PB and the hepatic hilar LNs were compared. In patients with BA, the ratios of both the total and active T reg cells in the hepatic hilar LNs were higher than those in the PB (total T reg cells: PB vs. LN; P < 0.001; active T reg cells: PB vs. LN; P = 0.001). In BA patients, the increase in the ratio of active T reg cells to the CD4 + cells in the LNs in comparison to the PB was greater than that in control patients. The ratio observed in the BA patients was almost double the ratio observed in the control patients. The median LN/PB ratio in the BA patients was 3.1, while that in controls was 1.6 (P = 0.03). The present study showed that the ratios of both total T reg cells and active T reg cells were higher in the hepatic hilar lymph nodes of BA patients. This finding could shed light on the pathogenesis of BA.

Cigarette advertising and children's smoking: why Reg was withdrawn.

PubMed

Hastings, G B; Ryan, H; Teer, P; MacKintosh, A M

1994-10-08

To examine the appeal of the Embassy Regal "Reg" campaign to young people. Three quantitative surveys and one piece of qualitative research: (a) self completion questionnaire administered in classrooms, (b) questionnaire led interviews with children, (c) questionnaire led interviews with adults, and (d) group discussions with children and adults. (a) Secondary and middle schools in England; (b) north of England, Scotland, and Wales; (c) north of England, Scotland, and Wales; and (d) Glasgow. (a) 5451 schoolchildren aged 11-15 recruited by stratified random sampling; (b) 437 children aged 5-10 recruited by quota sampling; (c) 814 adults aged 15-65 recruited by quota sampling; and (d) 12 groups of children aged 10-15, three groups of adults aged 18-24, and three groups of adults aged 35-55. Children were familiar with cigarette advertising and in particular the Reg campaign. Although younger children struggled to understand the creative content of the adverts, older and smoking children could understand and appreciate the humour. They considered Reg to be amusing and could relate to the type of joke used in the advert. In addition Reg's flippant attitude towards serious issues appealed to the children. While adults aged 18-24 understood the campaign they did not identify with it, and 35-55 year olds (the campaign's supposed target) were unappreciative of the campaign. The Reg campaign was getting through to children more effectively than it was to adults and held most appeal for teenagers, particularly 14-15 year old smokers. It clearly contravened the code governing tobacco advertising, which states that advertising must not appeal to children more than it does to adults, and it may have had a direct impact on teenage smoking. In view of these findings the Advertising Standards Authority's decision to withdraw the Reg campaign seems appropriate.

Regorafenib-induced hypothyroidism and cancer-related fatigue: is there a potential link?

PubMed

Pani, Fabiana; Massidda, Matteo; Pusceddu, Valeria; Puzzoni, Marco; Massa, Elena; Madeddu, Clelia; Scartozzi, Mario; Mariotti, Stefano

2017-07-01

Thyroid dysfunction has been reported during Regorafenib (Reg) administration, but no detailed study is presently available. Prospective, observational cohort study. Patients with documented metastatic colorectal cancer and progression of disease during or within 3 months after the last standard therapy, with no evidence and history of previous thyroid disease were enrolled. Twenty-five consecutive patients were evaluated before and 8-50 weeks after initiating Reg therapy by monthly clinical, ultrasound and laboratory (thyrotropin (TSH), free thyroxine (fT4), antithyroglobulin (TgAb) and antithyroid peroxidase (TPOAb)) evaluation. Thirteen/25 patients (52%) became hypothyroid (TSH: 12.5 ± 4.01 IU/L, range: 4.6-22.0) within 5 months of therapy. TPOAb became detectable (99-155 IU/mL) in 2/25 (8%) patients. Thyroid volume progressively decreased (from 8.6  ±  2.2 mL to 4.9 ± 2.4 mL after 5 months of Reg therapy, P  < 0.0001). The progression-free survival (PFS) was longer in patients developing hypothyroidism (43 weeks) than in those remaining euthyroid (17 weeks, P  < 0.01). Fatigue (the most common general serious Reg adverse event) was associated with hypothyroidism severity and reversed after levothyroxine therapy (L-T4). Reg rapidly causes hypothyroidism in about 50% of patients and in a minority of them also triggers thyroid autoimmunity. Reg-induced hypothyroidism was strictly related to fatigue, easily reversed by L-T4 administration and associated to longer survival. These results suggest that prompt recognition of hypothyroidism in patients with severe fatigue may prevent unnecessary Reg dose reduction or withdrawal. © 2017 European Society of Endocrinology.

A finite element analysis modeling tool for solid oxide fuel cell development: coupled electrochemistry, thermal and flow analysis in MARC®

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

Khaleel, Mohammad A.; Lin, Zijing; Singh, Prabhakar

2004-05-03

A 3D simulation tool for modeling solid oxide fuel cells is described. The tool combines the versatility and efficiency of a commercial finite element analysis code, MARC{reg_sign}, with an in-house developed robust and flexible electrochemical (EC) module. Based upon characteristic parameters obtained experimentally and assigned by the user, the EC module calculates the current density distribution, heat generation, and fuel and oxidant species concentration, taking the temperature profile provided by MARC{reg_sign} and operating conditions such as the fuel and oxidant flow rate and the total stack output voltage or current as the input. MARC{reg_sign} performs flow and thermal analyses basedmore » on the initial and boundary thermal and flow conditions and the heat generation calculated by the EC module. The main coupling between MARC{reg_sign} and EC is for MARC{reg_sign} to supply the temperature field to EC and for EC to give the heat generation profile to MARC{reg_sign}. The loosely coupled, iterative scheme is advantageous in terms of memory requirement, numerical stability and computational efficiency. The coupling is iterated to self-consistency for a steady-state solution. Sample results for steady states as well as the startup process for stacks with different flow designs are presented to illustrate the modeling capability and numerical performance characteristic of the simulation tool.« less

Vegetation limits the impact of a warm climate on boreal wildfires.

PubMed

Girardin, Martin P; Ali, Adam A; Carcaillet, Christopher; Blarquez, Olivier; Hély, Christelle; Terrier, Aurélie; Genries, Aurélie; Bergeron, Yves

2013-09-01

Strategic introduction of less flammable broadleaf vegetation into landscapes was suggested as a management strategy for decreasing the risk of boreal wildfires projected under climatic change. However, the realization and strength of this offsetting effect in an actual environment remain to be demonstrated. Here we combined paleoecological data, global climate models and wildfire modelling to assess regional fire frequency (RegFF, i.e. the number of fires through time) in boreal forests as it relates to tree species composition and climate over millennial time-scales. Lacustrine charcoals from northern landscapes of eastern boreal Canada indicate that RegFF during the mid-Holocene (6000-3000 yr ago) was significantly higher than pre-industrial RegFF (AD c. 1750). In southern landscapes, RegFF was not significantly higher than the pre-industrial RegFF in spite of the declining drought severity. The modelling experiment indicates that the high fire risk brought about by a warmer and drier climate in the south during the mid-Holocene was offset by a higher broadleaf component. Our data highlight an important function for broadleaf vegetation in determining boreal RegFF in a warmer climate. We estimate that its feedback may be large enough to offset the projected climate change impacts on drought conditions. © 2013 Her Majesty the Queen in Right of Canada New Phytologist © 2013 New Phytologist Trust.

Bacterially-Associated Transcriptional Remodelling in a Distinct Genomic Subtype of Colorectal Cancer Provides a Plausible Molecular Basis for Disease Development

PubMed Central

Goosen, Ryan W.

2016-01-01

The relevance of specific microbial colonisation to colorectal cancer (CRC) disease pathogenesis is increasingly recognised, but our understanding of possible underlying molecular mechanisms that may link colonisation to disease in vivo remains limited. Here, we investigate the relationships between the most commonly studied CRC-associated bacteria (Enterotoxigenic Bacteroides fragilis, pks+ Escherichia coli, Fusobacterium spp., afaC+ E. coli, Enterococcus faecalis & Enteropathogenic E. coli) and altered transcriptomic and methylation profiles of CRC patients, in order to gain insight into the potential contribution of these bacteria in the aetiopathogenesis of CRC. We show that colonisation by E. faecalis and high levels of Fusobacterium is associated with a specific transcriptomic subtype of CRC that is characterised by CpG island methylation, microsatellite instability and a significant increase in inflammatory and DNA damage pathways. Analysis of the significant, bacterially-associated changes in host gene expression, both at the level of individual genes as well as pathways, revealed a transcriptional remodeling that provides a plausible mechanistic link between specific bacterial colonisation and colorectal cancer disease development and progression in this subtype; these included upregulation of REG3A, REG1A and REG1P in the case of high-level colonization by Fusobacterium, and CXCL10 and BMI1 in the case of colonisation by E. faecalis. The enrichment of both E. faecalis and Fusobacterium in this CRC subtype suggests that polymicrobial colonisation of the colonic epithelium may well be an important aspect of colonic tumourigenesis. PMID:27846243

Culture promotes transfer of thyroid epithelial cell hyperplasia and proliferation by reducing regulatory T cell numbers.

PubMed

Kayes, Timothy D; Braley-Mullen, Helen

2013-01-01

IFN-γ(-/-) NOD.H-2h4 mice develop a spontaneous autoimmune thyroid disease, thyroid epithelial cell hyperplasia and proliferation (TEC H/P) when given NaI in their water for 7+ mo. TEC H/P can be transferred to IFN-γ(-/-) SCID mice by splenocytes from mice with severe (4-5+) disease, and transfer of TEC H/P is improved when splenocytes are cultured prior to transfer. Older (9+ mo) IFN-γ(-/-) NOD.H-2h4 mice have elevated numbers of FoxP3(+) T reg cells, up to 2-fold greater than younger (2 mo) mice. During culture, the number of T reg decreases and this allows the improved transfer of TEC H/P. Co-culture with IL-2 prior to transfer prevents the decrease of T reg and improves their in vitro suppressive ability resulting in reduced TEC H/P in recipient mice. Therefore, culturing splenocytes improves transfer of TEC H/P by reducing the number of T reg and IL-2 inhibits transfer by preserving T reg number and function. Copyright © 2013 Elsevier Inc. All rights reserved.

Online EEG artifact removal for BCI applications by adaptive spatial filtering.

PubMed

Guarnieri, Roberto; Marino, Marco; Barban, Federico; Ganzetti, Marco; Mantini, Dante

2018-06-28

The performance of brain computer interfaces (BCIs) based on electroencephalography (EEG) data strongly depends on the effective attenuation of artifacts that are mixed in the recordings. To address this problem, we have developed a novel online EEG artifact removal method for BCI applications, which combines blind source separation (BSS) and regression (REG) analysis. The BSS-REG method relies on the availability of a calibration dataset of limited duration for the initialization of a spatial filter using BSS. Online artifact removal is implemented by dynamically adjusting the spatial filter in the actual experiment, based on a linear regression technique. Our results showed that the BSS-REG method is capable of attenuating different kinds of artifacts, including ocular and muscular, while preserving true neural activity. Thanks to its low computational requirements, BSS-REG can be applied to low-density as well as high-density EEG data. We argue that BSS-REG may enable the development of novel BCI applications requiring high-density recordings, such as source-based neurofeedback and closed-loop neuromodulation. © 2018 IOP Publishing Ltd.

Initial Examination of Low Velocity Sphere Impact of Glass Ceramics

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

Morrissey, Timothy G; Fox, Ethan E; Wereszczak, Andrew A

This report summarizes US Army TARDEC sponsored work at Oak Ridge National Laboratory (ORNL) involving low velocity (< 30 m/s or < 65 mph) sphere impact testing of two materials from the lithium aluminosilicate family reinforced with different amounts of ceramic particulate, i.e., glass-ceramic materials, SCHOTT Resistan{trademark}-G1 and SCHOTT Resistan{trademark}-L. Both materials are provided by SCHOTT Glass (Duryea, PA). This work is a follow-up to similar sphere impact studies completed by the authors on PPG's Starphire{reg_sign} soda-lime silicate glass and SCHOTT BOROFLOAT{reg_sign} borosilicate glass. A gas gun or a sphere-drop test setup was used to produce controlled velocity delivery ofmore » silicon nitride (Si{sub 3}N{sub 4}) spheres against the glass ceramic tile targets. Minimum impact velocities to initiate fracture in the glass-ceramics were measured and interpreted in context to the kinetic energy of impact and the elastic property mismatch between sphere and target material. Quasistatic spherical indentation was also performed on both glass ceramics and their contact damage responses were compared to those of soda-lime silicate and borosilicate glasses. Lastly, variability of contact damage response was assessed by performing spherical indentation testing across the area of an entire glass ceramic tile. The primary observations from this low velocity (< 30 m/s or < 65 mph) testing were: (1) Resistan{trademark}-L glass ceramic required the highest velocity of sphere impact for damage to initiate. Starphire{reg_sign} soda-lime silicate glass was second best, then Resistan{trademark}-G1 glass ceramic, and then BOROFLOAT{reg_sign} borosilicate glass. (2) Glass-ceramic Resistan{trademark}-L also required the largest force to initiate ring crack from quasi-static indentation. That ranking was followed, in descending order, by Starphire{reg_sign} soda-lime silicate glass, Resistan{trademark}-G1 glass ceramic, and BOROFLOAT{reg_sign} borosilicate glass. (3) Spheres with a lower elastic modulus require less force to initiate fracture in Resistan{trademark}-G1 from quasi-static spherical indentation. This indicates that friction is affecting ring crack initiation in Resistan{trademark}-G1. Friction also affected ring crack initiation in Starphire{reg_sign} soda-lime silicate and BOROFLOAT{reg_sign} borosilicate glasses. Among these three materials, friction was the most pronounced (largest slope in the RCIF-elastic modulus graph) in the Starphire{reg_sign} and least pronounced in the BOROFLOAT{reg_sign}. The reason for this is not understood, but differences in deformation behavior under high contact stresses could be a cause or contributor to this. (4) The force necessary to initiate contact-induced fracture is higher under dynamic conditions than it is under quasi-static conditions in Resistan{trademark}-L and Resistan{trademark}-G1 glass ceramics. This is a trend observed too in Starphire{reg_sign} and BOROFLOAT{reg_sign}. (5) There is a subtle indication there was intra-tile differences in spherical indentation-induced ring crack initiation forces. This is not a material property nor is it exclusive to glass-ceramic Resistan{trademark}-G1 glass ceramic, rather, it is a statistical mechanical response to an accumulated history of processing and handling of that specific tile.« less

Alterations of type IV collagen alpha chains in patients with chronic acquired glomerulopathies: mRNA levels, protein expression and urinary loss.

PubMed

Sanna-Cherchi, Simone; Carnevali, Maria Luisa; Martorana, Davide; Cravedi, Paolo; Maggiore, Umberto; Alinovi, Rossella; Bovino, Achiropita; Mattei, Silvia; Orlandini, Guido; Gatti, Rita; Savi, Mario; Sado, Yoshikazu; Neri, Tauro M; Allegri, Landino

2007-01-01

Type IV collagen is a major structural component of the normal kidney glomerulus. However, its role in chronic acquired glomerulopathies has been only partially elucidated. Urinary levels of col(IV)alpha1, col(IV)alpha3 and col(IV)alpha5 collagen chains were analyzed in 107 patients with chronic acquired glomerulopathies. In a subgroup of 33 patients, tissue mRNA levels, protein expression and urinary excretion were evaluated for all col(IV)alpha chains, from col(IV)alpha1 to col(IV)alpha5. The renal specimens were examined to get a semiquantitative score of the acute and chronic activity of the histological lesions. Urines obtained from 13 healthy subjects and 10 normal renal tissue samples were used as controls. Urinary levels of col(IV)alpha1, col(IV)alpha3, col(IV)alpha5 chains were significantly higher in patients than in controls [p < 0.01 for all], while only col(IV)alpha1 and col(IV)alpha3 urinary excretion correlated with the degree of chronic histological damage [col(IV)alpha1 R = 0.44, p < 0.001; col(IV)alpha3: R = 0.47, p < 0.001]. Compared with controls, patients showed a renal expression of mRNA for col(IV)alpha5 chain significantly higher [p = 0.001], while having a significantly lower protein expression of col(IV)alpha3, col(IV)alpha4 and col(IV)alpha5 chains [p < 0.01 for all]. Patients with chronic acquired glomerulopathies show important alterations in the col(IV)alpha chain network mimicking some molecular features of the X-linked Alport's syndrome. Further studies are needed to show whether urinary levels of the col(IV)alpha chains may be used as markers for monitoring renal injury. Copyright 2007 S. Karger AG, Basel.

Mutant HNF-1{alpha} and mutant HNF-1{beta} identified in MODY3 and MODY5 downregulate DPP-IV gene expression in Caco-2 cells

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

Gu Ning; Laboratory of Neurochemistry, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto; Adachi, Tetsuya

2006-08-04

Dipeptidylpeptidase IV (DPP-IV) is a well-documented drug target for the treatment of type 2 diabetes. Hepatocyte nuclear factors (HNF)-1{alpha} and HNF-1{beta}, known as the causal genes of MODY3 and MODY5, respectively, have been reported to be involved in regulation of DPP-IV gene expression. But, it is not completely clear (i) that they play roles in regulation of DPP-IV gene expression, and (ii) whether DPP-IV gene activity is changed by mutant HNF-1{alpha} and mutant HNF-1{beta} in MODY3 and MODY5. To explore these questions, we investigated transactivation effects of wild HNF-1{alpha} and 13 mutant HNF-1{alpha}, as well as wild HNF-1{beta} and 2more » mutant HNF-1{beta}, on DPP-IV promoter luciferase gene in Caco-2 cells by means of a transient experiment. Both wild HNF-1{alpha} and wild HNF-1{beta} significantly transactivated DPP-IV promoter, but mutant HNF-1{alpha} and mutant HNF-1{beta} exhibited low transactivation activity. Moreover, to study whether mutant HNF-1{alpha} and mutant HNF-1{beta} change endogenous DPP-IV enzyme activity, we produced four stable cell lines from Caco-2 cells, in which wild HNF-1{alpha} or wild HNF-1{beta}, or else respective dominant-negative mutant HNF-1{alpha}T539fsdelC or dominant-negative mutant HNF-1{beta}R177X, was stably expressed. We found that DPP-IV gene expression and enzyme activity were significantly increased in wild HNF-1{alpha} cells and wild HNF-1{beta} cells, whereas they decreased in HNF-1{alpha}T539fsdelC cells and HNF-1{beta}R177X cells, compared with DPP-IV gene expression and enzyme activity in Caco-2 cells. These results suggest that both wild HNF-1{alpha} and wild HNF-1{beta} have a stimulatory effect on DPP-IV gene expression, but that mutant HNF-1{alpha} and mutant HNF-1{beta} attenuate the stimulatory effect.« less

Vagal nerve stimulation modulates the dendritic cell profile in posthemorrhagic shock mesenteric lymph.

PubMed

Morishita, Koji; Costantini, Todd W; Eliceiri, Brian; Bansal, Vishal; Coimbra, Raul

2014-03-01

Previous studies have established that posthemorrhagic shock mesenteric lymph (PHSML) contains proinflammatory mediators, while the cellular basis of PHSML is less well characterized in acute models of injury. CD103 dendritic cells (DCs) have been identified in the mesenteric lymph (ML) in models of chronic intestinal inflammation, suggesting an important role in the gut response to injury. We have previously demonstrated the ability of vagal nerve stimulation (VNS) to prevent gut barrier failure after trauma/hemorrhagic shock (T/HS); however, the ability of VNS to alter ML DCs is unknown. We hypothesized that the CD103 MHC-II DC population would change in PHSML and that VNS would prevent injury-induced changes in this population in PHSML. Male Sprague-Dawley rats were randomly assigned to trauma/sham shock or T/HS. T/HS was induced by midline laparotomy and 60 minutes of HS (blood pressure, 35 mm Hg), followed by fluid resuscitation. A separate cohort of animals underwent cervical VNS after the HS phase. Gut tissue was harvested at 2 hours after injury for histologic analysis. ML was collected during the pre-HS, HS, and post-HS phase. For flow cytometric analysis, ML cells were subjected to staining with CD103 and MHC-II antibodies, and this cell population was compared in the pre-HS and post-HS phase from the same animal. The CD4Foxp3 cell (T reg) population in the ML node (MLN) was also tested to determine effects of CD103 DC modulation in the ML. VNS reduced histologic gut injury and ML flow seen after injury. The CD103 MHC-II DC population in the PHSML was significantly decreased compared with pre-HS and was associated with decreased T reg expression in the MLN. VNS prevented the injury-induced decrease in the CD103 MHC-II+ DC population in the ML and restored the T reg population in the MLN. These findings suggest that VNS mediates the inflammatory responses in ML DCs and MLN T reg cells by affecting the set point of T/HS responsiveness.

75 FR 5890 - Suspension of Community Eligibility

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-05

...; May 19, 1992, Reg; February 17, 2010, Susp. Ross, Township of, 260624 July 24, 1975, ......do Do.... Evanston, City of, Uinta 560054 March 23, 1977, ......do Do. County. Emerg; January 15, 1988, Reg; February...

The effects of moderate exercise on chronic stress-induced intestinal barrier dysfunction and antimicrobial defense.

PubMed

Luo, Beibei; Xiang, Dao; Nieman, David C; Chen, Peijie

2014-07-01

The purpose of this study was to examine the effect of moderate exercise on repeated restraint stress (RRS)-induced intestinal barrier dysfunction and explore possible mechanisms in a mouse model. Male Balb/c mice (6weeks) were randomized into 7 groups: CON functioned as controls with no intervention; RRS was subjected to 6h per day RRS for 7 consecutive days; RRS+SWIM received 30min per day of swimming prior to RRS; CON+SWIM only received 30min per day of swimming; and the other groups received one session of 30min swimming prior to sacrifice at 1-, 3- and 6h recovery. Intestinal permeability was quantified with FITC-dextran. Bacterial translocation was determined by quantification of bacterial colony forming units (CFUs) in cultured mesenteric lymph nodes (MLN), and with fluorescence in situ hybridization (FISH). Antimicrobial related gene expression at baseline and 1h after one session of 30min swimming was tested by quantitative real-time polymerase chain reaction (Q-PCR) in small intestinal segments. Protein expression of 5 genes with statistically significant increase was measured at baseline, and 1-, 3- and 6h post-swimming using enzyme-linked immunosorbent assay (ELISA). Thirty minutes per day of swimming before RRS attenuated bacterial translocations and maintained intestinal permeability. Gene expression and protein levels for four antimicrobial peptides (α-defensin 5, β-defensin 1, RegIIIβ and RegIIIγ) were significantly increased after one 30min swimming session. In conclusion, moderate exercise attenuated chronic stress-induced intestinal barrier dysfunction in mice, possibly due to augmentation of antimicrobial responses in the small intestine. Copyright © 2013 Elsevier Inc. All rights reserved.

CoryneRegNet 3.0--an interactive systems biology platform for the analysis of gene regulatory networks in corynebacteria and Escherichia coli.

PubMed

Baumbach, Jan; Wittkop, Tobias; Rademacher, Katrin; Rahmann, Sven; Brinkrolf, Karina; Tauch, Andreas

2007-04-30

CoryneRegNet is an ontology-based data warehouse for the reconstruction and visualization of transcriptional regulatory interactions in prokaryotes. To extend the biological content of CoryneRegNet, we added comprehensive data on transcriptional regulations in the model organism Escherichia coli K-12, originally deposited in the international reference database RegulonDB. The enhanced web interface of CoryneRegNet offers several types of search options. The results of a search are displayed in a table-based style and include a visualization of the genetic organization of the respective gene region. Information on DNA binding sites of transcriptional regulators is depicted by sequence logos. The results can also be displayed by several layouters implemented in the graphical user interface GraphVis, allowing, for instance, the visualization of genome-wide network reconstructions and the homology-based inter-species comparison of reconstructed gene regulatory networks. In an application example, we compare the composition of the gene regulatory networks involved in the SOS response of E. coli and Corynebacterium glutamicum. CoryneRegNet is available at the following URL: http://www.cebitec.uni-bielefeld.de/groups/gi/software/coryneregnet/.

Stadis{reg_sign} 450 in Merox-sweetened jet fuels

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

Henry, C.P.

1995-05-01

Stadis{reg_sign} 450 has been used in aviation fuels since 1983, and in many cases is the additive of choice due to conductivity retention of treated fuels during distribution, and other characteristics. In the past several years, manufacture of Shell ASA-3 (the other aviation-approved static dissipator additive) has been discontinued; current stores are being drawn down and for some refiners conversion from ASA-3 to Stadis{reg_sign} 450 is underway. In fuels sweetened by hydrogen-treating, Stadis{reg_sign} 450 performs very well and there are few reported difficulties. Chemically sweetened fuels sometimes contain trace materials not removed by the sweetening process. When treated with Stadis{reg_sign}more » 450 some of these fuels have exhibited two behaviors which are being addressed: in one case, the formation of a precipitate which disarmed coalescers; in several other cases, reduced conductivity response and loss of conductivity during storage coupled with unusually large effects on the microseparatometer water separation properties. In late 1992, a Coordinating Research Council (CRC) Panel on Coalescer Deactivation was formed to address these problems. The results of DuPont and CRC efforts are discussed, along with actions taken and underway to eliminate these problems.« less

75 FR 19891 - Suspension of Community Eligibility

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-16

..., St. Clair County. Emerg; December 15, 1978, Reg; May 3, 2010, Susp. Ira, Township of, St. 260199... 310191 April 13, 1973, ......do -Do-. County. Emerg; January 16, 1980, Reg; May 3, 2010, Susp. La Vista...

21 CFR 177.2910 - Ultra-filtration membranes.

Code of Federal Regulations, 2010 CFR

2010-04-01

... of a sintered carbon support that is coated with zirconium oxide (CAS Reg. No. 1314-23-4) containing... of an aluminum oxide support that is coated with zirconium oxide (CAS Reg. No. 1314-23-4) containing...

Astragaloside IV inhibits pathological functions of gastric cancer-associated fibroblasts.

PubMed

Wang, Zhen-Fei; Ma, Da-Guang; Zhu, Zhe; Mu, Yong-Ping; Yang, Yong-Yan; Feng, Li; Yang, Hao; Liang, Jun-Qing; Liu, Yong-Yan; Liu, Li; Lu, Hai-Wen

2017-12-28

To investigate the inhibitory effect of astragaloside IV on the pathological functions of cancer-associated fibroblasts, and to explore the underlying mechanism. Paired gastric normal fibroblast (GNF) and gastric cancer-associated fibroblast (GCAF) cultures were established from resected tissues. GCAFs were treated with vehicle control or different concentrations of astragaloside IV. Conditioned media were prepared from GNFs, GCAFs, control-treated GCAFs, and astragaloside IV-treated GCAFs, and used to culture BGC-823 human gastric cancer cells. Proliferation, migration and invasion capacities of BGC-823 cells were determined by MTT, wound healing, and Transwell invasion assays, respectively. The action mechanism of astragaloside IV was investigated by detecting the expression of microRNAs and the expression and secretion of the oncogenic factor, macrophage colony-stimulating factor (M-CSF), and the tumor suppressive factor, tissue inhibitor of metalloproteinase 2 (TIMP2), in different groups of GCAFs. The expression of the oncogenic pluripotency factors SOX2 and NANOG in BGC-823 cells cultured with different conditioned media was also examined. GCAFs displayed higher capacities to induce BGC-823 cell proliferation, migration, and invasion than GNFs ( P < 0.01). Astragaloside IV treatment strongly inhibited the proliferation-, migration- and invasion-promoting capacities of GCAFs ( P < 0.05 for 10 μmol/L, P < 0.01 for 20 μmol/L and 40 μmol/L). Compared with GNFs, GCAFs expressed a lower level of microRNA-214 ( P < 0.01) and a higher level of microRNA-301a ( P < 0.01). Astragaloside IV treatment significantly up-regulated microRNA-214 expression ( P < 0.01) and down-regulated microRNA-301a expression ( P < 0.01) in GCAFs. Reestablishing the microRNA expression balance subsequently suppressed M-CSF production ( P < 0.01) and secretion ( P < 0.05), and elevated TIMP2 production ( P < 0.01) and secretion ( P < 0.05). Consequently, the ability of GCAFs to increase SOX2 and NANOG expression in BGC-823 cells was abolished by astragaloside IV. Astragaloside IV can inhibit the pathological functions of GCAFs by correcting their dysregulation of microRNA expression, and it is promisingly a potent therapeutic agent regulating tumor microenvironment.

Astragaloside IV inhibits pathological functions of gastric cancer-associated fibroblasts

PubMed Central

Wang, Zhen-Fei; Ma, Da-Guang; Zhu, Zhe; Mu, Yong-Ping; Yang, Yong-Yan; Feng, Li; Yang, Hao; Liang, Jun-Qing; Liu, Yong-Yan; Liu, Li; Lu, Hai-Wen

2017-01-01

AIM To investigate the inhibitory effect of astragaloside IV on the pathological functions of cancer-associated fibroblasts, and to explore the underlying mechanism. METHODS Paired gastric normal fibroblast (GNF) and gastric cancer-associated fibroblast (GCAF) cultures were established from resected tissues. GCAFs were treated with vehicle control or different concentrations of astragaloside IV. Conditioned media were prepared from GNFs, GCAFs, control-treated GCAFs, and astragaloside IV-treated GCAFs, and used to culture BGC-823 human gastric cancer cells. Proliferation, migration and invasion capacities of BGC-823 cells were determined by MTT, wound healing, and Transwell invasion assays, respectively. The action mechanism of astragaloside IV was investigated by detecting the expression of microRNAs and the expression and secretion of the oncogenic factor, macrophage colony-stimulating factor (M-CSF), and the tumor suppressive factor, tissue inhibitor of metalloproteinase 2 (TIMP2), in different groups of GCAFs. The expression of the oncogenic pluripotency factors SOX2 and NANOG in BGC-823 cells cultured with different conditioned media was also examined. RESULTS GCAFs displayed higher capacities to induce BGC-823 cell proliferation, migration, and invasion than GNFs (P < 0.01). Astragaloside IV treatment strongly inhibited the proliferation-, migration- and invasion-promoting capacities of GCAFs (P < 0.05 for 10 μmol/L, P < 0.01 for 20 μmol/L and 40 μmol/L). Compared with GNFs, GCAFs expressed a lower level of microRNA-214 (P < 0.01) and a higher level of microRNA-301a (P < 0.01). Astragaloside IV treatment significantly up-regulated microRNA-214 expression (P < 0.01) and down-regulated microRNA-301a expression (P < 0.01) in GCAFs. Reestablishing the microRNA expression balance subsequently suppressed M-CSF production (P < 0.01) and secretion (P < 0.05), and elevated TIMP2 production (P < 0.01) and secretion (P < 0.05). Consequently, the ability of GCAFs to increase SOX2 and NANOG expression in BGC-823 cells was abolished by astragaloside IV. CONCLUSION Astragaloside IV can inhibit the pathological functions of GCAFs by correcting their dysregulation of microRNA expression, and it is promisingly a potent therapeutic agent regulating tumor microenvironment. PMID:29358859

Therapeutic effect of astragaloside-IV on bradycardia is involved in up-regulating klotho expression.

PubMed

Qiu, Xuejia; Guo, Qiao; Xiong, Wei; Yang, Xia; Tang, Yi-qun

2016-01-01

In order to determine whether klotho is involved in the therapeutic effects of Astragaloside-IV on bradycardia, we evaluated the effect of ASG-IV on klotho and the effect of klotho on HCN4 and If. Administrating isoproterenol (5 mg/kg) for 15 days to establish a rat bradycardia model randomized SD rats into control, model (ISO) and ASG-IV (5 mg/kg/day) groups to explore the effect of ASG-IV on klotho. Rats were sacrificed on day 15 after heart rate and heart function were measured; SAN tissues were collected to measure the expression of klotho and HCN4. In vitro, neonatal rat myocardial cells were incubated with LPS for 24 h to inhibit the expression of HCN4 and incubated with LPS+ klotho to explore the effect of klotho on HCN4 expression. We also adopted full-patch-clamp technique to explore the effect of klotho on If. Heart rate in model group was significantly decreased (356.6±19.7 vs. 428.9±19.9 in control group, P<0.01) and ASG-IV can increase heart rate (401.4±12.0 vs. 356.6±19.7 in model group, P<0.01). The expression of klotho was also up-regulated (P<0.05). In vitro, after incubation with LPS for 24h, HCN4 expression was significantly decreased in neonatal rat myocardial cells (0.6±0.07 vs. 1.0, P<0.01) and If was significantly declined. Exogenous klotho showed protective effect on HCN4 expression (1.58±0.16 in ASG-IV group vs. 0.6±0.07 in LPS group, P<0.05) and If. Klotho is involved in the treatment mechanism of ASG-IV. Copyright © 2015 Elsevier Inc. All rights reserved.

On the ability of RegCM4 to simulate surface solar radiation patterns over Europe: An assessment using satellite-based observations

NASA Astrophysics Data System (ADS)

Alexandri, Georgia; Georgoulias, Aristeidis K.; Zanis, Prodromos; Tsikerdekis, Athanasios; Katragkou, Eleni; Kourtidis, Konstantinos; Meleti, Charikleia

2015-04-01

We assess here the ability of RegCM4 to simulate the surface solar radiation (SSR) patterns over the European domain. For the needs of this work, a decadal (1999-2009) simulation was implemented at a horizontal resolution of 50km using the first year as a spin-up. The model is driven by emissions from CMIP5 while ERA-interim data were used as lateral boundary conditions. The RegCM4 SSR fields were validated against satellite-based SSR observations from Meteosat First Generation (MFG) and Meteosat Second Generation (MSG) sensors (CM SAF SIS product). The RegCM4 simulations slightly overestimate SSR compared to CM SAF over Europe with the bias being +1.54% in case of MFG (2000-2005) and +3.34% in case of MSG (2006-2009). SSR from RegCM4 is much closer to SSR from CM SAF over land (bias of -1.59% for MFG and +0.66% for MSG) than over ocean (bias of +7.20% for MFG and 8.07% for MSG). In order to understand the reasons of this bias, we proceeded to a detailed assessment of various parameters that define the SSR levels (cloud fractional cover - CFC, cloud optical thickness - COT, cloud droplet effective radius - Re, aerosol optical thickness - AOD, asymmetry factor - ASY, single scattering albedo - SSA, water vapor - WV and surface albedo - ALB). We validated the simulated CFC, COT and Re from RegCM4 against satellite-based observations from MSG and we found that RegCM4 significantly underestimates CFC and Re, and overestimates COT over Europe. The aerosol-related parameters from RegCM4 were compared with values from the aerosol climatology taken into account within CM SAF SSR estimates. AOD is significantly underestimated in our simulations which leads to a positive SSR bias. The RegCM4 WV and ALB were compared with WV values from ERA-interim and ALB climatological observations from CERES which are also taken into account within CM SAF SSR estimates. Finally, with the use of a radiative transfer model (SBDART) we manage to quantify the relative contribution of each of the above mentioned parameters to the total bias appearing between RegCM4 and CM SAF SSR. The research leading to these results has received funding from the European Social Fund (ESF) and national resources under the operational programme Education and Lifelong Learning (EdLL) within the framework of the Action "Supporting Postdoctoral Researchers" (QUADIEEMS project), from EPAN II and PEP under the national action "Bilateral, multilateral and regional R&T cooperations" (AEROVIS Sino-Greek project) and from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 226144 (C8 project).

Cigarette advertising and children's smoking: why Reg was withdrawn.

PubMed Central

Hastings, G. B.; Ryan, H.; Teer, P.; MacKintosh, A. M.

1994-01-01

OBJECTIVE--To examine the appeal of the Embassy Regal "Reg" campaign to young people. DESIGN--Three quantitative surveys and one piece of qualitative research: (a) self completion questionnaire administered in classrooms, (b) questionnaire led interviews with children, (c) questionnaire led interviews with adults, and (d) group discussions with children and adults. SETTINGS--(a) Secondary and middle schools in England; (b) north of England, Scotland, and Wales; (c) north of England, Scotland, and Wales; and (d) Glasgow. SUBJECTS--(a) 5451 schoolchildren aged 11-15 recruited by stratified random sampling; (b) 437 children aged 5-10 recruited by quota sampling; (c) 814 adults aged 15-65 recruited by quota sampling; and (d) 12 groups of children aged 10-15, three groups of adults aged 18-24, and three groups of adults aged 35-55. RESULTS--Children were familiar with cigarette advertising and in particular the Reg campaign. Although younger children struggled to understand the creative content of the adverts, older and smoking children could understand and appreciate the humour. They considered Reg to be amusing and could relate to the type of joke used in the advert. In addition Reg's flippant attitude towards serious issues appealed to the children. While adults aged 18-24 understood the campaign they did not identify with it, and 35-55 year olds (the campaign's supposed target) were unappreciative of the campaign. CONCLUSIONS--The Reg campaign was getting through to children more effectively than it was to adults and held most appeal for teenagers, particularly 14-15 year old smokers. It clearly contravened the code governing tobacco advertising, which states that advertising must not appeal to children more than it does to adults, and it may have had a direct impact on teenage smoking. In view of these findings the Advertising Standards Authority's decision to withdraw the Reg campaign seems appropriate. Images p935-a PMID:7950668

Simulation of the summer circulation over South America by two regional climate models. Part I: Mean climatology

NASA Astrophysics Data System (ADS)

Fernandez, J. P. R.; Franchito, S. H.; Rao, V. B.

2006-09-01

This study investigates the capabilities of two regional models (the ICTP RegCM3 and the climate version of the CPTEC Eta model - EtaClim) in simulating the mean climatological features of the summer quasi-stationary circulations over South America. Comparing the results with the NCEP/DOE reanalysis II data it is seen that the RegCM3 simulates a weaker and southward shifted Bolivian high (BH). But, the Nordeste low (NL) is located close to its climatological position. In the EtaClim the position of the BH is reproduced well, but the NL is shifted towards the interior of the continent. To the east of Andes, the RegCM3 simulates a weaker low level jet and a weaker basic flow from the tropical Atlantic to Amazonia while they are stronger in the EtaClim. In general, the RegCM3 and EtaClim show, respectively a negative and positive bias in the surface temperature in almost all regions of South America. For both models, the correlation coefficients between the simulated precipitation and the GPCP data are high over most of South America. Although the RegCM3 and EtaClim overestimate the precipitation in the Andes region they show a negative bias in general over the entire South America. The simulations of upper and lower level circulations and precipitation fields in EtaClim were better than that of the RegCM3. In central Amazonia both models were unable to simulate the precipitation correctly. The results showed that although the RegCM3 and EtaClim are capable of simulating the main climatological features of the summer climate over South America, there are areas which need improvement. This indicates that the models must be more adequately tuned in order to give reliable predictions in the different regions of South America.

Role of resolution in regional climate change projections over China

NASA Astrophysics Data System (ADS)

Shi, Ying; Wang, Guiling; Gao, Xuejie

2017-11-01

This paper investigates the sensitivity of projected future climate changes over China to the horizontal resolution of a regional climate model RegCM4.4 (RegCM), using RCP8.5 as an example. Model validation shows that RegCM performs better in reproducing the spatial distribution and magnitude of present-day temperature, precipitation and climate extremes than the driving global climate model HadGEM2-ES (HadGEM, at 1.875° × 1.25° degree resolution), but little difference is found between the simulations at 50 and 25 km resolutions. Comparison with observational data at different resolutions confirmed the added value of the RCM and finer model resolutions in better capturing the probability distribution of precipitation. However, HadGEM and RegCM at both resolutions project a similar pattern of significant future warming during both winter and summer, and a similar pattern of winter precipitation changes including dominant increase in most areas of northern China and little change or decrease in the southern part. Projected precipitation changes in summer diverge among the three models, especially over eastern China, with a general increase in HadGEM, little change in RegCM at 50 km, and a mix of increase and decrease in RegCM at 25 km resolution. Changes of temperature-related extremes (annual total number of daily maximum temperature > 25 °C, the maximum value of daily maximum temperature, the minimum value of daily minimum temperature in the three simulations especially in the two RegCM simulations are very similar to each other; so are the precipitation-related extremes (maximum consecutive dry days, maximum consecutive 5-day precipitation and extremely wet days' total amount). Overall, results from this study indicate a very low sensitivity of projected changes in this region to model resolution. While fine resolution is critical for capturing the spatial variability of the control climate, it may not be as important for capturing the climate response to homogeneous forcing (in this case greenhouse gas concentration changes).

New insights into restless genital syndrome: static mechanical hyperesthesia and neuropathy of the nervus dorsalis clitoridis.

PubMed

Waldinger, Marcel D; Venema, Pieter L; van Gils, Ad P G; Schweitzer, Dave H

2009-10-01

Systematic study of dysesthetic and paresthetic regions contributing to persistent genital arousal in women with restless genital syndrome (ReGS) is needed for its clinical management. To investigate distinct localizations of ReGS. Twenty-three women, fulfilling all five criteria of persistent genital arousal disorder were included into the study. In-depth interviews, routine and hormonal investigations, electroencephalographs, and magnetic resonance imaging (MRI) of brain and pelvis were performed in all women. The localizations of genital sensations were investigated by physical examination of the ramus inferior of the pubic bone (RIPB) and by sensory testing of the skin of the genital area with a cotton swab (genital tactile mapping test or GTM test). Sensitivity of RIPB, GTM test. Of 23 women included in the study, 18(78%), 16(69%), and 12(52%) reported restless legs syndrome, overactive bladder syndrome, and urethra hypersensitivity. Intolerance of tight clothes and underwear (allodynia or hyperpathia) was reported by 19 (83%) women. All women were diagnosed with ReGS. Sitting aggravated ReGS in 20(87%) women. In all women, MRI showed pelvic varices of different degree in the vagina (91%), labia minora and/or majora (35%), and uterus (30%). Finger touch investigation of the dorsal nerve of the clitoris (DNC) along the RIPB provoked ReGS in all women. Sensory testing showed unilateral and bilateral static mechanical Hyperesthesia on various trigger points in the dermatome of the pudendal nerve, particularly in the part innervated by DNC, including pelvic bone. In three women, sensory testing induced an uninhibited orgasm during physical examination. ReGS is highly associated with pelvic varices and with sensory neuropathy of the pudendal nerve and DNC, whose symptoms are suggestive for small fiber neuropathy (SFN). Physical examination for static mechanical Hyperesthesia is a diagnostic test for ReGS and is recommended for all individuals with complaints of persistent restless genital arousal in absence of sexual desire.

A plant based protective antigen [PA(dIV)] vaccine expressed in chloroplasts demonstrates protective immunity in mice against anthrax.

PubMed

Gorantala, Jyotsna; Grover, Sonam; Goel, Divya; Rahi, Amit; Jayadev Magani, Sri Krishna; Chandra, Subhash; Bhatnagar, Rakesh

2011-06-15

The currently available anthrax vaccines are limited by being incompletely characterized, potentially reactogenic and have an expanded dosage schedule. Plant based vaccines offer safe alternative for vaccine production. In the present study, we expressed domain IV of Bacillus anthracis protective antigen gene [PA(dIV)] in planta (by nuclear agrobacterium and chloroplast transformation) and E. coli [rPA(dIV)]. The presence of transgene and the expression of PA(dIV) in planta was confirmed by molecular analysis. Expression levels up to 5.3% of total soluble protein (TSP) were obtained with AT rich (71.8% AT content) PA(dIV) gene in transplastomic plants while 0.8% of TSP was obtained in nuclear transformants. Further, we investigated the protective response of plant and E. coli derived PA(dIV) in mice by intraperitoneal (i.p.) and oral immunizations with or without adjuvant. Antibody titers of >10(4) were induced upon i.p. and oral immunizations with plant derived PA(dIV) and oral immunization with E. coli derived PA(dIV). Intraperitoneal injections with adjuvanted E. coli derived PA(dIV), generated highest antibody titers of >10(5). All the immunized groups demonstrated predominant IgG1 titers over IgG2a indicating a polarized Th2 type response. We also evaluated the mucosal antibody response in orally immunized groups. When fecal extracts were analyzed, low sIgA titer was demonstrated in adjuvanted plant and E. coli derived PA(dIV) groups. Further, PA(dIV) antisera enhanced B. anthracis spore uptake by macrophages in vitro and also demonstrated an anti-germinating effect suggesting a potent role at mucosal surfaces. The antibodies from various groups were efficient in neutralizing the lethal toxin in vitro. When mice were challenged with B. anthracis, mice immunized with adjuvanted plant PA(dIV) imparted 60% and 40% protection while E. coli derived PA(dIV) conferred 100% and 80% protection upon i.p. and oral immunizations. Thus, our study is the first attempt in highlighting the efficacy of plant expressed PA(dIV) by oral immunization in murine model. Copyright © 2011 Elsevier Ltd. All rights reserved.

76 FR 26938 - Suspension of Community Eligibility

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-10

.... Lewiston, City of, Cache 490018 June 29, 1976, ......do do. County. Emerg; July 29, 1980, Reg; May 24, 2011..., ......do do. County. Emerg; July 29, 1980, Reg; May 24, 2011, Susp. Region X Idaho: Caldwell, City of...

The enteric microbiota regulates jejunal Paneth cell number and function without impacting intestinal stem cells.

PubMed

Schoenborn, Alexi A; von Furstenberg, Richard J; Valsaraj, Smrithi; Hussain, Farah S; Stein, Molly; Shanahan, Michael T; Henning, Susan J; Gulati, Ajay S

2018-06-08

Paneth cells (PCs) are epithelial cells found in the small intestine, next to intestinal stem cells (ISCs) at the base of the crypts. PCs secrete antimicrobial peptides (AMPs) that regulate the commensal gut microbiota. In contrast, little is known regarding how the enteric microbiota reciprocally influences PC function. In this study, we sought to characterize the impact of the enteric microbiota on PC biology in the mouse small intestine. This was done by first enumerating jejunal PCs in germ-free (GF) versus conventionally-raised (CR) mice. We next evaluated the possible functional consequences of altered PC biology in these experimental groups by assessing epithelial proliferation, ISC numbers, and the production of AMPs. We found that PC numbers were significantly increased in CR versus GF mice; however, there were no differences in ISC numbers or cycling activity between groups. Of the AMPs assessed, only Reg3γ transcript expression was significantly increased in CR mice. Intriguingly, this increase was abrogated in cultured CR versus GF enteroids, and could not be re-induced with various bacterial ligands. Our findings demonstrate the enteric microbiota regulates PC function by increasing PC numbers and inducing Reg3γ expression, though the latter effect may not involve direct interactions between bacteria and the intestinal epithelium. In contrast, the enteric microbiota does not appear to regulate jejunal ISC census and proliferation. These are critical findings for investigators using GF mice and the enteroid system to study PC and ISC biology.

The histone deacetylase inhibitor, trichostatin A, inhibits the development of 2,4-dinitrofluorobenzene-induced dermatitis in NC/Nga mice.

PubMed

Kim, Tae-Ho; Jung, Jung-A; Kim, Gun-Dong; Jang, An-Hee; Cho, Jeong-Je; Park, Yong Seek; Park, Cheung-Seog

2010-10-01

Repetitive skin contact with a chemical hapten like 2,4-dinitrofluorobenzene (DNFB) evokes an atopic dermatitis (AD)-like dermatitis reaction in NC/Nga mice maintained under specific pathogen-free (SPF) conditions. The histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), modulates the expression of several genes by inhibiting the activity of HDACs. Furthermore, TSA has been reported to suppress inflammatory cytokine expression and to induce T cell-suppression by increasing regulatory T cell (T reg cell) numbers. In addition, histone deacetylase inhibitors (HDACi) are currently undergoing clinical trials for the treatment of inflammatory disorders. In the present study, we examined whether treatment with TSA suppresses AD-like skin lesions in NC/Nga mice treated with DNFB under SPF conditions. Intraperitoneal (i.p.) administration of TSA to DNFB-treated NC/Nga mice was found to inhibit ear thickness increases and the skin lesions induced by DNFB. Furthermore, IL-4 production by CD4+ T cells from the lymph nodes of DNFB-treated NC/Nga mice was significantly inhibited by TSA, although levels of IFN-γ were not. Flow cytometric analysis of lymphocytes showed an increase in CD4+ CD25+ T cell proportions in mice given TSA-i.p. These findings suggest that TSA suppresses the development of AD-like dermatitis in DNFB-treated NC/Nga mice by reducing IL-4 production and increasing the T reg cell population. Copyright © 2010 Elsevier B.V. All rights reserved.

The Capsicum annuum class IV chitinase ChitIV interacts with receptor-like cytoplasmic protein kinase PIK1 to accelerate PIK1-triggered cell death and defence responses

PubMed Central

Kim, Dae Sung; Kim, Nak Hyun; Hwang, Byung Kook

2015-01-01

The pepper receptor-like cytoplasmic protein kinase, CaPIK1, which mediates signalling of plant cell death and defence responses was previously identified. Here, the identification of a class IV chitinase, CaChitIV, from pepper plants (Capsicum annuum), which interacts with CaPIK1 and promotes CaPIK1-triggered cell death and defence responses, is reported. CaChitIV contains a signal peptide, chitin-binding domain, and glycol hydrolase domain. CaChitIV expression was up-regulated by Xanthomonas campestris pv. vesicatoria (Xcv) infection. Notably, avirulent Xcv infection rapidly induced CaChitIV expression in pepper leaves. Bimolecular fluorescence complementation and co-immunoprecipitation revealed that CaPIK1 interacts with CaChitIV in planta, and that the CaPIK1–CaChitIV complex is localized mainly in the cytoplasm and plasma membrane. CaChitIV is also localized in the endoplasmic reticulum. Transient co-expression of CaChitIV with CaPIK1 enhanced CaPIK1-triggered cell death response and reactive oxygen species (ROS) and nitric oxide (NO) bursts. Co-silencing of both CaChitIV and CaPIK1 in pepper plants conferred enhanced susceptibility to Xcv infection, which was accompanied by a reduced induction of cell death response, ROS and NO bursts, and defence response genes. Ectopic expression of CaPIK1 in Arabidopsis enhanced basal resistance to Hyaloperonospora arabidopsidis infection. Together, the results suggest that CaChitIV positively regulates CaPIK1-triggered cell death and defence responses through its interaction with CaPIK1. PMID:25694549

The Capsicum annuum class IV chitinase ChitIV interacts with receptor-like cytoplasmic protein kinase PIK1 to accelerate PIK1-triggered cell death and defence responses.

PubMed

Kim, Dae Sung; Kim, Nak Hyun; Hwang, Byung Kook

2015-04-01

The pepper receptor-like cytoplasmic protein kinase, CaPIK1, which mediates signalling of plant cell death and defence responses was previously identified. Here, the identification of a class IV chitinase, CaChitIV, from pepper plants (Capsicum annuum), which interacts with CaPIK1 and promotes CaPIK1-triggered cell death and defence responses, is reported. CaChitIV contains a signal peptide, chitin-binding domain, and glycol hydrolase domain. CaChitIV expression was up-regulated by Xanthomonas campestris pv. vesicatoria (Xcv) infection. Notably, avirulent Xcv infection rapidly induced CaChitIV expression in pepper leaves. Bimolecular fluorescence complementation and co-immunoprecipitation revealed that CaPIK1 interacts with CaChitIV in planta, and that the CaPIK1-CaChitIV complex is localized mainly in the cytoplasm and plasma membrane. CaChitIV is also localized in the endoplasmic reticulum. Transient co-expression of CaChitIV with CaPIK1 enhanced CaPIK1-triggered cell death response and reactive oxygen species (ROS) and nitric oxide (NO) bursts. Co-silencing of both CaChitIV and CaPIK1 in pepper plants conferred enhanced susceptibility to Xcv infection, which was accompanied by a reduced induction of cell death response, ROS and NO bursts, and defence response genes. Ectopic expression of CaPIK1 in Arabidopsis enhanced basal resistance to Hyaloperonospora arabidopsidis infection. Together, the results suggest that CaChitIV positively regulates CaPIK1-triggered cell death and defence responses through its interaction with CaPIK1. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Analysis of the present and future winter Pacific-North American teleconnection in the ECHAM5 global and RegCM3 regional climate models

USGS Publications Warehouse

Allan, Andrea M.; Hostetler, Steven W.; Alder, Jay R.

2014-01-01

We use the NCEP/NCAR Reanalysis (NCEP) and the MPI/ECHAM5 general circulation model to drive the RegCM3 regional climate model to assess the ability of the models to reproduce the spatiotemporal aspects of the Pacific-North American teleconnection (PNA) pattern. Composite anomalies of the NCEP-driven RegCM3 simulations for 1982–2000 indicate that the regional model is capable of accurately simulating the key features (500-hPa heights, surface temperature, and precipitation) of the positive and negative phases of the PNA with little loss of information in the downscaling process. The basic structure of the PNA is captured in both the ECHAM5 global and ECHAM5-driven RegCM3 simulations. The 1950–2000 ECHAM5 simulation displays similar temporal and spatial variability in the PNA index as that of NCEP; however, the magnitudes of the positive and negative phases are weaker than those of NCEP. The RegCM3 simulations clearly differentiate the climatology and associated anomalies of snow water equivalent and soil moisture of the positive and negative PNA phases. In the RegCM3 simulations of the future (2050–2100), changes in the location and extent of the Aleutian low and the continental high over North America alter the dominant flow patterns associated with positive and negative PNA modes. The future projections display a shift in the patterns of the relationship between the PNA and surface climate variables, which suggest the potential for changes in the PNA-related surface hydrology of North America.

Chemotherapy alters the increased numbers of myeloid-derived suppressor and regulatory T cells in children with acute lymphoblastic leukemia.

PubMed

Salem, Mohamed Labib; El-Shanshory, Mohamed R; Abdou, Said H; Attia, Mohamed S; Sobhy, Shymaa M; Zidan, Mona F; Zidan, Abdel-Aziz A

2018-04-01

Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children. The precise mechanism behind the relapse in this disease is not clearly known. One possible mechanism could be the accumulation of immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs) and T regulatory cells (T regs ) which we and others have reported to mediate suppression of anti-tumor immune responses. In this study, we aimed to analyze the numbers of these cells in a population of B-ALL pediatric patients. Peripheral blood samples withdrawn from B-ALL pediatric patients (n = 45 before, during and after the induction phase of chemotherapy. Using multi parametric flow cytometric analysis. MDSCs were identified as Lin - HLA-DR - CD33 + CD11b + ; and T reg cells were defined as CD4 + CD25 + CD127 -/low . Early diagnosed B-ALL patients showed significant increases in the numbers of MDSCs and T regs as compared to healthy volunteers. During induction of chemotherapy, however, the patients showed higher and lower numbers of MDSCs and T reg cells, respectively as compared to early diagnosed patients (i.e., before chemotherapy). After induction of chemotherapy, the numbers of MDSCs and T reg cells showed higher increases and decreases, respectively as compared to the numbers in patients during chemotherapy. Our results indicate that B-ALL patients harbor high numbers of both MDSCs and T regs cells. This pilot study opens a new avenue to investigate the mechanism mediating the emergence of these cells on larger number of B-ALL patients at different treatment stages.

Pilot test of Pickliq{reg_sign} process to determine energy and environmental benefits & economic feasibility

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

Olsen, D.R.

Green Technology Group (GTG) was awarded Grant No. DE-FG01-96EE 15657 in the amount of $99,904 for a project to advance GTG`s Pickliq{reg_sign} Process in the Copper and Steel Industries. The use of the Pickliq{reg_sign} Process can significantly reduce the production of waste acids containing metal salts. The Pickliq{reg_sign} Process can save energy and eliminate hazardous waste in a typical copper rod or wire mill or a typical steel wire mill. The objective of this pilot project was to determine the magnitude of the economic, energy and environmental benefits of the Pickliq{reg_sign} Process in two applications within the metal processing industry.more » The effectiveness of the process has already been demonstrated at facilities cleaning iron and steel with sulfuric acid. 9207 companies are reported to use sulfuric and hydrochloric acid in the USA. The USEPA TRI statistics of acid not recycled in the US is 2.4 x 10{sup 9} lbs (net) for Hydrochloric Acid and 2.0 x 10{sup 9} lbs (net) for Sulfuric Acid. The energy cost of not reclaiming acid is 10.7 x 10{sup 6} BTU/ton for Hydrochloric Acid and 21.6 x 10{sup 6} BTU/Ton for Sulfuric Acid. This means that there is a very large market for the application of the Pickliq{reg_sign} Process and the widespread use of the process will bring significant world wide savings of energy to the environment.« less

12 CFR 224.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... SECURITIES CREDIT (REGULATION X) § 224.2 Definitions. The terms used in this part have the meanings given to... total value of shares of all classes of stock. [Reg. X, 48 FR 56572, Dec. 22, 1983, as amended by Reg. X...

12 CFR 224.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... SECURITIES CREDIT (REGULATION X) § 224.2 Definitions. The terms used in this part have the meanings given to... total value of shares of all classes of stock. [Reg. X, 48 FR 56572, Dec. 22, 1983, as amended by Reg. X...

Intravenous infusion of hexamethonium and atropine but not propranolol diminishes apolipoprotein A-IV gene expression in rat ileum.

PubMed

Sonoyama, K; Tajima, K; Fujiwara, R; Kasai, T

2000-03-01

To clarify the role of neural factors in the regulation of apolipoprotein (apo) A-IV expression in the small intestine, we investigated the effect of neural blockers on mRNA levels of apo A-IV in rat small intestine. Either ganglionic blocker (hexamethonium), cholinergic blocker (atropine) or beta-adrenergic blocker (propranolol) was infused intravenously to unrestrained conscious rats for 8 h, and then total RNA was isolated from the small intestine and analyzed using Northern hybridization. Apo A-IV mRNA levels in the ileum were significantly lower in hexamethonium- or atropine-infused rats than in saline- (control) or propranolol-infused rats. Immunoblot analysis showed no difference in plasma apo A-IV concentrations between hexamethonium- and saline-infused groups. The lower mRNA levels of apo A-IV in the ileum of hexamethonium-infused rats were observed even in bile-drained rats, indicating that the lower expression was not due to any changes in bile availability. The ileal apo A-IV mRNA levels were significantly higher in rats infused with lipid emulsion into the ileum than in rats infused with glucose-saline, and the concomitant infusion of intravenous hexamethonium did not affect the higher levels of apo A-IV mRNA. These results suggest that the basal expression of the ileal A-IV gene is at least partially regulated in a site-specific manner by cholinergic neurons.

Astragaloside suppresses apoptosis of the podocytes in rats with diabetic nephropathy via miR-378/TRAF5 signaling pathway.

PubMed

Lei, Xiao; Zhang, Bo-da; Ren, Ji-Gang; Luo, Fang-Li

2018-05-21

Apoptosis of podocytes plays a crucial role in diabetic nephropathy (DN) development, and astragaloside (AS-IV) has a significant impact on podocyte apoptosis. This study aims to explore the effect of AS-IV on diabetic nephropathy progression. The diabetic nephropathy model was established in rats with streptozotocin (STZ) injection. The albuminuria was examined by using the enzyme linked immunosorbent assay (ELISA). The expression of miR-378, tumor-necrosis factor (TNF) receptor (TNFR)-associated factor 5 (TRAF5) mRNA and protein was analyzed by qRT-PCR and western blot, respectively. Cell transfection was conducted for modulating endogenous expression of miR-378. Dual luciferase reporter assay was used to evaluate the interaction between miR-378 and TRAF5. The terminal deoxynucleotidy transferase dUTP nick end labeling (TUNEL) staining assay was performed for apoptosis detection. AS-IV protected diabetic rats from developing into diabetic nephropathy. The expression of miR-378 was down-regulated in diabetic nephropathy rats, which was reversed by AS-IV. AS-IV enhanced the expression of miR-378 in podocytes treated with high glucose. MiR-378 negatively regulated TRAF5. AS-IV inhibited the expression of TRAF5 through miR-378. AS-IV suppressed apoptosis of podocytes via targeting miR-378. AS-IV suppresses apoptosis of the podocytes through the miR-378/TRAF5 signaling pathway, and thereby repressing diabetic nephropathy development. Copyright © 2017. Published by Elsevier Inc.

75 FR 66079 - National Grid USA; Notice of Filing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-27

... 11013 (Feb. 29, 2008), FERC Stats. & Regs. ] 31,264, at P 4-5, order on rehearing, Order No. 707-A, 73 FR 43072 (Jul. 24, 2008), FERC Stats. & Regs. ] 31,272 (2008). Any person desiring to intervene or to...

77 FR 5508 - Order on Intent To Revoke Market-Based Rate Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-03

.... 2001, FERC Stats. & Regs. ] 31,127, reh'g denied, Order No. 2001-A, 100 FERC ] 61,074, reconsideration... market-based rates.\\2\\ \\2\\ Order No. 2001, FERC Stats & Regs. ] 31,127 at P 222. 4. The Commission...

75 FR 34108 - National Grid USA; Notice of Filing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-16

.... 707, 73 FR 11013 (Feb. 29, 2008), FERC Stats. & Regs. ] 31,264, at P 4-5, order on rehearing, Order No. 707-A, 73 FR 43072 (Jul. 24, 2008), FERC Stats. & Regs. ] 31,272 (2008). Any person desiring to...

40 CFR 180.1023 - Propanoic acid; exemptions from the requirement of a tolerance.

Code of Federal Regulations, 2011 CFR

2011-07-01

... byproducts; milk, and egg when applied as a bactericide/fungicide to livestock drinking water, poultry litter... (CAS Reg. No. 79-09-4), propanioc acid, calcium salt (CAS Reg. No. 4075-81-4), and propanioc sodium...

BP Reg Experiment Operations

NASA Image and Video Library

2015-04-07

ISS043E091755 (04/07/2015) --- Expedition 43 Commander Terry Virts is seen here working inside of the Columbus laboratory on the Blood Pressure Regulation (BP Reg) experiment. Astronauts returning from long-duration space flights risk experiencing dizziness or fainting when they stand immediately after returning to Earth. This has an important health risk as it reduces the potential for astronauts to safely escape from an emergency situation. BP Reg will help researchers develop appropriate countermeasures so that astronauts returning from long-duration space flights will have very low risk of experiencing dizziness or fainting when they return to Earth.

BP Reg Experiment Operations

NASA Image and Video Library

2015-04-07

ISS043E091740 (04/07/2015) --- Expedition 43 Commander Terry Virts is seen here working inside of the Columbus laboratory on the Blood Pressure Regulation (BP Reg) experiment. Astronauts returning from long-duration space flights risk experiencing dizziness or fainting when they stand immediately after returning to Earth. This has an important health risk as it reduces the potential for astronauts to safely escape from an emergency situation. BP Reg will help researchers develop appropriate countermeasures so that astronauts returning from long-duration space flights will have very low risk of experiencing dizziness or fainting when they return to Earth.

Simulation and Sensitivity in a Nested Modeling System for South America. Part II: GCM Boundary Forcing.

NASA Astrophysics Data System (ADS)

Rojas, Maisa; Seth, Anji

2003-08-01

of this study, the RegCM's ability to simulate circulation and rainfall observed in the two extreme seasons was demonstrated when driven at the lateral boundaries by reanalyzed forcing. Seasonal integrations with the RegCM driven by GCM ensemble-derived lateral boundary forcing demonstrate that the nested model responds well to the SST forcing, by capturing the major features of the circulation and rainfall differences between the two years. The GCM-driven model also improves upon the monthly evolution of rainfall compared with that from the GCM. However, the nested model rainfall simulations for the two seasons are degraded compared with those from the reanalyses-driven RegCM integrations. The poor location of the Atlantic intertropical convergence zone (ITCZ) in the GCM leads to excess rainfall in Nordeste in the nested model.An expanded domain was tested, wherein the RegCM was permitted more internal freedom to respond to SST and regional orographic forcing. Results show that the RegCM is able to improve the location of the ITCZ, and the seasonal evolution of rainfall in Nordeste, the Amazon region, and the southeastern region of Brazil. However, it remains that the limiting factor in the skill of the nested modeling system is the quality of the lateral boundary forcing provided by the global model.

regSNPs: a strategy for prioritizing regulatory single nucleotide substitutions

PubMed Central

Teng, Mingxiang; Ichikawa, Shoji; Padgett, Leah R.; Wang, Yadong; Mort, Matthew; Cooper, David N.; Koller, Daniel L.; Foroud, Tatiana; Edenberg, Howard J.; Econs, Michael J.; Liu, Yunlong

2012-01-01

Motivation: One of the fundamental questions in genetics study is to identify functional DNA variants that are responsible to a disease or phenotype of interest. Results from large-scale genetics studies, such as genome-wide association studies (GWAS), and the availability of high-throughput sequencing technologies provide opportunities in identifying causal variants. Despite the technical advances, informatics methodologies need to be developed to prioritize thousands of variants for potential causative effects. Results: We present regSNPs, an informatics strategy that integrates several established bioinformatics tools, for prioritizing regulatory SNPs, i.e. the SNPs in the promoter regions that potentially affect phenotype through changing transcription of downstream genes. Comparing to existing tools, regSNPs has two distinct features. It considers degenerative features of binding motifs by calculating the differences on the binding affinity caused by the candidate variants and integrates potential phenotypic effects of various transcription factors. When tested by using the disease-causing variants documented in the Human Gene Mutation Database, regSNPs showed mixed performance on various diseases. regSNPs predicted three SNPs that can potentially affect bone density in a region detected in an earlier linkage study. Potential effects of one of the variants were validated using luciferase reporter assay. Contact: yunliu@iupui.edu Supplementary information: Supplementary data are available at Bioinformatics online PMID:22611130

MT2-MMP-dependent release of collagen IV NC1 domains regulates submandibular gland branching morphogenesis.

PubMed

Rebustini, Ivan T; Myers, Christopher; Lassiter, Keyonica S; Surmak, Andrew; Szabova, Ludmila; Holmbeck, Kenn; Pedchenko, Vadim; Hudson, Billy G; Hoffman, Matthew P

2009-10-01

Proteolysis is essential during branching morphogenesis, but the roles of MT-MMPs and their proteolytic products are not clearly understood. Here, we discover that decreasing MT-MMP activity during submandibular gland branching morphogenesis decreases proliferation and increases collagen IV and MT-MMP expression. Specifically, reducing epithelial MT2-MMP profoundly decreases proliferation and morphogenesis, increases Col4a2 and intracellular accumulation of collagen IV, and decreases the proteolytic release of collagen IV NC1 domains. Importantly, we demonstrate the presence of collagen IV NC1 domains in developing tissue. Furthermore, recombinant collagen IV NC1 domains rescue branching morphogenesis after MT2-siRNA treatment, increasing MT-MMP and proproliferative gene expression via beta1 integrin and PI3K-AKT signaling. Additionally, HBEGF also rescues MT2-siRNA treatment, increasing NC1 domain release, proliferation, and MT2-MMP and Hbegf expression. Our studies provide mechanistic insight into how MT2-MMP-dependent release of bioactive NC1 domains from collagen IV is critical for integrating collagen IV synthesis and proteolysis with epithelial proliferation during branching morphogenesis.

75 FR 2930 - Proposed Collection; Comment Request for Regulation Project

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-19

... DEPARTMENT OF THE TREASURY Internal Revenue Service [REG-106446-98] Proposed Collection; Comment Request for Regulation Project AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and... From Joint and Several Liability. OMB Number: 1545-1719. Regulation Project Number: REG-106446-98...

75 FR 61243 - Proposed Collection; Comment Request for Regulation Project

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-04

... DEPARTMENT OF THE TREASURY Internal Revenue Service [REG-209626-93] (TD 8796) Proposed Collection... soliciting comments concerning an existing Final Regulation, REG-209626-93 (TD 8796), Notice, Consent, and... (TD 8796). Abstract: These regulations provide guidance concerning the notice consent requirements...

Dose-dependent effects of wheel running on cocaine-seeking and prefrontal cortex Bdnf exon IV expression in rats.

PubMed

Peterson, Alexis B; Abel, Jean M; Lynch, Wendy J

2014-04-01

Physical activity, and specifically exercise, has shown promise as an intervention for drug addiction; however, the exercise conditions that produce the most efficacious response, as well as its underlying mechanism, are unknown. In this study, we examined the dose-dependent effects of wheel running, an animal model of exercise, during abstinence on subsequent cocaine-seeking and associated changes in prefrontal cortex (PFC) brain-derived neurotrophic factor (Bdnf) exon IV expression, a marker of epigenetic regulation implicated in cocaine relapse and known to be regulated by exercise. Cocaine-seeking was assessed under a within-session extinction/cue-induced reinstatement procedure following extended access cocaine or saline self-administration (24-h/day, 4 discrete trials/h, 10 days, 1.5 mg/kg/infusion) and a 14-day abstinence period. During abstinence, rats had either locked or unlocked running wheel access for 1, 2, or 6 h/day. Bdnf exon IV expression was assessed using quantitative real-time polymerase chain reaction. Cocaine-seeking was highest under the locked wheel condition, and wheel running dose dependently attenuated this effect. Cocaine increased Bdnf exon IV expression, and wheel running dose dependently attenuated this increase, with complete blockade in rats given 6-h/day access. Notably, the efficacy of exercise was inversely associated with Bdnf exon IV expression, and both its efficacy and its effects on Bdnf exon IV expression were mimicked by treatment during abstinence with sodium butyrate, a histone deacetylase inhibitor that, like exercise, modulates gene transcription, including Bdnf exon IV expression. Taken together, these results indicate that the efficacy of exercise is dose dependent and likely mediated through epigenetic regulation of PFC Bdnf.

Simulation of Optical Properties and Direct and Indirect Radiative Effects of Smoke Aerosols Over Marine Stratocumulus Clouds During Summer 2008 in California With the Regional Climate Model RegCM

NASA Astrophysics Data System (ADS)

Mallet, M.; Solmon, F.; Roblou, L.; Peers, F.; Turquety, S.; Waquet, F.; Jethva, H.; Torres, O.

2017-10-01

The regional climate model RegCM has been modified to better account for the climatic effects of biomass-burning particles. Smoke aerosols are represented by new tracers with consistent radiative and hygroscopic properties to simulate the direct radiative forcing (DRF), and a new parameterization has been integrated for relating the droplet number concentration to the aerosol concentration for marine stratocumulus clouds (Sc). RegCM has been tested during the summer of 2008 over California, when extreme concentration of smoke, together with the presence of Sc, is observed. This work indicates that significant aerosol optical depth (AOD) ( 1-2 at 550 nm) is related to the intense 2008 fires. Compared to Ozone Monitoring Instrument (OMI) and Moderate Resolution Imaging Spectroradiometer, the regional pattern of RegCM AOD is well represented although the magnitude is lower than satellite observations. Comparisons with Polarization and Directionality of Earth Reflectances (POLDER) above-clouds aerosol optical depth (ACAOD) show the ability of RegCM to simulate realistic ACAOD during the transport of smoke above the Pacific Ocean. The simulated single scattering albedo is 0.90 (at 550 nm) near biomass-burning sources, consistent with OMI and POLDER, and smoke leads to shortwave heating rates 1.5-2°K d-1. RegCM is not able to correctly resolve the daily patterns in cloud properties notably due to its coarse horizontal resolutions. However, the changes in the sign of the DRF at top of atmosphere (TOA) (negative to positive) from clear-sky to all-sky conditions is well simulated. Finally, the "aerosol-cloud" parameterization allows simulating an increase of the cloud optical depth for significant concentrations, leading to large perturbations of radiative fluxes at TOA.

Flor-Essence? Herbal Tonic Promotes Mammary Tumor Development in Sprague Dawley Rats

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

Bennett, L; Montgomery, J; Steinberg, S

Background: Women who are diagnosed with breast cancer often self-administer complementary and alternative medicines to augment their conventional treatments, improve health, or prevent recurrence. Flor-Essence{reg_sign} Tonic is a complex mixture of herbal extracts used by cancer patients because of anecdotal evidence that it can treat or prevent disease. Methods: Female Sprague Dawley rats were given water or exposed to 3% or 6% Flor-Essence{reg_sign} beginning at one day of age. Mammary tumors were induced with a single oral 40 mg/kg/bw dose of dimethylbenz(a)anthracene at 50 days of age and sacrificed at 23 weeks. Rats were maintained on AIN-76A diet. Results: Controlmore » rats had palpable mammary tumor incidence of 51.0% at 19 weeks of age compared to 65.0% and 59.4% for the 3% and 6% Flor-Essence{reg_sign} groups respectively. Overall, no significant difference in time until first palpable tumor was detected among any of the groups. At necropsy, mammary tumor incidence was 82.5% for controls compared to 90.0% and 97.3% for rats consuming 3% and 6% Flor-Essence{reg_sign}, respectively. Mean mammary tumor multiplicity ({+-}SES) for the controls was 2.8 ({+-} 0.5) and statistically different from the 3% or 6% Flor- Essence{reg_sign} groups with 5.2 ({+-} 0.7), and 4.8 ({+-} 0.6), respectively (p{<=}0.01). As expected, the majority of isolated tumors were diagnosed as adenocarcinomas. Conclusions: Flor-Essence{reg_sign} can promote mammary tumor development in the Sprague Dawley rat model. This observation is contrary to widely available anecdotal evidence as well as the desire of the consumer that this commercially available herbal tonic will suppress and/or inhibit tumor growth.« less

A Phase 2, randomized, partially blinded, active-controlled study assessing the efficacy and safety of variable anticoagulation reversal using the REG1 system in patients with acute coronary syndromes: results of the RADAR trial

PubMed Central

Povsic, Thomas J.; Vavalle, John P.; Aberle, Laura H.; Kasprzak, Jaroslaw D.; Cohen, Mauricio G.; Mehran, Roxana; Bode, Christoph; Buller, Christopher E.; Montalescot, Gilles; Cornel, Jan H.; Rynkiewicz, Andrzej; Ring, Michael E.; Zeymer, Uwe; Natarajan, Madhu; Delarche, Nicolas; Zelenkofske, Steven L.; Becker, Richard C.; Alexander, John H.

2013-01-01

Aims We sought to determine the degree of anticoagulation reversal required to mitigate bleeding, and assess the feasibility of using pegnivacogin to prevent ischaemic events in acute coronary syndrome (ACS) patients managed with an early invasive approach. REG1 consists of pegnivacogin, an RNA aptamer selective factor IXa inhibitor, and its complementary controlling agent, anivamersen. REG1 has not been studied in invasively managed patients with ACS nor has an optimal level of reversal allowing safe sheath removal been defined. Methods and results Non-ST-elevation ACS patients (n = 640) with planned early cardiac catheterization via femoral access were randomized 2:1:1:2:2 to pegnivacogin with 25, 50, 75, or 100% anivamersen reversal or heparin. The primary endpoint was total ACUITY bleeding through 30 days. Secondary endpoints included major bleeding and the composite of death, myocardial infarction, urgent target vessel revascularization, or recurrent ischaemia. Enrolment in the 25% reversal arm was suspended after 41 patients. Enrolment was stopped after three patients experienced allergic-like reactions. Bleeding occurred in 65, 34, 35, 30, and 31% of REG1 patients with 25, 50, 75, and 100% reversal and heparin. Major bleeding occurred in 20, 11, 8, 7, and 10% of patients. Ischaemic events occurred in 3.0 and 5.7% of REG1 and heparin patients, respectively. Conclusion At least 50% reversal is required to allow safe sheath removal after cardiac catheterization. REG1 appears a safe strategy to anticoagulate ACS patients managed invasively and warrants further investigation in adequately powered clinical trials of patients who require short-term high-intensity anticoagulation. Clinical Trials Registration: ClinicalTrials.gov NCT00932100. PMID:22859796

Antigen-specific, CD4+CD25+ regulatory T cell clones induced in Peyer's patches.

PubMed

Tsuji, Noriko M; Mizumachi, Koko; Kurisaki, Jun-Ichi

2003-04-01

Since intestine is exposed to numerous exogenous antigens such as food and commensal bacteria, the organ bears efficient mechanisms for establishment of tolerance and induction of regulatory T cells (T(reg)). Intestinal and inducible T(reg) include T(r)1-like and T(h)3 cells whose major effector molecules are IL-10 and transforming growth factor (TGF)-beta. These antigen-specific T(reg) are expected to become clinical targets to modify the inflammatory immune response associated with allergy, autoimmune diseases and transplantation. In the present study, we characterized the antigen-specific T(reg) induced in the intestine by orally administering high-dose beta-lactoglobulin (BLG) to BALB/c mice. Seven days after feeding, only Peyer's patch (PP) cells among different organs exerted significant suppressive effect on antibody production upon in vitro BLG stimulation. This suppressive effect was also prominent in six BLG-specific CD4(+) T cell clones (OPP1-6) established from PP from mice orally administered with high doses of BLG and was partially reversed by antibodies to TGF-beta. Intravenous transfer of OPP2 efficiently suppressed BLG-specific IgG1 production in serum following immunization, indicating the role of such T(reg) in the systemic tolerance after oral administration of antigen (oral tolerance). OPP clones secrete TGF-beta, IFN-gamma and low levels of IL-10, a cytokine pattern similar to that secreted by anergic T cells. OPP clones bear a CD4(+)CD25(+) phenotype and show significantly lower proliferative response compared to T(h)0 clones. This lower response is recovered by the addition of IL-2. Thus, antigen-specific CD4(+)CD25(+) T(reg), which have characteristics of anergic cells and actively suppress antibody production are induced in PP upon oral administration of protein antigen.

Mechanical behavior of glass and Blackglas{reg_sign} ceramic matrix composite

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

Stawovy, R.H.; Kampe, S.L.; Curtin, W.A.

Room temperature tensile tests are reported on two low-cost ceramic matrix composite materials, comprised of matrices of Blackglas{reg_sign} and a proprietary glass composition each reinforced with Nicalon{reg_sign} SiC-based fibers. The measured mechanical behaviors, supplemented by post-fracture analysis of fiber pullout and fiber fracture mirrors, are compared in detail to the performance predicted theoretically. This allows for an assessment of the roles of the matrix, fiber strength, residual stresses, fiber geometry, and the fiber/matrix interfacial properties in determining mechanical response. The Blackglas{reg_sign} matrix cracks extensively during processing, and so the mechanical response is controlled by the deformation and fracture of themore » fiber bundle. The interfacial sliding resistance, {tau}, is determined to be {approx} 17 MPa and the in-situ (post-processed) fiber characteristic strength, {sigma}{sub c} is found to be {approx} 2.0 GPa, both similar to values reported in the literature for Nicalon{reg_sign}/CAS-glass systems. For the glass matrix, the unidirectional and cross-ply materials show marked differences in mechanical behavior. In the cross-ply composites, {tau} {approx} 14 MPa and {sigma}{sub c} {approx} 2.9 GPa; in the unidirectional variants, these values were 1.7 MPa and 1.6 GPa, respectively. With these data and other derived micromechanical parameters, the stress-strain and failure point of these materials was predicted using existing models, and excellent agreement with the experiments was obtained. These materials thus perform as expected given the in-situ fiber and interface properties. Notably, the cross-ply glass matrix composites exhibit high fiber strength retention and hence show tensile strengths that are better than other Nicalon{reg_sign}-based materials tested to date.« less

Soybean and Fish Oil Mixture With Different ω-6/ω-3 Polyunsaturated Fatty Acid Ratios Modulates Dextran Sulfate Sodium-Induced Changes in Small Intestinal Intraepithelial γδT-Lymphocyte Expression in Mice.

PubMed

Pai, Man-Hui; Liu, Jun-Jen; Hou, Yu-Chen; Yeh, Chiu-Li

2016-03-01

This study investigated the effect of different ω-6/ω-3 polyunsaturated fatty acid (PUFA) ratios on dextran sulfate sodium (DSS)-induced changes to small intestinal intraepithelial lymphocyte (IEL) γδT-cell expression. Mice were assigned to 3 control and 3 DSS-treated groups and were maintained on a low-fat semipurified diet. One of the control (S) groups and a DSS (DS) group were provided with soybean oil; the other 2 control (Hω-3 and Lω-3) groups and 2 other DSS (DHω-3 and DLω-3) groups were fed either a soybean and fish oil mixture with a ω-6/ω-3 ratio of 2:1 or 4:1. After feeding the respective diets for 2 weeks, the DSS groups were given distilled water containing 2% DSS, and the control groups were given distilled water for 5 days. All groups were further provided distilled water 5 days for recovery, and the small intestinal IEL γδT-cell subset was isolated for analysis. DSS treatment resulted in a lower small intestinal IEL γδT-cell percentage and higher messenger RNA (mRNA) expressions of Reg IIIγ, keratinocyte growth factor (KGF), and complement 5a receptor (C5aR) by IEL γδT cells. Fish oil administration enhanced the proportion of small intestinal IEL γδT cells. Compared with the DLω-3 group, the DHω-3 group had lower Reg IIIγ, KGF, and C5aR mRNA expressions and higher expression of peroxisome proliferator-activated receptor (PPAR)-γ gene by small intestinal IEL γδT cells. Fish oil diets with a ω-6/ω-3 PUFA ratio of 2:1 were more effective than those with a ratio of 4:1 in improving DSS-induced small intestinal injury, and activation of PPAR-γ in IEL γδT cells may be associated with resolution of small intestinal inflammation. © 2014 American Society for Parenteral and Enteral Nutrition.

77 FR 19279 - Northern Indiana Public Service Company; Notice of Petition for Declaratory Order

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-30

... Transmission Investment Through Pricing Reform, Order No. 679, FERC Stats. & Regs. ] 31,222, order on reh'g, Order No. 679-A, FERC Stats. & Regs. ] 3l 31,236 (2006), order on reh'g, 119FERC ] 61,062 (2007). Any...

76 FR 30342 - Gulf South Pipeline Company, LP; Notice of Request for Waiver

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-25

... Conduct for Transmission Providers, FERC Stats. & Regs. 31,280 (2008) (Order No 717), order on reh'g, FERC Stats. & Regs. ] 31,297 (2009) (Order No. 717-A, order on reh'g, 129 FERC ]61,123 (2009) (Order No. 717B...

77 FR 25658 - Negotiated Rulemaking Committee; Public Hearings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-01

...://www2.ed.gov/policy/highered/reg/hearulemaking/2012/index.html or contact: Wendy Macias, U.S. Department... select, from the nominees, individual negotiators who reflect the diversity among program participants.../reg/retrospective-analysis/index.html ). The Department's plan creates a defined policy, method, and...

CATREG SOFTWARE FOR CATEGORICAL REGRESSION ANALYSIS

EPA Science Inventory

CatReg is a computer program, written in the R (http://cran.r-project.org) programming language, to support the conduct of exposure-response analyses by toxicologists and health scientists. CatReg can be used to perform categorical regressi...

75 FR 5850 - Proposed Collection; Comment Request for REG-166012-02

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-04

... 1995, Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning REG-166012-02, Notional Principal Contracts; Contingent Nonperiodic Payments. DATES: Written [email protected] . SUPPLEMENTARY INFORMATION: Title: Notional Principal Contracts; Contingent Nonperiodic...

76 FR 40449 - Proposed Collection; Comment Request for Regulation Project

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-08

... DEPARTMENT OF THE TREASURY Internal Revenue Service [REG-106010-98] Proposed Collection; Comment Request for Regulation Project AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and... Short-Term Leases. OMB Number: 1545-1661. Regulation Project Number: REG-106010-98, (TD 8901). Abstract...

78 FR 60021 - Proposed Collection: Comment Request for Regulation Project

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-30

... DEPARTMENT OF THE TREASURY Internal Revenue Service [REG-120616-03(TD 9346 Final Regulations and Removal of Temporary Regulations)] Proposed Collection: Comment Request for Regulation Project AGENCY.... Regulation Project Number: REG-120616-03 (T.D. 9346 Final Regulations and Removal of Temporary Regulations...

75 FR 2932 - Proposed Collection; Comment Request for Regulation Project

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-19

... DEPARTMENT OF THE TREASURY Internal Revenue Service [REG-116664-01] RIN 1545-BC15 Proposed Collection; Comment Request for Regulation Project AGENCY: Internal Revenue Service (IRS), Treasury. ACTION.... OMB Number: 1545-1868. Regulation Project Number: REG-116664-01 (TD 9300 (final)). Abstract: This...

77 FR 57032 - Suspension of Community Eligibility

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-17

.... Jefferson, Township of, 422050 March 26, 1976, ...... do Do. Somerset County. Emerg; August 19, 1985, Reg... of, 422520 February 10, 1976, ...... do Do. Somerset County. Emerg; September 24, 1984, Reg..., Susp. Shanksville, Borough of, 420802 March 2, 1977, Emerg; ...... do Do. Somerset County. September 24...

75 FR 60 - Suspension of Community Eligibility

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-04

..., 2010. Gloucester County. Emerg; March 11, 1983, Reg; January 20, 2010, Susp. Deptford, Township of..., Susp. East Greenwich, Township 340200 March 27, 1975, ......do Do. of, Gloucester County. Emerg... County. Emerg; April 1, 1983, Reg; January 20, 2010, Susp. Logan, Township of, 340206 June 29, 1976...

76 FR 67372 - Suspension of Community Eligibility

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-01

.... Goshen, Township of, 422382 March 8, 1976, ......do Do. Clearfield County. Emerg; April 1, 1986, Reg... in available in SFHAs community Region III Pennsylvania: Beccaria, Township of, 421512 April 8, 1976..., Township of, 421514 January 22, 1976, .....do Do. Clearfield County. Emerg; November 16, 1990, Reg...

Assessment of cerebral blood flow autoregulation (CBF AR) with rheoencephalography (REG): studies in animals

NASA Astrophysics Data System (ADS)

Popovic, Djordje; Bodo, Michael; Pearce, Frederick; van Albert, Stephen; Garcia, Alison; Settle, Tim; Armonda, Rocco

2013-04-01

The ability of cerebral vasculature to regulate cerebral blood flow (CBF) in the face of changes in arterial blood pressure (SAP) or intracranial pressure (ICP) is an important guard against secondary ischemia in acute brain injuries, and official guidelines recommend that therapeutic decisions be guided by continuous monitoring of CBF autoregulation (AR). The common method for CBF AR monitoring, which rests on real-time derivation of the correlation coefficient (PRx) between slow oscillations in SAP and ICP is, however, rarely used in clinical practice because it requires invasive ICP measurements. This study investigated whether the correlation coefficient between SAP and the pulsatile component of the non-invasive transcranial bioimpedance signal (rheoencephalography, REG) could be used to assess the state and lower limit of CBF AR. The results from pigs and rhesus macaques affirm the utility of REG; however, additional animal and clinical studies are warranted to assess selectivity of automatic REG-based evaluation of CBF AR.

Joint Real-Time Energy and Demand-Response Management using a Hybrid Coalitional-Noncooperative Game

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

He, Fulin; Gu, Yi; Hao, Jun

In order to model the interactions among utility companies, building demands and renewable energy generators (REGs), a hybrid coalitional-noncooperative game framework has been proposed. We formulate a dynamic non-cooperative game to study the energy dispatch within multiple utility companies, while we take a coalitional perspective on REGs and buildings demands through a hedonic coalition formation game approach. In this case, building demands request different power supply from REGs, then the building demands can be organized into an ultimate coalition structure through a distributed hedonic shift algorithm. At the same time, utility companies can also obtain a stable power generation profile.more » In addition, the interactive progress among the utility companies and building demands which cannot be supplied by REGs is implemented by distributed game theoretic algorithms. Numerical results illustrate that the proposed hybrid coalitional-noncooperative game scheme reduces the cost of both building demands and utility companies compared with the initial scene.« less

RegPrecise 3.0--a resource for genome-scale exploration of transcriptional regulation in bacteria.

PubMed

Novichkov, Pavel S; Kazakov, Alexey E; Ravcheev, Dmitry A; Leyn, Semen A; Kovaleva, Galina Y; Sutormin, Roman A; Kazanov, Marat D; Riehl, William; Arkin, Adam P; Dubchak, Inna; Rodionov, Dmitry A

2013-11-01

Genome-scale prediction of gene regulation and reconstruction of transcriptional regulatory networks in prokaryotes is one of the critical tasks of modern genomics. Bacteria from different taxonomic groups, whose lifestyles and natural environments are substantially different, possess highly diverged transcriptional regulatory networks. The comparative genomics approaches are useful for in silico reconstruction of bacterial regulons and networks operated by both transcription factors (TFs) and RNA regulatory elements (riboswitches). RegPrecise (http://regprecise.lbl.gov) is a web resource for collection, visualization and analysis of transcriptional regulons reconstructed by comparative genomics. We significantly expanded a reference collection of manually curated regulons we introduced earlier. RegPrecise 3.0 provides access to inferred regulatory interactions organized by phylogenetic, structural and functional properties. Taxonomy-specific collections include 781 TF regulogs inferred in more than 160 genomes representing 14 taxonomic groups of Bacteria. TF-specific collections include regulogs for a selected subset of 40 TFs reconstructed across more than 30 taxonomic lineages. Novel collections of regulons operated by RNA regulatory elements (riboswitches) include near 400 regulogs inferred in 24 bacterial lineages. RegPrecise 3.0 provides four classifications of the reference regulons implemented as controlled vocabularies: 55 TF protein families; 43 RNA motif families; ~150 biological processes or metabolic pathways; and ~200 effectors or environmental signals. Genome-wide visualization of regulatory networks and metabolic pathways covered by the reference regulons are available for all studied genomes. A separate section of RegPrecise 3.0 contains draft regulatory networks in 640 genomes obtained by an conservative propagation of the reference regulons to closely related genomes. RegPrecise 3.0 gives access to the transcriptional regulons reconstructed in bacterial genomes. Analytical capabilities include exploration of: regulon content, structure and function; TF binding site motifs; conservation and variations in genome-wide regulatory networks across all taxonomic groups of Bacteria. RegPrecise 3.0 was selected as a core resource on transcriptional regulation of the Department of Energy Systems Biology Knowledgebase, an emerging software and data environment designed to enable researchers to collaboratively generate, test and share new hypotheses about gene and protein functions, perform large-scale analyses, and model interactions in microbes, plants, and their communities.

Electroencephalographic monitoring of complex mental tasks

NASA Technical Reports Server (NTRS)

Guisado, Raul; Montgomery, Richard; Montgomery, Leslie; Hickey, Chris

1992-01-01

Outlined here is the development of neurophysiological procedures to monitor operators during the performance of cognitive tasks. Our approach included the use of electroencepalographic (EEG) and rheoencephalographic (REG) techniques to determine changes in cortical function associated with cognition in the operator's state. A two channel tetrapolar REG, a single channel forearm impedance plethysmograph, a Lead I electrocardiogram (ECG) and a 21 channel EEG were used to measure subject responses to various visual-motor cognitive tasks. Testing, analytical, and display procedures for EEG and REG monitoring were developed that extend the state of the art and provide a valuable tool for the study of cerebral circulatory and neural activity during cognition.

75 FR 40817 - City of Pella, Iowa, v. Midwest Independent Transmission System Operator, Inc., MidAmerican...

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75 FR 18203 - Desert Southwest Power, LLC; Notice of Petition for Declaratory Order

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2010-04-09

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2012-02-03

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Combining semiquantitative measures of fibrosis and qualitative features of parenchymal remodelling to identify fibrosis regression in hepatitis C: a multiple biopsy study.

PubMed

Pattullo, Venessa; Thein, Hla-Hla; Heathcote, Elizabeth Jenny; Guindi, Maha

2012-09-01

A fall in hepatic fibrosis stage may be observed in patients with chronic hepatitis C (CHC); however, parenchymal architectural changes may also signify hepatic remodelling associated with fibrosis regression. The aim of this study was to utilize semiquantitative and qualitative methods to report the prevalence and factors associated with fibrosis regression in CHC. Paired liver biopsies were scored for fibrosis (Ishak), and for the presence of eight qualitative features of parenchymal remodelling, to derive a qualitative regression score (QR score). Combined fibrosis regression was defined as ≥2-stage fall in Ishak stage (Reg-I) or <2-stage fall in Ishak stage with a rise in QR score (Reg-Qual). Among 159 patients (biopsy interval 5.4 ± 3.1 years), Reg-I was observed in 12 (7.5%) and Reg-Qual in 26 (16.4%) patients. The combined diagnostic criteria increased the diagnosis rate for fibrosis regression (38 patients, 23.9%) compared with use of Reg-I alone (P < 0.001). Combined fibrosis regression was observed in nine patients (50%) who achieved sustained virological response (SVR), and in 29 of 141 (21%) patients despite persistent viraemia. SVR was the only clinical factor associated independently with combined fibrosis regression (odds ratio 3.05). The combination of semiquantitative measures and qualitative features aids the identification of fibrosis regression in CHC. © 2012 Blackwell Publishing Ltd.

A clinicopathological study of the expression of extracellular matrix components in urothelial carcinoma.

PubMed

Ioachim, Elli; Michael, Michalis; Stavropoulos, Nicolaos E; Kitsiou, Evangelia; Salmas, Marios; Malamou-Mitsi, Vasiliki

2005-03-01

To measure the immunohistochemical expression of the extracellular matrix (ECM) components tenascin, fibronectin, collagen type IV and laminin in urothelial carcinomas, and to correlate their expression with clinicopathological features to clarify the prognostic value of these molecules and their role in tumour progression. Tumour specimens obtained during transurethral resection of bladder tumour (TURBT) from 103 patients (82 men and 2 1 women, mean age 66.7 years, range 27-89) were studied retrospectively. The expression of tenascin, fibronectin, collagen type IV and laminin was correlated with clinicopathological features (tumour grade and stage, multiplicity, simultaneous in situ component, the proliferative activity as estimated by the two proliferation associated indices, Ki-67 and proliferating cell nuclear antigen, the recurrence rate, and the progression of invading tumour). Specimens investigated for tenascin expression from patients with superficial bladder cancers were categorized into 28 treated by TURBT only and 53 who had TURBT followed by intravesical instillations of interferon. Cytoplasmic tenascin expression was detected in tumour cells in 20% of specimens. Tenascin was expressed in the tumour stroma in 76% of specimens, and was positively correlated with tumour grade and stage. Stromal tenascin expression was positively correlated with proliferative activity, and with the expression of fibronectin and collagen type IV. Fibronectin was expressed in the tumour stroma in 89% of specimens and was positively correlated with tumour stage, proliferative activity, and expression of collagen type IV and laminin. Collagen type IV was expressed in 93% of specimens, and was positively correlated with tumour grade and stage. Laminin was expressed in 78% of specimens and had no significant correlation with the clinicopathological features. Patients treated with TURBT alone and who had low levels of tenascin had a longer tumour-free interval than those with high levels of tenascin. Levels of tenascin might be valuable for predicting the risk of early recurrence. The expression of tenascin, fibronectin and collagen type IV seems to be correlated with more aggressive tumour behaviour. Furthermore, their interrelationships could indicate that they are involved in the remodelling of bladder cancer tissue, probably influencing tumour progression.

76 FR 39782 - Suspension of Community Eligibility

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78 FR 2622 - Suspension of Community Eligibility

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77 FR 3202 - Determination of Governmental Plan Status

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75 FR 44152 - Suspension of Community Eligibility

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2010-07-28

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76 FR 12596 - Suspension of Community Eligibility

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2011-03-08

... October 7, 1976, Emerg; -do- -do.- August 24, 1984, Reg; March 17, 2011, Susp. Barton County..., Westmoreland 420873 August 13, 1976, Emerg; -do- -do.- County. August 10, 1979, Reg; March 17, 2011, Susp. Cook...; March 17, 2011, Susp. Greensburg, City of, Westmoreland 420877 May 24, 1973, Emerg; -do- -do.- County...

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2012-12-26

... of, Kiowa 400088 November 12, ......do Do. County. 1976, Emerg; March 23, 1982, Reg; January 2, 2013...; March 4, 1986, Reg; January 2, 2013, Susp. Salyersville, City of, 210159 July 8, 1975, ......do Do..., 2013, Susp. Lone Wolf, Town of, Kiowa 400085 November 16, ......do Do. County. 1976, Emerg; June 29...

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75 FR 55280 - Suspension of Community Eligibility

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77 FR 59762 - Suspension of Community Eligibility

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75 FR 14356 - Suspension of Community Eligibility

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2010-03-25

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78 FR 5736 - Suspension of Community Eligibility

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2013-01-28

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77 FR 31981 - Eligible Obligations, Charitable Contributions, Nonmember Deposits, Fixed Assets, Investments...

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2012-05-31

... remove the automatic exemption from the nonmember deposits limit that had been granted to RegFlex FCUs... created a ``well capitalized standard'' based on the automatic designation criteria used in RegFlex. An... premises. ``Premises'' means any office, branch office, suboffice, service center, parking lot, facility...

MT2-MMP-dependent release of collagen IV NC1 domains regulates submandibular gland branching morphogenesis

PubMed Central

Rebustini, Ivan T.; Myers, Christopher; Lassiter, Keyonica S.; Surmak, Andrew; Szabova, Ludmila; Holmbeck, Kenn; Pedchenko, Vadim; Hudson, Billy G.; Hoffman, Matthew P.

2009-01-01

Summary Proteolysis is essential during branching morphogenesis, but the roles of MT-MMPs and their proteolytic products are not clearly understood. Here we discover that decreasing MT-MMP activity during submandibular gland branching morphogenesis decreases proliferation and increases collagen IV and MT-MMP expression. Importantly, reducing epithelial MT2-MMP profoundly decreases proliferation and morphogenesis, increases Col4a2 and intracellular accumulation of collagen IV, and decreases the proteolytic release of collagen IV NC1 domains. Importantly, we demonstrate the presence of collagen IV NC1 domains in developing tissue. Furthermore, recombinant collagen IV NC1 domains rescue branching morphogenesis after MT2-siRNA-treatment, increasing MT-MMP and pro-proliferative gene expression via β1 integrin and PI3K-AKT signaling. Additionally, HBEGF also rescues MT2-siRNA-treatment, increasing NC1 domain release, proliferation, and MT2-MMP and Hbegf expression. Our studies provide mechanistic insight into how MT2-MMP-dependent release of bioactive NC1 domains from collagen IV is critical for integrating collagen IV synthesis and proteolysis with epithelial proliferation during branching morphogenesis. PMID:19853562

Helicobacter pylori cagA+ Is Associated with Milder Duodenal Histological Changes in Chilean Celiac Patients.

PubMed

Lucero, Yalda; Oyarzún, Amaya; O'Ryan, Miguel; Quera, Rodrigo; Espinosa, Nelly; Valenzuela, Romina; Simian, Daniela; Alcalde, Elisa; Arce, Claudio; Farfán, Mauricio J; Vergara, Alejandra F; Gajardo, Iván; Mendez, Jocelyn; Carrasco, Jorge; Errázuriz, Germán; Gonzalez, Mónica; Ossa, Juan C; Maiza, Eduardo; Perez-Bravo, Francisco; Castro, Magdalena; Araya, Magdalena

2017-01-01

HIGHLIGHTS What is already known about this subject?Celiac disease (CD) has a high clinical and histological diversity and the mechanisms underlying this phenomenon remain elusive. H. pylori is a bacterium that chronically infect gastric and duodenal mucosa activating both a Th1/Th17 and T-reg pathways.The role of H. pylori (and the effect of their virulence factors) in CD have not yet completely elucidated.What are the new findings? cagA + H. pylori strains are associated to milder histological damage in infected CD patients.In active-CD patients the presence of cagA + H. pylori is associated to an increase in T-reg markers, contrasting with a downregulation in cagA + infected potential-CD individuals.How might it impact on clinical practice in the foreseeable future?The identification of microbiological factors that could modulate inflammation and clinical expression of CD may be used in the future as preventive strategies or as supplementary treatment in patients that cannot achieve complete remission, contributing to the better care of these patients. Background: Mechanisms underlying the high clinical and histological diversity of celiac disease (CD) remain elusive. Helicobacter pylori (Hp) chronically infects gastric and duodenal mucosa and has been associated with protection against some immune-mediated conditions, but its role (specifically of cagA + strains) in CD is unclear. Objective: To assess the relationship between gastric Hp infection ( cagA + strains) and duodenal histological damage in patients with CD. Design: Case-control study including patients with active-CD, potential-CD and non-celiac individuals. Clinical presentation, HLA genotype, Hp/ cagA gene detection in gastric mucosa, duodenal histology, Foxp3 positive cells and TGF-β expression in duodenal lamina propria were analyzed. Results: We recruited 116 patients, 29 active-CD, 37 potential-CD, and 50 non-CD controls. Hp detection was similar in the three groups (~30-40%), but cagA + strains were more common in infected potential-CD than in active-CD (10/11 vs. 4/10; p = 0.020) and non-CD (10/20; p = 0.025). Among active-CD patients, Foxp3 positivity was significantly higher in subjects with cagA + Hp+ compared to cagA- Hp+ ( p < 0.01) and Hp- ( p < 0.01). In cagA+ Hp+ individuals, Foxp3 positivity was also higher comparing active- to potential-CD ( p < 0.01). TGF-β expression in duodenum was similar in active-CD with cagA + Hp+ compared to Hp- and was significantly downregulated in cagA + potential-CD subjects compared to other groups. Conclusion: Hp infection rates were similar among individuals with/without CD, but infection with cagA + strains was associated with milder histological damage in celiac patients infected by Hp, and in active-CD cases with higher expression of T-reg markers. Results suggest that infection by cagA + Hp may be protective for CD progression, or conversely, that these strains are prone to colonize intestinal mucosa with less severe damage.

The regulatory role of B cells in autoimmunity, infections and cancer: Perspectives beyond IL10 production.

PubMed

Gorosito Serrán, Melisa; Fiocca Vernengo, Facundo; Beccaria, Cristian G; Acosta Rodriguez, Eva V; Montes, Carolina L; Gruppi, Adriana

2015-11-14

The term regulatory B cells (B regs) is ascribed to a heterogeneous population of B cells with the function of suppressing inflammatory responses. They have been described mainly during the last decade in the context of different immune-mediated diseases. Most of the work on B regs has been focused on IL-10-producing B cells. However, B cells can exert regulatory functions independently of IL-10 production. Here we discuss the phenotypes, development and effector mechanisms of B regs and advances in their role in autoimmunity, infections and cancer. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Comparison of the global gene expression of choroid plexus and meninges and associated vasculature under control conditions and after pronounced hyperthermia or amphetamine toxicity

PubMed Central

2013-01-01

Background The meninges (arachnoid and pial membranes) and associated vasculature (MAV) and choroid plexus are important in maintaining cerebrospinal fluid (CSF) generation and flow. MAV vasculature was previously observed to be adversely affected by environmentally-induced hyperthermia (EIH) and more so by a neurotoxic amphetamine (AMPH) exposure. Herein, microarray and RT-PCR analysis was used to compare the gene expression profiles between choroid plexus and MAV under control conditions and at 3 hours and 1 day after EIH or AMPH exposure. Since AMPH and EIH are so disruptive to vasculature, genes related to vasculature integrity and function were of interest. Results Our data shows that, under control conditions, many of the genes with relatively high expression in both the MAV and choroid plexus are also abundant in many epithelial tissues. These genes function in transport of water, ions, and solutes, and likely play a role in CSF regulation. Most genes that help form the blood–brain barrier (BBB) and tight junctions were also highly expressed in MAV but not in choroid plexus. In MAV, exposure to EIH and more so to AMPH decreased the expression of BBB-related genes such as Sox18, Ocln, and Cldn5, but they were much less affected in the choroid plexus. There was a correlation between the genes related to reactive oxidative stress and damage that were significantly altered in the MAV and choroid plexus after either EIH or AMPH. However, AMPH (at 3 hr) significantly affected about 5 times as many genes as EIH in the MAV, while in the choroid plexus EIH affected more genes than AMPH. Several unique genes that are not specifically related to vascular damage increased to a much greater extent after AMPH compared to EIH in the MAV (Lbp, Reg3a, Reg3b, Slc15a1, Sct and Fst) and choroid plexus (Bmp4, Dio2 and Lbp). Conclusions Our study indicates that the disruption of choroid plexus function and damage produced by AMPH and EIH is significant, but the changes may not be as pronounced as they are in the MAV, particularly for AMPH. Expression profiles in the MAV and choroid plexus differed to some extent and differences were not restricted to vascular related genes. PMID:23497014

Comparison of the global gene expression of choroid plexus and meninges and associated vasculature under control conditions and after pronounced hyperthermia or amphetamine toxicity.

PubMed

Bowyer, John F; Patterson, Tucker A; Saini, Upasana T; Hanig, Joseph P; Thomas, Monzy; Camacho, Luísa; George, Nysia I; Chen, James J

2013-03-05

The meninges (arachnoid and pial membranes) and associated vasculature (MAV) and choroid plexus are important in maintaining cerebrospinal fluid (CSF) generation and flow. MAV vasculature was previously observed to be adversely affected by environmentally-induced hyperthermia (EIH) and more so by a neurotoxic amphetamine (AMPH) exposure. Herein, microarray and RT-PCR analysis was used to compare the gene expression profiles between choroid plexus and MAV under control conditions and at 3 hours and 1 day after EIH or AMPH exposure. Since AMPH and EIH are so disruptive to vasculature, genes related to vasculature integrity and function were of interest. Our data shows that, under control conditions, many of the genes with relatively high expression in both the MAV and choroid plexus are also abundant in many epithelial tissues. These genes function in transport of water, ions, and solutes, and likely play a role in CSF regulation. Most genes that help form the blood-brain barrier (BBB) and tight junctions were also highly expressed in MAV but not in choroid plexus. In MAV, exposure to EIH and more so to AMPH decreased the expression of BBB-related genes such as Sox18, Ocln, and Cldn5, but they were much less affected in the choroid plexus. There was a correlation between the genes related to reactive oxidative stress and damage that were significantly altered in the MAV and choroid plexus after either EIH or AMPH. However, AMPH (at 3 hr) significantly affected about 5 times as many genes as EIH in the MAV, while in the choroid plexus EIH affected more genes than AMPH. Several unique genes that are not specifically related to vascular damage increased to a much greater extent after AMPH compared to EIH in the MAV (Lbp, Reg3a, Reg3b, Slc15a1, Sct and Fst) and choroid plexus (Bmp4, Dio2 and Lbp). Our study indicates that the disruption of choroid plexus function and damage produced by AMPH and EIH is significant, but the changes may not be as pronounced as they are in the MAV, particularly for AMPH. Expression profiles in the MAV and choroid plexus differed to some extent and differences were not restricted to vascular related genes.

Inhibition of CD26/DPP IV attenuates ischemia/reperfusion injury in orthotopic mouse lung transplants: the pivotal role of vasoactive intestinal peptide.

PubMed

Jungraithmayr, Wolfgang; De Meester, Ingrid; Matheeussen, Veerle; Inci, Ilhan; Augustyns, Koen; Scharpé, Simon; Weder, Walter; Korom, Stephan

2010-04-01

The T cell activation Ag CD26/dipeptidylpeptidase IV (DPP IV) combines co-stimulatory and enzymatic properties. Catalytically, it functions as an exopeptidase, modulating biological activity of key chemokines and peptides. Here we investigated the effect of organ-specific inhibition of DPP IV catalytic activity on ischemia/reperfusion injury after extended ischemia in the mouse model of orthotopic single lung transplantation. C57BL/6 mice were syngeneically, transplanted, grafts were perfused and stored in Perfadex with (treated) or without (control) a DPP IV enzymatic activity inhibitor (AB192). Transplantation was performed after 18h cold ischemia time; following 2-h reperfusion, grafts were analyzed for oxygenation, thiobarbituric acid-reactive substances, histomorphology, and immunohistochemistry was performed for leukocyte Ag 6, myeloperoxidase, hemoxygenase 1, vasoactive intestinal protein (VIP), and real-time PCR for VIP. Treatment with the DPP IV inhibitor AB192 resulted in significant improvement of gas exchange, less lipid oxidation, preservation of parenchymal ultrastructure, reduced neutrophil infiltration, reduced myeloperoxidase expression, increased hemoxygenase 1 expression, pronounced expression of VIP in alveolar macrophages and increased mRNA expression of VIP. Inhibition of intragraft DPP IV catalytic activity with AB192 strikingly ameliorates ischemia/reperfusion injury after extended ischemia. Furthermore, preservation of endogenous intragraft VIP levels correlate with maintaining lung function and structural integrity. Copyright (c) 2009 Elsevier Inc. All rights reserved.

21 CFR 178.3725 - Pigment dispersants.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... Phosphorylated tall oil fatty acids (CAS Reg. No. 68604-99-9), prepared by the reaction of dimethyl hydrogen phosphite with tall oil fatty acids For use only at levels not to exceed 1.0 percent by weight of the... materials. Substances Limitations Dimethylolpropionic acid (CAS Reg. No. 4767-03-7) For use only at levels...

Registration of two wheat germplasm lines fixed for Pm58

USDA-ARS?s Scientific Manuscript database

Powdery mildew, caused by Blumeria graminis (D.C.) f. sp. tritici, is a persistent threat to global wheat (Triticum aestivum L.) production. To broaden the genetic base for resistance to powdery mildew in wheat, germplasm lines U6714-A-011 (Reg. No.___, PI___) and U6714-B-056 (Reg. No.___, PI___) we...

75 FR 38184 - Proposed Collection; Comment Request for Regulation Project

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-01

... Reduction Act of 1995, Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning an existing final regulation, REG-251703-96 (TD 8813), Residence of Trusts and Estates... of Trusts and Estates-7701. OMB Number: 1545-1600. Regulation Project Number: REG-251703-96. Abstract...

77 FR 36229 - Portability of a Deceased Spousal Unused Exclusion Amount

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-18

... DEPARTMENT OF THE TREASURY Internal Revenue Service 26 CFR Parts 20 and 25 [REG-141832-11] RIN 1545-BK74 Portability of a Deceased Spousal Unused Exclusion Amount AGENCY: Internal Revenue Service...: Send submissions to CC:PA:LPD:PR (REG-141832-11), Room 5205, Internal Revenue Service, P.O. Box 7604...

75 FR 33740 - Indoor Tanning Services; Cosmetic Services; Excise Taxes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-15

... DEPARTMENT OF THE TREASURY Internal Revenue Service 26 CFR Parts 40 and 49 [REG-112841-10] RIN 1545-BJ40 Indoor Tanning Services; Cosmetic Services; Excise Taxes AGENCY: Internal Revenue Service.... ADDRESSES: Send submissions to: CC:PA:LPD:PR (REG-112841-10), Room 5203, Internal Revenue Service, P.O. Box...

Registration of Mp718 and Mp719 germplasm lines of maize

USDA-ARS?s Scientific Manuscript database

Maize (Zea mays L.) germplasm lines Mp718 (Reg. No. GP-xxxx, PI 662045) and Mp719 (Reg. No. GP-xxxx, PI 662046) were developed and released by USDA-ARS in cooperation with the Mississippi Agricultural and Forestry Experiment Station, Mississippi State, Mississippi, as sources of resistance to aflat...

75 FR 61839 - Proposed Collection; Comment Request for Regulation Project

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-06

..., the IRS is soliciting comments concerning REG-106177-98 (TD 8845), Adequate Disclosure of Gifts (Sec...: Adequate Disclosure of Gifts. OMB Number: 1545-1637. Regulation Project Number: REG-106177-98 (TD 8845). Abstract: Section 301.6501(c)-1(f) requires that, in order to commence the running of the gift tax statute...

Colorado SIP: Reg 11, Motor Vehicle Emissions Inspection Program—Part F, Maximum Allowable Emissions Limits for Motor Vehicle Exhaust, Evaporative and Visible Emissions for Light-Duty and Heavy-Duty Vehicles

EPA Pesticide Factsheets

Colorado SIP: Reg 11, Motor Vehicle Emissions Inspection Program—Part F, Maximum Allowable Emissions Limits for Motor Vehicle Exhaust, Evaporative and Visible Emissions for Light-Duty and Heavy-Duty Vehicles

78 FR 45462 - Suspension of Community Eligibility

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-29

... 090167 August 20, 1974, ......do Do. Association, New London Emerg; March 18, County. 1980, Reg; August 5, 2013, Susp. New London, City of, New 090100 March 24, 1972, ......do Do. London County. Emerg; May 2..., Borough of, New 090193 May 4, 1976, ......do Do. London County. Emerg; November 1, 1979, Reg; August 5...

77 FR 43004 - Suspension of Community Eligibility

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-23

... County. Emerg; April 15, 1977, Reg; August 2, 2012, Susp. Rush, Township of, Dauphin 421597 March 9, 1976...; August 2, 2012, Susp. Region VII Iowa: Fertile, City of, Worth 190301 March 19, 1976, ......do Do. County.... Dauphin County. Emerg; April 30, 1986, Reg; August 2, 2012, Susp. Dauphin, Borough of, 420375 March 16...

75 FR 33671 - Proposed Collection; Comment Request for Regulation Project

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-14

... Reduction Act of 1995, Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning an existing final regulation, REG-106917-99 (TD 8996), Changes in Accounting Periods... INFORMATION: Title: Changes in Accounting Periods. OMB Number: 1545-1748. Regulation Project Number: REG...

OSTEOCLAST-INDUCED FOXP3+ CD8 T-CELLS LIMIT BONE LOSS IN MICE

PubMed Central

Buchwald, Zachary S.; Kiesel, Jennifer R.; Yang, Chang; DiPaolo, Richard; Novack, Deborah V.; Aurora, Rajeev

2014-01-01

Osteoimmunology is the crosstalk between the skeletal and immune system. We have previously shown in vitro that osteoclasts (OC) crosspresent antigens to induce FoxP3 in CD8 T-cells (OCiTcREG), which then suppress osteoclast activity. Here we assessed the ability of OC-iTcREG to limit bone resorption in vivo. Mice lacking CD8 T-cells lose more bone in response to RANKL (Tnfsf11) administration. Using adoptive transfer experiments we demonstrate that FoxP3+ CD8 T-cells limit bone loss by RANKL administration. In ovariectomized mice, a murine model of postmenopausal osteoporosis, OC-iTcREG limited bone loss and increased bone density as assessed by serum markers, micro computed tomography (μCT) and histomorphometry. Indeed, OC-iTcREG—treated ovariectomized mice had decreased levels of effector T-cells in the bone marrow compared to untreated mice, and increased bone formation rates relative to bisphosphonate-treated mice. Our results provide the first in vivo evidence that OC-iTcREG have anti-resorptive activity and repress the immune system, thus extending the purview of osteoimmunology. PMID:23756229

Changes in Gene Expression Profiles in Adult Rat Brain Structures after Neonatal Action of Dipeptidyl Peptidase-IV Inhibitors.

PubMed

Zubkov, Eugene A; Zorkina, Yana A; Orshanskaya, Elena V; Khlebnikova, Nadezhda N; Krupina, Natalia A; Chekhonin, Vladimir P

2017-01-01

Previous studies have shown the development of emotional and motivational disorders, such as anxiety-depression-like disorders with increased aggression in adolescent and adult Wistar rats, occurs after neonatal exposure to the dipeptidyl peptidase-IV (DPP-IV, EC 3.4.14.5) inhibitors diprotin A and sitagliptin (postnatal days 5-18). In this study, using real-time PCR, we evaluated changes in the gene expression of serine protease DPP-IV and prolyl endopeptidase (PREP, EC 3.4.21.26; dpp4 and prep genes), monoamine oxidase А (maoA) and B (maoB), and serotonin transporter (SERT; sert) in the brain structures from 3-month-old rats after postnatal action of DPP-IV inhibitors diprotin A and sitagliptin. Dpp4, sert, and maoB gene expression increased and maoA gene expression changed with a tendency to increase in the striatum of rats with neonatal sitagliptin action. The increase of maoA gene expression was also shown in the amygdala. An increase in prep gene expression was found in the striatum of rats with the neonatal action of diprotin A, and a decrease in maoB gene expression was observed in the amygdala. We detected a significant downward trend in sert gene expression in the frontal cortex and amygdala, as well as a tendency to increase in maoA gene expression in the hypothalamus. These findings suggest that changes in the expression of the abovementioned genes are associated with the development of anxiety and depression, with increased aggression caused by the neonatal action of diprotin A and sitagliptin. © 2018 S. Karger AG, Basel.

Effects of reducing blood pressure on renal outcomes in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME.

PubMed

Scheen, A J; Delanaye, P

2017-04-01

Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has enabled remarkable reductions in cardiovascular and all-cause mortality as well as in renal outcomes in patients with type 2 diabetes (T2D) and a history of cardiovascular disease in the EMPA-REG OUTCOME. These results have been attributed to haemodynamic rather than metabolic effects, in part due to the osmotic/diuretic action of empagliflozin and the reduction in arterial blood pressure (BP). The present narrative review includes the results of meta-analyses of trials evaluating the effects on renal outcomes of lowering BP in patients with T2D, with a special focus on the influence of baseline and achieved systolic BP, and compares the renal outcome results of the EMPA-REG OUTCOME with those of other major trials with inhibitors of the renin-angiotensin system in patients with T2D and the preliminary findings with other SGLT2 inhibitors, and also evaluates post hoc analyses from the EMPA-REG OUTCOME of special interest as regards the BP-lowering hypothesis and renal function. While systemic BP reduction associated to empagliflozin therapy may have contributed to the renal benefits reported in EMPA-REG OUTCOME, other local mechanisms related to kidney homoeostasis most probably also played a role in the overall protection observed in the trial. Copyright © 2017. Published by Elsevier Masson SAS.

Effects of reducing blood pressure on cardiovascular outcomes and mortality in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME.

PubMed

Scheen, André J

2016-11-01

Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has shown a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes (T2D) and antecedents of cardiovascular disease in the EMPA-REG OUTCOME trial. This effect has been attributed to a hemodynamic rather than a metabolic effect, partly due to the osmotic/diuretic effect of empagliflozin and to the reduction in arterial blood pressure. The present review will: (1) summarize the results of specific studies having tested the blood pressure lowering effects of SGLT2 inhibitors; (2) describe the results of meta-analyses of trials having evaluated the effects on mortality and cardiovascular outcomes of lowering blood pressure in patients with T2D, with a special focus on baseline and target blood pressures; (3) compare the cardiovascular outcome results in EMPA-REG OUTCOME versus other major trials with antihypertensive agents in patients with T2D; and (4) evaluate post-hoc analyses from EMPA-REG OUTCOME, especially subgroups of patients of special interest regarding the blood pressure lowering hypothesis. Although BP reduction associated to empagliflozin therapy may partly contribute to the benefits reported in EMPA-REG OUTCOME, other mechanisms most probably play a greater role in the overall CV protection and reduction in mortality observed in this trial. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Description and evaluation of the Earth System Regional Climate Model (RegCM-ES)

NASA Astrophysics Data System (ADS)

Farneti, Riccardo; Sitz, Lina; Di Sante, Fabio; Fuentes-Franco, Ramon; Coppola, Erika; Mariotti, Laura; Reale, Marco; Sannino, Gianmaria; Barreiro, Marcelo; Nogherotto, Rita; Giuliani, Graziano; Graffino, Giorgio; Solidoro, Cosimo; Giorgi, Filippo

2017-04-01

The increasing availability of satellite remote sensing data, of high temporal frequency and spatial resolution, has provided a new and enhanced view of the global ocean and atmosphere, revealing strong air-sea coupling processes throughout the ocean basins. In order to obtain an accurate representation and better understanding of the climate system, its variability and change, the inclusion of all mechanisms of interaction among the different sub-components, at high temporal and spatial resolution, becomes ever more desirable. Recently, global coupled models have been able to progressively refine their horizontal resolution to attempt to resolve smaller-scale processes. However, regional coupled ocean-atmosphere models can achieve even finer resolutions and provide additional information on the mechanisms of air-sea interactions and feedbacks. Here we describe a new, state-of-the-art, Earth System Regional Climate Model (RegCM-ES). RegCM-ES presently includes the coupling between atmosphere, ocean, land surface and sea-ice components, as well as an hydrological and ocean biogeochemistry model. The regional coupled model has been implemented and tested over some of the COordinated Regional climate Downscaling Experiment (CORDEX) domains. RegCM-ES has shown improvements in the representation of precipitation and SST fields over the tested domains, as well as realistic representations of coupled air-sea processes and interactions. The RegCM-ES model, which can be easily implemented over any regional domain of interest, is open source making it suitable for usage by the large scientific community.

Histological Evaluation of the Healing Process of Various Bone Graft Materials after Engraftment into the Human Body.

PubMed

Jo, Sang Hyun; Kim, Young-Kyun; Choi, Yong-Hoon

2018-05-02

The purpose of this study was to measure the level of new bone formation induced by various bone graft materials to provide clinicians with more choices. The samples were divided into three groups: group 1 ( n = 9: allograft + xenograft, DBX ® , San Francisco, CA, USA + Bio-Oss ® , Princeton, NJ, USA), group 2 ( n = 10: xenograft, Bio-Oss ® ), and group 3 ( n = 8: autogenous tooth bone graft, AutoBT ® , Korea Tooth Bank, Seoul, Korea). The average duration of evaluation was 9.56, 2.50, and 3.38 months, respectively. A tissue sample was taken from 27 patients during the second implant surgery. New bone formation was measured via histomorphometry, using a charge-coupled device camera, adaptor, and image analysis software. Total bone area, total area, and ((total bone area/total area) × 100) was measured to determine the extent of new bone formation. The mean value of the total bone area was 152,232.63 μm²; the mean value of the total area was 1,153,696.46 μm²; and the mean total bone area/total area ratio was 13.50%. In each comparison, there was no significant difference among the groups; no inflammation or complications were found in any of the groups. AutoBT ® , an autogenous tooth bone graft, resulted in a level of bone formation similar to that using allografts and xenografts.

EULAR task force recommendations on annual cardiovascular risk assessment for patients with rheumatoid arthritis: an audit of the success of implementation in a rheumatology outpatient clinic.

PubMed

Ikdahl, Eirik; Rollefstad, Silvia; Olsen, Inge C; Kvien, Tore K; Hansen, Inger Johanne Widding; Soldal, Dag Magnar; Haugeberg, Glenn; Semb, Anne Grete

2015-01-01

EULAR recommendations for cardiovascular disease (CVD) risk management include annual CVD risk assessments for patients with rheumatoid arthritis (RA). We evaluated the recording of CVD risk factors (CVD-RF) in a rheumatology outpatient clinic, where EULAR recommendations had been implemented. Further, we compared CVD-RF recordings between a regular rheumatology outpatient clinic (RegROC) and a structured arthritis clinic (AC). In 2012, 1142 RA patients visited the rheumatology outpatient clinic: 612 attended RegROC and 530 attended AC. We conducted a search in the patient journals to ascertain the rate of CVD-RF recording. The overall CVD-RF recording rate was 40.1% in the rheumatology outpatient clinic, reflecting a recording rate of 59.1% in the AC and 23.6% in the RegROC. The odds ratios for having CVD-RFs recorded for patients attending AC compared to RegROC were as follows: blood pressure: 12.4, lipids: 5.0-6.0, glucose: 9.1, HbA1c: 6.1, smoking: 1.4, and for having all the CVD-RFs needed to calculate the CVD risk by the systematic coronary risk evaluation (SCORE): 21.0. The CVD-RF recording rate was low in a rheumatology outpatient clinic. However, a systematic team-based model was superior compared to a RegROC. Further measures are warranted to improve CVD-RF recording in RA patients.

Traction cytometry: regularization in the Fourier approach and comparisons with finite element method.

PubMed

Kulkarni, Ankur H; Ghosh, Prasenjit; Seetharaman, Ashwin; Kondaiah, Paturu; Gundiah, Namrata

2018-05-09

Traction forces exerted by adherent cells are quantified using displacements of embedded markers on polyacrylamide substrates due to cell contractility. Fourier Transform Traction Cytometry (FTTC) is widely used to calculate tractions but has inherent limitations due to errors in the displacement fields; these are mitigated through a regularization parameter (γ) in the Reg-FTTC method. An alternate finite element (FE) approach computes tractions on a domain using known boundary conditions. Robust verification and recovery studies are lacking but essential in assessing the accuracy and noise sensitivity of the traction solutions from the different methods. We implemented the L2 regularization method and defined a maximum curvature point in the traction with γ plot as the optimal regularization parameter (γ*) in the Reg-FTTC approach. Traction reconstructions using γ* yield accurate values of low and maximum tractions (Tmax) in the presence of up to 5% noise. Reg-FTTC is hence a clear improvement over the FTTC method but is inadequate to reconstruct low stresses such as those at nascent focal adhesions. FE, implemented using a node-by-node comparison, showed an intermediate reconstruction compared to Reg-FTTC. We performed experiments using mouse embryonic fibroblast (MEF) and compared results between these approaches. Tractions from FTTC and FE showed differences of ∼92% and 22% as compared to Reg-FTTC. Selection of an optimum value of γ for each cell reduced variability in the computed tractions as compared to using a single value of γ for all the MEF cells in this study.

viking: identification and characterization of a second type IV collagen in Drosophila.

PubMed

Yasothornsrikul, S; Davis, W J; Cramer, G; Kimbrell, D A; Dearolf, C R

1997-10-01

We have taken an enhancer trap approach to identify genes that are expressed in hematopoietic cells and tissues of Drosophila. We conducted a molecular analysis of two P-element insertion strains that have reporter gene expression in embryonic hemocytes, strain 197 and vikingICO. This analysis has determined that viking encodes a collagen type IV gene, alpha2(IV). The viking locus is located adjacent to the previously described DCg1, which encodes collagen alpha1(IV), and in the opposite orientation. The alpha2(IV) and alpha1(IV) collagens are structurally very similar to one another, and to vertebrate type IV collagens. In early development, viking and DCg1 are transcribed in the same tissue-specific pattern, primarily in the hemocytes and fat body cells. Our results suggest that both the alpha1 and alpha2 collagen IV chains may contribute to basement membranes in Drosophila. This work also provides the foundation for a more complete genetic dissection of collagen type IV molecules and their developmental function in Drosophila.

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

Walker, J.F.; Johnson, L.; Simpson, N.B.

In arctic tundra soil N is highly limiting, N mineralization is slow and organic N greatly exceeds inorganic N. We studied the effects of fungistatics (azoxystrobin [Quadris{reg_sign}] or propiconazole [Tilt{reg_sign}]) on the fungi isolated from ericaceous plant roots in vitro. In addition to testing the phytotoxicity of the two fungistatics we also tested their effects on growth and nitrogen uptake of an ericaceous plant (Vaccinium uliginosum) in a closed Petri plate system without root-associated fungi. Finally, to evaluate the fungistatic effects in an in vivo experiment we applied fungistatics and nitrogen isotopes to intact tundra soil cores from Toolik Lake,more » Alaska, and examined the ammonium-N and glycine-N use by Vaccinium vitis-idaea with and without fungistatics. The experiments on fungal pure cultures showed that Tilt{reg_sign} was more effective in reducing fungal colony growth in vitro than Quadris{reg_sign}, which was highly variable among the fungal strains. Laboratory experiments aiming to test the fungistatic effects on plant performance in vitro showed that neither Quadris{reg_sign} nor Tilt{reg_sign} affected V. uliginosum growth or N uptake. In this experiment V. uliginosum assimilated more than an order of magnitude more ammonium-N than glycine-N. The intact tundra core experiment provided contrasting results. After 10 wk of fungistatic application in the growth chamber V. vitis-idaea leaf %N was 10% lower and the amount of leaf {sup 15}N acquired was reduced from labeled ammonium (33%) and glycine (40%) during the 4 d isotope treatment. In contrast to the in vitro experiment leaf {sup 15}N assimilation from glycine was three times higher than from {sup 15}NH{sub 4} in the treatments that received no-fungistatics. We conclude that the function of the fungal communities is essential to the acquisition of N from organic sources and speculate that N acquisition from inorganic sources is mainly inhibited by competition with complex soil microbial communities.« less

Astragaloside IV attenuates injury caused by myocardial ischemia/reperfusion in rats via regulation of toll-like receptor 4/nuclear factor-κB signaling pathway.

PubMed

Lu, Meili; Tang, Futian; Zhang, Jing; Luan, Aina; Mei, Meng; Xu, Chonghua; Zhang, Suping; Wang, Hongxin; Maslov, Leonid N

2015-04-01

Myocardial ischemia/reperfusion (MI/R) injury, in which inflammatory response and cell apoptosis play a vital role, is frequently encountered in clinical practice. Astragaloside IV (AsIV), a small molecular saponin of Astragalus membranaceus, has been shown to confer protective effects against many cardiovascular diseases. The present study was aimed to investigate the antiinflammatory and antiapoptotic effects and the possible mechanism of AsIV on MI/R injury in rats. Rats were randomly divided into sham operation group, MI/R group and groups with combinations of MI/R and different doses of AsIV. The results showed that the expressions of myocardial toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) were significantly increased, and apoptosis of cardiomyocytes was induced in MI/R group compared with that in sham operation group. Administration of AsIV attenuated MI/R injury, downregulated the expressions of TLR4 and NF-κB and inhibited cell apoptosis as evidenced by decreased terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells, B-cell lymphoma-2 associated X protein and caspase-3 expressions and increased B-cell lymphoma-2 expression compared with that in MI/R group. In addition, AsIV treatment reduced levels of inflammatory cytokines induced by MI/R injury. In conclusion, our results demonstrated that AsIV downregulates TLR4/NF-κB signaling pathway and inhibits cell apoptosis, subsequently attenuating MI/R injury in rats. Copyright © 2015 John Wiley & Sons, Ltd.

Registration of PR0806-80 and PR0806-81 white bean germplasm lines with resistance to BGYMV, BCMV, BCMNV and rust

USDA-ARS?s Scientific Manuscript database

PR0806-80 (Reg. No. GP-___, PI ______) and PR0806-81 (Reg. No. GP-___, PI ______) are multiple disease resistant dry bean (Phaseolus vulgaris L.) germplasm lines, adapted to the humid tropics, that were developed and released cooperatively by the University of Puerto Rico Agricultural Experiment Sta...

77 FR 62620 - Proposed Collection; Comment Request for Information Collection Tools

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-15

... Form 706-GS(T), Generation-Skipping Transfer Tax Return For Terminations; REG-130477-00; REG-130481-00... Terminations. OMB Number: 1545-1145. Form Number: 706-GS(T). Abstract: Form 706-GS(T) is used by trustees to.... Estimated Number of Respondents: 500. Estimated Time per Respondent: 1 hr., 22 min. Estimated Total Annual...

40 CFR 52.2270 - Identification of plan.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 115.153 Alternate Control Requirements 4/26/02 2/27/08, 73 FR 10383 Section 115.155 Approved Test... for Permits by Rule 9/25/2002 3/20/2009, 74 FR 11851. Chapter 111 (Reg 1)—Control of Air Pollution.../2009, 74 FR 19144 Chapter 112 (Reg 2)—Control of Air Pollution From Sulfur Compounds Section 112.1...

Registration of LONREN-1 and LONREN-2 germplasm lines of Upland Cotton resistant to reniform nematode

USDA-ARS?s Scientific Manuscript database

Cotton (Gossypium hirsutum L.) germplasm lines LONREN-1 (Reg. No. GP-977, PI 669509) and LONREN-2 (Reg. No. GP978, PI 669510) were developed and released by the USDA-ARS, Texas Agricultural Experiment Station and Cotton Incorporated in 2007 to provide breeders with desirable germplasm resistant to t...

21 CFR 178.3910 - Surface lubricants used in the manufacture of metallic articles.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Surface lubricants used in the manufacture of...--hydroxypoly (oxyethylene)-poly (oxypropylene) (CAS Reg. No. 9038-95-3) produced by random condensation of a 1... molecular weight of 1000 α-Lauroyl-Ω-hydroxpoly(oxyethylene) (CAS Reg. No. 9004-81-3) having a minimum...

21 CFR 178.3910 - Surface lubricants used in the manufacture of metallic articles.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Surface lubricants used in the manufacture of...--hydroxypoly (oxyethylene)-poly (oxypropylene) (CAS Reg. No. 9038-95-3) produced by random condensation of a 1... molecular weight of 1000 α-Lauroyl-Ω-hydroxpoly(oxyethylene) (CAS Reg. No. 9004-81-3) having a minimum...

21 CFR 178.3910 - Surface lubricants used in the manufacture of metallic articles.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Surface lubricants used in the manufacture of...--hydroxypoly (oxyethylene)-poly (oxypropylene) (CAS Reg. No. 9038-95-3) produced by random condensation of a 1... molecular weight of 1000 α-Lauroyl-Ω-hydroxpoly(oxyethylene) (CAS Reg. No. 9004-81-3) having a minimum...

Registration of two double rust resistant germplasms, HA-R12 and HA-R13 for confection sunflower

USDA-ARS?s Scientific Manuscript database

The confection sunflower (Helianthus annuus L.) germplasms HA-R12 (Reg. No. ______, PI 673104) and HA-R13 (Reg. No. ______, PI 673105) were developed by the USDA-ARS, Sunflower and Plant Biology Research Unit in collaboration with the North Dakota Agricultural Experiment Station, and released in Jul...

12 CFR 210.5 - Sender's agreement; recovery by Reserve Bank.

Code of Federal Regulations, 2014 CFR

2014-01-01

... (REGULATION J) Collection of Checks and Other Items By Federal Reserve Banks § 210.5 Sender's agreement... that— (i) The electronic image portion of the item accurately represents all of the information on the... amended at 51 FR 21745, June 16, 1986; Reg. J, 59 FR 22965, May 4, 1994; 62 FR 48171, Sept. 15, 1997, Reg...

12 CFR 210.5 - Sender's agreement; recovery by Reserve Bank.

Code of Federal Regulations, 2012 CFR

2012-01-01

... (REGULATION J) Collection of Checks and Other Items By Federal Reserve Banks § 210.5 Sender's agreement... that— (i) The electronic image portion of the item accurately represents all of the information on the... amended at 51 FR 21745, June 16, 1986; Reg. J, 59 FR 22965, May 4, 1994; 62 FR 48171, Sept. 15, 1997, Reg...

12 CFR 210.5 - Sender's agreement; recovery by Reserve Bank.

Code of Federal Regulations, 2010 CFR

2010-01-01

... (REGULATION J) Collection of Checks and Other Items By Federal Reserve Banks § 210.5 Sender's agreement... that— (i) The electronic image portion of the item accurately represents all of the information on the... amended at 51 FR 21745, June 16, 1986; Reg. J, 59 FR 22965, May 4, 1994; 62 FR 48171, Sept. 15, 1997, Reg...

12 CFR 210.5 - Sender's agreement; recovery by Reserve Bank.

Code of Federal Regulations, 2013 CFR

2013-01-01

... (REGULATION J) Collection of Checks and Other Items By Federal Reserve Banks § 210.5 Sender's agreement... that— (i) The electronic image portion of the item accurately represents all of the information on the... amended at 51 FR 21745, June 16, 1986; Reg. J, 59 FR 22965, May 4, 1994; 62 FR 48171, Sept. 15, 1997, Reg...

12 CFR 210.6 - Status, warranties, and liability of Reserve Bank.

Code of Federal Regulations, 2012 CFR

2012-01-01

... FEDWIRE (REGULATION J) Collection of Checks and Other Items By Federal Reserve Banks § 210.6 Status... it transfers or presents that item that— (A) The electronic image portion of the item accurately... 21984, June 13, 1988; Reg. J, 59 FR 22966, May 4, 1994; 62 FR 48172, Sept. 15, 1997; Reg. J, 69 FR 62559...

12 CFR 210.6 - Status, warranties, and liability of Reserve Bank.

Code of Federal Regulations, 2013 CFR

2013-01-01

... FEDWIRE (REGULATION J) Collection of Checks and Other Items By Federal Reserve Banks § 210.6 Status... it transfers or presents that item that— (A) The electronic image portion of the item accurately... 21984, June 13, 1988; Reg. J, 59 FR 22966, May 4, 1994; 62 FR 48172, Sept. 15, 1997; Reg. J, 69 FR 62559...

12 CFR 210.6 - Status, warranties, and liability of Reserve Bank.

Code of Federal Regulations, 2011 CFR

2011-01-01

... FEDWIRE (REGULATION J) Collection of Checks and Other Items By Federal Reserve Banks § 210.6 Status... it transfers or presents that item that— (A) The electronic image portion of the item accurately... 21984, June 13, 1988; Reg. J, 59 FR 22966, May 4, 1994; 62 FR 48172, Sept. 15, 1997; Reg. J, 69 FR 62559...

12 CFR 210.6 - Status, warranties, and liability of Reserve Bank.

Code of Federal Regulations, 2010 CFR

2010-01-01

... FEDWIRE (REGULATION J) Collection of Checks and Other Items By Federal Reserve Banks § 210.6 Status... it transfers or presents that item that— (A) The electronic image portion of the item accurately... 21984, June 13, 1988; Reg. J, 59 FR 22966, May 4, 1994; 62 FR 48172, Sept. 15, 1997; Reg. J, 69 FR 62559...

12 CFR 210.5 - Sender's agreement; recovery by Reserve Bank.

Code of Federal Regulations, 2011 CFR

2011-01-01

... (REGULATION J) Collection of Checks and Other Items By Federal Reserve Banks § 210.5 Sender's agreement... that— (i) The electronic image portion of the item accurately represents all of the information on the... amended at 51 FR 21745, June 16, 1986; Reg. J, 59 FR 22965, May 4, 1994; 62 FR 48171, Sept. 15, 1997, Reg...

12 CFR 210.6 - Status, warranties, and liability of Reserve Bank.

Code of Federal Regulations, 2014 CFR

2014-01-01

... FEDWIRE (REGULATION J) Collection of Checks and Other Items By Federal Reserve Banks § 210.6 Status... it transfers or presents that item that— (A) The electronic image portion of the item accurately... 21984, June 13, 1988; Reg. J, 59 FR 22966, May 4, 1994; 62 FR 48172, Sept. 15, 1997; Reg. J, 69 FR 62559...

Registration of STARS 1501B and STARS 1502B barley germplasm with Rsg2 resistance to greenbug

USDA-ARS?s Scientific Manuscript database

STARS 1501B (Reg. No. GP- , PI 675335) greenbug-resistant, six-rowed, spring, feed barley (Hordeum vulgare L.) germplasm and STARS 1502B (Reg. No. GP-, PI 675336) greenbug-resistant, six-rowed, winter, feed barley germplasm, tested as GR 001 and GR 010 respectively, were developed and released by US...

Multiparametric in situ mRNA hybridization analysis to predict disease recurrence in patients with colon carcinoma.

PubMed Central

Kitadai, Y.; Ellis, L. M.; Tucker, S. L.; Greene, G. F.; Bucana, C. D.; Cleary, K. R.; Takahashi, Y.; Tahara, E.; Fidler, I. J.

1996-01-01

We examined the expression level of several genes that regulate different steps of metastasis in formalin-fixed, paraffin-embedded archival specimens of primary human colon carcinomas from patients with at least 5 years of follow-up. The expression of epidermal growth factor receptor, basic fibroblast growth factor, type IV collagenase, E-cadherin, and multidrug resistance (mdr-1) was examined by a colorimetric in situ mRNA hybridization technique concentrating on reactivity at the periphery of the neoplasms. The in situ hybridization technique revealed inter- and intratumor heterogeneity for expression of the metastasis-related genes. The expression of basic fibroblast growth factor, collagenase type IV, epidermal growth factor receptor, and mdr-1 mRNA was higher in Dukes's stage D than in Dukes' stage B tumors. Among the 22 Dukes' stage B neoplasms, 5 specimens exhibited a high expression level of epidermal growth factor receptor, basic fibroblast growth factor, and collagenase type IV. Clinical outcome data (5-year follow-up) revealed that all 5 patients with Dukes' stage B tumors developed distant metastasis (recurrent disease), whereas the other 17 patients with Dukes' stage B tumors expressing low levels of the metastasis-related genes were disease-free. Multivariate analysis identified high levels of expression of collagenase type IV and low levels of expression of E-cadherin as independent factors significantly associated with metastasis or recurrent disease. More specifically, metastatic or recurrent disease was associated with a high ratio (> 1.35) of expression of collagenase type IV to E-cadherin (specificity of 95%). Collectively, the data show that multiparametric in situ hybridization analysis for several metastasis-related genes may predict the metastatic potential, and hence the clinical outcome, of individual lymph-node-negative human colon cancers. Images Figure 1 Figure 2 PMID:8909244

Recovering Protein-Protein and Domain-Domain Interactions from Aggregation of IP-MS Proteomics of Coregulator Complexes

PubMed Central

Mazloom, Amin R.; Dannenfelser, Ruth; Clark, Neil R.; Grigoryan, Arsen V.; Linder, Kathryn M.; Cardozo, Timothy J.; Bond, Julia C.; Boran, Aislyn D. W.; Iyengar, Ravi; Malovannaya, Anna; Lanz, Rainer B.; Ma'ayan, Avi

2011-01-01

Coregulator proteins (CoRegs) are part of multi-protein complexes that transiently assemble with transcription factors and chromatin modifiers to regulate gene expression. In this study we analyzed data from 3,290 immuno-precipitations (IP) followed by mass spectrometry (MS) applied to human cell lines aimed at identifying CoRegs complexes. Using the semi-quantitative spectral counts, we scored binary protein-protein and domain-domain associations with several equations. Unlike previous applications, our methods scored prey-prey protein-protein interactions regardless of the baits used. We also predicted domain-domain interactions underlying predicted protein-protein interactions. The quality of predicted protein-protein and domain-domain interactions was evaluated using known binary interactions from the literature, whereas one protein-protein interaction, between STRN and CTTNBP2NL, was validated experimentally; and one domain-domain interaction, between the HEAT domain of PPP2R1A and the Pkinase domain of STK25, was validated using molecular docking simulations. The scoring schemes presented here recovered known, and predicted many new, complexes, protein-protein, and domain-domain interactions. The networks that resulted from the predictions are provided as a web-based interactive application at http://maayanlab.net/HT-IP-MS-2-PPI-DDI/. PMID:22219718

Discriminative Relational Topic Models.

PubMed

Chen, Ning; Zhu, Jun; Xia, Fei; Zhang, Bo

2015-05-01

Relational topic models (RTMs) provide a probabilistic generative process to describe both the link structure and document contents for document networks, and they have shown promise on predicting network structures and discovering latent topic representations. However, existing RTMs have limitations in both the restricted model expressiveness and incapability of dealing with imbalanced network data. To expand the scope and improve the inference accuracy of RTMs, this paper presents three extensions: 1) unlike the common link likelihood with a diagonal weight matrix that allows the-same-topic interactions only, we generalize it to use a full weight matrix that captures all pairwise topic interactions and is applicable to asymmetric networks; 2) instead of doing standard Bayesian inference, we perform regularized Bayesian inference (RegBayes) with a regularization parameter to deal with the imbalanced link structure issue in real networks and improve the discriminative ability of learned latent representations; and 3) instead of doing variational approximation with strict mean-field assumptions, we present collapsed Gibbs sampling algorithms for the generalized relational topic models by exploring data augmentation without making restricting assumptions. Under the generic RegBayes framework, we carefully investigate two popular discriminative loss functions, namely, the logistic log-loss and the max-margin hinge loss. Experimental results on several real network datasets demonstrate the significance of these extensions on improving prediction performance.

Interleukin-17 exacerbates hepatic steatosis and inflammation in non-alcoholic fatty liver disease.

PubMed

Tang, Y; Bian, Z; Zhao, L; Liu, Y; Liang, S; Wang, Q; Han, X; Peng, Y; Chen, X; Shen, L; Qiu, D; Li, Z; Ma, X

2011-11-01

Mechanisms associated with the progression of simple steatosis to non-alcoholic fatty liver disease (NAFLD) remain undefined. Regulatory T cells (T(regs)) play a critical role in regulating inflammatory processes in non-alcoholic steatohepatitis (NASH) and because T helper type 17 (Th17) functionally oppose T(reg)-mediated responses, this study focused on characterizing the role of Th17 cells using a NAFLD mouse model. C57BL/6 mice were fed either a normal diet (ND) or high fat (HF) diet for 8 weeks. Mice in the HF group had a significantly higher frequency of liver Th17 cells compared to ND-fed mice. Neutralization of interleukin (IL)-17 in HF mice ameliorated lipopolysaccharide (LPS)-induced liver injury reflected by decreased serum alanine aminotransferase (ALT) levels and reduced inflammatory cell infiltrates in the liver. In vitro, HepG2 cells cultured in the presence of free fatty acids (FFA; oleic acid and palmitic acid) for 24 h and IL-17 developed steatosis via insulin-signalling pathway interference. IL-17 and FFAs synergized to induce IL-6 production by HepG2 cells and murine primary hepatocytes which, in combination with transforming growth factor (TGF-β), expanded Th17 cells. It is likely that a similar process occurs in NASH patients, as there were significant levels of IL-17(+) cell infiltrates in NASH patient livers. The hepatic expression of Th17 cell-related genes [retinoid-related orphan receptor gamma (ROR)γt, IL-17, IL-21 and IL-23] was also increased significantly in NASH patients compared to healthy controls. Th17 cells and IL-17 were associated with hepatic steatosis and proinflammatory response in NAFLD and facilitated the transition from simple steatosis to steatohepatitis. Strategies designed to alter the balance between Th17 cells and T(regs) should be explored as a means of preventing progression to NASH and advanced liver diseases in NAFLD patients. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

Dietary, nondigestible oligosaccharides and Bifidobacterium breve M-16V suppress allergic inflammation in intestine via targeting dendritic cell maturation.

PubMed

de Kivit, Sander; Kostadinova, Atanaska I; Kerperien, JoAnn; Morgan, Mary E; Muruzabal, Veronica Ayechu; Hofman, Gerard A; Knippels, Leon M J; Kraneveld, Aletta D; Garssen, Johan; Willemsen, Linette E M

2017-07-01

Dietary intervention with short-chain galacto-oligosaccharides (scGOS), long-chain fructo-oligosaccharides (lcFOS) and Bifidobacterium breve M-16V ( Bb ) (GF/ Bb ) suppresses food allergic symptoms in mice, potentially via intestinal epithelial cell (IEC)-derived galectin-9. Furthermore, in vitro studies showed galacto- and fructo-oligosaccharides (GF) to enhance the immunomodulatory capacity of a TLR9 ligand representing bacterial CpG DNA when exposed to IEC. In this study, we investigated whether GF/ Bb modulates dendritic cells (DCs) and subsequent Th2 and regulatory T cell (T reg ) frequency in the small intestinal lamina propria (SI-LP). BALB/c mice were fed GF/ Bb during oral OVA sensitization. DC and T cell phenotype were determined in SI-LP mononuclear cells using flow cytometry. Murine bone marrow-derived DCs (BMDCs) were exposed to recombinant galectin-9 or human monocyte-derived DCs (moDCs) and were cultured in IEC-conditioned medium from GF and TLR9 ligand-exposed HT-29 cells. GF/ Bb reduced allergic symptoms and enhanced serum galectin-9 levels, while suppressing activation, restoring phagocytic capacity, and normalizing CD103 expression of SI-LP DCs of OVA-allergic mice. In vitro, galectin-9 suppressed LPS-induced activation markers and cytokine secretion by BMDCs, and IEC-conditioned medium suppressed moDC activation in a galectin-9-dependent manner. Besides suppression of SI-LP DC activation, dietary GF/ Bb also lowered the frequency of activated Th2 cells, while enhancing T reg in the SI-LP of OVA-allergic mice compared to the control diet. Dietary intervention with GF/ Bb enhances galectin-9 and suppresses allergic symptoms of OVA-allergic mice in association with reduced intestinal DC and Th2 activation and increased T reg frequency in these mice. © Society for Leukocyte Biology.

A Molecular-Genetic Study of the Arabidopsis Toc75 Gene Family1

PubMed Central

Baldwin, Amy; Wardle, Anthony; Patel, Ramesh; Dudley, Penny; Park, Soon Ki; Twell, David; Inoue, Kentaro; Jarvis, Paul

2005-01-01

Toc75 (translocon at the outer envelope membrane of chloroplasts, 75 kD) is the protein translocation channel at the outer envelope membrane of plastids and was first identified in pea (Pisum sativum) using biochemical approaches. The Arabidopsis (Arabidopsis thaliana) genome contains three Toc75-related sequences, termed atTOC75-I, atTOC75-III, and atTOC75-IV, which we studied using a range of molecular, genetic, and biochemical techniques. Expression of atTOC75-III is strongly regulated and at its highest level in young, rapidly expanding tissues. By contrast, atTOC75-IV is expressed uniformly throughout development and at a much lower level than atTOC75-III. The third sequence, atTOC75-I, is a pseudogene that is not expressed due to a gypsy/Ty3 transposon insertion in exon 1, and numerous nonsense, frame-shift, and splice-junction mutations. The expressed genes, atTOC75-III and atTOC75-IV, both encode integral envelope membrane proteins. Unlike atToc75-III, the smaller atToc75-IV protein is not processed upon targeting to the envelope, and its insertion does not require ATP at high concentrations. The atTOC75-III gene is essential for viability, since homozygous atToc75-III knockout mutants (termed toc75-III) could not be identified, and aborted seeds were observed at a frequency of approximately 25% in the siliques of self-pollinated toc75-III heterozygotes. Homozygous toc75-III embryos were found to abort at the two-cell stage. Homozygous atToc75-IV knockout plants (termed toc75-IV) displayed no obvious visible phenotypes. However, structural abnormalities were observed in the etioplasts of toc75-IV seedlings and atTOC75-IV overexpressing lines, and toc75-IV plants were less efficient at deetiolation than wild type. These results suggest some role for atToc75-IV during growth in the dark. PMID:15908591

Inflammation and nerve injury induce expression of pancreatitis-associated protein-II in primary sensory neurons.

PubMed

He, Shao-Qiu; Yao, Jun-Ru; Zhang, Fang-Xiong; Wang, Qiong; Bao, Lan; Zhang, Xu

2010-04-26

Pancreatitis-associated protein (PAP)-I and -II, lectin-related secretory proteins, are members of the regenerating gene (Reg) family. Although expression of PAP-I was found in the dorsal root ganglion (DRG) neurons following peripheral nerve injury and cystitis, whether PAP-II could be expressed in DRG neurons in chronic pain models remains unclear. The present study shows an inflammation- and nerve injury-triggered expression of PAP-II in rat DRG neurons. In situ hybridization showed that only a few DRG neurons normally contained PAP-I and -II mRNAs. After peripheral inflammation, PAP-I and -II mRNAs were present in over half of small DRG neurons. Such an elevated expression of PAP-I and -II reached the peak level on the second day. Immunostaining showed that the expression of PAP-II was mostly increased in the isolectin B4-positive subset of small DRG neurons after inflammation. Furthermore, the expression of PAP-II was also induced in DRG neurons after peripheral nerve injury. Interestingly, PAP-II expression was shifted from small neurons on day 2 to large DRG neurons that expressed neuropeptide Y during the later post-injury days. These results suggest that PAP-II may play potential roles in the modulation of spinal sensory pathways in pathological pain states.

Artesunate modulates expression of matrix metalloproteinases and their inhibitors as well as collagen-IV to attenuate pulmonary fibrosis in rats.

PubMed

Wang, Y; Huang, G; Mo, B; Wang, C

2016-06-03

The aim of this study was to determine the effect of artesunate on extracellular matrix (ECM) accumulation and the expression of collagen-IV, matrix metalloproteinase (MMP), and tissue inhibitor of matrix metalloproteinase (TIMP) to understand the pharmacological role of artesunate in pulmonary fibrosis. Eighty Sprague-Dawley rats were randomly assigned to four groups that were administered saline alone, bleomycin (BLM) alone, BLM + artesunate, or artesunate alone for 28 days. Lung tissues from 10 rats in each group were used to obtain lung fibroblast (LF) primary cells, and the rest were used to analyze protein expression. The mRNA expression of collagen-IV, MMP-2, MMP-9, TIMP-1, and TIMP-2 in lung fibroblasts was detected by real-time quantitative reverse transcriptase polymerase chain reaction. The protein levels of collagen-IV, MMP-2, MMP-9, TIMP-1, and TIMP-2 protein in lung tissues were analyzed by western blotting. Artesunate treatment alleviated alveolitis and pulmonary fibrosis induced by bleomycin in rats, as indicated by a decreased lung coefficient and improvement of lung tissue morphology. Artesunate treatment also led to decreased collagen-IV protein levels, which might be a result of its downregulated expression and increased MMP-2 and MMP-9 protein and mRNA levels. Increased TIMP-1 and TIMP- 2 protein and mRNA levels were detected after artesunate treatment in lung tissues and primary lung fibroblast cells and may contribute to enhanced activity of MMP-2 and -9. These findings suggested that artesunate attenuates alveolitis and pulmonary fibrosis by regulating expression of collagen-IV, TIMP-1 and 2, as well as MMP-2 and -9, to reduce ECM accumulation.

BRCA1 expression and improved survival in ovarian cancer patients treated with intraperitoneal cisplatin and paclitaxel: a Gynecologic Oncology Group Study.

PubMed

Lesnock, J L; Darcy, K M; Tian, C; Deloia, J A; Thrall, M M; Zahn, C; Armstrong, D K; Birrer, M J; Krivak, T C

2013-04-02

Breast cancer 1, early onset (BRCA1) is a tumour-suppressor gene associated with familial epithelial ovarian cancer (EOC). Reduced BRCA1 expression is associated with enhanced sensitivity to platinum-based chemotherapy. We sought to examine the prognostic relevance of BRCA1 expression in EOC patients treated with intraperitoneal platinum/taxane. The GOG-172 was a phase III, multi-institutional randomised trial of intravenous paclitaxel and cisplatin (IV therapy) vs intravenous paclitaxel, intraperitoneal cisplatin plus paclitaxel (IP therapy) in patients with optimally resected stage III EOC. The BRCA1 expression was assessed with immunohistochemistry (IHC) staining blinded to clinical outcome in archival tumour specimens. Slides with 10% staining were defined as aberrant and >10% as normal. Correlations between BRCA1 expression and progression-free survival (PFS) and overall survival (OS) were analysed using Kaplan-Meier method and Cox regression analysis. Of the 393 patients, 189 tumours had aberrant expression, and 204 had normal BRCA1 expression. There was an interaction between BRCA1 expression and route of administration on OS (P=0.014) but not PFS (P=0.054). In tumours with normal BRCA1 expression, the median OS was 58 months for IP group vs 50 months for IV group (P=0.818). In tumours with aberrant BRCA1 expression, the median OS was 84 vs 47 months in the IP vs IV group, respectively (P=0.0002). Aberrant BRCA1 expression was an independent prognostic factor for better survival in women randomised to IP therapy (hazard ratio (HR)=0.67, 95% confidence interval (CI)=0.47-0.97, P=0.032). Similar survival was observed in the IV and IP patients with normal BRCA1 expression. Multivariate but not univariate modelling demonstrated that IV patients with aberrant vs normal BRCA1 expression had worse survival. Decreased BRCA1 expression is associated with a 36-month survival improvement in patients with EOC treated with IP chemotherapy. Although these results merit validation in future studies, the results suggest that decreased BRCA1 expression predicts for improved response to cisplatin-based IP chemotherapy with cisplatin and paclitaxel.

Colorado SIP: 5 CCR 1001-13, Reg 11, Motor Vehicle Emissions Inspection Program—Part A, General Provisions, Area of Applicability, Schedules for Obtaining Certification of Emissions Control, Definitions, Exemptions, and Clean Screening/Remote Sensing

EPA Pesticide Factsheets

Colorado SIP: 5 CCR 1001-13, Reg 11, Motor Vehicle Emissions Inspection Program—Part A, General Provisions, Area of Applicability, Schedules for Obtaining Certification of Emissions Control, Definitions, Exemptions, and Clean Screening/Remote Sensing

21 CFR 184.1845 - Stannous chloride (anhydrous and dihydrated).

Code of Federal Regulations, 2010 CFR

2010-04-01

.... Anhydrous stannous chloride (SnCl2, CAS Reg. No. 7772-99-8) is the chloride salt of metallic tin. It is prepared by reacting molten tin with either chlorine or gaseous tin tetrachloride. Dihydrated stannous chloride (SnCl2·2H2O, CAS Reg. No. 10025-0969-091) is the chloride salt of metallic tin that contains two...

21 CFR 184.1845 - Stannous chloride (anhydrous and dihydrated).

Code of Federal Regulations, 2013 CFR

2013-04-01

.... Anhydrous stannous chloride (SnCl2, CAS Reg. No. 7772-99-8) is the chloride salt of metallic tin. It is prepared by reacting molten tin with either chlorine or gaseous tin tetrachloride. Dihydrated stannous chloride (SnCl2·2H2O, CAS Reg. No. 10025-69-1) is the chloride salt of metallic tin that contains two...

21 CFR 184.1845 - Stannous chloride (anhydrous and dihydrated).

Code of Federal Regulations, 2011 CFR

2011-04-01

.... Anhydrous stannous chloride (SnCl2, CAS Reg. No. 7772-99-8) is the chloride salt of metallic tin. It is prepared by reacting molten tin with either chlorine or gaseous tin tetrachloride. Dihydrated stannous chloride (SnCl2·2H2O, CAS Reg. No. 10025-0969-091) is the chloride salt of metallic tin that contains two...

21 CFR 184.1845 - Stannous chloride (anhydrous and dihydrated).

Code of Federal Regulations, 2012 CFR

2012-04-01

.... Anhydrous stannous chloride (SnCl2, CAS Reg. No. 7772-99-8) is the chloride salt of metallic tin. It is prepared by reacting molten tin with either chlorine or gaseous tin tetrachloride. Dihydrated stannous chloride (SnCl2·2H2O, CAS Reg. No. 10025-69-1) is the chloride salt of metallic tin that contains two...

40 CFR 180.910 - Inert ingredients used pre- and post-harvest; exemptions from the requirement of a tolerance.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., carrier Lactic acid Solvent Lactic acid, 2-ethylhexyl ester (CAS Reg. No. 6283-86-9) Solvent Lactic acid, 2-ethylhexyl ester, (2S)- (CAS Reg. No. 186817-80-1) Solvent Lactic acid, n-propyl ester, (S); (CAS... coating agent Petroleum wax, conforming to 21 CFR 172.886(d) Coating agent Phosphoric acid Buffer...

Registration of two confection sunflower germplasm Lines, HA-R10 and HA-R11, Resistant to sunflower rust

USDA-ARS?s Scientific Manuscript database

Two confection sunflower (Helianthus annuus L.) germplasm lines, HA-R10 (Reg. No.xxx, PI670043) and HA-R11 (Reg. No.xxx, PI670044) were developed by the USDA-ARS Sunflower and Plant Biology Research Unit in collaboration with the North Dakota Agricultural Experiment Station and released December, 20...

21 CFR 184.1193 - Calcium chloride.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Calcium chloride. 184.1193 Section 184.1193 Food... Specific Substances Affirmed as GRAS § 184.1193 Calcium chloride. (a) Calcium chloride (CaCl2·2H2O, CAS Reg. No. 10035-04-8) or anhydrous calcium chloride (CaCl2, CAS Reg. No. 10043-52-4) may be commercially...

21 CFR 184.1193 - Calcium chloride.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Calcium chloride. 184.1193 Section 184.1193 Food... Specific Substances Affirmed as GRAS § 184.1193 Calcium chloride. (a) Calcium chloride (CaCl2·2H2O, CAS Reg. No. 10035-04-8) or anhydrous calcium chloride (CaCl2, CAS Reg. No. 10043-52-4) may be commercially...

21 CFR 184.1193 - Calcium chloride.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Calcium chloride. 184.1193 Section 184.1193 Food... GRAS § 184.1193 Calcium chloride. (a) Calcium chloride (CaCl2·2H2O, CAS Reg. No. 10035-04-8) or anhydrous calcium chloride (CaCl2, CAS Reg. No. 10043-52-4) may be commercially obtained as a byproduct in...

Sustained suppression by Foxp3+ regulatory T cells is vital for infectious transplantation tolerance

PubMed Central

Kendal, Adrian R.; Chen, Ye; Regateiro, Frederico S.; Ma, Jianbo; Adams, Elizabeth; Cobbold, Stephen P.; Hori, Shohei

2011-01-01

A paradigm shift in immunology has been the recent discovery of regulatory T cells (T reg cells), of which CD4+Foxp3+ cells are proven as essential to self-tolerance. Using transgenic B6.Foxp3hCD2 mice to isolate and ablate Foxp3+ T reg cells with an anti-hCD2 antibody, we show for the first time that CD4+Foxp3+ cells are crucial for infectious tolerance induced by nonablative anti–T cell antibodies. In tolerant animals, Foxp3+ T reg cells are constantly required to suppress effector T cells still capable of causing tissue damage. Tolerated tissue contains T cells that are capable of rejecting it, but are prevented from doing so by therapeutically induced Foxp3+ T reg cells. Finally, Foxp3+ cells have been confirmed as the critical missing link through which infectious tolerance operates in vivo. Peripherally induced Foxp3+ cells sustain tolerance by converting naive T cells into the next generation of Foxp3+ cells. Empowering Foxp3+ regulatory T cells in vivo offers a tractable route to avoid and correct tissue immunopathology. PMID:21875958

Applications and mechanisms of immunotherapy in allergic rhinitis and asthma.

PubMed

Kappen, Jasper H; Durham, Stephen R; Veen, Hans In 't; Shamji, Mohamed H

2017-01-01

Clinical and immunologic tolerance are hallmarks of successful allergen immunotherapy (AIT). Clinical benefits such as reduced symptoms, pharmacotherapy intake and improvement of quality of life persist following cessation of treatment. Successful AIT is associated with suppression of allergic inflammatory cells such as mast cells, eosinophils and basophils in target organs. Furthermore, AIT down-regulates type 2 innate lymphoid cells and allergen-specific type 2 T-helper (Th2) cells. The immunologic tolerant state following AIT is associated with the induction of distinct phenotypes of regulatory T-cells (T-regs) including interleukin (IL)-10-, IL-35- and transforming growth factor (TGF)-β- producing T-regs and FoxP3 + T-regs. B-cell responses, including the induction of IL-10 + regulatory B-cells (B-regs) and the production of IgG4-associated blocking antibodies are also induced following successful AIT. These events are associated with the suppression of antigen-specific Th2 responses and delayed immune deviation in favour of Th1 type responses. Insight into the mechanisms of AIT has allowed identification of novel biomarkers with potential to predict the clinical response to AIT and also novel therapeutic strategies for more effective and safer AIT.

49 CFR 555.6 - Basis for application.

Code of Federal Regulations, 2011 CFR

2011-10-01

... achieved either by design changes or termination of production of nonconforming vehicles; and (v) The total... failure to meet the standard, expressed as comparative performance levels; and (iv) Reasons why the... standard, expressed as comparative performance levels; (iv) The results of any tests conducted on the...

49 CFR 555.6 - Basis for application.

Code of Federal Regulations, 2013 CFR

2013-10-01

... achieved either by design changes or termination of production of nonconforming vehicles; and (v) The total... failure to meet the standard, expressed as comparative performance levels; and (iv) Reasons why the... standard, expressed as comparative performance levels; (iv) The results of any tests conducted on the...

49 CFR 555.6 - Basis for application.

Code of Federal Regulations, 2012 CFR

2012-10-01

... achieved either by design changes or termination of production of nonconforming vehicles; and (v) The total... failure to meet the standard, expressed as comparative performance levels; and (iv) Reasons why the... standard, expressed as comparative performance levels; (iv) The results of any tests conducted on the...

49 CFR 555.6 - Basis for application.

Code of Federal Regulations, 2010 CFR

2010-10-01

... achieved either by design changes or termination of production of nonconforming vehicles; and (v) The total... failure to meet the standard, expressed as comparative performance levels; and (iv) Reasons why the... standard, expressed as comparative performance levels; (iv) The results of any tests conducted on the...

49 CFR 555.6 - Basis for application.

Code of Federal Regulations, 2014 CFR

2014-10-01

... achieved either by design changes or termination of production of nonconforming vehicles; and (v) The total... failure to meet the standard, expressed as comparative performance levels; and (iv) Reasons why the... standard, expressed as comparative performance levels; (iv) The results of any tests conducted on the...

Angiotensin IV and the human esophageal mucosa: An exploratory study in healthy subjects and gastroesophageal reflux disease patients.

PubMed

Björkman, Eleonora; Edebo, Anders; Fändriks, Lars; Casselbrant, Anna

2015-09-01

The human esophageal mucosa expresses various components of the renin-angiotensin system (RAS), e.g. the main effector peptide angiotensin II (AngII). The aim of this study was to investigate the esophageal presence of angiotensin III (AngIII) and angiotensin IV (AngIV) forming enzymes and the AngIV receptor (AT4R). The aim was also to study the actions of AngIV and to look for aberrations in patients with gastroesophageal reflux disease (GERD). Esophageal biopsies were collected from healthy volunteers (n: 19) and individuals with erosive reflux disease (n: 14). Gene transcripts and protein expression of aminopeptidase A, -B and -M, and the AT4R were investigated by reverse transcriptase polymerase chain reaction (rt-PCR), western blot (WB) and immunohistochemistry (IHC). The functional impact of AngIV was examined in an Ussing chamber. Aminopeptidase A, -B and -M and the AT4R were expressed in the esophageal epithelium. The AT4R was less prominent in certain areas in the mucosa of reflux patients. AngIV influenced the esophageal epithelial ion transport. The impact was lower in patients with GERD. The AT4R and formation enzymes of AngIII and AngIV are present in the human esophageal epithelium. Moreover, the present results suggest that AngIV exert regulatory impact on the epithelium and that RAS is involved in mucosal aberrations associated with GERD. © The Author(s) 2014.

A Modular Lentiviral and Retroviral Construction System to Rapidly Generate Vectors for Gene Expression and Gene Knockdown In Vitro and In Vivo

PubMed Central

Geiling, Benjamin; Vandal, Guillaume; Posner, Ada R.; de Bruyns, Angeline; Dutchak, Kendall L.; Garnett, Samantha; Dankort, David

2013-01-01

The ability to express exogenous cDNAs while suppressing endogenous genes via RNAi represents an extremely powerful research tool with the most efficient non-transient approach being accomplished through stable viral vector integration. Unfortunately, since traditional restriction enzyme based methods for constructing such vectors are sequence dependent, their construction is often difficult and not amenable to mass production. Here we describe a non-sequence dependent Gateway recombination cloning system for the rapid production of novel lentiviral (pLEG) and retroviral (pREG) vectors. Using this system to recombine 3 or 4 modular plasmid components it is possible to generate viral vectors expressing cDNAs with or without inhibitory RNAs (shRNAmirs). In addition, we demonstrate a method to rapidly produce and triage novel shRNAmirs for use with this system. Once strong candidate shRNAmirs have been identified they may be linked together in tandem to knockdown expression of multiple targets simultaneously or to improve the knockdown of a single target. Here we demonstrate that these recombinant vectors are able to express cDNA and effectively knockdown protein expression using both cell culture and animal model systems. PMID:24146852

Insertion device calculations with mathematica

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

Carr, R.; Lidia, S.

1995-02-01

The design of accelerator insertion devices such as wigglers and undulators has usually been aided by numerical modeling on digital computers, using code in high level languages like Fortran. In the present era, there are higher level programming environments like IDL{reg_sign}, MatLab{reg_sign}, and Mathematica{reg_sign} in which these calculations may be performed by writing much less code, and in which standard mathematical techniques are very easily used. The authors present a suite of standard insertion device modeling routines in Mathematica to illustrate the new techniques. These routines include a simple way to generate magnetic fields using blocks of CSEM materials, trajectorymore » solutions from the Lorentz force equations for given magnetic fields, Bessel function calculations of radiation for wigglers and undulators and general radiation calculations for undulators.« less

Minor Type IV Collagen α5 Chain Promotes Cancer Progression through Discoidin Domain Receptor-1

PubMed Central

Xiao, Qian; Jiang, Yan; Liu, Qingbo; Yue, Jiao; Liu, Chunying; Zhao, Xiaotong; Qiao, Yuemei; Ji, Hongbin; Chen, Jianfeng; Ge, Gaoxiang

2015-01-01

Type IV collagens (Col IV), components of basement membrane, are essential in the maintenance of tissue integrity and proper function. Alteration of Col IV is related to developmental defects and diseases, including cancer. Col IV α chains form α1α1α2, α3α4α5 and α5α5α6 protomers that further form collagen networks. Despite knowledge on the functions of major Col IV (α1α1α2), little is known whether minor Col IV (α3α4α5 and α5α5α6) plays a role in cancer. It also remains to be elucidated whether major and minor Col IV are functionally redundant. We show that minor Col IV α5 chain is indispensable in cancer development by using α5(IV)-deficient mouse model. Ablation of α5(IV) significantly impeded the development of KrasG12D-driven lung cancer without affecting major Col IV expression. Epithelial α5(IV) supports cancer cell proliferation, while endothelial α5(IV) is essential for efficient tumor angiogenesis. α5(IV), but not α1(IV), ablation impaired expression of non-integrin collagen receptor discoidin domain receptor-1 (DDR1) and downstream ERK activation in lung cancer cells and endothelial cells. Knockdown of DDR1 in lung cancer cells and endothelial cells phenocopied the cells deficient of α5(IV). Constitutively active DDR1 or MEK1 rescued the defects of α5(IV)-ablated cells. Thus, minor Col IV α5(IV) chain supports lung cancer progression via DDR1-mediated cancer cell autonomous and non-autonomous mechanisms. Minor Col IV can not be functionally compensated by abundant major Col IV. PMID:25992553

Stromal fibroblasts are associated with collagen IV in scar tissues of alkali-burned and lacerated corneas.

PubMed

Ishizaki, M; Shimoda, M; Wakamatsu, K; Ogro, T; Yamanaka, N; Kao, C W; Kao, W W

1997-04-01

Corneal wound healing frequently leads to the formation of opaque scar tissue. We examined whether stromal fibroblastic cells of injured corneas express collagen IV and contributes to the formation of a basal lamina-like structure. Rabbits were anesthetized, and central corneal alkali burn (8 mm in diameter; 1 M NaOH, 1 min) or laceration (8 mm long) were produced. The injured corneas, which had healed for 1, 7, 21 and 45 days, were subjected to histological and immunohistochemical studies with goat anti-collagen IV antibodies, using light and electron microscopy, and in situ hybridization with an antisense digoxigenin-labeled riboprobe of collagen alpha 1(IV) mRNA. For comparison, twenty-day-old fetal corneas were subjected to immunohistochemical study and transmission electron microscopy (TEM). TEM examinations revealed that the stromal collagenous matrix was organized in orthogonal lamellae during corneal development, whereas that of alkali-burned cornea, which had healed for 3 weeks, was disorganized. The stroma of twenty-day-old fetal cornea was not labeled by the anti-collagen IV antibodies. In contrast, one week after injury, specific collagen IV immunostaining was detected in the injured stroma. As the healing proceeded (21-45 days), the antibodies reacted with fibroblastic cells and the extracellular matrix of scar tissues located in the anterior portion of alkali-burned corneas, as well as the posterior portion of lacerated corneas. The middle portion of the stromal tissues was weakly labeled by the anti-collagen IV antibodies with the exception of the blood vessel wall. Immuno-electron microscopic study showed that collagen IV and fibronectin were closely associated with the fibroblastic cells. In situ hybridization demonstrated that epithelial and endothelial cells and fibroblastic cells in the wounded corneal stroma and retro-corneal membrane expressed alpha 1(IV) mRNA, whereas in normal corneas the expression of alpha 1(IV) mRNA was limited to epithelial and endothelial cells. The enhanced expression of collagen IV by the fibroblastic cells in the stroma of injured corneas is consistent with the notion that they may contribute to the formation of basal lamina-like structures in injured corneas.

The regional climate model RegCM3 performances over several regions and climate regimes

NASA Astrophysics Data System (ADS)

Coppola, E.; Rauscher, S.; Gao, X.; Giorgi, F.; Im, E. S.; Mariotti, L.; Seth, A.; Sylla, M. B.

2009-04-01

Regional Climate models are more and more needed to provide high resolution regional climate information in climate impact studies. Water availability in a future scenario is the main request of policy makers for adaptation and mitigation purposes. However precipitation changes are unlikely to be as spatially coherent as temperature changes and they are closely related to the regional model itself. In addition model skill varies regionally. An example of several ICTP regional climate model (RegCM3) simulations is reported over China, Korea, Africa, Central and Southern America, Europe and Australia. Over China, Australia, and Korea the regional model improves the simulation compared to the driving GCM when compared with CRU observations. In China, for example, the higher resolution of the regional model inhibits the penetration of the monsoon precipitation front from the southern slope of the Himalaya onto the Tibetan Plateau. In Korea the nested domain simulation (20 km) shows an encouraging performance with regard to capturing extreme precipitation episodes and the finer spatial distribution reflects the detailed geography of the Korean Peninsula. Over South America, RegCM captures the annual cycle of precipitation over Northeast Brazil and the South American Monsoon region, although the monsoon onset occurs too early in the model. Precipitation over the Amazon is not well captured, with too little precipitation associated with weak easterlies and reduced moisture transport into the interior of the continent. RegCM simulates the annual cycle of precipitation over Central America and the Caribbean fairly well; in particular, the complex spatial distribution of the Mid-Summer Drought, a decrease in precipitation that occurs during the middle of the rainy season in July and August, is better captured by RegCM than by the GCM. In addition, RegCM simulates the strength and position of the Caribbean low level jet, a mesoscale feature related to precipitation anomalies in the region. Over Africa our analysis shows that RegCM3 is able to reproduce fairly well the spatial variability of seasonal mean temperature, precipitation and the associated low-level circulation. However, monsoon flow is over predicted while African Easterly Jet (AEJ) core underestimated and shifted a bit northward. Finally, over Europe the regional model shows a cold bias for most part of the year and a wet bias in winter and spring. Rain frequency is too high especially over the mountainous regions. The spatial patter of the precipitation extreme is well represented in the model although a slight overestimation of the 95, 98 99 percentile is evident.

Spinal cord MRI signal changes at 1 year after cervical decompression surgery is useful for predicting midterm clinical outcome: an observational study using propensity scores.

PubMed

Ikegami, Shota; Takahashi, Jun; Misawa, Hiromichi; Tsutsumimoto, Takahiro; Yui, Mutsuki; Kuraishi, Shugo; Futatsugi, Toshimasa; Uehara, Masashi; Oba, Hiroki; Kato, Hiroyuki

2018-05-01

There is little information on the relationship between magnetic resonance imaging (MRI) T2-weighted high signal change (T2HSC) in the spinal cord and surgical outcome for cervical myelopathy. We therefore examined whether T2HSC regression at 1 year postoperatively reflected a 5-year prognosis after adjustment using propensity scores for potential confounding variables, which have been a disadvantage of earlier observational studies. The objective of this study was to clarify the usefulness of MRI signal changes for the prediction of midterm surgical outcome in patients with cervical myelopathy. This is a retrospective cohort study. We recruited 137 patients with cervical myelopathy who had undergone surgery between 2007 and 2012 at a median age of 69 years (range: 39-87 years). The outcome measures were the recovery rates of the Japanese Orthopaedic Association (JOA) scores and the visual analog scale (VAS) scores for complaints at several body regions. The subjects were divided according to the spinal MRI results at 1 year post surgery into the MRI regression group (Reg+ group, 37 cases) with fading of T2HSC, or the non-regression group (Reg- group, 100 cases) with either no change or an enlargement of T2HSC. The recovery rates of JOA scores from 1 to 5 years postoperatively along with the 5-year postoperative VAS scores were compared between the groups using t test. Outcome scores were adjusted for age, sex, diagnosis, symptom duration, and preoperative JOA score by the inverse probability weighting method using propensity scores. The mean recovery rates in the Reg- group were 35.1%, 34.6%, 27.6%, 28.0%, and 30.1% from 1 to 5 years post surgery, respectively, whereas those in the Reg+ group were 52.0%, 52.0%, 51.1%, 49.0%, and 50.1%, respectively. The recovery rates in the Reg+ group were significantly higher at all observation points. At 5 years postoperatively, the VAS score for pain or numbnessin the arms or hands of the patients in the Reg+ group (24.7 mm) was significantly milder than that of the patients in the Reg- group (42.2 mm). Spinal T2HSC improvement at 1 year postoperatively may predict a favorable recovery until up to 5 years after surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Helicobacter pylori cagA+ Is Associated with Milder Duodenal Histological Changes in Chilean Celiac Patients

PubMed Central

Lucero, Yalda; Oyarzún, Amaya; O'Ryan, Miguel; Quera, Rodrigo; Espinosa, Nelly; Valenzuela, Romina; Simian, Daniela; Alcalde, Elisa; Arce, Claudio; Farfán, Mauricio J.; Vergara, Alejandra F.; Gajardo, Iván; Mendez, Jocelyn; Carrasco, Jorge; Errázuriz, Germán; Gonzalez, Mónica; Ossa, Juan C.; Maiza, Eduardo; Perez-Bravo, Francisco; Castro, Magdalena; Araya, Magdalena

2017-01-01

HIGHLIGHTS What is already known about this subject?Celiac disease (CD) has a high clinical and histological diversity and the mechanisms underlying this phenomenon remain elusive.H. pylori is a bacterium that chronically infect gastric and duodenal mucosa activating both a Th1/Th17 and T-reg pathways.The role of H. pylori (and the effect of their virulence factors) in CD have not yet completely elucidated.What are the new findings?cagA+ H. pylori strains are associated to milder histological damage in infected CD patients.In active-CD patients the presence of cagA+ H. pylori is associated to an increase in T-reg markers, contrasting with a downregulation in cagA+ infected potential-CD individuals.How might it impact on clinical practice in the foreseeable future?The identification of microbiological factors that could modulate inflammation and clinical expression of CD may be used in the future as preventive strategies or as supplementary treatment in patients that cannot achieve complete remission, contributing to the better care of these patients. Background: Mechanisms underlying the high clinical and histological diversity of celiac disease (CD) remain elusive. Helicobacter pylori (Hp) chronically infects gastric and duodenal mucosa and has been associated with protection against some immune-mediated conditions, but its role (specifically of cagA+ strains) in CD is unclear. Objective: To assess the relationship between gastric Hp infection (cagA+ strains) and duodenal histological damage in patients with CD. Design: Case-control study including patients with active-CD, potential-CD and non-celiac individuals. Clinical presentation, HLA genotype, Hp/cagA gene detection in gastric mucosa, duodenal histology, Foxp3 positive cells and TGF-β expression in duodenal lamina propria were analyzed. Results: We recruited 116 patients, 29 active-CD, 37 potential-CD, and 50 non-CD controls. Hp detection was similar in the three groups (~30–40%), but cagA+ strains were more common in infected potential-CD than in active-CD (10/11 vs. 4/10; p = 0.020) and non-CD (10/20; p = 0.025). Among active-CD patients, Foxp3 positivity was significantly higher in subjects with cagA+ Hp+ compared to cagA- Hp+ (p < 0.01) and Hp- (p < 0.01). In cagA+ Hp+ individuals, Foxp3 positivity was also higher comparing active- to potential-CD (p < 0.01). TGF-β expression in duodenum was similar in active-CD with cagA+ Hp+ compared to Hp- and was significantly downregulated in cagA+ potential-CD subjects compared to other groups. Conclusion: Hp infection rates were similar among individuals with/without CD, but infection with cagA+ strains was associated with milder histological damage in celiac patients infected by Hp, and in active-CD cases with higher expression of T-reg markers. Results suggest that infection by cagA+ Hp may be protective for CD progression, or conversely, that these strains are prone to colonize intestinal mucosa with less severe damage. PMID:28879170

Histoplasma capsulatum encodes a dipeptidyl peptidase active against the mammalian immunoregulatory peptide, substance P.

PubMed

Cooper, Kendal G; Zarnowski, Robert; Woods, Jon P

2009-01-01

The pathogenic fungus Histoplasma capsulatum secretes dipeptidyl peptidase (Dpp) IV enzyme activity and has two putative DPPIV homologs (HcDPPIVA and HcDPPIVB). We previously showed that HcDPPIVB is the gene responsible for the majority of secreted DppIV activity in H. capsulatum culture supernatant, while we could not detect any functional contribution from HcDPPIVA. In order to determine whether HcDPPIVA encodes a functional DppIV enzyme, we expressed HcDPPIVA in Pichia pastoris and purified the recombinant protein. The recombinant enzyme cleaved synthetic DppIV substrates and had similar biochemical properties to other described DppIV enzymes, with temperature and pH optima of 42 degrees C and 8, respectively. Recombinant HcDppIVA cleaved the host immunoregulatory peptide substance P, indicating the enzyme has the potential to affect the immune response during infection. Expression of HcDPPIVA under heterologous regulatory sequences in H. capsulatum resulted in increased secreted DppIV activity, indicating that the encoded protein can be expressed and secreted by its native organism. However, HcDPPIVA was not required for virulence in a murine model of histoplasmosis. This work reports a fungal enzyme that can function to cleave the immunomodulatory host peptide substance P.

21 CFR 176.300 - Slimicides.

Code of Federal Regulations, 2014 CFR

2014-04-01

...(monobromoacetoxy) ethane [CA Reg. No. 3785-34-0] At a maximum level of 0.10 pound per ton of dry weight fiber. Bis... Methylenebisthiocyanate 2-Nitrobutyl bromoacetate [CA Reg. No. 32815-96-6] At a maximum level of 0.15 pound per ton of dry.... No. 55566-30-8) Maximum use level of 84 mg/kg in the pulp slurry. The additive may also be added to...

Registration of cotton germplasm USDA MD 16-1 and USDA MD 16-2 with enhanced lint yield and fiber quality.

USDA-ARS?s Scientific Manuscript database

Upland cotton germplasm USDA MD 16-1 (Reg. No. __ and PI ___ ), and USDA MD 16-2 (Reg. No. ___ and PI___) (Gossypium hirsutum L.), have enhanced yield and good fiber quality. These germplasm lines were developed by the USDA-ARS, Stoneville, MS and released in 2017. Two crosses, MD 25-51 X MD 10-9-1 ...

40 CFR 52.173 - Visibility protection.

Code of Federal Regulations, 2013 CFR

2013-07-01

... disapproved; (iii) Reg. 19.1505 (A)(1) and (2), (B), (C), (D)(1) and (2), (E), (F)(1) and (2), (G)(1) and (2... the State regulation is disapproved; (iii) Reg. 19.1505 (A)(1) and (2), (B), (C), (D)(1) and (2), (E.... 19.1505 (A)(1) and (2), (B), (C), (D)(1) and (2), (E), (F)(1) and (2), (G)(1) and (2), (H), (I)(1...

40 CFR 52.173 - Visibility protection.

Code of Federal Regulations, 2012 CFR

2012-07-01

... disapproved; (iii) Reg. 19.1505 (A)(1) and (2), (B), (C), (D)(1) and (2), (E), (F)(1) and (2), (G)(1) and (2... the State regulation is disapproved; (iii) Reg. 19.1505 (A)(1) and (2), (B), (C), (D)(1) and (2), (E.... 19.1505 (A)(1) and (2), (B), (C), (D)(1) and (2), (E), (F)(1) and (2), (G)(1) and (2), (H), (I)(1...

40 CFR 52.173 - Visibility protection.

Code of Federal Regulations, 2014 CFR

2014-07-01

... disapproved; (iii) Reg. 19.1505 (A)(1) and (2), (B), (C), (D)(1) and (2), (E), (F)(1) and (2), (G)(1) and (2... the State regulation is disapproved; (iii) Reg. 19.1505 (A)(1) and (2), (B), (C), (D)(1) and (2), (E.... 19.1505 (A)(1) and (2), (B), (C), (D)(1) and (2), (E), (F)(1) and (2), (G)(1) and (2), (H), (I)(1...

Assessing regional climate simulations of the last 30 years (1982-2012) over Ganges-Brahmaputra-Meghna River Basin

NASA Astrophysics Data System (ADS)

Khandu; Awange, Joseph L.; Anyah, Richard; Kuhn, Michael; Fukuda, Yoichi

2017-10-01

The Ganges-Brahmaputra-Meghna (GBM) River Basin presents a spatially diverse hydrological regime due to it's complex topography and escalating demand for freshwater resources. This presents a big challenge in applying the current state-of-the-art regional climate models (RCMs) for climate change impact studies in the GBM River Basin. In this study, several RCM simulations generated by RegCM4.4 and PRECIS are assessed for their seasonal and interannual variations, onset/withdrawal of the Indian monsoon, and long-term trends in precipitation and temperature from 1982 to 2012. The results indicate that in general, RegCM4.4 and PRECIS simulations appear to reasonably reproduce the mean seasonal distribution of precipitation and temperature across the GBM River Basin, although the two RCMs are integrated over a different domain size. On average, the RegCM4.4 simulations overestimate monsoon precipitation by {˜ }26 and {˜ }5% in the Ganges and Brahmaputra-Meghna River Basin, respectively, while PRECIS simulations underestimate (overestimate) the same by {˜ }7% ({˜ }16%). Both RegCM4.4 and PRECIS simulations indicate an intense cold bias (up to 10° C) in the Himalayas, and are generally stronger in the RegCM4.4 simulations. Additionally, they tend to produce high precipitation between April and May in the Ganges (RegCM4.4 simulations) and Brahmaputra-Meghna (PRECIS simulations) River Basins, resulting in early onset of the Indian monsoon in the Ganges River Basin. PRECIS simulations exhibit a delayed monsoon withdrawal in the Brahmaputra-Meghna River Basin. Despite large spatial variations in onset and withdrawal periods across the GBM River Basin, the basin-averaged results agree reasonably well with the observed periods. Although global climate model (GCM) driven simulations are generally poor in representing the interannual variability of precipitation and winter temperature variations, they tend to agree well with observed precipitation anomalies when driven by perfect boundary conditions. It is also seen that all GCM driven simulations feature significant positive surface temperature trends consistent with the observed datasets.

Work and family: associations with long-term sick-listing in Swedish women - a case-control study.

PubMed

Sandmark, Hélène

2007-10-11

The number of Swedish women who are long-term sick-listed is high, and twice as high as for men. Also the periods of sickness absence have on average been longer for women than for men. The objective of this study was to investigate the associations between factors in work- and family life and long-term sick-listing in Swedish women. This case-control study included 283 women on long-term sick-listing > or =90 days, and 250 female referents, randomly chosen, living in five counties in Sweden. Bivariate and multivariate logistic regression analyses with odds ratios were calculated to estimate the associations between long-term sick-listing and factors related to occupational work and family life. Long-term sick-listing in women is associated with self-reported lack of competence for work tasks (OR 2.42 1.23-11.21 log reg), workplace dissatisfaction (OR 1.89 1.14-6.62 log reg), physical workload above capacity (1.78 1.50-5.94), too high mental strain in work tasks (1.61 1.08-5.01 log reg), number of employers during work life (OR 1.39 1.35-4.03 log reg), earlier part-time work (OR 1.39 1.18-4.03 log reg), and lack of influence on working hours (OR 1.35 1.47-3.86 log reg). A younger age at first child, number of children, and main responsibility for own children was also found to be associated with long-term sick-listing. Almost all of the sick-listed women (93%) wanted to return to working life, and 54% reported they could work immediately if adjustments at work or part-time work were possible. Factors in work and in family life could be important to consider to prevent women from being long-term sick-listed and promote their opportunities to remain in working life. Measures ought to be taken to improve their mobility in work life and control over decisions and actions regarding theirs lives.

Characterizing moisture sources over Mediterranean Basin in a Regional Earth System Model

NASA Astrophysics Data System (ADS)

Batibeniz, F.; Ashfaq, M.; Turuncoglu, U. U.; Onol, B.

2017-12-01

We investigate precipitation dynamics over the Mediterranean region using Reanalysis data and a coupled Regional Earth System Model (RegESM). The RegESM model is run in coupled (RegCM4 coupled with ROMS) and uncoupled mode (atmosphere -land only) for 1979-2013 period using Era-Interim Reanalysis. RegESM incorporates atmosphere, ocean, river routing and wave components and thereby is better capable to improve the understanding of coupled climate system processes. We compare two model configurations to investigate the role of air sea interaction in the simulation of key processes that govern precipitation variability over the study region. Seasonal trend analyses have been performed to understand the changes in precipitation tendencies over the 35 years of the simulation period and observations. Additionally, two moisture flux analyses (Eulerian and Lagrangian) have been implemented to understand the role of various oceanic and terrestrial evaporative sources in seasonal precipitation distribution and long-term trends over the Mediterranean basin. In Eulerian approach, we use 7 different terrestrial regions to identify sources and sinks using the inflows and outflows from their boundaries. In Lagrangian approach, we divide the whole region in 9 parts to backtrack moisture coming from each region to the core Mediterranean region at intra-seasonal time-scales. Variation in the moisture contribution from each source region is investigated to quantify its role in the observed precipitation variability particularly during the extreme wet and dry years. Overall, our results highlight the importance of air-sea interaction in precipitation distribution at intra-seasonal to inter-decadal timescales over Mediterranean region as coupled RegESM configuration is able to improve of many limitations that are found in the standalone configuration.

Co-regulated Approach to Feeding Preterm Infants with Lung Disease: Effects During Feeding

PubMed Central

Thoyre, Suzanne M.; Holditch-Davis, Diane; Schwartz, Todd A.; Melendez Roman, Carlos R.; Nix, William

2015-01-01

Background Very preterm infants are at risk for poor oral feeding endurance, early cessation of eating, poor fluid management with aspiration risk, behavioral distress, and unstable heart rate and oxygenation during feeding. Objective To determine the preliminary effectiveness of a Co-Regulated Approach (CoReg) to oral feeding for very preterm infants at risk for lung disease. Method A randomized, within-subjects, cross-over design was used with 20 very preterm infants requiring oxygen at the start of oral feeding. Infants were bottle fed by the Usual Care approach and by the CoReg approach on 2 consecutive days for an average of four feedings each. Intervention components included co-regulation of suck, swallow, and breathe rhythms using enhanced auditory assessment, infant-guided feeding onsets, and infant positioning in a semielevated, side-lying position. Infant physiology metrics (heart rate, SaO2) were collected continuously prior to and during the feeding. Behavioral and auditory indicators of regulation were coded continuously from videotape during the feeding. Results Seventy feedings were analyzed (38 Usual Care, 32 CoReg) using repeated measures modeling. CoReg feedings were characterized by more frequent preparation of the infant for the feeding, were more commonly initiated in response to infant readiness cues, had more rest periods and breath regulation events, and had fewer sucking stimulation events. CoReg feedings had less SaO2 variability, decline, and time spent in a desaturated state; less heart rate fluctuation and decline; less behavioral disorganization; better fluid management; and less observed effort to breathe. Discussion Support is provided for a co-regulated approach to feeding vulnerable infants. Enhanced auditory assessment of infant feeding rhythms increases the responsiveness of the feeder and improves infant behavioral and physiologic responses. PMID:22565102

Chemical Basis for Qualitative and Quantitative Differences Between ABO Blood Groups and Subgroups: Implications for Organ Transplantation.

PubMed

Jeyakanthan, M; Tao, K; Zou, L; Meloncelli, P J; Lowary, T L; Suzuki, K; Boland, D; Larsen, I; Burch, M; Shaw, N; Beddows, K; Addonizio, L; Zuckerman, W; Afzali, B; Kim, D H; Mengel, M; Shapiro, A M J; West, L J

2015-10-01

Blood group ABH(O) carbohydrate antigens are carried by precursor structures denoted type I-IV chains, creating unique antigen epitopes that may differ in expression between circulating erythrocytes and vascular endothelial cells. Characterization of such differences is invaluable in many clinical settings including transplantation. Monoclonal antibodies were generated and epitope specificities were characterized against chemically synthesized type I-IV ABH and related glycans. Antigen expression was detected on endomyocardial biopsies (n = 50) and spleen (n = 11) by immunohistochemical staining and on erythrocytes by flow cytometry. On vascular endothelial cells of heart and spleen, only type II-based ABH antigens were expressed; type III/IV structures were not detected. Type II-based ABH were expressed on erythrocytes of all blood groups. Group A1 and A2 erythrocytes additionally expressed type III/IV precursors, whereas group B and O erythrocytes did not. Intensity of A/B antigen expression differed among group A1 , A2 , A1 B, A2 B and B erythrocytes. On group A2 erythrocytes, type III H structures were largely un-glycosylated with the terminal "A" sugar α-GalNAc. Together, these studies define qualitative and quantitative differences in ABH antigen expression between erythrocytes and vascular tissues. These expression profiles have important implications that must be considered in clinical settings of ABO-incompatible transplantation when interpreting anti-ABO antibodies measured by hemagglutination assays with reagent erythrocytes. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Proline residues in transmembrane segment IV are critical for activity, expression and targeting of the Na+/H+ exchanger isoform 1.

PubMed Central

Slepkov, Emily R; Chow, Signy; Lemieux, M Joanne; Fliegel, Larry

2004-01-01

NHE1 (Na+/H+ exchanger isoform 1) is a ubiquitously expressed integral membrane protein that regulates intracellular pH in mammalian cells. Proline residues within transmembrane segments have unusual properties, acting as helix breakers and increasing flexibility of membrane segments, since they lack an amide hydrogen. We examined the importance of three conserved proline residues in TM IV (transmembrane segment IV) of NHE1. Pro167 and Pro168 were mutated to Gly, Ala or Cys, and Pro178 was mutated to Ala. Pro168 and Pro178 mutant proteins were expressed at levels similar to wild-type NHE1 and were targeted to the plasma membrane. However, the mutants P167G (Pro167-->Gly), P167A and P167C were expressed at lower levels compared with wild-type NHE1, and a significant portion of P167G and P167C were retained intracellularly, possibly indicating induced changes in the structure of TM IV. P167G, P167C, P168A and P168C mutations abolished NHE activity, and P167A and P168G mutations caused markedly decreased activity. In contrast, the activity of the P178A mutant was not significantly different from that of wild-type NHE1. The results indicate that both Pro167 and Pro168 in TM IV of NHE1 are required for normal NHE activity. In addition, mutation of Pro167 affects the expression and membrane targeting of the exchanger. Thus both Pro167 and Pro168 are strictly required for NHE function and may play critical roles in the structure of TM IV of the NHE. PMID:14680478

75 FR 14438 - PPL Montana, LLC; Notice of Petition for Declaratory Order

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-25

..., 68 FR 49,846 (Aug. 19, 2003), FERC Stats. & Regs ] 31,146 (2003) (Order No. 2003); order on reh'g, Order No. 2003-A, 69 FR 15,932 (Mar. 26, 2004), FERC Stats. & Regs. 31,160, at P 531 (2004) (Order No. 2003-A); order on reh'g, Order No. 2003-B, 70 FR 265 (Jan. 4, 2005) (Order No. 2003-B) FERC Stats...

Improving Public Diplomacy, the Frontline of Soft Power

DTIC Science & Technology

2009-05-01

State A paper submitted to the Faculty of the Joint Advanced Warfighting School in partial satisfaction of the requirements of a Master of Science...3 U.S. Department of State, Dictionary of International Relations Terms, Washington D.C., 1987, p. 85. 4...education, wine , public order, irrigation, roads, a fresh water system and public health,” Reg demands, “what have the Romans ever done for us?” 13 For Reg

[Cerebral hemodynamics in patients with neurosensory hearing loss before and after magnetotherapy].

PubMed

Morenko, V M; Enin, I P

2001-01-01

Magnetotherapy effects on cerebral hemodynamics were studied using rheoencephalography (REG). When the treatment results and changes in cerebral hemodynamics were compared it was evident that normalization or improvement of vascular status in vertebrobasilar and carotid territories registered at REG results in better hearing. This confirms the role of vascular factor in pathogenesis of neurosensory hypoacusis of different etiology and effectiveness of magnetotherapy in such patients.

Simulation and spatiotemporal pattern of air temperature and precipitation in Eastern Central Asia using RegCM.

PubMed

Meng, Xianyong; Long, Aihua; Wu, Yiping; Yin, Gang; Wang, Hao; Ji, Xiaonan

2018-02-26

Central Asia is a region that has a large land mass, yet meteorological stations in this area are relatively scarce. To address this data issues, in this study, we selected two reanalysis datasets (the ERA40 and NCEP/NCAR) and downscaled them to 40 × 40 km using RegCM. Then three gridded datasets (the CRU, APHRO, and WM) that were extrapolated from the observations of Central Asian meteorological stations to evaluate the performance of RegCM and analyze the spatiotemporal distribution of precipitation and air temperature. We found that since the 1960s, the air temperature in Xinjiang shows an increasing trend and the distribution of precipitation in the Tianshan area is quite complex. The precipitation is increasing in the south of the Tianshan Mountains (Southern Xinjiang, SX) and decreasing in the mountainous areas. The CRU and WM data indicate that precipitation in the north of the Tianshan Mountains (Northern Xinjiang, NX) is increasing, while the APHRO data show an opposite trend. The downscaled results from RegCM are generally consistent with the extrapolated gridded datasets in terms of the spatiotemporal patterns. We believe that our results can provide useful information in developing a regional climate model in Central Asia where meteorological stations are scarce.

Correlation of cerebrovascular disorder and anxiety: The Kecskemet study

NASA Astrophysics Data System (ADS)

Sipos, Kornel; Bodo, Michael; Szalay, Piroska; Szucs, Attila

2010-04-01

In order to test the hypothesis that anxiety is a risk factor for cardiovascular disease, specifically stroke, we simultaneously measured anxiety and cerebral vascular alternation, using a computer-based system, "Cerberus." Sixty nine psychiatric patients (including an alcoholic subgroup) were selected as subjects for measurements conducted in Kecskemet, Hungary. The five-item short form of anxiety test (STAI) was administered twice during the same session. Between each test, brain pulse waves were recorded by rheoencephalogram (REG). A REG peak time above 180 milliseconds was considered a cerebrovascular alteration (modified after Jenkner). Data were sorted into two groups: low anxiety (N=10) and high anxiety (N=10). Significant differences were found between cardiovascular risk factors (p< 0.001), REG peak time (p<0.043), and heart rate (p< 0.045). Six subjects showed cerebrovascular alteration in the high anxiety group, and two in the low anxiety group. For the two anxiety groups, there were no significant differences in body mass index, cardiovascular sympathetic-parasympathetic balance, age and symptoms of transient ischemic attack. The correlation of REG and age was significantly different only for the alcoholic subgroup (Szalay et al, 2007). These data support the hypothesis that a correlation exists between cerebrovascular disorder and anxiety in the studied population.

Effect of rocker shoe radius on oxygen consumption rate in young able-bodied persons.

PubMed

Hansen, Andrew H; Wang, Charles C

2011-04-07

We studied oxygen consumption rate of eleven young able-bodied persons walking at self-selected speed with five different pairs of shoes: one regular pair without rocker soles (REG) and four pairs with uniform hardness (35-40 shore A durometer) rocker soles of different radii (25% of leg length (LL) (R25), 40% LL (R40), 55% LL (R55), and infinite radius (FLAT)). Rocker soled shoes in the study were developed to provide similar vertical lift (three inches higher than the REG shoes condition). Oxygen consumption rate was significantly affected by the use of the different shoes (p<0.001) and pairwise comparisons indicated that persons consumed significantly less oxygen (per minute per kilogram of body mass) when walking on the R40 shoes when compared with both the FLAT (p<0.001) and REG (p=0.021) shoe conditions. Oxygen consumption was also significantly less for the R25 shoes compared with the FLAT shoes (p=0.005) and for the R55 shoes compared with FLAT shoes (p=0.027). The three-inch lift on the FLAT shoe did not cause a significant change in oxygen consumption compared to the shoe without the lift (REG). Published by Elsevier Ltd.

Apolipoprotein A-IV inhibits AgRP/NPY neurons and activates POMC neurons in the arcuate nucleus

USDA-ARS?s Scientific Manuscript database

Apolipoprotein A-IV (apoA-IV) in the brain potently suppresses food intake. However the mechanisms underlying its anorexigenic effects remain to be identified. We first examined the effects of apoA-IV on cellular activities in hypothalamic neurons that co-express agouti-related peptide (AgRP) and ne...

Histoplasma capsulatum Encodes a Dipeptidyl Peptidase Active against the Mammalian Immunoregulatory Peptide, Substance P

PubMed Central

Cooper, Kendal G.; Zarnowski, Robert; Woods, Jon P.

2009-01-01

The pathogenic fungus Histoplasma capsulatum secretes dipeptidyl peptidase (Dpp) IV enzyme activity and has two putative DPPIV homologs (HcDPPIVA and HcDPPIVB). We previously showed that HcDPPIVB is the gene responsible for the majority of secreted DppIV activity in H. capsulatum culture supernatant, while we could not detect any functional contribution from HcDPPIVA. In order to determine whether HcDPPIVA encodes a functional DppIV enzyme, we expressed HcDPPIVA in Pichia pastoris and purified the recombinant protein. The recombinant enzyme cleaved synthetic DppIV substrates and had similar biochemical properties to other described DppIV enzymes, with temperature and pH optima of 42°C and 8, respectively. Recombinant HcDppIVA cleaved the host immunoregulatory peptide substance P, indicating the enzyme has the potential to affect the immune response during infection. Expression of HcDPPIVA under heterologous regulatory sequences in H. capsulatum resulted in increased secreted DppIV activity, indicating that the encoded protein can be expressed and secreted by its native organism. However, HcDPPIVA was not required for virulence in a murine model of histoplasmosis. This work reports a fungal enzyme that can function to cleave the immunomodulatory host peptide substance P. PMID:19384411

Lack of promoter IV-driven BDNF transcription results in depression-like behavior.

PubMed

Sakata, K; Jin, L; Jha, S

2010-10-01

Transcription of Bdnf is controlled by multiple promoters, in which promoter IV contributes significantly to activity-dependent Bdnf transcription. We have generated promoter IV mutant mice [brain-derived neurotrophic factor (BDNF)-KIV] in which promoter IV-driven expression of BDNF is selectively disrupted by inserting a green fluorescent protein (GFP)-STOP cassette within the Bdnf exon IV locus. BDNF-KIV animals exhibited depression-like behavior as shown by the tail suspension test (TST), sucrose preference test (SPT) and learned helplessness test (LHT). In addition, BDNF-KIV mice showed reduced activity in the open field test (OFT) and reduced food intake in the novelty-suppressed feeding test (NSFT). The mutant mice did not display anxiety-like behavior in the light and dark box test and elevated plus maze tests. Interestingly, the mutant mice showed defective response inhibition in the passive avoidance test (PAT) even though their learning ability was intact when measured with the active avoidance test (AAT). These results suggest that promoter IV-dependent BDNF expression plays a critical role in the control of mood-related behaviors. This is the first study that directly addressed the effects of endogenous promoter-driven expression of BDNF in depression-like behavior. © 2010 The Authors. Genes, Brain and Behavior © 2010 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

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

Liu, Xiu-Li, E-mail: usually.158@163.com; Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, No 169 Donghu Road, Wuchang District, Wuhan 430071; Peng, Chun-Wei, E-mail: pqc278@163.com

Highlights: {yields} HER2 level is closely related to the biologic behaviors of breast cancer cells. {yields} A new method to simultaneously image HER2 and type IV collagen was established. {yields} HER2 status and type IV collagen degradation predict breast cancer invasion. {yields} The complex interactions between tumor and its environment were revealed. -- Abstract: It has been well recognized that human epidermal growth factor receptor 2 (HER2) level in breast cancer (BC) is closely related to the malignant biologic behaviors of the tumor, including invasion and metastasis. Yet, there has been a lack of directly observable evidence to support suchmore » notion. Here we report a quantum dots (QDs)-based double-color imaging technique to simultaneously show the HER2 level on BC cells and the type IV collagen in the tumor matrix. In benign breast tumor, the type IV collagen was intact. With the increasing of HER2 expression level, there has been a progressive decrease in type IV collagen around the cancer nest. At HER2 (3+) expression level, there has virtually been a total destruction of type IV collagen. Moreover, HER2 (3+) BC cells also show direct invasion into the blood vessels. This novel imaging method provides direct observable evidence to support the theory that the HER2 expression level is directly related to BC invasion.« less

Decreased NK cell activity after partial vulvectomy in pregnant patient with vulvar intraepithelial neoplasia 3 (VIN3).

PubMed

Jerzak, Malgorzata; Nowakowski, Andrzej; Ohams, Monika; Górski, Andrzej; Baranowsk, Włodzimierz

2017-09-21

The study presents the problem of immune disturbances in pregnant women with vulvar carcinoma in situ (VIN3). NK cell and T reg activity in the study patient were analysed using flow cytometry. Decreased NK cell activity and but increased T reg activity were observed after vulvectomy, with subsequent successful pregnancy outcome. Although vulvar cancer may influence immune cell activity, this issue merits further study.

21 CFR 184.1721 - Sodium acetate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Sodium acetate. 184.1721 Section 184.1721 Food and....1721 Sodium acetate. (a) Sodium acetate (C2H3O2Na, CAS Reg. No. 127-09-3 or C2H3O2Na·3H2O, CAS Reg. No. 6131-90-4) is the sodium salt of acetic acid and occurs naturally in plant and animal tissues. Sodium...

Evaluating the impact of chemical boundary conditions on near surface ozone in regional climate-air quality simulations over Europe

NASA Astrophysics Data System (ADS)

Akritidis, D.; Zanis, P.; Katragkou, E.; Schultz, M. G.; Tegoulias, I.; Poupkou, A.; Markakis, K.; Pytharoulis, I.; Karacostas, Th.

2013-12-01

A modeling system based on the air quality model CAMx driven off-line by the regional climate model RegCM3 is used for assessing the impact of chemical lateral boundary conditions (LBCs) on near surface ozone over Europe for the period 1996-2000. The RegCM3 and CAMx simulations were performed on a 50 km × 50 km grid over Europe with RegCM3 driven by the NCEP meteorological reanalysis fields and CAMx with chemical LBCs from ECHAM5/MOZART global model. The recent past period (1996-2000) was simulated in three experiments. The first simulation was forced using time and space invariant LBCs, the second was based on ECHAM5/MOZART chemical LBCs fixed for the year 1996 and the third was based on ECHAM5/MOZART chemical LBCs with interannual variability. Anthropogenic and biogenic emissions were kept identical for the three sensitivity runs.

FOXP3: required but not sufficient. the role of GARP (LRRC32) as a safeguard of the regulatory phenotype.

PubMed

Probst-Kepper, M; Balling, R; Buer, J

2010-08-01

FOXP3 is essential for the development and function of regulatory CD4(+)CD25(hi) T (T(reg)) cells. However, recent evidence suggests that FOXP3 alone is not sufficient to completely explain the regulatory phenotype of these key players in autoimmunity and inflammation: after being activated, conventional human CD4(+) T cells transiently up-regulate FOXP3 without acquiring a regulatory function. Researchers have recently found that glycoprotein A repetitions predominant (GARP, or LRRC32) is a T(reg)-specific receptor that binds latent TGF-beta and dominantly controls FOXP3 and the regulatory phenotype via a positive feedback loop. This finding provides a missing link in our molecular understanding of FOXP3 in T(reg) cells. This viewpoint focuses on GARP as safeguard of FOXP3 and the regulatory phenotype.

Field Test Program for Long-Term Operation of a COHPAC System for Removing Mercury from Coal-Fired Flue Gas

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

Jean Bustard; Charles Lindsey; Paul Brignac

With the Nation's coal-burning utilities facing the possibility of tighter controls on mercury pollutants, the U.S. Department of Energy is funding projects that could offer power plant operators better ways to reduce these emissions at much lower costs. Sorbent injection technology represents one of the simplest and most mature approaches to controlling mercury emissions from coal-fired boilers. It involves injecting a solid material such as powdered activated carbon into the flue gas. The gas-phase mercury in the flue gas contacts the sorbent and attaches to its surface. The sorbent with the mercury attached is then collected by the existing particlemore » control device along with the other solid material, primarily fly ash. During 2001, ADA Environmental Solutions (ADA-ES) conducted a full-scale demonstration of sorbent-based mercury control technology at the Alabama Power E.C. Gaston Station (Wilsonville, Alabama). This unit burns a low-sulfur bituminous coal and uses a hot-side electrostatic precipitator (ESP) in combination with a Compact Hybrid Particulate Collector (COHPAC{reg_sign}) baghouse to collect fly ash. The majority of the fly ash is collected in the ESP with the residual being collected in the COHPAC{reg_sign} baghouse. Activated carbon was injected between the ESP and COHPAC{reg_sign} units to collect the mercury. Short-term mercury removal levels in excess of 90% were achieved using the COHPAC{reg_sign} unit. The test also showed that activated carbon was effective in removing both forms of mercury-elemental and oxidized. However, a great deal of additional testing is required to further characterize the capabilities and limitations of this technology relative to use with baghouse systems such as COHPAC{reg_sign}. It is important to determine performance over an extended period of time to fully assess all operational parameters. The project described in this report focuses on fully demonstrating sorbent injection technology at a coal-fired power generating plant that is equipped with a COHPAC{reg_sign} system. The overall objective is to evaluate the long-term effects of sorbent injection on mercury capture and COHPAC{reg_sign} performance. The work is being done on one-half of the gas stream at Alabama Power Company's Plant Gaston Unit 3 (nominally 135 MW). Data from the testing will be used to determine: (1) If sorbent injection into a high air-to-cloth ratio baghouse is a viable, long-term approach for mercury control; and (2) Design criteria and costs for new baghouse/sorbent injection systems that will use a similar, polishing baghouse (TOXECON{trademark}) approach.« less

Jejunal wall triglyceride concentration of morbidly obese persons is lower in those with type 2 diabetes mellitus

PubMed Central

Soriguer, F.; García-Serrano, S.; Garrido-Sánchez, L.; Gutierrez-Repiso, C.; Rojo-Martínez, G.; Garcia-Escobar, E.; García-Arnés, J.; Gallego-Perales, J. L.; Delgado, V.; García-Fuentes, Eduardo

2010-01-01

The overproduction of intestinal lipoproteins may contribute to the dyslipidemia found in diabetes. We studied the influence of diabetes on the fasting jejunal lipid content and its association with plasma lipids and the expression of genes involved in the synthesis and secretion of these lipoproteins. The study was undertaken in 27 morbidly obese persons, 12 of whom had type 2 diabetes mellitus (T2DM). The morbidly obese persons with diabetes had higher levels of chylomicron (CM) triglycerides (P < 0.001) and apolipoprotein (apo)B48 (P = 0.012). The jejunum samples obtained from the subjects with diabetes had a lower jejunal triglyceride content (P = 0.012) and angiopoietin-like protein 4 (ANGPTL4) mRNA expression (P = 0.043). However, the apoA-IV mRNA expression was significantly greater (P = 0.036). The jejunal triglyceride content correlated negatively with apoA-IV mRNA expression (r = −0.587, P = 0.027). The variables that explained the jejunal triglyceride content in a multiple linear regression model were the insulin resistance state and the apoA-IV mRNA expression. Our results show that the morbidly obese subjects with diabetes had lower jejunal lipid content and that this correlated negatively with apoA-IV mRNA expression. These findings show that the jejunum appears to play an active role in lipid homeostasis in the fasting state. PMID:20855567

Altered expression of extracellular matrix molecules and their receptors in chronic pancreatitis and pancreatic adenocarcinoma in comparison with normal pancreas.

PubMed

Shimoyama, S; Gansauge, F; Gansauge, S; Oohara, T; Beger, H G

1995-12-01

The aim of this study was to elucidate the expression and distribution patterns of both integrins and extracellular matrix (ECM) molecules in chronic pancreatitis (CP) and pancreatic adenocarcinoma (PC) compared with normal pancreas (NP). Expression of nine alpha-subunits (alpha 2-alpha 6, alpha V, alpha L, alpha M, and alpha X), four beta-subunits (beta 1, beta 3-beta 5), and four ECM molecules (type IV collagen, laminin, fibronectin, and vitronectin) was investigated immunohistochemically. In CP, all integrins except alpha V showed nearly the same staining patterns compared with NP. Some acinar cells in CP expressed alpha V. Whereas alpha 2, alpha 3, and alpha 6 expression was stronger and diffuse, no alpha 5 expression was seen in PC. Basement membrane (BM) showed continuous staining in CP, whereas it showed discontinuous/absent staining in PC with antitype IV collagen, laminin, and vitronectin antibodies. Some carcinoma cells showed reverse correlation between alpha 2, alpha 3, and alpha 6 expression and type IV collagen and laminin expression. Fibronectin showed diffuse stromal expression in CP and PC. Some acinar cells or duct cells in CP carcinoma cells in PC showed intracellular VN expression. These results suggest that these integrins and ECM molecules are involved in inflammatory and malignant processes in pancreas.

Apolipoprotein A-IV interacts synergistically with melanocortins to reduce food intake.

PubMed

Gotoh, Koro; Liu, Min; Benoit, Stephen C; Clegg, Deborah J; Davidson, W Sean; D'Alessio, David; Seeley, Randy J; Tso, Patrick; Woods, Stephen C

2006-01-01

Apolipoprotein (apo) A-IV is an anorexigenic gastrointestinal peptide that is also synthesized in the hypothalamus. The goal of these experiments was to determine whether apo A-IV interacts with the central melanocortin (MC) system in the control of feeding. The third ventricular (i3vt) administration of a subthreshold dose of apo A-IV (0.5 microg) potentiated i3vt MC-induced (metallothionein-II, 0.03 nmol) suppression of 30-min feeding in Long-Evans rats. A subthreshold dose of the MC antagonist (SHU9119, 0.1 nmol, i3vt) completely attenuated the anorectic effect of i3vt apo A-IV (1.5 microg). The i3vt apo A-IV significantly elevated the expression of c-Fos in neurons of the paraventricular nucleus of the hypothalamus, but not in the arcuate nucleus or median eminence. In addition, c-Fos expression was not colocalized with proopiomelanocortin-positive neurons. These data support a synergistic interaction between apo A-IV and melanocortins that reduces food intake by acting downstream of the arcuate.

75 FR 42444 - Change in Bank Control Notices; Acquisition of Shares of Bank or Bank Holding Companies

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-21

... Governors. Interested persons may express their views in writing to the Reserve Bank indicated for that...; WLR Recovery Fund IV, L.P.; WLR IV Parallel ESC, L.P.; Invesco North America Holdings, Inc.; Invesco WLR IV Associates LLC; WLR Recovery Associates IV LLC; WL Ross Group L.P.; and EL Vedado LLC, all of...

Evidence for an interaction between leptin, T cell costimulatory antigens CD28, CTLA-4 and CD26 (dipeptidyl peptidase IV) in BCG-induced immune responses of leptin- and leptin receptor-deficient mice.

PubMed

Rüter, Jens; Hoffmann, Torsten; Demuth, Hans-Ulrich; Moschansky, Petra; Klapp, Burghard F; Hildebrandt, Martin

2004-06-01

We assessed changes of the enzyme dipeptidyl peptidase IV (DPP IV, CD26) in the context of leptin or leptin receptor deficiency. C57BL/6 mice, Leptin-deficient mice (ob/ob mice, B6.V-Lep) and Leptin-receptor-deficient mice (db/db mice, B6.Cg-m+/+Lepr) were infected with B. Calmette-Guerin (BCG) and sacrificed three days later. DPP IV activity in serum was higher in ob/ob mice and in db/db mice than in wild-type mice. The expression of DPP IV/CD26 on splenocytes was higher in ob/ob mice than in wild-type animals, and lower in db/db mice, and decreased upon stimulation with BCG in ob/ob mice only. Several T cell antigens including CTLA-4 were expressed aberrantly in ob/ob and in db/db mice. Our observations provide evidence for a relationship between DPP IV and leptin.

Synthesis of prolyl 4-hydroxylase alpha subunit and type IV collagen in hemocytic granular cells of silkworm, Bombyx mori: Involvement of type IV collagen in self-defense reaction and metamorphosis.

PubMed

Adachi, Takahiro; Tomita, Masahiro; Yoshizato, Katsutoshi

2005-04-01

The present study shows that hemocytic granular cells synthesize and secrete type IV collagen (ColIV) in the silkworm Bombyx mori (B. mori) and suggests that these cells play roles in the formation of basement membrane, the encapsulation of foreign bodies, and the metamorphic remodeling of the gut. The full- and partial-length cDNA of B. mori prolyl 4-hydroxylase alpha subunit (BmP4Halpha) and B. mori ColIV (BmColIV) were cloned, respectively. In situ hybridization and immunocytochemistry on larval tissues and cells identified hemocytic granular cells as the cells that express mRNAs and proteins of both BmP4Halpha and BmColIV. Immunohistochemistry and immunocytochemistry demonstrated that BmColIV was present in the basement membrane and in the secretory granules of granular cells, respectively. Granular cells in culture secreted BmColIV without accompanying the degranulation and discharged it from the granules when the cells were degranulated. Nylon threads were inserted into the hemocoel of larvae. Granular cells concentrated around the nylon threads and encapsulated them as a self-defense reaction. BmColIV was found to be a component of the capsules. Furthermore, the present study showed that actively BmColIV-expressing granular cells accumulated around the midgut epithelium and formed BmColIV-rich thick basal lamina-like structures there in larval to pupal metamorphosis.

SELECTIVE REMOVAL OF STRONTIUM AND CESIUM FROM SIMULATED WASTE SOLUTION WITH TITANATE ION EXCHANGERS IN A FILTER CARTRIDGE CONFIGURATION

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

Oji, L.; Martin, K.; Hobbs, D.

2011-05-26

This report describes experimental results for the selective removal of strontium and cesium from simulated waste solutions using monosodium titanate (MST) and crystalline silicotitanate (CST)-laden filter cartridges. Four types of ion exchange cartridge media (CST and MST designed by both 3M and POROX{reg_sign}) were evaluated. In these proof-of-principle tests effective uptake of both Sr-85 and Cs-137 was observed. However, the experiments were not performed long enough to determine the saturation levels or breakthrough curve for each filter cartridge. POREX{reg_sign} MST cartridges, which by design were based on co-sintering of the active titanates with polyethylene particles, seem to perform as wellmore » as the 3M-designed MST cartridges (impregnated filter membrane design) in the uptake of strontium. At low salt simulant conditions (0.29 M Na{sup +}), the instantaneous decontamination factor (D{sub F}) for Sr-85 with the 3M-design MST cartridge measured 26, representing the removal of 96% of the Sr-85. On the other hand, the Sr-85 instantaneous D{sub F} with the POREX{reg_sign} design MST cartridge measured 40 or 98% removal of the Sr-85. Strontium removal with the 3M-design MST and CST cartridges placed in series filter arrangement produced an instantaneous decontamination factor of 41 or 97.6% removal compared to an instantaneous decontamination factor of 368 or 99.7% removal of the strontium with the POREX{reg_sign} MST and CST cartridge design placed in series. At high salt simulant conditions (5.6 M Na{sup +}), strontium removal with 3M-designed MST cartridge only and with 3M-designed MST and CST cartridges operated in a series configuration were identical. The instantaneous decontamination factor and the strontium removal efficiency, under the above configuration, averaged 8.6 and 88%, respectively. There were no POREX{reg_sign} cartridge experiments using the higher ionic strength simulant solution. At low salt simulant conditions, the uptake of Cs-137 with POREX{reg_sign} CST cartridge out performed the 3M-designed CST cartridges. The POREX{reg_sign} CST cartridge, with a Cs-137 instantaneous decontamination factor of 55 and a Cs-137 removal efficiency of 98% does meet the Cs-137 decontamination goals in the low salt simulant liquor. The Cs-137 removal with 3M-designed CST cartridge produced a decontamination factor of 2 or 49% removal efficiency. The Cs-137 performance graph for the 3M-designed CST cartridge showed an early cessation in the uptake of cesium-137. This behavior was not observed with the POREX{reg_sign} CST cartridges. No Cs-137 uptake tests were performed with the POREX{reg_sign} CST cartridges at high salt simulant conditions. The 3M-designed CST cartridges, with an instantaneous Cs-137 decontamination factor of less than 3 and a Cs-137 removal efficiency of less than 50% failed to meet the Cs-137 decontamination goals in both the low and high salt simulant liquors. This poor performance in the uptake of Cs-137 by the 3M CST cartridges may be attributed to fabrication flaws for the 3M-designed CST cartridges. The reduced number of CST membrane wraps per cartridge during the cartridge design phase, from 3-whole wraps to about 1.5, may have contributed to Cs-137 laden simulant channeling/by-pass which led to the poor performance in terms of Cs-137 sorption characteristics for the 3M designed CST cartridges. The grinding of CST ion exchange materials, to reduce the particle size distribution and thus enhance their easy incorporation into the filter membranes and the co-sintering of MST with polyethylene particles, did not adversely affect the sorption kinetics of both CST and MST in the uptake of Cs-137 and Sr-85, respectively. In general, the POREX{reg_sign} based cartridges showed more resistance to simulant flow through the filter cartridges as evidenced by higher pressure differences across the cartridges. Based on these findings they conclude that incorporating MST and CST sorbents into filter membranes represent a promising method for the semi-continuous removal of radioisotopes of strontium and cesium from waste solutions.« less

Performance of ICTP's RegCM4 in Simulating the Rainfall Characteristics over the CORDEX-SEA Domain

NASA Astrophysics Data System (ADS)

Neng Liew, Ju; Tangang, Fredolin; Tieh Ngai, Sheau; Chung, Jing Xiang; Narisma, Gemma; Cruz, Faye Abigail; Phan Tan, Van; Thanh, Ngo-Duc; Santisirisomboon, Jerasron; Milindalekha, Jaruthat; Singhruck, Patama; Gunawan, Dodo; Satyaningsih, Ratna; Aldrian, Edvin

2015-04-01

The performance of the RegCM4 in simulating rainfall variations over the Southeast Asia regions was examined. Different combinations of six deep convective parameterization schemes, namely i) Grell scheme with Arakawa-Schubert closure assumption, ii) Grell scheme with Fritch-Chappel closure assumption, iii) Emanuel MIT scheme, iv) mixed scheme with Emanuel MIT scheme over the Ocean and the Grell scheme over the land, v) mixed scheme with Grell scheme over the land and Emanuel MIT scheme over the ocean and (vi) Kuo scheme, and three ocean flux treatments were tested. In order to account for uncertainties among the observation products, four different gridded rainfall products were used for comparison. The simulated climate is generally drier over the equatorial regions and slightly wetter over the mainland Indo-China compare to the observation. However, simulation with MIT cumulus scheme used over the land area consistently produces large amplitude of positive rainfall biases, although it simulates more realistic annual rainfall variations. The simulations are found less sensitive to treatment of ocean fluxes. Although the simulations produced the rainfall climatology well, all of them simulated much stronger interannual variability compare to that of the observed. Nevertheless, the time evolution of the inter-annual variations was well reproduced particularly over the eastern part of maritime continent. Over the mainland Southeast Asia (SEA), unrealistic rainfall anomalies processes were simulated. The lacking of summer season air-sea interaction results in strong oceanic forcings over the regions, leading to positive rainfall anomalies during years with warm ocean temperature anomalies. This incurs much stronger atmospheric forcings on the land surface processes compare to that of the observed. A score ranking system was designed to rank the simulations according to their performance in reproducing different aspects of rainfall characteristics. The result suggests that the simulation with Emanuel MIT convective scheme and BATs land surface scheme produces better collective performance compare to the rest of the simulations.

Cigarette Filter Ventilation and Smoking Protocol Influence Aldehyde Smoke Yields

PubMed Central

2018-01-01

The WHO study group on tobacco product regulation (TobReg) advised regulating and lowering toxicant levels in cigarette smoke. Aldehydes are one of the chemical classes on the TobReg smoke toxicants priority list. To provide insight in factors determining aldehyde yields, the levels of 12 aldehydes in mainstream cigarette smoke of 11 Dutch brands were quantified. Variations in smoking behavior and cigarette design affecting human exposure to aldehydes were studied by using four different machine testing protocols. Machine smoking was based on the International Standardization Organization (ISO) and Health Canada Intense (HCI) regime, both with and without taping the filter vents. The 11 cigarette brands differed in (i) design and blend characteristics; (ii) tar, nicotine, and carbon monoxide (TNCO) levels; (iii) popularity; and (iv) manufacturer. Cigarette smoke was trapped on a Cambridge filter pad and carboxen cartridge. After being dissolved in methanol/CS2 and derivatization with DNPH, the aldehyde yields were determined using HPLC-DAD. Using an intense smoking regime (increased puff volume, shorter puff interval) significantly increased aldehyde yields, following the pattern: ISO < ISO-taped < HCI-untaped < HCI. For all of the regimes, acetaldehyde and acrolein yields were strongly correlated (r = 0.804). The difference in TNCO and aldehyde levels between regular and highly ventilated low-TNCO cigarettes (as measured using ISO) diminished when smoking intensely; this effect is stronger when combined with taping filter vents. The highly ventilated low-TNCO brands showed six times more aldehyde production per mg nicotine for the intense smoking regimes. In conclusion, acetaldehyde and acrolein can be used as representatives for the class of volatile aldehydes for the different brands and smoking regimes. The aldehyde-to-nicotine ratio increased when highly ventilated cigarettes were smoked intensely, similar to real smokers. Thus, a smoker of highly ventilated low-TNCO cigarettes has an increased potential for higher aldehyde exposures compared to a smoker of regular cigarettes. PMID:29727173

Identification and tissue distribution of mRNAs encoding salmon-type calcitonins-IV and -V in the rainbow trout.

PubMed

Hidaka, Yoshie; Suzuki, Masakazu

2004-06-01

Four types of calcitonin are produced in salmonid fish, although their functional diversity is almost unknown. To explore the significance of these isoforms, we have characterized salmon-type calcitonin (sCT) mRNAs in the rainbow trout (Oncorhynchus mykiss), and examined their tissue distribution. In addition to the previously isolated sCT-I cDNAs, two new forms of sCT cDNA were cloned from the ultimobranchial gland, and one of them (sCT-IV cDNA) was predicted to encode an N-terminal peptide of 80 amino acid residues, a putative cleavage site Lys-Arg, sCT-IV, a cleavage and amidation sequence Gly-Lys-Lys-Arg, and a C-terminal peptide of 18 amino acids. The sCT-IV precursor was 78% identical with the rainbow trout sCT-I precursors. The other cloned cDNA encoded a precursor for a novel CT, sCT-V. The sCT-V peptide was different from sCT-IV by only one amino acid residue: Val at position 8 in the latter was replaced by Met. The sCT-V precursor had 80 and 90% identity with the sCT-I and -IV precursors respectively. No cDNA clones were obtained for sCTs-II or -III.Tissue distribution of sCT-I, -IV and -V mRNAs was examined by RT-PCR and specific cleavage with restriction enzymes. An amplified fragment from sCT-I mRNA was detected not only in the ultimobranchial gland, but also in the gills, testis and ovary. RT-PCR analysis coupled to restriction digestion further revealed that sCT-IV mRNA was expressed in both the testis and the ultimobranchial gland. The expression sites of sCT-IV mRNA were localized to the Leydig cells of the testis and to the parenchymal cells of the ultimobranchial gland, by in situ hybridization histochemistry. Although the amino acid sequence of sCT-V peptide was nearly the same as that of sCT-IV, the sCT-V gene showed a much wider pattern of expression: the band amplified by RT-PCR was detected in all the tissues examined except the kidney, gills and blood cells. The sCT-V mRNA was shown to be localized in the parenchymal cells of the ultimobranchial gland, but not in other tissues at the cellular level, suggesting very low expression of sCT-V mRNA in those tissues. Our results show different patterns of tissue expression of three types of sCT genes in the rainbow trout, suggesting that sCTs-I, -IV and -V might differ in their local actions.

Best convective parameterization scheme within RegCM4 to downscale CMIP5 multi-model data for the CORDEX-MENA/Arab domain

NASA Astrophysics Data System (ADS)

Almazroui, Mansour; Islam, Md. Nazrul; Al-Khalaf, A. K.; Saeed, Fahad

2016-05-01

A suitable convective parameterization scheme within Regional Climate Model version 4.3.4 (RegCM4) developed by the Abdus Salam International Centre for Theoretical Physics, Trieste, Italy, is investigated through 12 sensitivity runs for the period 2000-2010. RegCM4 is driven with European Centre for Medium-Range Weather Forecasts (ECMWF) ERA-Interim 6-hourly boundary condition fields for the CORDEX-MENA/Arab domain. Besides ERA-Interim lateral boundary conditions data, the Climatic Research Unit (CRU) data is also used to assess the performance of RegCM4. Different statistical measures are taken into consideration in assessing model performance for 11 sub-domains throughout the analysis domain, out of which 7 (4) sub-domains give drier (wetter) conditions for the area of interest. There is no common best option for the simulation of both rainfall and temperature (with lowest bias); however, one option each for temperature and rainfall has been found to be superior among the 12 options investigated in this study. These best options for the two variables vary from region to region as well. Overall, RegCM4 simulates large pressure and water vapor values along with lower wind speeds compared to the driving fields, which are the key sources of bias in simulating rainfall and temperature. Based on the climatic characteristics of most of the Arab countries located within the study domain, the drier sub-domains are given priority in the selection of a suitable convective scheme, albeit with a compromise for both rainfall and temperature simulations. The most suitable option Grell over Land and Emanuel over Ocean in wet (GLEO wet) delivers a rainfall wet bias of 2.96 % and a temperature cold bias of 0.26 °C, compared to CRU data. An ensemble derived from all 12 runs provides unsatisfactory results for rainfall (28.92 %) and temperature (-0.54 °C) bias in the drier region because some options highly overestimate rainfall (reaching up to 200 %) and underestimate temperature (reaching up to -1.16 °C). Overall, a suitable option (GLEO wet) is recommended for downscaling the Coupled Model Intercomparison Project Phase 5 (CMIP5) multi-model database using RegCM4 for the CORDEX-MENA/Arab domain for its use in future climate change impact studies.

Alterations in circulating T-cell lymphocyte populations in children with obstructive sleep apnea.

PubMed

Tan, Hui-Leng; Gozal, David; Wang, Yang; Bandla, Hari P R; Bhattacharjee, Rakesh; Kulkarni, Richa; Kheirandish-Gozal, Leila

2013-06-01

Changes in lymphocyte phenotype and functionality have been described in adult patients with obstructive sleep apnea (OSA). We hypothesized that OSA is associated with T lymphocyte alterations in children, particularly in T regulatory lymphocytes (T regs), and aimed to characterize circulating T lymphocyte subsets in children with OSA. Cross-sectional. Kosair Children's Hospital (Louisville, KY, USA) and Comer Children's Hospital (Chicago, IL, USA). Consecutively recruited children being evaluated for habitual snoring. N/A. Overnight polysomnography (PSG) was performed and a fasting blood sample was obtained from the patients. Flow cytometry was performed on peripheral blood mononuclear cells stained for CD3, CD4, CD8, CD25, FOXP3, interleukin-4 (IL-4), interferon-γ (IFN-γ), and IL-17. Patients were divided into three groups based on their PSG: controls (apnea-hypopnea indices [AHI] < 1/h total sleep time [TST]), mild OSA (1 ≤ AHI < 5/hTST), moderate-severe OSA (AHI ≥ 5/h TST). The percentage of CD4+ and T reg lymphocytes differed across groups. Children with moderate-severe OSA had significantly reduced T reg than control children (median [interquartile range] 4.8 [3.8-5.7% CD4+] versus 7.8 [7.0-9.2% CD4+]; P < 0.001). There were also significant differences in the percentage of T helper 1 (Th1) lymphocytes and in Th1:Th2 ratios between groups. Children with moderate-severe OSA had increased Th1 cells (P = 0.001) and Th1:Th2 ratios (P = 0.0026) compared with children with mild OSA and control children. Associations between AHI and T reg (P = 0.0003; r = -0.46), CD4+ lymphocytes (P = 0.0047; r = -0.37), and Th1:Th2 ratios (P = 0.0009; r = 0.43) emerged. In addition, the percentage of T reg was inversely correlated with Th1:Th2 ratios (P = 0.029; r = -0.29). Pediatric OSA is associated with reduced T reg population and altered Th1:Th2 balance toward Th1 predominance, suggesting a shift to a proinflammatory state. The changes in lymphocytic phenotypes associated with OSA may contribute to the variance in systemic inflammation and downstream morbidities associated with this condition.

Intra-field on-product overlay improvement by application of RegC and TWINSCAN corrections

NASA Astrophysics Data System (ADS)

Sharoni, Ofir; Dmitriev, Vladimir; Graitzer, Erez; Perets, Yuval; Gorhad, Kujan; van Haren, Richard; Cekli, Hakki E.; Mulkens, Jan

2015-03-01

The on product overlay specification and Advanced Process Control (APC) is getting extremely challenging particularly after the introduction of multi-patterning applications like Spacer Assisted Double Patterning (SADP) and multipatterning techniques like N-repetitive Litho-Etch steps (LEN, N >= 2). When the latter is considered, most of the intrafield overlay contributors drop out of the overlay budget. This is a direct consequence of the fact that the scanner settings (like dose, illumination settings, etc.) as well as the subsequent processing steps can be made very similar for two consecutive Litho-Etch layers. The major overlay contributor that may require additional attention is the Image Placement Error (IPE). When the inter-layer overlay is considered, controlling the intra-field overlay contribution gets more complicated. In addition to the IPE contribution, the TWINSCANTM lens fingerprint in combination with the exposure settings is going to play a role as well. Generally speaking, two subsequent functional layers have different exposure settings. This results in a (non-reticle) additional overlay contribution. In this paper, we have studied the wafer overlay correction capability by RegC® in addition to the TWINSCANTM intrafield corrections to improve the on product overlay performance. RegC® is a reticle intra-volume laser writing technique that causes a predictable deformation element (RegC® deformation element) inside the quartz (Qz) material of a reticle. This technique enables to post-process an existing reticle to correct for instance for IPE. Alternatively, a pre-determined intra-field fingerprint can be added to the reticle such that it results in a straight field after exposure. This second application might be very powerful to correct for instance for (cold) lens fingerprints that cannot be corrected by the scanner itself. Another possible application is the intra-field processing fingerprint. One should realize that a RegC® treatment of a reticle generally results in global distortion of the reticle. This is not a problem as long as these global distortions can be corrected by the TWINSCANTM system (currently up to the third order). It is anticipated that the combination of the RegC® and the TWINSCANTM corrections act as complementary solutions. These solutions perfectly fit into the ASML Litho InSight (LIS) product in which feedforward and feedback corrections based on YieldStar overlay measurements are used to improve the on product overlay.

Lithium promotes DNA stability and survival of ischemic retinal neurocytes by upregulating DNA ligase IV.

PubMed

Yang, Ying; Wu, Nandan; Tian, Sijia; Li, Fan; Hu, Huan; Chen, Pei; Cai, Xiaoxiao; Xu, Lijun; Zhang, Jing; Chen, Zhao; Ge, Jian; Yu, Keming; Zhuang, Jing

2016-11-17

Neurons display genomic fragility and show fragmented DNA in pathological degeneration. A failure to repair DNA breaks may result in cell death or apoptosis. Lithium protects retinal neurocytes following nutrient deprivation or partial nerve crush, but the underlying mechanisms are not well defined. Here we demonstrate that pretreatment with lithium protects retinal neurocytes from ischemia-induced damage and enhances light response in rat retina following ischemia-reperfusion injury. Moreover, we found that DNA nonhomologous end-joining (NHEJ) repair is implicated in this process because in ischemic retinal neurocytes, lithium significantly reduces the number of γ-H2AX foci (well-characterized markers of DNA double-strand breaks in situ) and increases the DNA ligase IV expression level. Furthermore, we also demonstrate that nuclear respiratory factor 1 (Nrf-1) and phosphorylated cyclic AMP-response element binding protein-1 (P-CREB1) bind to ligase IV promoter to cause upregulation of ligase IV in neurocytes. The ischemic upregulation of Nrf-1 and lithium-induced increase of P-CREB1 cooperate to promote transcription of ligase IV. Short hairpin RNAs against Nrf-1 and CREB1 could significantly inhibit the increase in promoter activity and expression of ligase IV observed in the control oligos following lithium treatment in retinal neurocytes. More importantly, ischemic stimulation triggers the expression of ligase IV. Taken together, our results thus reveal a novel mechanism that lithium offers neuroprotection from ischemia-induced damage by enhancing DNA NHEJ repair.

Lithium promotes DNA stability and survival of ischemic retinal neurocytes by upregulating DNA ligase IV

PubMed Central

Yang, Ying; Wu, Nandan; Tian, Sijia; Li, Fan; Hu, Huan; Chen, Pei; Cai, Xiaoxiao; Xu, Lijun; Zhang, Jing; Chen, Zhao; Ge, Jian; Yu, Keming; Zhuang, Jing

2016-01-01

Neurons display genomic fragility and show fragmented DNA in pathological degeneration. A failure to repair DNA breaks may result in cell death or apoptosis. Lithium protects retinal neurocytes following nutrient deprivation or partial nerve crush, but the underlying mechanisms are not well defined. Here we demonstrate that pretreatment with lithium protects retinal neurocytes from ischemia-induced damage and enhances light response in rat retina following ischemia–reperfusion injury. Moreover, we found that DNA nonhomologous end-joining (NHEJ) repair is implicated in this process because in ischemic retinal neurocytes, lithium significantly reduces the number of γ-H2AX foci (well-characterized markers of DNA double-strand breaks in situ) and increases the DNA ligase IV expression level. Furthermore, we also demonstrate that nuclear respiratory factor 1 (Nrf-1) and phosphorylated cyclic AMP-response element binding protein-1 (P-CREB1) bind to ligase IV promoter to cause upregulation of ligase IV in neurocytes. The ischemic upregulation of Nrf-1 and lithium-induced increase of P-CREB1 cooperate to promote transcription of ligase IV. Short hairpin RNAs against Nrf-1 and CREB1 could significantly inhibit the increase in promoter activity and expression of ligase IV observed in the control oligos following lithium treatment in retinal neurocytes. More importantly, ischemic stimulation triggers the expression of ligase IV. Taken together, our results thus reveal a novel mechanism that lithium offers neuroprotection from ischemia-induced damage by enhancing DNA NHEJ repair. PMID:27853172

The oculo-dento-digital syndrome: male-to-male transmission and variable expression in a family.

PubMed

Ioan, D M; Dumitriu, L; Belengeariu, V; Fryns, J P

1997-01-01

We report two siblings--a 5 1/2 year old female and her 4 1/2 year old brother, both presenting the classical clinical findings of oculo-dento-digital dysplasia (ODD). 1. Digital anomalies: bilateral complete cutaneous syndactyly of fingers IV-V (III-IV-V at the left hand of the boy) and camptodactyly IV. 2. Facial and ocular anomalies: microphtalamos-epicanthal folds, small midfacies, thin nose with hypoplastic alae nasi and small nares. 3. Dental anomalies with partial dental agenesis and enamel hypoplasia. Examination of the parents showed a bilateral cutaneous syndactyly IV-V in the father as the sole partial manifestation of ODD. The findings in the present family confirm the autosomal dominant inheritance of ODD with great variability in clinical expression. Moreover, the facial morphology (thin, hypoplastic nose) observed in several ODD patients suggests nosological overlap with the Hallerman-Streiff syndrome and could indicate that both syndromes are variable expressions of a contiguous gene deletion syndrome.

Nonproteolytic Roles of 19S ATPases in Transcription of CIITApIV Genes

PubMed Central

Maganti, Nagini; Moody, Tomika D.; Truax, Agnieszka D.; Thakkar, Meghna; Spring, Alexander M.; Germann, Markus W.; Greer, Susanna F.

2014-01-01

Accumulating evidence shows the 26S proteasome is involved in the regulation of gene expression. We and others have demonstrated that proteasome components bind to sites of gene transcription, regulate covalent modifications to histones, and are involved in the assembly of activator complexes in mammalian cells. The mechanisms by which the proteasome influences transcription remain unclear, although prior observations suggest both proteolytic and non-proteolytic activities. Here, we define novel, non-proteolytic, roles for each of the three 19S heterodimers, represented by the 19S ATPases Sug1, S7, and S6a, in mammalian gene expression using the inflammatory gene CIITApIV. These 19S ATPases are recruited to induced CIITApIV promoters and also associate with CIITA coding regions. Additionally, these ATPases interact with elongation factor PTEFb complex members CDK9 and Hexim-1 and with Ser5 phosphorylated RNA Pol II. Both the generation of transcripts from CIITApIV and efficient recruitment of RNA Pol II to CIITApIV are negatively impacted by siRNA mediated knockdown of these 19S ATPases. Together, these results define novel roles for 19S ATPases in mammalian gene expression and indicate roles for these ATPases in promoting transcription processes. PMID:24625964

21 CFR 184.1721 - Sodium acetate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium acetate. 184.1721 Section 184.1721 Food and... Substances Affirmed as GRAS § 184.1721 Sodium acetate. (a) Sodium acetate (C2H3O2Na, CAS Reg. No. 127-09-3 or C2H3O2Na·3H2O, CAS Reg. No. 6131-90-4) is the sodium salt of acetic acid and occurs naturally in plant and...

21 CFR 184.1721 - Sodium acetate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Sodium acetate. 184.1721 Section 184.1721 Food and... Substances Affirmed as GRAS § 184.1721 Sodium acetate. (a) Sodium acetate (C2H3O2Na, CAS Reg. No. 127-09-3 or C2H3O2Na·3H2O, CAS Reg. No. 6131-90-4) is the sodium salt of acetic acid and occurs naturally in plant and...

21 CFR 184.1721 - Sodium acetate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Sodium acetate. 184.1721 Section 184.1721 Food and... Substances Affirmed as GRAS § 184.1721 Sodium acetate. (a) Sodium acetate (C2H3O2Na, CAS Reg. No. 127-09-3 or C2H3O2Na·3H2O, CAS Reg. No. 6131-90-4) is the sodium salt of acetic acid and occurs naturally in plant and...

21 CFR 184.1721 - Sodium acetate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Sodium acetate. 184.1721 Section 184.1721 Food and... Substances Affirmed as GRAS § 184.1721 Sodium acetate. (a) Sodium acetate (C2H3O2Na, CAS Reg. No. 127-09-3 or C2H3O2Na·3H2O, CAS Reg. No. 6131-90-4) is the sodium salt of acetic acid and occurs naturally in plant and...

Rheoencephalography (REG) as a Non-Invasive Monitoring Alternative for the Assessment of Brain Blood Flow

DTIC Science & Technology

2004-09-01

arterial pressure of 40 mmHg, and then held there until experimental intervention, resuscitation, decompensation or death occurred. The experiment was...regulations relating to animals and experiments involving animals and adheres to principles stated in the Guide for the Care and Use of Laboratory Animals...Rheoencephalography (REG) as a Non-Invasive Monitoring Alternative for the Assessment of Brain Blood Flow P3 - 12 RTO-MP-HFM-109 experiments we

Regenerative medicine: then and now – an update of recent history into future possibilities

PubMed Central

Polykandriotis, E; Popescu, L M; Horch, R E

2010-01-01

Abstract The fields of tissue engineering (TE) and regenerative medicine (RegMed) are yet to bring about the anticipated therapeutic revolution. After two decades of extremely high expectations and often disappointing returns both in the medical as well as in the financial arena, this scientific field reflects the sense of a new era and suggests the feeling of making a fresh start although many scientists are probably seeking reorientation. Much of research was industry driven, so that especially in the aftermath of the recent financial meltdown in the last 2 years we have witnessed a biotech asset yard sale. Despite any monetary shortcomings, from a technological point of view there have been great leaps that are yet to find their way to the patient. RegMed is definitely bound to play a major role in our life because it embodies one of the primordial dreams of mankind, such as: everlasting youth, flying, remote communication and setting foot on the moon. The Journal of Cellular and Molecular Medicine has been at the frontier of these developments in TE and RegMed from its beginning and reflects recent scientific advances in both fields. Therefore this review tries to look at RegMed through the keyhole of history which might just be like looking ‘back to the future’. PMID:20825521

Contrary melanoma-associated antigen-A expression at the tumor front and center: A comparative analysis of stage I and IV head and neck squamous cell carcinoma

PubMed Central

Hartmann, Stefan; Brisam, Muna; Rauthe, Stephan; Driemel, Oliver; Brands, Roman C.; Rosenwald, Andreas; Kübler, Alexander C.; Müller-Richter, Urs D. A.

2016-01-01

There is a growing body of evidence indicating that several melanoma-associated antigen-A (MAGE-A) subgroups contribute to the malignancy of head and neck cancer. The present study retrospectively analyzed the expression of all known MAGE-A subgroups in the tumor front and center of 38 head and neck cancer patients (Union for International Cancer Control stage I or IV) by immunohistochemistry. MAGE-A1, -A6, -A8, -A9 and -A11 were expressed at significantly higher levels at the tumor front of stage IV specimens compared with the tumor front of stage I specimens. In stage I cancer, the tumor center and front ratio (C/F ratio) for each subgroup was >1.0. In stage IV cancer, the C/F ratio was <1.0 in 9/11 subgroups. The most significant change in the expression pattern was observed for MAGE-A11. These results indicated that there is a marked alteration and shift to the invasive front of almost all MAGE-A subgroups, but particularly MAGE-A11, during the progression of head and neck squamous cell carcinoma. PMID:27703530

Astragaloside IV attenuates inflammatory cytokines by inhibiting TLR4/NF-кB signaling pathway in isoproterenol-induced myocardial hypertrophy.

PubMed

Yang, Juan; Wang, Hong-Xin; Zhang, Ying-Jie; Yang, Yu-Hong; Lu, Mei-Li; Zhang, Jing; Li, Sheng-Tao; Zhang, Su-Ping; Li, Guang

2013-10-25

Astragaloside IV(As IV) is one of the main effective components isolated from the traditional Chinese medical herb Astragalus membranaceus. The protective effect of Astragalus membranaceus on myocardial hypertrophy has been extensively proved. To test the hypothesis that Astragaloside IV can ameliorate the myocardial hypertrophy and inflammatory effect induced by β-adrenergic hyperactivity, we carried out in vivo and in vitro experiments. In in vivo study, the isoproterenol(Iso) (5mg.kg -1 .d -1 ) was used as a model of myocardial hypertrophy by intraperitoneal injection. SD rats were randomly assigned to following six groups: A:the control；B: Iso group；C: Iso plus As IV 20mg.kg -1 .d -1 ；D: Iso plus As IV 40mg.kg -1 .d -1 ；E: Iso plus As IV 80mg.kg -1 .d -1 ；F: Iso plus Propranolol 40mg.kg -1 .d -1 . In in vitro study, cultured neonatal rat cardiomyocytes were pretreated with As IV(3, 10, 30μmol.L -1 ), Propranolol(2μmol.L -1 ) and BAY11-7082(5μmol.L -1 ) for 30minutes, and then incubated with Iso(10μmol.L -1 ) for 48 hours. For the rats in each group, the heart mass index (HMI) and the left ventricular mass index (LVMI) were measured. To measure the transverse diameter of left ventricular myocardial cells (TDM), the hematoxylin-eosin (HE) staining method was applied. In addition, the volume and the total protein content of cardiomyocytes were measured, the mRNA expression of ANP and TLR4 were quantified by RT-PCR, the protein expression of TLR4, IκBα and p65 were quantified by Western blot, and the level of TNF-α and IL-6 were measured by ELISA. In vivo: Comparing the Iso group to the control, the HMI, LVMI, TDM were significantly increased; the protein expression of TLR4 and p65 were increased, while the IκBα were decreased; the expression of ANP, TLR4 mRNA, and TNF-α, IL-6 in serum were significantly increased. These changes could be partly prevented by As IV and Pro. In vitro: the over-expression of the cell size, total protein content could remarkably down-regulated by As IV and Pro, and the results of RT-PCR, Western blot and ELISA were similar to those of in vivo. The results of these studies indicate that Astragaloside IV has good protective effect on myocardial hypertrophy induced by isoproterenol. More specifically, the cardioprotection is related to inhibiting the TLR4/NF-кB signaling pathway and the attenuating inflammatory effect. Astragaloside IV (PubChem CID:122690); BAY 11-7082 (PubChem CID:5353431); Propranolol (PubChem CID:62882); Isoproterenol (PubChem CID: 5806). © 2013 The Authors. Published by Elsevier Ireland Ltd All rights reserved.

Schizophrenia Risk Variation in the NRG1 gene Exerts Effects on NRG1-IV Splicing During Fetal and Early Postnatal Human Neocortical Development

PubMed Central

Paterson, Clare; Wang, Yanhong; Kleinman, Joel E.; Law, Amanda J.

2015-01-01

OBJECTIVE Neuregulin 1 (NRG1) is a multifunctional neurotrophin and a critical mediator of neurodevelopment and risk for schizophrenia. NRG1 undergoes extensive alternative splicing, and association of brain NRG1-IV isoform expression with the schizophrenia-risk polymorphism, rs6994992, is a potential molecular mechanism of risk. Novel splice variants of NRG1-IV (NRG1-IVNV), with predicted unique signaling capabilities, have been cloned in fetal brain. Because the developmental expression and genetic regulation of NRG1-IVNV in human brain and relationship to schizophrenia is unknown, the authors investigated the temporal dynamics of NRG1-IVNV transcription, compared to the major NRG1 isoforms (types I-IV), across human prenatal and postnatal prefrontal cortical development and examined the association of rs6994992 with NRG1-IVNV expression. METHOD NRG1, types I-IV and NRG1-IVNV isoform expression was evaluated using quantitative real-time PCR in prefrontal cortex during human fetal brain development (14-39 weeks gestation: N=41) and postnatally through aging (age range 0-83 years: N=195). The association of rs6994992 genotype with NRG1-IVNV expression was determined. In-vitro assays were performed to determine the subcellular distribution and proteolytic processing of NRG1-IVNV isoforms. RESULTS Expression of NRG1, types I, II, III was temporally regulated during human prenatal and postnatal neocortical development and the trajectory of NRG1-IVNV was unique, being expressed from 16 weeks gestation until 3 years of age, after which it was undetectable. NRG1-IVNVs expression was associated with rs6994992 genotype, whereby homozygosity for the schizophrenia-risk allele (T) conferred lower cortical NRG1-IVNV levels. Finally, in-vitro cellular assays demonstrate that NRG1-IVNV is a novel nuclear enriched, truncated NRG1 protein that is resistant to proteolytic processing. CONCLUSION This study provides the first quantitative map of NRG1 isoform expression during human neocortical development and aging and identifies a potential mechanism of early developmental risk for schizophrenia at the NRG1 locus, involving a novel class of NRG1 proteins. PMID:24935406

Genomic characterization and expression analysis of four apolipoprotein A-IV paralogs in Senegalese sole (Solea senegalensis Kaup).

PubMed

Roman-Padilla, J; Rodríguez-Rua, A; Claros, M G; Hachero-Cruzado, I; Manchado, M

2016-01-01

The apolipoprotein A-IV (ApoA-IV) plays a key role in lipid transport and feed intake regulation. In this work, four cDNA sequences encoding ApoA-IV paralogs were identified. Sequence analysis revealed conserved structural features including the common 33-codon block and nine repeated motifs. Gene structure analysis identified four exons and three introns except for apoA-IVAa1 (with only 3 exons). Synteny analysis showed that the four paralogs were structured into two clusters (cluster A containing apoA-IVAa1 and apoA-IVAa2 and cluster B with apoA-IVBa3 and apoA-IVBa4) linked to an apolipoprotein E. Phylogenetic analysis clearly separated the paralogs according to their cluster organization as well as revealed four subclades highly conserved in Acanthopterygii. Whole-mount analyses (WISH) in early larvae (0 and 1day post-hatch (dph)) showed that the four paralogs were mainly expressed in yolk syncytial layer surrounding the oil globules. Later, at 3 and 5dph, the four paralogs were mainly expressed in liver and intestine although with differences in their relative abundance and temporal expression patterns. Diet supply triggered the intensity of WISH signals in the intestine of the four paralogs. Quantification of mRNA abundance by qPCR using whole larvae only detected the induction by diet at 5dph. Moreover, transcript levels increased progressively with age except for apoA-IVAa2, which appeared as a low-expressed isoform. Expression analysis in juvenile tissues confirmed that the four paralogs were mainly expressed in liver and intestine and secondary in other tissues. The role of these ApoA-IV genes in lipid transport and the possible role of apoA-IVAa2 as a regulatory form are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of an aerodynamic helmet on head temperature, core temperature, and cycling power compared with a traditional helmet.

PubMed

Lee, Joshua F; Brown, Skyler R; Lange, Andrew P; Brothers, R Matthew

2013-12-01

Nonvented "aerodynamic helmets" reduce wind resistance but may increase head (Th) and gastrointestinal (Tgi) temperature and reduce performance when worn in hot conditions. This study tested the hypothesis that Th and Tgi would be greater during low-intensity cycling (LIC) in the heat while wearing an aero helmet (AERO) vs. a traditional vented racing helmet (REG). This study also tested the hypothesis that Th, Tgi, and finish time would be greater, and power output would be reduced during a self-paced time trial in the heat with AERO vs. REG. Ten highly trained heat-acclimated endurance athletes conducted LIC (50% V[Combining Dot Above]O2max, LIC) and a high-intensity 12-km self-paced time trial (12-km TT) on a cycle ergometer in 39° C on 2 different days (AERO and REG), separated by >48 hours. During LIC, Th was higher at minute 7.5 and all time points thereafter in AERO vs. REG (p < 0.05). Similarly, during the 12-km TT, Th was higher at minutes 12.5, 15, and 17.5 in AERO vs. REG (p < 0.05). Heart rate (HR) and Tgi increased during LIC and during 12-km TT (both p < 0.001); however, no significant interaction (helmet × time) existed for HR or Tgi at either intensity (all p > 0.05). No group differences existed for finish time or power output during the 12-km TT (both p > 0.05). In conclusion, Th becomes elevated during cycling in the heat with an aero helmet compared with a traditional vented racing helmet during LIC and high-intensity cycling, yet Tgi and HR responses are similar irrespective of helmet type and Th. Furthermore, the higher Th that develops when an aero helmet is worn during cycling in the heat does not affect power output or cycling performance during short-duration high-intensity events.

Genome-scale strain designs based on regulatory minimal cut sets.

PubMed

Mahadevan, Radhakrishnan; von Kamp, Axel; Klamt, Steffen

2015-09-01

Stoichiometric and constraint-based methods of computational strain design have become an important tool for rational metabolic engineering. One of those relies on the concept of constrained minimal cut sets (cMCSs). However, as most other techniques, cMCSs may consider only reaction (or gene) knockouts to achieve a desired phenotype. We generalize the cMCSs approach to constrained regulatory MCSs (cRegMCSs), where up/downregulation of reaction rates can be combined along with reaction deletions. We show that flux up/downregulations can virtually be treated as cuts allowing their direct integration into the algorithmic framework of cMCSs. Because of vastly enlarged search spaces in genome-scale networks, we developed strategies to (optionally) preselect suitable candidates for flux regulation and novel algorithmic techniques to further enhance efficiency and speed of cMCSs calculation. We illustrate the cRegMCSs approach by a simple example network and apply it then by identifying strain designs for ethanol production in a genome-scale metabolic model of Escherichia coli. The results clearly show that cRegMCSs combining reaction deletions and flux regulations provide a much larger number of suitable strain designs, many of which are significantly smaller relative to cMCSs involving only knockouts. Furthermore, with cRegMCSs, one may also enable the fine tuning of desired behaviours in a narrower range. The new cRegMCSs approach may thus accelerate the implementation of model-based strain designs for the bio-based production of fuels and chemicals. MATLAB code and the examples can be downloaded at http://www.mpi-magdeburg.mpg.de/projects/cna/etcdownloads.html. krishna.mahadevan@utoronto.ca or klamt@mpi-magdeburg.mpg.de Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

High percentage of regulatory T cells before and after vitamin B12 treatment in patients with pernicious anemia.

PubMed

Watanabe, Satoru; Ide, Norifumi; Ogawara, Hatsue; Yokohama, Akihiko; Mitsui, Takeki; Handa, Hiroshi; Koiso, Hiromi; Tsukamoto, Norifumi; Saitoh, Takayuki; Murakami, Hirokazu

2015-01-01

In some previous studies, vitamin B12 treatment showed immunomodulatory effects and restored the immunological abnormalities in patients with pernicious anemia (PA). In the present study, peripheral blood T cell subsets, including regulatory T cells (T(reg)s), were examined before and after vitamin B12 treatment in PA patients. The percentages of CD4, CD8, Th1, Th2 and T(reg)s were examined in 23 PA patients before vitamin B12 treatment, in 23 other PA patients after vitamin B12 treatment and in 28 healthy controls. The mean percentage of CD8+ T cells was significantly higher in the control group (23.0%; 95% CI, 20.4-25.6%) than in the pre- (16.0%; 95% CI, 12.1-20.0%) and posttreatment groups (15.2%; 95% CI, 11.8-18.6%; p < 0.05). The CD4/CD8 ratio was significantly lower in the control group (2.01; 95% CI, 1.66-2.34) than in the pre- (3.45; 95% CI, 2.55-7.80) and posttreatment groups (2.97; 95% CI, 2.22-3.72; p < 0.05). There was no significant difference in the mean Th1/Th2 ratio among these groups. There were significant increases in the mean percentage of T(reg)s in the pre- (6.29%; 95% CI, 5.04-7.54%) and posttreatment groups (7.77%; 95% CI, 6.34-9.20%) compared with the control group (4.18%; 95% CI, 3.92-4.47%; p < 0.05). The percentage of T(reg)s was significantly higher in PA patients than in normal subjects, and this high T(reg) percentage was not different before and after vitamin B12 treatment. Other immunological alterations also did not recover after vitamin B12 treatment, so that these immunological changes appear to be the cause of PA and are not induced by vitamin B12 deficiency. © 2014 S. Karger AG, Basel.

Connection between nitrogen and manganese cycles revealed by transcriptomic analysis in Shewanella algae C6G3

NASA Astrophysics Data System (ADS)

Michotey, V.; Aigle, A.; Armougom, F.; Mejean, V.; Guasco, S.; Bonin, P.

2016-02-01

In sedimentary systems, the repartition of terminal electron-accepting molecules is often stratified on a permanent or seasonal basis. Just below to oxic zone, the suboxic one is characterized by high concentrations of oxidized inorganic compounds such as nitrate, manganese oxides (MnIII/IV) and iron oxides that are in close vicinity. Several studies have reported unexpected anaerobic nitrite/nitrate production at the expense of ammonium mediated by MnIII/IV, however this transient processes is difficult to discern and poorly understood. In the frame of this study, genes organization of nitrate and MnIII/IV respiration was investigated in S.algae. Additional genes were identified in S. algae compare to S. oneidensis: genes coding for nitrate and nitrite reductase (napA-a and nrfA-2) and an OMC protein (mtrH). In contrast to S. oneidensis, an anaerobic transitory nitrite accumulation at the expense of ammonium was observed in S. algae during growth with MnIII/IV, concomitantly with expression of nitrate/nitrite reductase genes (napA, nrfA, nrfA-2). Among the hypothesis explaining this data, the potential putative expression of unidentified gene able to perform ammonium oxidation was not observed on the global transcriptional level, however several signs of oxidative stress were detected and the existence of a secondary reaction generated by a putative oxidative s could not be excluded. Another option could be the action of reverse reaction by an enzyme such as NrfA or NrfA-2 due to the electron flow equilibrium. Whatever the electron acceptor (Nitrate/ MnIII/IV), the unexpected expression level of of omcA, mtrF, mtrH, mtrC was observed and peaked at the end of the exponential phase. Different expression patterns of the omc genes were observed depending on electron acceptor and growth phase. Only mtrF-2 gene was specifically expressed in Mn(III/IV) condition. Nitrate and Mn(III/IV) respirations seem connected at physiological as well as at transcriptional level

Gene Expression Analysis Reveals New Possible Mechanisms of Vancomycin-Induced Nephrotoxicity and Identifies Gene Markers Candidates

PubMed Central

Dieterich, Christine; Puey, Angela; Lyn, Sylvia; Swezey, Robert; Furimsky, Anna; Fairchild, David; Mirsalis, Jon C.; Ng, Hanna H.

2009-01-01

Vancomycin, one of few effective treatments against methicillin-resistant Staphylococcus aureus, is nephrotoxic. The goals of this study were to (1) gain insights into molecular mechanisms of nephrotoxicity at the genomic level, (2) evaluate gene markers of vancomycin-induced kidney injury, and (3) compare gene expression responses after iv and ip administration. Groups of six female BALB/c mice were treated with seven daily iv or ip doses of vancomycin (50, 200, and 400 mg/kg) or saline, and sacrificed on day 8. Clinical chemistry and histopathology demonstrated kidney injury at 400 mg/kg only. Hierarchical clustering analysis revealed that kidney gene expression profiles of all mice treated at 400 mg/kg clustered with those of mice administered 200 mg/kg iv. Transcriptional profiling might thus be more sensitive than current clinical markers for detecting kidney damage, though the profiles can differ with the route of administration. Analysis of transcripts whose expression was changed by at least twofold compared with vehicle saline after high iv and ip doses of vancomycin suggested the possibility of oxidative stress and mitochondrial damage in vancomycin-induced toxicity. In addition, our data showed changes in expression of several transcripts from the complement and inflammatory pathways. Such expression changes were confirmed by relative real-time reverse transcription–polymerase chain reaction. Finally, our results further substantiate the use of gene markers of kidney toxicity such as KIM-1/Havcr1, as indicators of renal injury. PMID:18930951

Gene expression analysis reveals new possible mechanisms of vancomycin-induced nephrotoxicity and identifies gene markers candidates.

PubMed

Dieterich, Christine; Puey, Angela; Lin, Sylvia; Lyn, Sylvia; Swezey, Robert; Furimsky, Anna; Fairchild, David; Mirsalis, Jon C; Ng, Hanna H

2009-01-01

Vancomycin, one of few effective treatments against methicillin-resistant Staphylococcus aureus, is nephrotoxic. The goals of this study were to (1) gain insights into molecular mechanisms of nephrotoxicity at the genomic level, (2) evaluate gene markers of vancomycin-induced kidney injury, and (3) compare gene expression responses after iv and ip administration. Groups of six female BALB/c mice were treated with seven daily iv or ip doses of vancomycin (50, 200, and 400 mg/kg) or saline, and sacrificed on day 8. Clinical chemistry and histopathology demonstrated kidney injury at 400 mg/kg only. Hierarchical clustering analysis revealed that kidney gene expression profiles of all mice treated at 400 mg/kg clustered with those of mice administered 200 mg/kg iv. Transcriptional profiling might thus be more sensitive than current clinical markers for detecting kidney damage, though the profiles can differ with the route of administration. Analysis of transcripts whose expression was changed by at least twofold compared with vehicle saline after high iv and ip doses of vancomycin suggested the possibility of oxidative stress and mitochondrial damage in vancomycin-induced toxicity. In addition, our data showed changes in expression of several transcripts from the complement and inflammatory pathways. Such expression changes were confirmed by relative real-time reverse transcription-polymerase chain reaction. Finally, our results further substantiate the use of gene markers of kidney toxicity such as KIM-1/Havcr1, as indicators of renal injury.

Bevacizumab, an anti-vascular endothelial growth factor antibody, inhibits osteoarthritis.

PubMed

Nagai, Toshihiro; Sato, Masato; Kobayashi, Miyuki; Yokoyama, Munetaka; Tani, Yoshiki; Mochida, Joji

2014-09-18

Angiogenesis is an important factor in the development of osteoarthritis (OA). We investigated the efficacy of bevacizumab, an antibody against vascular endothelial growth factor and an inhibitor of angiogenesis, in the treatment of OA using a rabbit model of anterior cruciate ligament transection. First, we evaluated the response of gene expression and histology of the normal joint to bevacizumab treatment. Next, in a rabbit model of OA induced by anterior cruciate ligament transection, we used macroscopic and histological evaluations and real-time polymerase chain reaction (PCR) to examine the responses to intravenous (systemic) administration of bevacizumab (OAB IV group). We also investigated the efficacy of intra-articular (local) administration of bevacizumab in OA-induced rabbits (OAB IA group). Histologically, bevacizumab had no negative effect in normal joints. Bevacizumab did not increase the expression of genes for catabolic factors in the synovium, subchondral bone, or articular cartilage, but it increased the expression of collagen type 2 in the articular cartilage. Macroscopically and histologically, the OAB IV group exhibited a reduction in articular cartilage degeneration and less osteophyte formation and synovitis compared with the control group (no bevacizumab; OA group). Real-time PCR showed significantly lower expression of catabolic factors in the synovium in the OAB IV group compared with the OA group. In articular cartilage, expression levels of aggrecan, collagen type 2, and chondromodulin-1 were higher in the OAB IV group than in the OA group. Histological evaluation and assessment of pain behaviour showed a superior effect in the OAB IA group compared with the OAB IV group 12 weeks after administration of bevacizumab, even though the total dosage given to the OAB IA group was half that received by the OAB IV group. Considering the dosage and potential adverse effects of bevacizumab, the local administration of bevacizumab is a more advantageous approach than systemic administration. Our results suggest that intra-articular bevacizumab may offer a new therapeutic approach for patients with post-traumatic OA.

Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of T(reg) cells and macrophages in adipose tissue.

PubMed

Lynch, Lydia; Michelet, Xavier; Zhang, Sai; Brennan, Patrick J; Moseman, Ashley; Lester, Chantel; Besra, Gurdyal; Vomhof-Dekrey, Emilie E; Tighe, Mike; Koay, Hui-Fern; Godfrey, Dale I; Leadbetter, Elizabeth A; Sant'Angelo, Derek B; von Andrian, Ulrich; Brenner, Michael B

2015-01-01

Invariant natural killer T cells (iNKT cells) are lipid-sensing innate T cells that are restricted by the antigen-presenting molecule CD1d and express the transcription factor PLZF. iNKT cells accumulate in adipose tissue, where they are anti-inflammatory, but the factors that contribute to their anti-inflammatory nature, as well as their targets in adipose tissue, are unknown. Here we found that iNKT cells in adipose tissue had a unique transcriptional program and produced interleukin 2 (IL-2) and IL-10. Unlike other iNKT cells, they lacked PLZF but expressed the transcription factor E4BP4, which controlled their IL-10 production. The adipose iNKT cells were a tissue-resident population that induced an anti-inflammatory phenotype in macrophages and, through the production of IL-2, controlled the number, proliferation and suppressor function of regulatory T cells (Treg cells) in adipose tissue. Thus, iNKT cells in adipose tissue are unique regulators of immunological homeostasis in this tissue.

Study of the relationship between mononuclear inflammatory infiltrate and Ki-67 and basement membrane and extracellular matrix protein expression in radicular cysts.

PubMed

Mourão, R V C; Júnior, E C Pinheiro; Barros Silva, P G; Turatti, E; Mota, M R L; Alves, A P N N

2016-05-01

To evaluate the relationship between mononuclear inflammatory infiltrate and the expression of a proliferative immunomarker (Ki-67) as well as to evaluate basement membrane and extracellular matrix proteins (laminin and collagen type IV) in radicular cysts and dentigerous cysts (DC). Immunohistochemical analyses were performed in heavily inflamed radicular cysts (HIRC), slightly inflamed radicular cysts (SIRC) and DC (n = 20) using Ki-67 (Dako(®) , 1 : 50), anticollagen type IV (DBS(®) , 1 : 40) and antilaminin (DBS(®) , 1 : 20). The data were analysed using anova/Tukey's test (Ki-67) and Kruskal-Wallis/Dunn's test (collagen type IV and laminin) (P < 0.05). The immunoexpression of Ki-67 was significantly greater in the SIRC group compared with the HIRC and DC (P = 0.0040). Likewise, the immunoexpression of collagen type IV in the basement membrane of the SIRC group was significantly more continuous (P = 0.0475) than in the HIRC group. DC had significantly less collagen type IV in extracellular matrix immunoexpression than HIRC and SIRC (P = 0.0246). Laminin was absent in the basement membrane in the SIRC and DC groups, and the extracellular matrix of the HIRC was weak and punctate. The presence of inflammatory factors in the radicular cyst wall modified the expression of proliferation factors in the epithelial lining and the expression of collagen type IV and laminin in the basement membrane, but did not modify extracellular matrix behaviour in radicular cysts. © 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Methylation of CIITA promoter IV causes loss of HLA-II inducibility by IFN-γ in promyelocytic cells

PubMed Central

De Ambrosis, Alessandro; Banelli, Barbara; Pira, Giuseppina Li; Aresu, Ottavia; Romani, Massimo; Ferrini, Silvano; Accolla, Roberto S.

2008-01-01

The human promyelocytic cell line THP-1 expresses high level of HLA class II (HLA-II) molecules after IFN-γ treatment. Here, we report a variant of THP-1 that does not express HLA-II after IFN-γ. The variant's HLA-II phenotype is constant over time in culture and it is not related to a defective IFN-γ-signalling pathway. Transfection of CIITA, the HLA-II transcriptional activator, under the control of a cytomegalovirus promoter rescues high level of HLA-DR surface expression in the variant indicating that the biosynthetic block resides in the expression of CIITA and not in the CIITA-dependent transactivation of the HLA-II promoters. Treatment of the variant with 5-azacytidine (5-aza), which inhibits CpG methylation, restores inducibility of HLA-II by IFN-γ both at transcriptional and phenotypic level and antigen presenting and processing function of the variant. DNA studies demonstrate that the molecular defect of the THP-1 variant originates from the methylation of the CIITA promoter IV. Furthermore, treatment with 5-aza produces a substantial demethylation of CIITA promoter IV and a significant increase of IFN-γ-dependent HLA-II expression in another myelomonocytic cell line, U937. Therefore hyper-methylation of CIITA promoter IV may be a relevant mechanism of epigenetic control preventing HLA-II IFN-γ inducibility in the myelomonocytic cell lineage. PMID:18829986

Evaluation of XIENCE V everolimus-eluting and Taxus Express2 paclitaxel-eluting coronary stents in patients with jailed side branches from the SPIRIT IV trial at 2 years.

PubMed

Forrest, John K; Lansky, Alexandra J; Meller, Stephanie M; Hou, Liming; Sood, Poornima; Applegate, Robert J; Wang, John C; Skelding, Kimberly A; Shah, Aakar; Kereiakes, Dean J; Sudhir, Krishnankutty; Cristea, Ecaterina; Yaqub, Manejeh; Stone, Gregg W

2013-06-01

The aim of this study was to determine whether patients from the Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions (SPIRIT) IV trial who underwent percutaneous coronary intervention, who had target lesions with jailed side branches, had improved clinical outcomes when treated with the XIENCE V versus Taxus Express(2) drug-eluting stent. In the SPIRIT III randomized trial, patients with target lesions with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had lower 2-year rates of major adverse cardiac events. The SPIRIT IV trial represents a larger more diverse patient population compared with SPIRIT III. In the large-scale, prospective, multicenter, randomized SPIRIT IV trial, 3,687 patients who underwent coronary stenting with up to 3 de novo native coronary artery lesions were randomized 2:1 to receive XIENCE V versus Taxus Express(2) stents. Two-year clinical outcomes of patients with or without jailed side branches after stenting were compared. A jailed side branch was defined as any side branch >1.0 mm in diameter within the target segment being stented, excluding bifurcations deemed to require treatment. Of the 3,687 patients in SPIRIT IV, a total of 1,426 had side branches that were jailed during angioplasty of the target lesion. Patients with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had significantly lower 2-year rates of target lesion failure (6.5% vs 11.9%, p = 0.001), major adverse cardiac events (6.6% vs 12.2%, p = 0.0008), ischemia-driven target vessel revascularization (4.1% vs 7.9%, p = 0.004), and stent thrombosis (0.6% vs 2.8%, p = 0.001). In conclusion, patients with jailed side branches after stenting with XIENCE V compared to Taxus Express(2) devices had superior clinical outcomes at 2 years in the large-scale randomized SPIRIT IV trial. Copyright © 2013 Elsevier Inc. All rights reserved.

Integrative analysis of differentially expressed microRNAs of pulmonary alveolar macrophages from piglets during H1N1 swine influenza A virus infection

PubMed Central

Jiang, Pengfei; Zhou, Na; Chen, Xinyu; Zhao, Xing; Li, Dengyun; Wang, Fen; Bi, Lijun; Zhang, Deli

2015-01-01

H1N1 swine influenza A virus (H1N1 SwIV) is one key subtype of influenza viruses with pandemic potential. MicroRNAs (miRNAs) are endogenous small RNA molecules that regulate gene expression. MiRNAs relevant with H1N1 SwIV have rarely been reported. To understand the biological functions of miRNAs during H1N1 SwIV infection, this study profiled differentially expressed (DE) miRNAs in pulmonary alveolar macrophages from piglets during the H1N1 SwIV infection using a deep sequencing approach, which was validated by quantitative real-time PCR. Compared to control group, 70 and 16 DE miRNAs were respectively identified on post-infection day (PID) 4 and PID 7. 56 DE miRNAs were identified between PID 4 and PID 7. Our results suggest that most host miRNAs are down-regulated to defend the H1N1 SwIV infection during the acute phase of swine influenza whereas their expression levels gradually return to normal during the recovery phase to avoid the occurrence of too severe porcine lung damage. In addition, targets of DE miRNAs were also obtained, for which bioinformatics analyses were performed. Our results would be useful for investigating the functions and regulatory mechanisms of miRNAs in human influenza because pig serves as an excellent animal model to study the pathogenesis of human influenza. PMID:25639204

HIF-1α signaling activation by post-ischemia treatment with astragaloside IV attenuates myocardial ischemia-reperfusion injury.

PubMed

Si, Jingwen; Wang, Ning; Wang, Huan; Xie, Juan; Yang, Jian; Yi, Hui; Shi, Zixuan; Ma, Jing; Wang, Wen; Yang, Lifang; Yu, Shiqiang; Li, Junchang

2014-01-01

In this study, we evaluated the effect of astragaloside IV (Ast IV) post-ischemia treatment on myocardial ischemia-reperfusion (IR) injury (IRI). We also examined whether hypoxia inducible factor-1α (HIF-1α) and its downstream gene-inducible nitric oxide (NO) synthase (iNOS) play roles in the cardioprotective effect of Ast IV. Cultured cardiomyocytes and perfused isolated rat hearts were exposed to Ast IV during reperfusion in the presence or absence of the HIF-1α inhibitor 2-methoxyestradiol (2-MeOE2). The post-ischemia treatment with Ast IV protected cardiomyocytes from the apoptosis and death induced by simulated IRI (SIRI). Additionally, in cardiomyocytes, 2-MeOE2 and HIF-1α siRNA treatment each not only abolished the anti-apoptotic effect of post-ischemia treatment with Ast IV but also reversed the upregulation of HIF-1α and iNOS expression. Furthermore, after treatment with Ast IV, post-ischemic cardiac functional recovery and lactate dehydrogenase (LDH) release in the coronary flow (CF) were improved, and the myocardial infarct size was decreased. Moreover, the number of apoptotic cells was reduced, and the upregulation of the anti-apoptotic protein Bcl2 and downregulation of the pro-apoptotic protein Caspase3 were reversed. 2-MeOE2 reversed these effects of Ast IV on IR-injured hearts. These results suggest that post-ischemia treatment with Ast IV can attenuate IRI by upregulating HIF-1α expression, which transmits a survival signal to the myocardium.

Expression of heat shock protein 47 is increased in remnant kidney and correlates with disease progression

PubMed Central

SUNAMOTO, MASAAKI; KUZE, KOGO; IEHARA, NORIYUKI; TAKEOKA, HIROYA; NAGATA, KAZUHIRO; KITA, TORU; DOI, TOSHIO

1998-01-01

Glomerulosclerosis is characterized by accumulation of the mesangial extracellular matrix, including type I and IV collagen. The processing for the collagens in the glomeruli may play a critical role for development of glomerulosclerosis. We examined the expression of heat shock protein 47 (HSP47), a collagen-binding molecular chaperone in the progresive glomerulosclerosis model. Subtotally nephrectomized rats, unlike sham-operated rats, developed focal and segmental glomerulosclerosis. Immunological staining demonstrated an increased expression of HSP47 which paralleled the expression of type I and IV collagen in the glomeruli of the nephrectomized rats as the glomerulosclerosis developed. The mRNA levels encoding type I and type IV collagen and HSP47 were increased 3.4 fold, 3.6 fold and 2.8 fold, respectively, at week 7 after nephrectomy. By in situ hybridization, the expression of HSP47 mRNA was determined to be localized to the glomeruli with segmental sclerosis. These results suggest that HSP47 may play a central role in the process of extracellular matrix accumulation during the development of glomerulosclerosis. PMID:9741355

Antibody Response to Serpin B13 Induces Adaptive Changes in Mouse Pancreatic Islets and Slows Down the Decline in the Residual Beta Cell Function in Children with Recent Onset of Type 1 Diabetes Mellitus.

PubMed

Kryvalap, Yury; Lo, Chi-Wen; Manuylova, Ekaterina; Baldzizhar, Raman; Jospe, Nicholas; Czyzyk, Jan

2016-01-01

Type 1 diabetes mellitus (T1D) is characterized by a heightened antibody (Ab) response to pancreatic islet self-antigens, which is a biomarker of progressive islet pathology. We recently identified a novel antibody to clade B serpin that reduces islet-associated T cell accumulation and is linked to the delayed onset of T1D. As natural immunity to clade B arises early in life, we hypothesized that it may influence islet development during that time. To test this possibility healthy young Balb/c male mice were injected with serpin B13 mAb or IgG control and examined for the number and cellularity of pancreatic islets by immunofluorescence and FACS. Beta cell proliferation was assessed by measuring nucleotide analog 5-ethynyl-2'-deoxyuridine (5-EdU) incorporation into the DNA and islet Reg gene expression was measured by real time PCR. Human studies involved measuring anti-serpin B13 autoantibodies by Luminex. We found that injecting anti-serpin B13 monoclonal Ab enhanced beta cell proliferation and Reg gene expression, induced the generation of ∼80 pancreatic islets per animal, and ultimately led to increase in the beta cell mass. These findings are relevant to human T1D because our analysis of subjects just diagnosed with T1D revealed an association between baseline anti-serpin activity and slower residual beta cell function decline in the first year after the onset of diabetes. Our findings reveal a new role for the anti-serpin immunological response in promoting adaptive changes in the endocrine pancreas and suggests that enhancement of this response could potentially help impede the progression of T1D in humans. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Comparative quantitative proteomic analysis of disease stratified laser captured microdissected human islets identifies proteins and pathways potentially related to type 1 diabetes.

PubMed

Nyalwidhe, Julius O; Grzesik, Wojciech J; Burch, Tanya C; Semeraro, Michele L; Waseem, Tayab; Gerling, Ivan C; Mirmira, Raghavendra G; Morris, Margaret A; Nadler, Jerry L

2017-01-01

Type 1 diabetes (T1D) is a chronic inflammatory disease that is characterized by autoimmune destruction of insulin-producing pancreatic beta cells. The goal of this study was to identify novel protein signatures that distinguish Islets from patients with T1D, patients who are autoantibody positive without symptoms of diabetes, and from individuals with no evidence of disease. High resolution high mass accuracy label free quantitative mass spectrometry analysis was applied to islets isolated by laser capture microdissection from disease stratified human pancreata from the Network for Pancreatic Organ Donors with Diabetes (nPOD), these included donors without diabetes, donors with T1D-associated autoantibodies in the absence of diabetes, and donors with T1D. Thirty-nine proteins were found to be differentially regulated in autoantibody positive cases compared to the no-disease group, with 25 upregulated and 14 downregulated proteins. For the T1D cases, 63 proteins were differentially expressed, with 24 upregulated and 39 downregulated, compared to the no disease controls. We have identified functional annotated enriched gene families and multiple protein-protein interaction clusters of proteins are involved in biological and molecular processes that may have a role in T1D. The proteins that are upregulated in T1D cases include S100A9, S100A8, REG1B, REG3A and C9 amongst others. These proteins have important biological functions, such as inflammation, metabolic regulation, and autoimmunity, all of which are pathways linked to the pathogenesis of T1D. The identified proteins may be involved in T1D development and pathogenesis. Our findings of novel proteins uniquely upregulated in T1D pancreas provides impetus for further investigations focusing on their expression profiles in beta cells/ islets to evaluate their role in the disease pathogenesis. Some of these molecules may be novel therapeutic targets T1D.

Innovative remote monitoring of plant health for environmental applications: A joint effort between EPCOT{reg_sign} and the DOE

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

Robitaille, H.; Capelle, G.; Di Benedetto, J.

1996-12-31

In September of 1994, the US Department of Energy (DOE), Environmental Management, Office of Science and Technology for (OST) and Epcot{reg_sign} in the WALT DISNEY WORLD{reg_sign} Resort (Epcot) signed an agreement to cooperate on the research, development, and public communication and display of environmental technologies. Although Epcot and OST have distinctive missions, certain areas of their respective research and development efforts are common, including the integration of remote sensors with robotics platforms, airborne surveys for environmental characterization and monitoring, and ground based measurements of vegetation stress. The first area of cooperative R&D pursued under the agreement is the evaluation ofmore » laser-induced fluorescence imaging (LIFI), a technology developed by OST and proven effective for uranium detection. This paper describes the efforts being conducted under the Epcot-OST agreement and presents initial results. An appendix describing LIFI technology is also included.« less

Conventional versus computer-assisted technique for total knee arthroplasty: a minimum of 5-year follow-up of 200 patients in a prospective randomized comparative trial.

PubMed

Cip, Johannes; Widemschek, Mark; Luegmair, Matthias; Sheinkop, Mitchell B; Benesch, Thomas; Martin, Arno

2014-09-01

In the literature, studies of computer-assisted total knee arthroplasty (TKA) after mid-term period are not conclusive and long-term data are rare. In a prospective, randomized, comparative study 100 conventional TKAs (group REG) were compared with 100 computer-assisted TKAs (group NAV). Minimum follow-up was 5years. No difference in implant failure was found with 1.1% in group NAV versus 4.6% in group REG (P=0.368). Group NAV showed a significantly less mean deviation of mechanical limb axis (P=0.015), more TKAs (90% versus 81% in group REG) were within 3° varus/valgus and a higher tibial slope and lateral distal femoral angle (LDFA) accuracy was found (P≤0.034). Clinical investigational parameters showed no differences (P≥0.058). Insall and HSS score total were also higher in group NAV (P≤0.016). Copyright © 2014 Elsevier Inc. All rights reserved.

Astragaloside IV prevents damage to human mesangial cells through the inhibition of the NADPH oxidase/ROS/Akt/NF‑κB pathway under high glucose conditions.

PubMed

Sun, Li; Li, Weiping; Li, Weizu; Xiong, Li; Li, Guiping; Ma, Rong

2014-07-01

Glomerular hypertrophy and hyperfiltration are the two major pathological characteristics of the early stages of diabetic nephropathy (DN), which are respectively related to mesangial cell (MC) proliferation and a decrease in calcium influx conducted by canonical transient receptor potential cation channel 6 (TRPC6). The marked increase in the production of reactive oxygen species (ROS) induced by hyperglycemia is the main sponsor of multiple pathological pathways in DN. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important source of ROS production in MCs. Astragaloside IV (AS‑IV) is an active ingredient of Radix Astragali which has a potent antioxidative effect. In this study, we aimed to investigate whether high glucose (HG)‑induced NADPH oxidase activation and ROS production contribute to MC proliferation and the downregulation of TRPC6 expression; we also wished to determine the effects of AS‑IV on MCs under HG conditions. Using a human glomerular mesangial cell line, we found that treatment with AS‑IV for 48 h markedly attenuated HG‑induced proliferation and the hypertrophy of MCs in a dose‑dependent manner. The intracellular ROS level was also markedly reduced following treatment with AS‑IV. In addition, the enhanced activity of NADPH oxidase and the expression level of NADPH oxidase 4 (Nox4) protein were decreased. Treatment with AS‑IV also inhibited the phosphorylation level of Akt and IκBα in the MCs. In addition, TRPC6 protein expression and the intracellular free calcium concentration were also markedly reduced following treatment with AS‑IV under HG conditions. These results suggest that AS‑IV inhibits HG‑induced mesangial cell proliferation and glomerular contractile dysfunction through the NADPH oxidase/ROS/Akt/nuclear factor‑κB (NF‑κB) pathway, providing a new perspective for the clinical treatment of DN.

Subchronic Exposure to Arsenic Represses the TH/TRβ1-CaMK IV Signaling Pathway in Mouse Cerebellum.

PubMed

Guan, Huai; Li, Shuangyue; Guo, Yanjie; Liu, Xiaofeng; Yang, Yi; Guo, Jinqiu; Li, Sheng; Zhang, Cong; Shang, Lixin; Piao, Fengyuan

2016-01-26

We previously reported that arsenic (As) impaired learning and memory by down-regulating calmodulin-dependent protein kinase IV (CaMK IV) in mouse cerebellum. It has been documented that the thyroid hormone receptor (TR)/retinoid X receptor (RXR) heterodimer and thyroid hormone (TH) may be involved in the regulation of CaMK IV. To investigate whether As affects the TR/RXR heterodimer and TH, we determined As concentration in serum and cerebellum, 3,5,3'-triiodothyronine (T3) and thyroxin (T4) levels in serum, and expression of CaMK IV, TR and RXR in cerebellum of mice exposed to As. Cognition function was examined by the step-down passive avoidance task and Morris water maze (MWM) tests. Morphology of the cerebellum was observed by Hematoxylin-Eosin staining under light microscope. Our results showed that the concentrations of As in the serum and cerebellum of mice both increased with increasing As-exposure level. A significant positive correlation was found between the two processes. Adeficit in learning and memory was found in the exposed mice. Abnormal morphologic changes of Purkinje cells were observed in cerebellum of the exposed mice. Moreover, the cerebellar expressions of CaMK IV protein and the TRβ gene, and TRβ1 protein were significantly lower in As-exposed mice than those in controls. Subchronic exposure to As appears to increase its level in serum and cerebella of mice, impairing learning and memory and down-regulating expression of TRβ1 as well as down-stream CaMK IV. It is also suggested that the increased As may be responsible for down-regulation of TRβ1 and CaMK IV in cerebellum and that the down-regulated TRβ1 may be involved in As-induced impairment of learning and memory via inhibiting CaMK IV and its down-stream pathway.

Immunohistochemical expression of basement membrane proteins of verrucous carcinoma of the oral mucosa.

PubMed

Arduino, Paolo G; Carrozzo, Marco; Pagano, Marco; Broccoletti, Roberto; Scully, Crispian; Gandolfo, Sergio

2010-06-01

Squamous cell carcinoma (SCC) of the oral cavity is an extremely invasive tumour of stratified squamous epithelium that spreads throughout degradation of the basement membrane (BM) and extra-cellular matrix. Oral verrucous carcinoma (VC) is a rare low-grade variant of oral SCC that penetrates into the subepithelial connective tissue. It also has a different clinical behaviour from classical oral SCC. We investigated the immunohistochemical expression of laminin, laminin-5, collagen IV and fibronectin in VC, severe epithelial dysplasia (SED) and SCC in order to analyse if the pattern of these molecules expression contributes to the differences in the biological behaviour of these diseases. The staining pattern of laminin was less intensive in SCC compared with SED and VC, and collagen IV expression was increased in VC compared with SED. Discontinuities of laminin, collagen IV and fibronectin were more evident in SED than in VC. This study indicates that VC has a biological behaviour different from SED or SCC, observable by immunohistochemistry in the BM zone.

Interleukin-22-deficiency and microbiota contribute to the exacerbation of Toxoplasma gondii-induced intestinal inflammation.

PubMed

Couturier-Maillard, A; Froux, N; Piotet-Morin, J; Michaudel, C; Brault, L; Le Bérichel, J; Sénéchal, A; Robinet, P; Chenuet, P; Jejou, S; Dumoutier, L; Renauld, J C; Iovanna, J; Huber, S; Quesniaux, Vfj; Sokol, H; Ryffel, B

2018-05-04

Upon oral infection with Toxoplasma gondii cysts (76 K strain) tachyzoites are released into the intestinal lumen and cross the epithelial barrier causing damage and acute intestinal inflammation in C57BL/6 (B6) mice. Here we investigated the role of microbiota and IL-22 in T.gondii-induced small intestinal inflammation. Oral T.gondii infection in B6 mice causes inflammation with IFNγ and IL-22 production. In IL-22-deficient mice, T.gondii infection augments the Th1 driven inflammation. Deficiency in either IL-22bp, the soluble IL-22 receptor or Reg3γ, an IL-22-dependent antimicrobial lectin/peptide, did not reduce inflammation. Under germ-free conditions, T.gondii-induced inflammation was reduced in correlation with parasite load. But intestinal inflammation is still present in germ-free mice, at low level, in the lamina propria, independently of IL-22 expression. Exacerbated intestinal inflammation driven by absence of IL-22 appears to be independent of IL-22 deficiency associated-dysbiosis as similar inflammation was observed after fecal transplantation of IL-22 -/- or WT microbiota to germ-free-WT mice. Our results suggest cooperation between parasite and intestinal microbiota in small intestine inflammation development and endogenous IL-22 seems to exert a protective role independently of its effect on the microbiota. In conclusion, IL-22 participates in T.gondii induced acute small intestinal inflammation independently of microbiota and Reg3γ.

Rainfall forecast in the Upper Mahaweli basin in Sri Lanka using RegCM model

NASA Astrophysics Data System (ADS)

Muhammadh, K. M.; Mafas, M. M. M.; Weerakoon, S. B.

2017-04-01

The Upper Mahaweli basin is the upper most sub basin of 788 km2 in size above Polgolla barrage in the Mahaweli River, the longest river in Sri Lanka which starts from the central hills of the island and drains to the sea at the North-east coast. Rainfall forecast in the Upper Mahaweli basin is important for issuing flood warning in the river downstream of the reservoirs, landslide warning in the settlements in hilly areas. Anticipatory water management in the basin including reservoir operations, barrage gate operation for releasing water for irrigation and flood control also require reliable rainfall and runoff prediction in the sub basin. In this study, the Regional Climate Model (RegCM V4.4.5.11) is calibrated for the basin to dynamically downscale reanalysis weather data of Global Climate Model (GCM) to forecast the rainfall in the basin. Observed rainfalls at gauging stations within the basin were used for model calibration and validation. The observed rainfall data was analysed using ARC GIS and the output of RegCM was analysed using GrADS tool. The output of the model and the observed precipitation were obtained on grids of size 0.1 degrees and the accuracy of the predictions were analysed using RMSE and Mean Model Absolute Error percentage (MAME %). The predictions by the calibrated RegCM model for the basin is shown to be satisfactory. The model is a useful tool for rainfall forecast in the Upper Mahaweli River basin.

Measurement of acute toxicity to Mysidopsis bahia using DaphniaQuant{reg_sign} instrument and protocol

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

Blankemeyer, J.T.; Nguyen, T.; Burks, S.L.

1994-12-31

DaphniaQuant{reg_sign} uses a fluorescent dye to permeate the cells of aquatic organisms. The technique has been used on frog embryos, fish embryos, and bovine erythrocytes. Two wavelengths of light are used to excite the fluorescent dye, Di-4-ANEPPS. The blue excitation wavelength measures the cell membrane potential while the yellow excitation wavelength measures the amount of dye loaded into the organisms. The authors applied the technique to the shrimp, Mysidopsis bahia, used in marine toxicity testing. The authors used from 1 to 10 shrimp, loaded into a 3 ml spectrofluorometry plastic cuvette. The fluorescent dye, Di-4-ANEPPS, was mixed with the 3more » ml of ASW in the cuvette at a final Di-4ANEPPS concentration of 10{sub {minus}6} M. After a thirty minute incubation, the fluorescence of Di-4-ANEPPS was measured in the DaphniaQuant{reg_sign} instrument. A similar protocol was used to test various concentrations of standard assay chemicals and effluents. The test chemical was mixed with ASW and Di-4-ANEPPS and incubated with the shrimp for thirty minutes. After thirty minutes, the fluorescence was measured and compared to the fluorescence of the control shrimp. The authors found that the fluorescence from a single shrimp was detectable and gave similar toxicity data as did the replicates using 10 shrimp. They conclude that the DaphniaQuant{reg_sign} assay can be successfully adapted to marine organisms, particularly Mysidopsis bahia.« less

Ketamine induces brain-derived neurotrophic factor expression via phosphorylation of histone deacetylase 5 in rats.

PubMed

Choi, Miyeon; Lee, Seung Hoon; Park, Min Hyeop; Kim, Yong-Seok; Son, Hyeon

2017-08-05

Ketamine shows promise as a therapeutic agent for the treatment of depression. The increased expression of brain-derived neurotrophic factor (BDNF) has been associated with the antidepressant-like effects of ketamine, but the mechanism of BDNF induction is not well understood. In the current study, we demonstrate that the treatment of rats with ketamine results in the dose-dependent rapid upregulation of Bdnf promoter IV activity and expression of Bdnf exon IV mRNAs in rat hippocampal neurons. Transfection of histone deacetylase 5 (HDAC5) into rat hippocampal neurons similarly induces Bdnf mRNA expression in response to ketamine, whereas transfection of a HDAC5 phosphorylation-defective mutant (Ser259 and Ser498 replaced by Ala259 and Ala498), results in the suppression of ketamine-mediated BDNF promoter IV transcriptional activity. Viral-mediated hippocampal knockdown of HDAC5 induces Bdnf mRNA and protein expression, and blocks the enhancing effects of ketamine on BDNF expression in both unstressed and stressed rats, and thereby providing evidence for the role of HDAC5 in the regulation of Bdnf expression. Taken together, our findings implicate HDAC5 in the ketamine-induced transcriptional regulation of Bdnf, and suggest that the phosphorylation of HDAC5 regulates the therapeutic actions of ketamine. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic Fusions of a CFA/I/II/IV MEFA (Multiepitope Fusion Antigen) and a Toxoid Fusion of Heat-Stable Toxin (STa) and Heat-Labile Toxin (LT) of Enterotoxigenic Escherichia coli (ETEC) Retain Broad Anti-CFA and Antitoxin Antigenicity

PubMed Central

Ruan, Xiaosai; Sack, David A.; Zhang, Weiping

2015-01-01

Immunological heterogeneity has long been the major challenge in developing broadly effective vaccines to protect humans and animals against bacterial and viral infections. Enterotoxigenic Escherichia coli (ETEC) strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunologically different colonization factor antigens (CFAs) and two distinct enterotoxins [heat-labile toxin (LT) and heat-stable toxin type Ib (STa or hSTa)]. ETEC strains expressing any one or two CFAs and either toxin cause diarrhea, therefore vaccines inducing broad immunity against a majority of CFAs, if not all, and both toxins are expected to be effective against ETEC. In this study, we applied the multiepitope fusion antigen (MEFA) strategy to construct ETEC antigens and examined antigens for broad anti-CFA and antitoxin immunogenicity. CFA MEFA CFA/I/II/IV [CVI 2014, 21(2):243-9], which carried epitopes of seven CFAs [CFA/I, CFA/II (CS1, CS2, CS3), CFA/IV (CS4, CS5, CS6)] expressed by the most prevalent and virulent ETEC strains, was genetically fused to LT-STa toxoid fusion monomer 3xSTaA14Q-dmLT or 3xSTaN12S-dmLT [IAI 2014, 82(5):1823-32] for CFA/I/II/IV-STaA14Q-dmLT and CFA/I/II/IV-STaN12S-dmLT MEFAs. Mice intraperitoneally immunized with either CFA/I/II/IV-STa-toxoid-dmLT MEFA developed antibodies specific to seven CFAs and both toxins, at levels equivalent or comparable to those induced from co-administration of the CFA/I/II/IV MEFA and toxoid fusion 3xSTaN12S-dmLT. Moreover, induced antibodies showed in vitro adherence inhibition activities against ETEC or E. coli strains expressing these seven CFAs and neutralization activities against both toxins. These results indicated CFA/I/II/IV-STa-toxoid-dmLT MEFA or CFA/I/II/IV MEFA combined with 3xSTaN12S-dmLT induced broadly protective anti-CFA and antitoxin immunity, and suggested their potential application in broadly effective ETEC vaccine development. This MEFA strategy may be generally used in multivalent vaccine development. PMID:25803825

Genetic fusions of a CFA/I/II/IV MEFA (multiepitope fusion antigen) and a toxoid fusion of heat-stable toxin (STa) and heat-labile toxin (LT) of enterotoxigenic Escherichia coli (ETEC) retain broad anti-CFA and antitoxin antigenicity.

PubMed

Ruan, Xiaosai; Sack, David A; Zhang, Weiping

2015-01-01

Immunological heterogeneity has long been the major challenge in developing broadly effective vaccines to protect humans and animals against bacterial and viral infections. Enterotoxigenic Escherichia coli (ETEC) strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunologically different colonization factor antigens (CFAs) and two distinct enterotoxins [heat-labile toxin (LT) and heat-stable toxin type Ib (STa or hSTa)]. ETEC strains expressing any one or two CFAs and either toxin cause diarrhea, therefore vaccines inducing broad immunity against a majority of CFAs, if not all, and both toxins are expected to be effective against ETEC. In this study, we applied the multiepitope fusion antigen (MEFA) strategy to construct ETEC antigens and examined antigens for broad anti-CFA and antitoxin immunogenicity. CFA MEFA CFA/I/II/IV [CVI 2014, 21(2):243-9], which carried epitopes of seven CFAs [CFA/I, CFA/II (CS1, CS2, CS3), CFA/IV (CS4, CS5, CS6)] expressed by the most prevalent and virulent ETEC strains, was genetically fused to LT-STa toxoid fusion monomer 3xSTaA14Q-dmLT or 3xSTaN12S-dmLT [IAI 2014, 82(5):1823-32] for CFA/I/II/IV-STaA14Q-dmLT and CFA/I/II/IV-STaN12S-dmLT MEFAs. Mice intraperitoneally immunized with either CFA/I/II/IV-STa-toxoid-dmLT MEFA developed antibodies specific to seven CFAs and both toxins, at levels equivalent or comparable to those induced from co-administration of the CFA/I/II/IV MEFA and toxoid fusion 3xSTaN12S-dmLT. Moreover, induced antibodies showed in vitro adherence inhibition activities against ETEC or E. coli strains expressing these seven CFAs and neutralization activities against both toxins. These results indicated CFA/I/II/IV-STa-toxoid-dmLT MEFA or CFA/I/II/IV MEFA combined with 3xSTaN12S-dmLT induced broadly protective anti-CFA and antitoxin immunity, and suggested their potential application in broadly effective ETEC vaccine development. This MEFA strategy may be generally used in multivalent vaccine development.

Transcriptional repression by ApiAP2 factors is central to chronic toxoplasmosis

PubMed Central

Worth, Danielle; Huang, Sherri

2018-01-01

Tachyzoite to bradyzoite development in Toxoplasma is marked by major changes in gene expression resulting in a parasite that expresses a new repertoire of surface antigens hidden inside a modified parasitophorous vacuole called the tissue cyst. The factors that control this important life cycle transition are not well understood. Here we describe an important transcriptional repressor mechanism controlling bradyzoite differentiation that operates in the tachyzoite stage. The ApiAP2 factor, AP2IV-4, is a nuclear factor dynamically expressed in late S phase through mitosis/cytokinesis of the tachyzoite cell cycle. Remarkably, deletion of the AP2IV-4 locus resulted in the expression of a subset of bradyzoite-specific proteins in replicating tachyzoites that included tissue cyst wall components BPK1, MCP4, CST1 and the surface antigen SRS9. In the murine animal model, the mis-timing of bradyzoite antigens in tachyzoites lacking AP2IV-4 caused a potent inflammatory monocyte immune response that effectively eliminated this parasite and prevented tissue cyst formation in mouse brain tissue. Altogether, these results indicate that suppression of bradyzoite antigens by AP2IV-4 during acute infection is required for Toxoplasma to successfully establish a chronic infection in the immune-competent host. PMID:29718996

Transcriptional repression by ApiAP2 factors is central to chronic toxoplasmosis.

PubMed

Radke, Joshua B; Worth, Danielle; Hong, David; Huang, Sherri; Sullivan, William J; Wilson, Emma H; White, Michael W

2018-05-01

Tachyzoite to bradyzoite development in Toxoplasma is marked by major changes in gene expression resulting in a parasite that expresses a new repertoire of surface antigens hidden inside a modified parasitophorous vacuole called the tissue cyst. The factors that control this important life cycle transition are not well understood. Here we describe an important transcriptional repressor mechanism controlling bradyzoite differentiation that operates in the tachyzoite stage. The ApiAP2 factor, AP2IV-4, is a nuclear factor dynamically expressed in late S phase through mitosis/cytokinesis of the tachyzoite cell cycle. Remarkably, deletion of the AP2IV-4 locus resulted in the expression of a subset of bradyzoite-specific proteins in replicating tachyzoites that included tissue cyst wall components BPK1, MCP4, CST1 and the surface antigen SRS9. In the murine animal model, the mis-timing of bradyzoite antigens in tachyzoites lacking AP2IV-4 caused a potent inflammatory monocyte immune response that effectively eliminated this parasite and prevented tissue cyst formation in mouse brain tissue. Altogether, these results indicate that suppression of bradyzoite antigens by AP2IV-4 during acute infection is required for Toxoplasma to successfully establish a chronic infection in the immune-competent host.

Physiological and glycomic characterization of N-acetylglucosaminyltransferase-IVa and -IVb double deficient mice

PubMed Central

Takamatsu, Shinji; Antonopoulos, Aristotelis; Ohtsubo, Kazuaki; Ditto, David; Chiba, Yasunori; Le, Dzung T.; Morris, Howard R.; Haslam, Stuart M.; Dell, Anne; Marth, Jamey D.; Taniguchi, Naoyuki

2010-01-01

N-Acetylglucosaminyltransferase-IV (GnT-IV) has two isoenzymes, GnT-IVa and GnT-IVb, which initiate the GlcNAcβ1-4 branch synthesis on the Manα1-3 arm of the N-glycan core thereby increasing N-glycan branch complexity and conferring endogenous lectin binding epitopes. To elucidate the physiological significance of GnT-IV, we engineered and characterized GnT-IVb-deficient mice and further generated GnT-IVa/-IVb double deficient mice. In wild-type mice, GnT-IVa expression is restricted to gastrointestinal tissues, whereas GnT-IVb is broadly expressed among organs. GnT-IVb deficiency induced aberrant GnT-IVa expression corresponding to the GnT-IVb distribution pattern that might be attributed to increased Ets-1, which conceivably activates the Mgat4a promoter, and thereafter preserved apparent GnT-IV activity. The compensative GnT-IVa expression might contribute to amelioration of the GnT-IVb-deficient phenotype. GnT-IVb deficiency showed mild phenotypic alterations in hematopoietic cell populations and hemostasis. GnT-IVa/-IVb double deficiency completely abolished GnT-IV activity that resulted in the disappearance of the GlcNAcβ1-4 branch on the Manα1-3 arm that was confirmed by MALDI-TOF MS and GC-MS linkage analyses. Comprehensive glycomic analyses revealed that the abundance of terminal moieties was preserved in GnT-IVa/-IVb double deficiency that was due to the elevated expression of glycosyltransferases regarding synthesis of terminal moieties. Thereby, this may maintain the expression of glycan ligands for endogenous lectins and prevent cellular dysfunctions. The fact that the phenotype of GnT-IVa/-IVb double deficiency largely overlapped that of GnT-IVa single deficiency can be attributed to the induced glycomic compensation. This is the first report that mammalian organs have highly organized glycomic compensation systems to preserve N-glycan branch complexity. PMID:20015870

The importance of Foxp3 antibody and fixation/permeabilization buffer combinations in identifying CD4+CD25+Foxp3+ regulatory T cells.

PubMed

Law, Jacqueline P; Hirschkorn, Dale F; Owen, Rachel E; Biswas, Hope H; Norris, Philip J; Lanteri, Marion C

2009-12-01

Foxp3 is a key marker for CD4(+) regulatory T cells (T(regs)) and was used in developing a multiparameter flow cytometric panel to identify T(regs). Achieving reproducible staining and analysis first required optimization of Foxp3 staining. We present a comparative study of PCH101, 236A/E7, 3G3, 206D, 150D, and 259D/C7 clones of anti-human-Foxp3 antibodies used in combination with five different fixation/permeabilization buffers. Staining for CD25, CD152, and CD127 was also compared between fixation/permeabilization treatments. Promising antibody/buffer combinations were tested in a panel of peripheral blood mononuclear cells from 10 individuals, and then on fresh versus frozen cells from four individuals. Finally, different fluorochromes coupled to two representative antibodies were compared to optimize separation of Foxp3(+) from Foxp3(-) events. Foxp3 gates were set using two gating strategies based on CD127(+)CD25(-) "non-T(regs)" or based on isotype controls. For Foxp3 staining, the best conditions for fixation/permeabilization were obtained using the eBioscience Foxp3, Imgenex, BioLegend, and BD Foxp3 buffers. Comparing results from 10 subjects, 259D/C7, PCH101, 236A/E7, and 206D antibodies yielded statistically higher levels of Foxp3 cells than those by 150D and 3G3 antibodies (mean = 6.9, 5.1, 4.7, and 3.7% compared with 1.7, and 0.3% of CD25(+)Foxp3(+) events within CD4(+) cells, respectively). Importantly, the "nonspecificity" of some antibodies observed with a Foxp3 gate based on isotype controls could be eliminated by setting the Foxp3 gate on "non-T(regs)". Better separation of Foxp3(+) and Foxp3(-) populations was observed using the PCH101 clone coupled to Alexa647 compared with FITC or the 259D/C7 clone coupled to PE compared with Alexa488 fluorochrome. Foxp3 staining can be highly variable and depends on the choice of antibody/buffer pair and the fluorochrome used. Selecting the correct population for setting the Foxp3 gate is critical to avoid including non-T(regs) in the Foxp3(+) gate. The experiments presented here will aid in optimization of flow cytometry staining panels to quantify T(reg) frequencies in humans.

Physiological and transcriptional approaches reveal connection between nitrogen and manganese cycles in Shewanella algae C6G3.

PubMed

Aigle, Axel; Bonin, Patricia; Iobbi-Nivol, Chantal; Méjean, Vincent; Michotey, Valérie

2017-03-20

To explain anaerobic nitrite/nitrate production at the expense of ammonium mediated by manganese oxide (Mn(IV)) in sediment, nitrate and manganese respirations were investigated in a strain (Shewanella algae C6G3) presenting these features. In contrast to S. oneidensis MR-1, a biotic transitory nitrite accumulation at the expense of ammonium was observed in S. algae during anaerobic growth with Mn(IV) under condition of limiting electron acceptor, concomitantly, with a higher electron donor stoichiometry than expected. This low and reproducible transitory accumulation is the result of production and consumption since the strain is able to dissimilative reduce nitrate into ammonium. Nitrite production in Mn(IV) condition is strengthened by comparative expression of the nitrate/nitrite reductase genes (napA, nrfA, nrfA-2), and rates of the nitrate/nitrite reductase activities under Mn(IV), nitrate or fumarate conditions. Compared with S. oneidensis MR-1, S. algae contains additional genes that encode nitrate and nitrite reductases (napA-α and nrfA-2) and an Outer Membrane Cytochrome (OMC)(mtrH). Different patterns of expression of the OMC genes (omcA, mtrF, mtrH and mtrC) were observed depending on the electron acceptor and growth phase. Only gene mtrF-2 (SO1659 homolog) was specifically expressed under the Mn(IV) condition. Nitrate and Mn(IV) respirations seem connected at the physiological and transcriptional levels.

Physiological and transcriptional approaches reveal connection between nitrogen and manganese cycles in Shewanella algae C6G3

NASA Astrophysics Data System (ADS)

Aigle, Axel; Bonin, Patricia; Iobbi-Nivol, Chantal; Méjean, Vincent; Michotey, Valérie

2017-03-01

To explain anaerobic nitrite/nitrate production at the expense of ammonium mediated by manganese oxide (Mn(IV)) in sediment, nitrate and manganese respirations were investigated in a strain (Shewanella algae C6G3) presenting these features. In contrast to S. oneidensis MR-1, a biotic transitory nitrite accumulation at the expense of ammonium was observed in S. algae during anaerobic growth with Mn(IV) under condition of limiting electron acceptor, concomitantly, with a higher electron donor stoichiometry than expected. This low and reproducible transitory accumulation is the result of production and consumption since the strain is able to dissimilative reduce nitrate into ammonium. Nitrite production in Mn(IV) condition is strengthened by comparative expression of the nitrate/nitrite reductase genes (napA, nrfA, nrfA-2), and rates of the nitrate/nitrite reductase activities under Mn(IV), nitrate or fumarate conditions. Compared with S. oneidensis MR-1, S. algae contains additional genes that encode nitrate and nitrite reductases (napA-α and nrfA-2) and an Outer Membrane Cytochrome (OMC)(mtrH). Different patterns of expression of the OMC genes (omcA, mtrF, mtrH and mtrC) were observed depending on the electron acceptor and growth phase. Only gene mtrF-2 (SO1659 homolog) was specifically expressed under the Mn(IV) condition. Nitrate and Mn(IV) respirations seem connected at the physiological and transcriptional levels.

Expression of the rat CD26 antigen (dipeptidyl peptidase IV) on subpopulations of rat lymphocytes.

PubMed

Gorrell, M D; Wickson, J; McCaughan, G W

1991-04-15

The T cell activation antigen CD26 has been recently identified as the cell surface ectopeptidase dipeptidyl peptidase IV (DPP-IV). DPP-IV is found on many cell types, including lymphocytes, epithelial cells, and certain endothelial cells. The MRC OX61 monoclonal antibody (MAb) which specifically recognises rat DPP-IV was used to examine the expression of CD26/DPP-IV on rat lymphocytes. The molecular nature of the antigen was examined by immunoprecipitation from thymocytes, splenocytes, and hepatocytes. Analysis by one- and two-dimensional gel electrophoresis indicated that the native form of CD26 includes a 220-kDa homodimer. On tissue sections MRC OX61 MAb stained nearly all thymocytes and in the spleen and lymph nodes predominantly stained the T cell areas. However, in immunofluorescence experiments OX61 stained 80 to 87% of lymph node cells and 78 to 85% of spleen cells. Furthermore, two-colour immunofluorescence analysis of the CD4+, CD8+, and Ig+ lymphocyte subsets indicated that only 2 to 5% of each of these subsets lacked OX61 staining. Spleen cells and thymocytes of both CD4+ and CD8+ subsets stained much more intensely with OX61 after these cells were stimulated with phytohemagglutinin. These findings indicate that rat CD26 antigen expression is not confined to the T cell population as has been suggested, but also occurs on B cells, and is increased on T cells following their activation.

Physiological and transcriptional approaches reveal connection between nitrogen and manganese cycles in Shewanella algae C6G3

PubMed Central

Aigle, Axel; Bonin, Patricia; Iobbi-Nivol, Chantal; Méjean, Vincent; Michotey, Valérie

2017-01-01

To explain anaerobic nitrite/nitrate production at the expense of ammonium mediated by manganese oxide (Mn(IV)) in sediment, nitrate and manganese respirations were investigated in a strain (Shewanella algae C6G3) presenting these features. In contrast to S. oneidensis MR-1, a biotic transitory nitrite accumulation at the expense of ammonium was observed in S. algae during anaerobic growth with Mn(IV) under condition of limiting electron acceptor, concomitantly, with a higher electron donor stoichiometry than expected. This low and reproducible transitory accumulation is the result of production and consumption since the strain is able to dissimilative reduce nitrate into ammonium. Nitrite production in Mn(IV) condition is strengthened by comparative expression of the nitrate/nitrite reductase genes (napA, nrfA, nrfA-2), and rates of the nitrate/nitrite reductase activities under Mn(IV), nitrate or fumarate conditions. Compared with S. oneidensis MR-1, S. algae contains additional genes that encode nitrate and nitrite reductases (napA-α and nrfA-2) and an Outer Membrane Cytochrome (OMC)(mtrH). Different patterns of expression of the OMC genes (omcA, mtrF, mtrH and mtrC) were observed depending on the electron acceptor and growth phase. Only gene mtrF-2 (SO1659 homolog) was specifically expressed under the Mn(IV) condition. Nitrate and Mn(IV) respirations seem connected at the physiological and transcriptional levels. PMID:28317859