Genome-wide genetic homogeneity between sexes and populations for human height and body mass index.

PubMed

Yang, Jian; Bakshi, Andrew; Zhu, Zhihong; Hemani, Gibran; Vinkhuyzen, Anna A E; Nolte, Ilja M; van Vliet-Ostaptchouk, Jana V; Snieder, Harold; Esko, Tonu; Milani, Lili; Mägi, Reedik; Metspalu, Andres; Hamsten, Anders; Magnusson, Patrik K E; Pedersen, Nancy L; Ingelsson, Erik; Visscher, Peter M

2015-12-20

Sex-specific genetic effects have been proposed to be an important source of variation for human complex traits. Here we use two distinct genome-wide methods to estimate the autosomal genetic correlation (rg) between men and women for human height and body mass index (BMI), using individual-level (n = ∼44 000) and summary-level (n = ∼133 000) data from genome-wide association studies. Results are consistent and show that the between-sex genetic correlation is not significantly different from unity for both traits. In contrast, we find evidence of genetic heterogeneity between sexes for waist-hip ratio (rg = ∼0.7) and between populations for BMI (rg = ∼0.9 between Europe and the USA) but not for height. The lack of evidence for substantial genetic heterogeneity for body size is consistent with empirical findings across traits and species. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of ginseol k-g3, an Rg3-enriched fraction, on scopolamine-induced memory impairment and learning deficit in mice

PubMed Central

Peña, Ike dela; Yoon, Seo Young; Kim, Hee Jin; Park, Sejin; Hong, Eun Young; Ryu, Jong Hoon; Park, Il Ho; Cheong, Jae Hoon

2013-01-01

Background Although ginsenosides such as Rg1, Rb1 and Rg3 have shown promise as potential nutraceuticals for cognitive impairment, their use has been limited due to high production cost and low potency. In particular, the process of extracting pure Rg3 from ginseng is laborious and expensive. Methods We described the methods in preparing ginseol k-g3, an Rg3-enriched fraction, and evaluated its effects on scopolamine-induced memory impairment in mice. Results Ginseol k-g3 (25–200 mg/kg) significantly reversed scopolamine-induced cognitive impairment in the passive avoidance, but not in Y-maze testing. Ginseol k-g3 (50 and 200 mg/kg) improved escape latency in training trials and increased swimming times within the target zone of the Morris water maze. The effect of ginseol k-g3 on the water maze task was more potent than that of Rg3 or Red ginseng. Acute or subchronic (6 d) treatment of ginseol k-g3 did not alter normal locomotor activity of mice in an open field. Ginseol k-g3 did not inhibit acetylcholinesterase activity, unlike donezepil, an acetylcholinesterase inhibitor. Rg3 enrichment through the ginseol k-g3 fraction enhanced the efficacy of Rg3 in scopolamine-induced memory impairment in mice as demonstrated in the Morris water maze task. Conclusion The effects of ginseol k-g3 in ameliorating scopolamine-induced memory impairment in the passive avoidance and Morris water maze tests indicate its specific influence on reference or long-term memory. The mechanism underlying the reversal of scopolamine-induced amnesia by ginseol k-g3 is not yet known, but is not related to anticholinesterase-like activity. PMID:24558303

Defining a Contemporary Ischemic Heart Disease Genetic Risk Profile Using Historical Data.

PubMed

Mosley, Jonathan D; van Driest, Sara L; Wells, Quinn S; Shaffer, Christian M; Edwards, Todd L; Bastarache, Lisa; McCarty, Catherine A; Thompson, Will; Chute, Christopher G; Jarvik, Gail P; Crosslin, David R; Larson, Eric B; Kullo, Iftikhar J; Pacheco, Jennifer A; Peissig, Peggy L; Brilliant, Murray H; Linneman, James G; Denny, Josh C; Roden, Dan M

2016-12-01

Continued reductions in morbidity and mortality attributable to ischemic heart disease (IHD) require an understanding of the changing epidemiology of this disease. We hypothesized that we could use genetic correlations, which quantify the shared genetic architectures of phenotype pairs and extant risk factors from a historical prospective study to define the risk profile of a contemporary IHD phenotype. We used 37 phenotypes measured in the ARIC study (Atherosclerosis Risk in Communities; n=7716, European ancestry subjects) and clinical diagnoses from an electronic health record (EHR) data set (n=19 093). All subjects had genome-wide single-nucleotide polymorphism genotyping. We measured pairwise genetic correlations (rG) between the ARIC and EHR phenotypes using linear mixed models. The genetic correlation estimates between the ARIC risk factors and the EHR IHD were modestly linearly correlated with hazards ratio estimates for incident IHD in ARIC (Pearson correlation [r]=0.62), indicating that the 2 IHD phenotypes had differing risk profiles. For comparison, this correlation was 0.80 when comparing EHR and ARIC type 2 diabetes mellitus phenotypes. The EHR IHD phenotype was most strongly correlated with ARIC metabolic phenotypes, including total:high-density lipoprotein cholesterol ratio (rG=-0.44, P=0.005), high-density lipoprotein (rG=-0.48, P=0.005), systolic blood pressure (rG=0.44, P=0.02), and triglycerides (rG=0.38, P=0.02). EHR phenotypes related to type 2 diabetes mellitus, atherosclerotic, and hypertensive diseases were also genetically correlated with these ARIC risk factors. The EHR IHD risk profile differed from ARIC and indicates that treatment and prevention efforts in this population should target hypertensive and metabolic disease. © 2016 American Heart Association, Inc.

[Genetic-statistical analysis of environmental and genetic influences on the outcome of the juvenile and breeding performance tests for behaviour traits in Hovawart dogs].

PubMed

Boenigk, Katharina; Hamann, Henning; Distl, Ottmar

2006-01-01

The objective of the present study was to evaluate the importance of genetic and environmental sources of variation for results of behaviour tests recorded at juvenile and breeding performance tests in the Hovawart dog. For these analyses behaviour test results of 1882 (juvenile evaluation), respectively 929 dogs (breeding performance test) born in 1995 to 2000 had been used. Variance component estimation was performed for the traits appearance, play instinct, hunting affinity, group of people, shoot, acoustical and optical influences and temperament using multivariate linear animal models and Residual Maximum Likelihood (REML). The models included test-year-season, sex, litter size, age and inbreeding coefficient of the animal as fixed effects. Additive genetic effects of the animal, permanent environmental effect of the litter and the effect of the kennel were considered as random factors. The sex of the dog was significant for appearance, play instinct, hunting affinity, acoustical and optical influences of juvenile evaluation and for the traits temperament, play instinct, hunting affinity, acoustical and one of the optical influences of breeding performance test. The age of the dog at test significantly influenced the traits play instinct, hunting affinity and acoustical influences of juvenile evaluation and optical influences and hunting affinity of breeding performance test. All traits with exception of hunting affinity and group of people were significantly affected by the test-year-season. The inbreeding coefficient was significant for appearance of juvenile evaluation and play affinity of breeding performance test. The effect litter size did not influence any of the traits significantly. The estimated heritabilities for the behaviour traits of juvenile and breeding performance test ranged from h2 = 0.01 to h2 = 0.13, respectively h2 = 0.01 to h2 = 0.14, with standard errors of up to 0.03. The additive genetic correlations between most of the traits were moderately to highly positive (r(g) = 0.20 to r(g) = 1.0, respectively r(g) = 0.29 to r(g) = 1.0). Negative additive genetic correlations were only found for a few traits of juvenile (r(g) = -0.02 to r(g) = -0.58) and breeding performance test (r(g) = -0.28 to r(g) = -0.83). Progress in breeding for the behaviour traits investigated here may only be meaningful when information from all relatives is used in an animal model instead of selection based on the phenotype of the single animal.

Chicken meat quality: genetic variability and relationship with growth and muscle characteristics

PubMed Central

Le Bihan-Duval, Elisabeth; Debut, Martine; Berri, Cécile M; Sellier, Nadine; Santé-Lhoutellier, Véronique; Jégo, Yves; Beaumont, Catherine

2008-01-01

Background The qualitative properties of the meat are of major importance for poultry breeding, since meat is now widely consumed as cuts or as processed products. The aim of this study was to evaluate the genetic parameters of several breast meat quality traits and their genetic relationships with muscle characteristics in a heavy commercial line of broilers. Results Significant levels of heritability (averaging 0.3) were obtained for breast meat quality traits such as pH at 15 min post-slaughter, ultimate pH (pHu), color assessed by lightness L*, redness a* and yellowness b*, drip loss, thawing-cooking loss and shear-force. The rate of decrease in pH early post-mortem and the final pH of the meat were shown to be key factors of chicken meat quality. In particular, a decrease in the final pH led to paler, more exudative and tougher breast meat. The level of glycogen stored in breast muscle estimated by the Glycolytic Potential (GP) at slaughter time was shown to be highly heritable (h2 0.43). There was a very strong negative genetic correlation (rg) with ultimate meat pH (rg -0.97), suggesting a common genetic control for GP and pHu. While breast muscle weight was genetically positively correlated with fiber size (rg 0.76), it was negatively correlated with the level of glycogen stored in the muscle (rg -0.58), and as a consequence it was positively correlated with the final pH of the meat (rg 0.84). Conclusion This genetic study confirmed that selection should be useful to improve meat characteristics of meat-type chickens without impairing profitability because no genetic conflict was detected between meat quality and meat quantity. Moreover, the results suggested relevant selection criteria such as ultimate pH, which is strongly related to color, water-holding capacity and texture of the meat in this heavy chicken line. PMID:18706119

Novel use of a N2-specific enzyme-linked immunosorbent assay for differentiation of infected from vaccinated animals (DIVA)-based identification of avian influenza.

PubMed

Kwon, Ji-Sun; Kim, Min-Chul; Jeong, Ok-Mi; Kang, Hyun-Mi; Song, Chang-Seon; Kwon, Jun-Hun; Lee, Youn-Jeong

2009-05-21

Proper vaccination with validated companion differentiation of infected from vaccinated animals (DIVA) tests using a vaccine containing a heterologous neuraminidase to the field virus can be effective to control avian influenza (AI). However, indirect immunofluorescent assay, the only field validated DIVA test, has limitations to be set up as high throughput screening test and the assay requires subjective interpretation of the results. To apply the DIVA strategy to the Korean H9N2 low pathogenic AI (LPAI) vaccine program and overcome these limitations, we generated a reassortant H9N8 virus (rgH9N8) vaccine using plasmid-based reverse genetics and developed a novel N2-specific enzyme-linked immunosorbent assay (N2-ELISA). The rgH9N8 vaccine showed adequate immunogenicity and protection, and the optimized N2-ELISA showed that the sensitivity was 97.0% and specificity was 96.4% compared with a hemagglutination inhibition test. In vaccination-challenge experiments in specific pathogen-free chickens, the sera of chickens vaccinated with rgH9N8 vaccine and uninfected were negative by the N2-ELISA (S/P< or =0.4), whereas infected sera with H9N2 were positive (S/P>0.4). These results suggest that the rgH9N8 vaccine and the companion DIVA test, N2-ELISA, allow the utilization of the DIVA strategy for the control of H9N2 LPAI infections in Korea.

Estimation of the Proportion of Variation Accounted for by DNA Tests. I: Genetic Variance

USDA-ARS?s Scientific Manuscript database

The proportion of genetic variation accounted for (Rg2) is an important characteristic of a DNA test. For each of 3 levels of narrow sense heritability of the observed trait (h2gy) and 4 levels of Rg2, 500 independent replicates of an observed trait and a molecular breeding value (MBV) for 1000 offs...

Ginsenoside Rg3 increases nitric oxide production via increases in phosphorylation and expression of endothelial nitric oxide synthase: Essential roles of estrogen receptor-dependent PI3-kinase and AMP-activated protein kinase

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

Hien, Tran Thi; Kim, Nak Doo; Pokharel, Yuba Raj

2010-08-01

We previously showed that ginsenosides increase nitric oxide (NO) production in vascular endothelium and that ginsenoside Rg3 (Rg3) is the most active one among ginseng saponins. However, the mechanism for Rg3-mediated nitric oxide production is still uncertain. In this study, we determined whether Rg3 affects phosphorylation and expression of endothelial nitric oxide synthase (eNOS) in ECV 304 human endothelial cells. Rg3 increased both the phosphorylation and the expression of eNOS in a concentration-dependent manner and a maximal effect was found at 10 {mu}g/ml of Rg3. The enzyme activities of phosphatidylinositol 3-kinase (PI3-kinase), c-Jun N-terminal kinase (JNK), and p38 kinase weremore » enhanced as were estrogen receptor (ER)- and glucocorticoid receptor (GR)-dependent reporter gene transcriptions in Rg3-treated endothelial cells. Rg3-induced eNOS phosphorylation required the ER-mediated PI3-kinase/Akt pathway. Moreover, Rg3 activates AMP-activated protein kinase (AMPK) through up-regulation of CaM kinase II and Rg3-stimulated eNOS phosphorylation was reversed by AMPK inhibition. The present results provide a mechanism for Rg3-stimulated endothelial NO production.« less

Phenotypic dissection of bone mineral density reveals skeletal site specificity and facilitates the identification of novel loci in the genetic regulation of bone mass attainment.

PubMed

Kemp, John P; Medina-Gomez, Carolina; Estrada, Karol; St Pourcain, Beate; Heppe, Denise H M; Warrington, Nicole M; Oei, Ling; Ring, Susan M; Kruithof, Claudia J; Timpson, Nicholas J; Wolber, Lisa E; Reppe, Sjur; Gautvik, Kaare; Grundberg, Elin; Ge, Bing; van der Eerden, Bram; van de Peppel, Jeroen; Hibbs, Matthew A; Ackert-Bicknell, Cheryl L; Choi, Kwangbom; Koller, Daniel L; Econs, Michael J; Williams, Frances M K; Foroud, Tatiana; Zillikens, M Carola; Ohlsson, Claes; Hofman, Albert; Uitterlinden, André G; Davey Smith, George; Jaddoe, Vincent W V; Tobias, Jonathan H; Rivadeneira, Fernando; Evans, David M

2014-06-01

Heritability of bone mineral density (BMD) varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we estimated the genetic (rg) and residual (re) correlations between BMD measured at the upper limbs (UL-BMD), lower limbs (LL-BMD) and skull (SK-BMD), using total-body DXA scans of ∼ 4,890 participants recruited by the Avon Longitudinal Study of Parents and their Children (ALSPAC). Point estimates of rg indicated that appendicular sites have a greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.78) between them, than with the skull (UL-/SK-BMD rg = 0.58 and LL-/SK-BMD rg = 0.43). Likewise, the residual correlation between BMD at appendicular sites (r(e) = 0.55) was higher than the residual correlation between SK-BMD and BMD at appendicular sites (r(e) = 0.20-0.24). To explore the basis for the observed differences in rg and re, genome-wide association meta-analyses were performed (n ∼ 9,395), combining data from ALSPAC and the Generation R Study identifying 15 independent signals from 13 loci associated at genome-wide significant level across different skeletal regions. Results suggested that previously identified BMD-associated variants may exert site-specific effects (i.e. differ in the strength of their association and magnitude of effect across different skeletal sites). In particular, variants at CPED1 exerted a larger influence on SK-BMD and UL-BMD when compared to LL-BMD (P = 2.01 × 10(-37)), whilst variants at WNT16 influenced UL-BMD to a greater degree when compared to SK- and LL-BMD (P = 2.31 × 10(-14)). In addition, we report a novel association between RIN3 (previously associated with Paget's disease) and LL-BMD (rs754388: β = 0.13, SE = 0.02, P = 1.4 × 10(-10)). Our results suggest that BMD at different skeletal sites is under a mixture of shared and specific genetic and environmental influences. Allowing for these differences by performing genome-wide association at different skeletal sites may help uncover new genetic influences on BMD.

DC-SIGN mediates avian H5N1 influenza virus infection in cis and in trans

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

Wang, S.-F.; Huang, Jason C.; AIDS Prevention and Research Center, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan

2008-09-05

DC-SIGN, a C-type lectin receptor expressed in dendritic cells (DCs), has been identified as a receptor for human immunodeficiency virus type 1, hepatitis C virus, Ebola virus, cytomegalovirus, dengue virus, and the SARS coronavirus. We used H5N1 pseudotyped and reverse-genetics (RG) virus particles to study their ability to bind with DC-SIGN. Electronic microscopy and functional assay results indicate that pseudotyped viruses containing both HA and NA proteins express hemagglutination and are capable of infecting cells expressing {alpha}-2,3-linked sialic acid receptors. Results from a capture assay show that DC-SIGN-expressing cells (including B-THP-1/DC-SIGN and T-THP-1/DC-SIGN) and peripheral blood dendritic cells are capablemore » of transferring H5N1 pseudotyped and RG virus particles to target cells; this action can be blocked by anti-DC-SIGN monoclonal antibodies. In summary, (a) DC-SIGN acts as a capture or attachment molecule for avian H5N1 virus, and (b) DC-SIGN mediates infections in cis and in trans.« less

Phenotypic and Genetic Correlations of Feed Efficiency Traits with Growth and Carcass Traits in Nellore Cattle Selected for Postweaning Weight.

PubMed

Ceacero, Thais Matos; Mercadante, Maria Eugênia Zerlotti; Cyrillo, Joslaine Noely Dos Santos Gonçalves; Canesin, Roberta Carrilho; Bonilha, Sarah Figueiredo Martins; de Albuquerque, Lucia Galvão

2016-01-01

This study evaluated phenotypic (rph) and genetic correlations (rg) between 8 feed efficiency traits and other traits of economic interest including weight at selection (WS), loin-eye area (LEA), backfat thickness (BF), and rump fat thickness (RF) in Nellore cattle. Feed efficiency traits were gain:feed, residual feed intake (RFI), residual feed intake adjusted for backfat thickness (RFIb) and for backfat and rump fat thickness (RFIsf), residual body weight gain (RG), residual intake and body weight gain (RIG), and residual intake and body weight gain using RFIb (RIGb) and RFIsf (RIGsf). The variance components were estimated by the restricted maximum likelihood method using a two-trait animal model. The heritability estimates (h2) were 0.14, 0.24, 0.20, 0.22, 0.19, 0.15, 0.11 and 0.11 for gain:feed, RFI, RFIb, RFIsf, RG, RIG, RIGb and RIGsf, respectively. All rph values between traits were close to zero, except for the correlation of feed efficiency traits with dry matter intake and average daily gain. High rg values were observed for the correlation of dry matter intake, average daily gain and metabolic weight with WS and hip height (>0.61) and low to medium values (0.15 to 0.48) with the carcass traits (LEA, BF, RF). Among the feed efficiency traits, RG showed the highest rg with WS and hip height (0.34 and 0.25) and the lowest rg with subcutaneous fat thickness (-0.17 to 0.18). The rg values of RFI, RFIb and RFIsf with WS (0.17, 0.23 and 0.22), BF (0.37, 0.33 and 0.33) and RF (0.30, 0.31 and 0.32) were unfavorable. The rg values of gain:feed, RIG, RIGb and RIGsf with WS were low and favorable (0.07 to 0.22), while medium and unfavorable (-0.22 to -0.45) correlations were observed with fat thickness. The inclusion of subcutaneous fat thickness in the models used to calculate RFI did not reduce the rg between these traits. Selecting animals for higher feed efficiency will result in little or no genetic change in growth and will decrease subcutaneous fat thickness in the carcass.

Antidepressant-like effects of ginsenoside Rg1 are due to activation of the BDNF signalling pathway and neurogenesis in the hippocampus

PubMed Central

Jiang, Bo; Xiong, Zhe; Yang, Jun; Wang, Wei; Wang, Yue; Hu, Zhuang-Li; Wang, Fang; Chen, Jian-Guo

2012-01-01

BACKGROUND AND PURPOSE Ginsenoside Rg1 (Rg1) is one of the major bioactive ingredients of Panax ginseng with little toxicity and has been shown to have neuroprotective effects. In this study, we investigated the antidepressant-like effect of Rg1 in models of depression in mice. EXPERIMENTAL APPROACH The effects of Rg1 were assessed in the forced swimming test (FST) and tail suspension test (TST) in mice. Rg1 was also investigated in the chronic mild stress (CMS) mouse model of depression with imipramine as the positive control. Changes in hippocampal neurogenesis and spine density, the brain-derived neurotrophic factor (BDNF) signalling pathway, and serum corticosterone level after chronic stress and Rg1 treatment were then investigated. The tryptophan hydroxylase inhibitor and the tyrosine kinase B inhibitor were also used to explore the antidepressive mechanisms of Rg1. KEY RESULTS Ginsenoside Rg1 exhibited antidepressant-like activity in the FST and TST in mice without affecting locomotor activity. It was also effective in the CMS model of depression. Furthermore, Rg1 up-regulated the BDNF signalling pathway in the hippocampus and down-regulated serum corticosterone level during the CMS procedure. In addition, Rg1 was able to reverse the decrease in dendritic spine density and hippocampal neurogenesis caused by CMS. However, Rg1 had no discernable effect on the monoaminergic system. CONCLUSIONS AND IMPLICATIONS Our results provide the first evidence that Rg1 has antidepressant activity via activation of the BDNF signalling pathway and up-regulation of hippocampal neurogenesis. PMID:22335772

Pharmacology of RG W-2938: a cardiotonic agent with vasodilator activity.

PubMed

Barrett, J A; Woltmann, R F; Swillo, R S; Kasiewski, C; Faith, W C; Campbell, H F; Perrone, M H

1990-10-01

The cardiovascular effects of RG W-2938, 6-[6-(3,4-dihydro-3-methyl-2(1H)-2-oxoquinazolinyl)]-4,5-dihydro-3 (2H-pyridazinone, a new nonglycoside, noncatecholamine cardiotonic/vasodilator agent were examined in vivo in anesthetized and conscious dogs and in vitro in isolated guinea pig hearts; in the latter, RG W-2938 5 nmol-5 mumol increased contractility in a dose-related fashion. RG W-2938 30-300 micrograms/kg administered intravenously (i.v.) to anesthetized dogs increased contractile force while decreasing arterial pressure and total peripheral resistance (TPR) in a dose-related manner. Heart rate (HR) was only slightly increased, and aortic flow was not appreciably altered. A single oral dose of RG W-2938 0.3 mg/kg administered to conscious chronically instrumented dogs produced a marked and sustained increase in contractility 15-240 min after treatment while only slightly increasing HR. The effects of RG W-2938 30-300 micrograms/kg, i.v. were studied in a mecamylamine-propranolol-induced model of heart failure. RG W-2938 effectively reversed the drug-induced heart failure by increasing myocardial contractility and decreasing arterial pressure while only slightly affecting HR. These studies show that RG W-2938 is an orally effective positive inotropic/vasodilator agent.

Cross-protective efficacies of highly-pathogenic avian influenza H5N1 vaccines against a recent H5N8 virus.

PubMed

Park, Su-Jin; Si, Young-Jae; Kim, Jihye; Song, Min-Suk; Kim, Se-Mi; Kim, Eun-Ha; Kwon, Hyeok-Il; Kim, Young-Il; Lee, Ok-Jun; Shin, Ok Sarah; Kim, Chul-Joong; Shin, Eui-Cheol; Choi, Young Ki

2016-11-01

To investigate cross-protective vaccine efficacy of highly-pathogenic avian influenza H5N1 viruses against a recent HPAI H5N8 virus, we immunized C57BL/6 mice and ferrets with three alum-adjuvanted inactivated whole H5N1 vaccines developed through reverse-genetics (Rg): [Vietnam/1194/04xPR8 (clade 1), Korea/W149/06xPR8 (clade 2.2), and Korea/ES223N/03xPR8 (clade 2.5)]. Although relatively low cross-reactivities (10-40 HI titer) were observed against heterologous H5N8 virus, immunized animals were 100% protected from challenge with the 20 mLD50 of H5N8 virus, with the exception of mice vaccinated with 3.5μg of Rg Vietnam/1194/04xPR8. Of note, the Rg Korea/ES223N/03xPR8 vaccine provided not only effective protection, but also markedly inhibited viral replication in the lungs and nasal swabs of vaccine recipients within five days of HPAI H5N8 virus challenge. Further, we demonstrated that antibody-dependent cell-mediated cytotoxicity (ADCC) of an antibody-coated target cell by cytotoxic effector cells also plays a role in the heterologous protection of H5N1 vaccines against H5N8 challenge. Copyright © 2016 Elsevier Inc. All rights reserved.

The Impact of Risk Information Exposure on Women’s Beliefs about Direct-to-Consumer Genetic Testing for BRCA Mutations

PubMed Central

Gray, Stacy W.; Hornik, Robert C.; Schwartz, J. Sanford; Armstrong, Katrina

2011-01-01

Despite an increase in direct-to-consumer (DTC) genetic testing, little is known about how variations in website content might alter consumer behavior. We evaluated the impact of risk information provision on women’s attitudes about DTC BRCA testing. We conducted a randomized experiment; women viewed a “mock” BRCA testing website without (control group: CG) or with information on the potential risks of DTC testing (RG; framed two ways: unattributed information [UR] and information presented by experts [ER]). 767 women participated; mean age was 37 years, mean education was 15 years, and 79% of subjects were white. Women in the RG had less positive beliefs about DTC testing (mean RG=23.8, CG=25.2; p=0.001), lower intentions to get tested (RG= 2.8, CG= 3.1; p=0.03), were more likely to prefer clinic-based testing (RG=5.1, CG=4.8; p=0.03) and to report that they had seen enough risk information (RG=5.3, CG= 4.7; p<0.001). UR and ER exposure produced similar effects. Effects did not differ for women with or without a personal/family history of breast/ovarian cancer. Exposing women to the potential risks of DTC BRCA testing altered their beliefs, preferences, and intentions. Risk messages appear to be salient to women irrespective of their chance of having a BRCA mutation. PMID:21992449

Time-Reversal Based Range Extension Technique for Ultra-Wideband (UWB) Sensors and Applications in Tactical Communications and Networking

DTIC Science & Technology

2009-07-16

Frequency (MHz) Figure 3.4: CABLE SMA/SMA 24" RG-316DS. CABLE SMA PLUG-PLUG HF -.086 8" 3.1. TRANSMITTER IMPLEMENTATION 13 Length: 8.0" (203.2mm) Color...Gray RG Type: Hand Formable .086 Connector: Type SMA Male to SMA Male Features: Shielded "• JI Figure 3.5: CABLE SMA PLUG-PLUG HF -.086 8...34 . • CABLE SMA PLUG-PLUG HF -.141 8" Length: 8.0" (203.2mm) Color: Gray RG Type: Hand Formable .141 14 CHAPTER 3. 2 BY I MISO SYSTEM DEVELOPMENT

In vitro and in vivo evidence of a potential A(H1N1)pdm09 antigenic drift mediated by escape mutations in the haemagglutinin Sa antigenic site.

PubMed

Retamal, Miguel; Abed, Yacine; Rhéaume, Chantal; Baz, Mariana; Boivin, Guy

2017-06-01

Influenza A(H1N1)pdm09 virus continues to circulate worldwide without evidence of significant antigenic drift between 2009 and 2016. By using escape mutants, we previously identified six haemagglutinin (HA) changes (T80R, G143E, G158E, N159D, K166E and A198E) that were located within antigenic sites. Combinations of these mutations were introduced into the A(H1N1)pdm09 HA plasmid by mutagenesis. Reassortant 6 : 2 viruses containing both the HA and NA genes of the A(H1N1)pdm09 and the six internal gene segments of A/PR/8/34 were rescued by reverse genetics. In vitro, HA inhibition and microneutralization assays showed that the HA hexa-mutant reassortant virus (RG1) escaped A(H1N1)pdm09 hyper-immune ferret antiserum recognition. C57Black/6 mice that received the vaccine formulated with A/California/07/09 were challenged with 2×104 p.f.u. of either the 6 : 2 wild-type (WT) or RG1 viruses. Reductions in body weight loss, mortality rate and lung viral titre were observed in immunized animals challenged with the 6 : 2 WT virus compared to non-immunized mice. However, immunization did not protect mice challenged with RG1 virus. To further characterize the mutations causing this antigenic change, 11 additional RG viruses whose HA gene contained single or combinations of mutations were evaluated in vitro. Although the RG1 virus was still the least reactive against hyper-immune serum by HAI testing, mutations G158E and N159D within the Sa antigenic site appeared to play the major role in the altered antigenicity of the A(H1N1)pdm09 virus. These results show that the Sa antigenic site contains the most prominent epitopes susceptible to cause an antigenic drift, escaping actual vaccine protection.

Critical research gaps and recommendations to inform research prioritisation for more effective prevention and improved outcomes in colorectal cancer.

PubMed

Lawler, Mark; Alsina, Deborah; Adams, Richard A; Anderson, Annie S; Brown, Gina; Fearnhead, Nicola S; Fenwick, Stephen W; Halloran, Stephen P; Hochhauser, Daniel; Hull, Mark A; Koelzer, Viktor H; McNair, Angus G K; Monahan, Kevin J; Näthke, Inke; Norton, Christine; Novelli, Marco R; Steele, Robert J C; Thomas, Anne L; Wilde, Lisa M; Wilson, Richard H; Tomlinson, Ian

2018-01-01

Colorectal cancer (CRC) leads to significant morbidity/mortality worldwide. Defining critical research gaps (RG), their prioritisation and resolution, could improve patient outcomes. RG analysis was conducted by a multidisciplinary panel of patients, clinicians and researchers (n=71). Eight working groups (WG) were constituted: discovery science; risk; prevention; early diagnosis and screening; pathology; curative treatment; stage IV disease; and living with and beyond CRC. A series of discussions led to development of draft papers by each WG, which were evaluated by a 20-strong patient panel. A final list of RGs and research recommendations (RR) was endorsed by all participants. Fifteen critical RGs are summarised below: RG1 : Lack of realistic models that recapitulate tumour/tumour micro/macroenvironment; RG2 : Insufficient evidence on precise contributions of genetic/environmental/lifestyle factors to CRC risk; RG3 : Pressing need for prevention trials; RG4 : Lack of integration of different prevention approaches; RG5 : Lack of optimal strategies for CRC screening; RG6 : Lack of effective triage systems for invasive investigations; RG7 : Imprecise pathological assessment of CRC; RG8 : Lack of qualified personnel in genomics, data sciences and digital pathology; RG9 : Inadequate assessment/communication of risk, benefit and uncertainty of treatment choices; RG10 : Need for novel technologies/interventions to improve curative outcomes; RG11 : Lack of approaches that recognise molecular interplay between metastasising tumours and their microenvironment; RG12 : Lack of reliable biomarkers to guide stage IV treatment; RG13 : Need to increase understanding of health related quality of life (HRQOL) and promote residual symptom resolution; RG14 : Lack of coordination of CRC research/funding; RG15 : Lack of effective communication between relevant stakeholders. Prioritising research activity and funding could have a significant impact on reducing CRC disease burden over the next 5 years. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Critical research gaps and recommendations to inform research prioritisation for more effective prevention and improved outcomes in colorectal cancer

PubMed Central

Lawler, Mark; Alsina, Deborah; Adams, Richard A; Anderson, Annie S; Brown, Gina; Fearnhead, Nicola S; Fenwick, Stephen W; Hochhauser, Daniel; Koelzer, Viktor H; McNair, Angus G K; Norton, Christine; Novelli, Marco R; Steele, Robert J C; Thomas, Anne L; Wilde, Lisa M; Wilson, Richard H

2018-01-01

Objective Colorectal cancer (CRC) leads to significant morbidity/mortality worldwide. Defining critical research gaps (RG), their prioritisation and resolution, could improve patient outcomes. Design RG analysis was conducted by a multidisciplinary panel of patients, clinicians and researchers (n=71). Eight working groups (WG) were constituted: discovery science; risk; prevention; early diagnosis and screening; pathology; curative treatment; stage IV disease; and living with and beyond CRC. A series of discussions led to development of draft papers by each WG, which were evaluated by a 20-strong patient panel. A final list of RGs and research recommendations (RR) was endorsed by all participants. Results Fifteen critical RGs are summarised below: RG1: Lack of realistic models that recapitulate tumour/tumour micro/macroenvironment; RG2: Insufficient evidence on precise contributions of genetic/environmental/lifestyle factors to CRC risk; RG3: Pressing need for prevention trials; RG4: Lack of integration of different prevention approaches; RG5: Lack of optimal strategies for CRC screening; RG6: Lack of effective triage systems for invasive investigations; RG7: Imprecise pathological assessment of CRC; RG8: Lack of qualified personnel in genomics, data sciences and digital pathology; RG9: Inadequate assessment/communication of risk, benefit and uncertainty of treatment choices; RG10: Need for novel technologies/interventions to improve curative outcomes; RG11: Lack of approaches that recognise molecular interplay between metastasising tumours and their microenvironment; RG12: Lack of reliable biomarkers to guide stage IV treatment; RG13: Need to increase understanding of health related quality of life (HRQOL) and promote residual symptom resolution; RG14: Lack of coordination of CRC research/funding; RG15: Lack of effective communication between relevant stakeholders. Conclusion Prioritising research activity and funding could have a significant impact on reducing CRC disease burden over the next 5 years. PMID:29233930

Heritable influences on amygdala and orbitofrontal cortex contribute to genetic variation in core dimensions of personality

PubMed Central

Lewis, G.J.; Panizzon, M.S.; Eyler, L.; Fennema-Notestine, C.; Chen, C.-H.; Neale, M.C.; Jernigan, T.L.; Lyons, M.J.; Dale, A.M.; Kremen, W.S.; Franz, C.E.

2015-01-01

While many studies have reported that individual differences in personality traits are genetically influenced, the neurobiological bases mediating these influences have not yet been well characterized. To advance understanding concerning the pathway from genetic variation to personality, here we examined whether measures of heritable variation in neuroanatomical size in candidate regions (amygdala and medial orbitofrontal cortex) were associated with heritable effects on personality. A sample of 486 middle-aged (mean = 55 years) male twins (complete MZ pairs = 120; complete DZ pairs = 84) underwent structural brain scans and also completed measures of two core domains of personality: positive and negative emotionality. After adjusting for estimated intracranial volume, significant phenotypic (rp) and genetic (rg) correlations were observed between left amygdala volume and positive emotionality (rp = .16, p < .01; rg = .23, p < .05, respectively). In addition, after adjusting for mean cortical thickness, genetic and nonshared-environmental correlations (re) between left medial orbitofrontal cortex thickness and negative emotionality were also observed (rg = .34, p < .01; re = −.19, p < .05, respectively). These findings support a model positing that heritable bases of personality are, at least in part, mediated through individual differences in the size of brain structures, although further work is still required to confirm this causal interpretation. PMID:25263286

Genetic correlations between body weight change and reproduction traits in Merino ewes depend on age.

PubMed

Rose, G; Mulder, H A; van der Werf, J H J; Thompson, A N; van Arendonk, J A M

2014-08-01

Merino sheep in Australia experience periods of variable feed supply. Merino sheep can be bred to be more resilient to this variation by losing less BW when grazing poor quality pasture and gaining more BW when grazing good quality pasture. Therefore, selection on BW change might be economically attractive but correlations with other traits in the breeding objective need to be known. The genetic correlations (rg) between BW, BW change, and reproduction were estimated using records from approximately 7,350 fully pedigreed Merino ewes managed at Katanning in Western Australia. Number of lambs and total weight of lambs born and weaned were measured on approximately 5,300 2-yr-old ewes, approximately 4,900 3-yr-old ewes, and approximately 3,600 4-yr-old ewes. On a proportion of these ewes BW change was measured: approximately 1,950 2-yr-old ewes, approximately 1,500 3-yr-old ewes, and approximately 1,100 4-yr-old ewes. The BW measurements were for 3 periods. The first period was during mating period over 42 d on poor pasture. The second period was during pregnancy over 90 d for ewes that got pregnant on poor and medium quality pasture. The third period was during lactation over 130 d for ewes that weaned a lamb on good quality pasture. Genetic correlations between weight change and reproduction were estimated within age classes. Genetic correlations were tested to be significantly greater magnitude than 0 using likelihood ratio tests. Nearly all BW had significant positive genetic correlations with all reproduction traits. In 2-yr-old ewes, BW change during the mating period had a positive genetic correlation with number of lambs weaned (rg = 0.58); BW change during pregnancy had a positive genetic correlation with total weight of lambs born (rg = 0.33) and a negative genetic correlation with number of lambs weaned (rg = -0.49). All other genetic correlations were not significantly greater magnitude than 0 but estimates of genetic correlations for 3-yr-old ewes were generally consistent with these findings. The direction of the genetic correlations mostly coincided with the energy requirements of the ewes and the stage of maturity of the ewes. In conclusion, optimized selection strategies on BW changes to increase resilience will depend on the genetic correlations with reproduction and are dependent on age.

Ginsenoside Rg3 up-regulates the expression of vascular endothelial growth factor in human dermal papilla cells and mouse hair follicles.

PubMed

Shin, Dae Hyun; Cha, Youn Jeong; Yang, Kyeong Eun; Jang, Ik-Soon; Son, Chang-Gue; Kim, Bo Hyeon; Kim, Jung Min

2014-07-01

Crude Panax ginseng has been documented to possess hair growth activity and is widely used to treat alopecia, but the effects of ginsenoside Rg3 on hair growth have not to our knowledge been determined. The aim of the current study was to identify the molecules through which Rg3 stimulates hair growth. The thymidine incorporation for measuring cell proliferation was determined. We used DNA microarray analysis to measure gene expression levels in dermal papilla (DP) cells upon treatment with Rg3. The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) in human DP cells were measured by real-time polymerase chain reaction and immunohistochemistry, respectively. We also used immunohistochemistry assays to detect in vivo changes in VEGF and 3-stemness marker expressions in mouse hair follicles. Reverse transcription polymerase chain reaction showed dose-dependent increases in VEGF mRNA levels on treatment with Rg3. Immunohistochemical analysis showed that expression of VEGF was significantly up-regulated by Rg3 in a dose-dependent manner in human DP cells and in mouse hair follicles. In addition, the CD8 and CD34 were also up-regulated by Rg3 in the mouse hair follicles. It may be concluded that Rg3 might increase hair growth through stimulation of hair follicle stem cells and it has the potential to be used in hair growth products. Copyright © 2013 John Wiley & Sons, Ltd.

Inhibitory effect of ginsenoside Rg1 on extracellular matrix production via extracellular signal-regulated protein kinase/activator protein 1 pathway in nasal polyp-derived fibroblasts.

PubMed

Cho, Jung-Sun; Moon, You-Mi; Um, Ji-Young; Moon, Jun-Hyeok; Park, Il-Ho; Lee, Heung-Man

2012-06-01

Nasal polyps are associated with chronic inflammation of the sinonasal mucosa and are involved in myofibroblast differentiation and extracellular matrix (ECM) accumulation. Ginsenoside Rg1, a compound derived from Panax ginseng, shows antifibrotic and anticancer effects. However, the molecular effects of Rg1 on myofibroblast differentiation and ECM production remain unknown. The aims of this study were to investigate the effect of Rg1 on transforming growth factor (TGF)-β1-induced myofibroblast differentiation and ECM production and to determine the molecular mechanism of Rg1 in nasal polyp-derived fibroblasts (NPDFs). NPDFs were isolated from nasal polyps of seven patients who had chronic rhinosinusitis with nasal polyp. NPDFs were exposed to TGF-β1 with or without Rg1. Expression levels of α-smooth muscle actin (SMA), fibronectin and collagen type Iα1 were determined by reverse transcription polymerase chain reaction, Western blot and immunofluorescent staining. TGF-β1 signaling molecules, including Smad2/3, extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 were analyzed by Western blotting. Transcription factors involved with TGF-β1 signaling, nuclear factor (NF)-κB and activator protein 1 (AP-1) were also assessed by Western blot. The cytotoxic effect of Rg1 was measured by an established viability assay. The mRNA and protein expression levels of α-SMA, fibronectin and collagen type Iα1 were increased in TGF-β1-induced NPDFs. Rg1 inhibited these effects. The inhibitory molecular mechanism of Rg1 was involved in the ERK pathway. Rg1 inhibited the transcription factor activation of AP-1. Rg1 itself was not cytotoxic. The ginsenoside Rg1 has inhibitory effects on myofibroblast differentiation and ECM production. The inhibitory mechanism of Rg1 is involved with the ERK and AP-1 signaling pathways. Rg1 may be useful as an inhibitor of ECM deposition, and has potential to be used as a novel treatment option for nasal polyps.

New insights into the endophenotypic status of cognition in bipolar disorder: genetic modelling study of twins and siblings.

PubMed

Georgiades, Anna; Rijsdijk, Fruhling; Kane, Fergus; Rebollo-Mesa, Irene; Kalidindi, Sridevi; Schulze, Katja K; Stahl, Daniel; Walshe, Muriel; Sahakian, Barbara J; McDonald, Colm; Hall, Mei-Hua; Murray, Robin M; Kravariti, Eugenia

2016-06-01

Twin studies have lacked statistical power to apply advanced genetic modelling techniques to the search for cognitive endophenotypes for bipolar disorder. To quantify the shared genetic variability between bipolar disorder and cognitive measures. Structural equation modelling was performed on cognitive data collected from 331 twins/siblings of varying genetic relatedness, disease status and concordance for bipolar disorder. Using a parsimonious AE model, verbal episodic and spatial working memory showed statistically significant genetic correlations with bipolar disorder (rg = |0.23|-|0.27|), which lost statistical significance after covarying for affective symptoms. Using an ACE model, IQ and visual-spatial learning showed statistically significant genetic correlations with bipolar disorder (rg = |0.51|-|1.00|), which remained significant after covarying for affective symptoms. Verbal episodic and spatial working memory capture a modest fraction of the bipolar diathesis. IQ and visual-spatial learning may tap into genetic substrates of non-affective symptomatology in bipolar disorder. © The Royal College of Psychiatrists 2016.

Genetic and Environmental Influences on Sleep, Pain, and Depression Symptoms in a Community Sample of Twins.

PubMed

Gasperi, Marianna; Herbert, Matthew; Schur, Ellen; Buchwald, Dedra; Afari, Niloofar

We used quantitative genetic methods to evaluate whether sleep quality, pain, and depression symptoms share a common genetic diathesis, to estimate the genetic and environmental sources of covariance among these symptoms, and to test for possible causal relationships. A community sample of 400 twins from the University of Washington Twin Registry completed standardized self-report questionnaires. We used biometric modeling to assess genetic and environmental contribution to the association between sleep quality measured by the Pittsburgh Sleep Quality Index, pain measured by the Brief Pain Inventory, and depression symptoms measured by the Brief Symptom Inventory. Trivariate Cholesky structural equation models were used to decompose correlations among the phenotypes. Heritability was estimated at 37% (95% confidence interval = 20%-51%) for sleep quality, 25% (9%-41%) for pain, and 39% (22%-53%) for depression. Nonshared environmental influences accounted for the remaining variance. The genetic correlation between sleep quality and pain had an rg value of .69 (95% confidence interval [CI] = 0.33-0.97), rg value of .56 (95% CI = 0.55-0.98) between pain and depression, and rg value of .61 (95% CI = 0.44-0.88) between depression and sleep quality. Nonshared environmental overlap was present between pain and sleep quality as well as depression and sleep quality. The link between sleep quality, pain, and depression was primarily explained by shared genetic influences. The genetic factors influencing sleep quality and pain were highly correlated even when accounting for depression. Findings support the hypothesis of a genetic link between depression and pain as well as potential causality for the association of sleep quality with pain and depression.

Improved Inflammatory Balance of Human Skeletal Muscle during Exercise after Supplementations of the Ginseng-Based Steroid Rg1

PubMed Central

Hou, Chien-Wen; Lee, Shin-Da; Kao, Chung-Lan; Cheng, I-Shiung; Lin, Yu-Nan; Chuang, Sheng-Ju; Chen, Chung-Yu; Ivy, John L.; Huang, Chih-Yang; Kuo, Chia-Hua

2015-01-01

The purpose of the study was to determine the effect of ginseng-based steroid Rg1 on TNF-alpha and IL-10 gene expression in human skeletal muscle against exercise challenge, as well as on its ergogenic outcomes. Randomized double-blind placebo-controlled crossover trials were performed, separated by a 4-week washout. Healthy young men were randomized into two groups and received capsule containing either 5 mg of Rg1 or Placebo one night and one hour before exercise. Muscle biopsies were conducted at baseline, immediately and 3 h after a standardized 60-min cycle ergometer exercise. While treatment differences in glycogen depletion rate of biopsied quadriceps muscle during exercise did not reach statistical significance, Rg1 supplementations enhanced post-exercise glycogen replenishment and increased citrate synthase activity in the skeletal muscle 3 h after exercise, concurrent with improved meal tolerance during recovery (P<0.05). Rg1 suppressed the exercise-induced increases in thiobarbituric acids reactive substance (TBARS) and reversed the increased TNF-alpha and decreased IL-10 mRNA of quadriceps muscle against the exercise challenge. PGC-1 alpha and GLUT4 mRNAs of exercised muscle were not affected by Rg1. Maximal aerobic capacity (VO2max) was not changed by Rg1. However, cycling time to exhaustion at 80% VO2max increased significantly by ~20% (P<0.05). Conclusion: Our result suggests that Rg1 is an ergogenic component of ginseng, which can minimize unwanted lipid peroxidation of exercised human skeletal muscle, and attenuate pro-inflammatory shift under exercise challenge. PMID:25617625

Improved inflammatory balance of human skeletal muscle during exercise after supplementations of the ginseng-based steroid Rg1.

PubMed

Hou, Chien-Wen; Lee, Shin-Da; Kao, Chung-Lan; Cheng, I-Shiung; Lin, Yu-Nan; Chuang, Sheng-Ju; Chen, Chung-Yu; Ivy, John L; Huang, Chih-Yang; Kuo, Chia-Hua

2015-01-01

The purpose of the study was to determine the effect of ginseng-based steroid Rg1 on TNF-alpha and IL-10 gene expression in human skeletal muscle against exercise challenge, as well as on its ergogenic outcomes. Randomized double-blind placebo-controlled crossover trials were performed, separated by a 4-week washout. Healthy young men were randomized into two groups and received capsule containing either 5 mg of Rg1 or Placebo one night and one hour before exercise. Muscle biopsies were conducted at baseline, immediately and 3 h after a standardized 60-min cycle ergometer exercise. While treatment differences in glycogen depletion rate of biopsied quadriceps muscle during exercise did not reach statistical significance, Rg1 supplementations enhanced post-exercise glycogen replenishment and increased citrate synthase activity in the skeletal muscle 3 h after exercise, concurrent with improved meal tolerance during recovery (P<0.05). Rg1 suppressed the exercise-induced increases in thiobarbituric acids reactive substance (TBARS) and reversed the increased TNF-alpha and decreased IL-10 mRNA of quadriceps muscle against the exercise challenge. PGC-1 alpha and GLUT4 mRNAs of exercised muscle were not affected by Rg1. Maximal aerobic capacity (VO2max) was not changed by Rg1. However, cycling time to exhaustion at 80% VO2max increased significantly by ~20% (P<0.05). Our result suggests that Rg1 is an ergogenic component of ginseng, which can minimize unwanted lipid peroxidation of exercised human skeletal muscle, and attenuate pro-inflammatory shift under exercise challenge.

Drosophila mutants of the autism candidate gene neurobeachin (rugose) exhibit neuro-developmental disorders, aberrant synaptic properties, altered locomotion, and impaired adult social behavior and activity patterns.

PubMed

Wise, Alexandria; Tenezaca, Luis; Fernandez, Robert W; Schatoff, Emma; Flores, Julian; Ueda, Atsushi; Zhong, Xiaotian; Wu, Chun-Fang; Simon, Anne F; Venkatesh, Tadmiri

2015-01-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder in humans characterized by complex behavioral deficits, including intellectual disability, impaired social interactions, and hyperactivity. ASD exhibits a strong genetic component with underlying multigene interactions. Candidate gene studies have shown that the neurobeachin (NBEA) gene is disrupted in human patients with idiopathic autism ( Castermans et al., 2003 ). The NBEA gene spans the common fragile site FRA 13A and encodes a signal scaffold protein ( Savelyeva et al., 2006 ). In mice, NBEA has been shown to be involved in the trafficking and function of a specific subset of synaptic vesicles. ( Medrihan et al., 2009 ; Savelyeva et al., 2006 ). Rugose (rg) is the Drosophila homolog of the mammalian and human NBEA. Our previous genetic and molecular analyses have shown that rg encodes an A kinase anchor protein (DAKAP 550), which interacts with components of the epidermal growth factor receptor or EGFR and Notch-mediated signaling pathways, facilitating cross talk between these and other pathways ( Shamloula et al., 2002 ). We now present functional data from studies on the larval neuromuscular junction that reveal abnormal synaptic architecture and physiology. In addition, adult rg loss-of-function mutants exhibit defective social interactions, impaired habituation, aberrant locomotion, and hyperactivity. These results demonstrate that Drosophila NBEA (rg) mutants exhibit phenotypic characteristics reminiscent of human ASD and thus could serve as a genetic model for studying ASDs.

Genetics Home Reference: multiple familial trichoepithelioma

MedlinePlus

... 13. Citation on PubMed Bowen S, Gill M, Lee DA, Fisher G, Geronemus RG, Vazquez ME, Celebi JT. ... Fernandez-Figueras, Maria Tereza]. Citation on PubMed Lee DA, Grossman ME, Schneiderman P, Celebi JT. Genetics of ...

Genetics Home Reference: Brooke-Spiegler syndrome

MedlinePlus

... article on PubMed Central Bowen S, Gill M, Lee DA, Fisher G, Geronemus RG, Vazquez ME, Celebi JT. ... 124(5):919-20. Citation on PubMed Lee DA, Grossman ME, Schneiderman P, Celebi JT. Genetics of ...

The Tomato (Solanum Lycopersicum cv. Micro-Tom) Natural Genetic Variation Rg1 and the DELLA Mutant Procera Control the Competence Necessary to Form Adventitious Roots and Shoots

PubMed Central

Peres, Lázaro Eustáquio Pereira

2012-01-01

Despite the wide use of plant regeneration for biotechnological purposes, the signals that allow cells to become competent to assume different fates remain largely unknown. Here, it is demonstrated that the Regeneration1 (Rg1) allele, a natural genetic variation from the tomato wild relative Solanum peruvianum, increases the capacity to form both roots and shoots in vitro; and that the gibberellin constitutive mutant procera (pro) presented the opposite phenotype, reducing organogenesis on either root-inducing medium (RIM) or shoot-inducing medium (SIM). Mutants showing alterations in the formation of specific organs in vitro were the auxin low-sensitivity diageotropica (dgt), the lateral suppresser (ls), and the KNOX-overexpressing Mouse ears (Me). dgt failed to form roots on RIM, Me increased shoot formation on SIM, and the high capacity for in vitro shoot formation of ls contrasted with its recalcitrance to form axillary meristems. Interestingly, Rg1 rescued the in vitro organ formation capacity in proRg1 and dgtRg1 double mutants and the ex vitro low lateral shoot formation in pro and ls. Such epistatic interactions were also confirmed in gene expression and histological analyses conducted in the single and double mutants. Although Me phenocopied the high shoot formation of Rg1 on SIM, it failed to increase rooting on RIM and to rescue the non-branching phenotype of ls. Taken together, these results suggest REGENERATION1 and the DELLA mutant PROCERA as controlling a common competence to assume distinct cell fates, rather than the specific induction of adventitious roots or shoots, which is controlled by DIAGEOTROPICA and MOUSE EARS, respectively. PMID:22915742

The tomato (Solanum lycopersicum cv. Micro-Tom) natural genetic variation Rg1 and the DELLA mutant procera control the competence necessary to form adventitious roots and shoots.

PubMed

Lombardi-Crestana, Simone; da Silva Azevedo, Mariana; e Silva, Geraldo Felipe Ferreira; Pino, Lílian Ellen; Appezzato-da-Glória, Beatriz; Figueira, Antonio; Nogueira, Fabio Tebaldi Silveira; Peres, Lázaro Eustáquio Pereira

2012-09-01

Despite the wide use of plant regeneration for biotechnological purposes, the signals that allow cells to become competent to assume different fates remain largely unknown. Here, it is demonstrated that the Regeneration1 (Rg1) allele, a natural genetic variation from the tomato wild relative Solanum peruvianum, increases the capacity to form both roots and shoots in vitro; and that the gibberellin constitutive mutant procera (pro) presented the opposite phenotype, reducing organogenesis on either root-inducing medium (RIM) or shoot-inducing medium (SIM). Mutants showing alterations in the formation of specific organs in vitro were the auxin low-sensitivity diageotropica (dgt), the lateral suppresser (ls), and the KNOX-overexpressing Mouse ears (Me). dgt failed to form roots on RIM, Me increased shoot formation on SIM, and the high capacity for in vitro shoot formation of ls contrasted with its recalcitrance to form axillary meristems. Interestingly, Rg1 rescued the in vitro organ formation capacity in proRg1 and dgtRg1 double mutants and the ex vitro low lateral shoot formation in pro and ls. Such epistatic interactions were also confirmed in gene expression and histological analyses conducted in the single and double mutants. Although Me phenocopied the high shoot formation of Rg1 on SIM, it failed to increase rooting on RIM and to rescue the non-branching phenotype of ls. Taken together, these results suggest REGENERATION1 and the DELLA mutant PROCERA as controlling a common competence to assume distinct cell fates, rather than the specific induction of adventitious roots or shoots, which is controlled by DIAGEOTROPICA and MOUSE EARS, respectively.

The efficiency of genome-wide selection for genetic improvement of net merit.

PubMed

Togashi, K; Lin, C Y; Yamazaki, T

2011-10-01

Four methods of selection for net merit comprising 2 correlated traits were compared in this study: 1) EBV-only index (I₁), which consists of the EBV of both traits (i.e., traditional 2-trait BLUP selection); 2) GEBV-only index (I₂), which comprises the genomic EBV (GEBV) of both traits; 3) GEBV-assisted index (I₃), which combines both the EBV and the GEBV of both traits; and 4) GBV-assisted index (I₄), which combines both the EBV and the true genomic breeding value (GBV) of both traits. Comparisons of these indices were based on 3 evaluation criteria [selection accuracy, genetic response (ΔH), and relative efficiency] under 64 scenarios that arise from combining 2 levels of genetic correlation (r(G)), 2 ratios of genetic variances between traits, 2 ratios of the genomic variance to total genetic variances for trait 1, 4 accuracies of EBV, and 2 proportions of r(G) explained by the GBV. Both selection accuracy and genetic responses of the indices I₁, I₃, and I₄ increased as the accuracy of EBV increased, but the efficiency of the indices I₃ and I₄ relative to I₁ decreased as the accuracy of EBV increased. The relative efficiency of both I₃ and I₄ was generally greater when the accuracy of EBV was 0.6 than when it was 0.9, suggesting that the genomic markers are most useful to assist selection when the accuracy of EBV is low. The GBV-assisted index I₄ was superior to the GEBV-assisted I₃ in all 64 cases examined, indicating the importance of improving the accuracy of prediction of genomic breeding values. Other parameters being identical, increasing the genetic variance of a high heritability trait would increase the genetic response of the genomic indices (I₂, I₃, and I₄). The genetic responses to I₂, I₃, and I(4) was greater when the genetic correlation between traits was positive (r(G) = 0.5) than when it was negative (r(G) = -0.5). The results of this study indicate that the effectiveness of the GEBV-assisted index I₃ is affected by heritability of and genetic correlation between traits, the ratio of genetic variances between traits, the genomic-genetic variance ratio of each index trait, the proportion of genetic correlation accounted for by the genomic markers, and the accuracy of predictions of both EBV and GBV. However, most of these affecting factors are genetic characteristics of a population that is beyond the control of the breeders. The key factor subject to manipulation is to maximize both the proportion of the genetic variance explained by GEBV and the accuracy of both GEBV and EBV. The developed procedures provide means to investigate the efficiency of various genomic indices for any given combination of the genetic factors studied.

Genetic analysis of litter size, parturition length, and birth assistance requirements in primiparous sows using a joint linear-threshold animal model.

PubMed

Holm, B; Bakken, M; Vangen, O; Rekaya, R

2004-09-01

The aim of this study was to investigate whether selection for number of live born piglets has led to prolonged parturition and increased requirement for birth assistance, resulting in increased numbers of stillborn piglets. Data were collected from 6,718 primiparous Norwegian Landrace sows farrowing between 2001 and 2003. The need for birth assistance was recorded as a binary response. Physical intervention in the birth of piglets and/or hormonal treatment by the farmer was recorded as birth assistance. The duration of the parturition was analyzed as a binary trait (<4 h and >4 h). The statistical model used for analysis included contemporary groups of herd-year, litter breed, season of farrowing, parity in which the sow was born, a regression on the age of sow at farrowing, an additive genetic effect, and a service sire effect. A full Bayesian approach via Gibbs sampling was adopted to estimate the genetic relationships between these four traits. A total chain length of 100,000 iterations was run. The first 10,000 samples were discarded as burn-in, and the remaining 90,000 iterations were retained without thinning for post-Gibbs analysis. The highest direct heritability was estimated for the number of live-born piglets (h2 = 0.07), followed by the duration of farrowing (h2 = 0.05), the need for birth assistance (h2 = 0.05), and the number of stillborn piglets (h2 = 0.04). The genetic correlations revealed that the number of live and stillborn piglets was uncorrelated; however, the number of live piglets born had a moderate genetic correlation to the need for birth assistance (rg = 0.24 +/- 0.01) and duration of farrowing (rg = -0.20 +/- 0.01), whereas the number of stillborn piglets was highly correlated to the need for birth assistance (rg = 0.74 +/- 0.01) and the duration of parturition (rg = 0.66 +/- 0.01). The duration of farrowing and the need for birth assistance were genetically highly correlated (rg = 0.89 +/- 0.00). For all traits, the service sire variance was approximately one quarter in magnitude compared with its respective genetic variance. The results showed that selection for the number of live born piglets is not expected to influence the number of stillborn piglets. Increasing the number of live piglets born through selection should have a slight negative effect on farrowing duration and a minor increase in the need for birth assistance. Sows with a high genetic potential for birth assistance and prolonged parturition were more likely to give birth to greater numbers of stillborn piglets.

Dopamine D3 receptor gene locus: Association with schizophrenia, as well age of onset

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

Nimgsonkar, V.L.; Zhang, X.R.; Brar, J.S.

Genetic factors are clearly involved in the etiology of schizophrenia, but their specific nature is unknown. If the genetic etiology is multifactorial or polygenic, the role of specific genes as susceptibility factors can be directly evaluated by examining allelic variation at these loci among cases in comparison with controls. Two studies have independently demonstrated an association of schizophrenia with homozygosity at the dopamine D3 receptor gene (D3RG) locus, using a biallelic polymorphism in the first exon of D3RG. These results are important because D3RG is a favored candidate gene. Three other studies have identified associations among sub-groups of patients, butmore » the majority were negative. The present study involved patients with schizophrenia (DSM-III-R criteria) of Caucasian or African-American ethnicity (n=130). Two groups of controls, matched for ethnicity, were used: adults screened for schizophrenia (n=128) and unselected neonates (n=160). Multivariate analysis revealed an association between allele no. 1 homozygosity and schizophrenia in comparison with adult, but not neonatal controls. The association was most marked among Caucasian patients with a family history of schizophrenia (odds ratio 13.7, C.I. 1.8, 104.3). An association of the D3RG locus with age of onset (AOO) was also noted. The discrepancies in earlier studies may due to variations in control groups, differencies in mean AOO among different cohorts, or ethnic variations in susceptibility attributable to D3RG.« less

Preventive effects of ginsenoside Rg1 on post-traumatic stress disorder (PTSD)-like behavior in male C57/B6 mice.

PubMed

Wang, Zhongli; Zhu, Kexuan; Chen, Lin; Ou Yang, Liufeng; Huang, Yufang; Zhao, Yunan

2015-09-25

We investigated the preventive effects of Rg1 on a model of mouse post-traumatic stress disorder (PTSD) induced by electric shock combined with situation reminder and explored the underlying mechanism. In the experiment, before the PTSD animal model was developed, Rg1 (10, 5, and 2.5mg/kg) was orally administered for one week. After the animal model was established, PTSD-like behavior was observed using elevated plus maze, black and light box, and open field tests. One hour after the behavior test, all mice were sacrificed, and then serum corticosterone (CORT) and hypothalamus corticotrophin-releasing hormone (CRH) assays were performed. Results showed that Rg1 (5mg/kg) treatments relieved PTSD-like behavior by altering elevated serum corticosterone and hypothalamus CRH levels. By contrast, fluoxetine (3mg/kg) treatment reversed the behavior changes and had no effect on increased CORT and CRH levels. These findings confirmed the preventive effect of Rg1 in PTSD model. Decreasing CORT and CRH levels may be one of the underlying mechanisms. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The evolution of phenotypes and genetic parameters under preferential mating

PubMed Central

Roff, Derek A; Fairbairn, Daphne J

2014-01-01

This article extends and adds more realism to Lande's analytical model for evolution under mate choice by using individual-based simulations in which females sample a finite number of males and the genetic architecture of the preference and preferred trait evolves. The simulations show that the equilibrium heritabilities of the preference and preferred trait and the genetic correlation between them (rG), depend critically on aspects of the mating system (the preference function, mode of mate choice, choosiness, and number of potential mates sampled), the presence or absence of natural selection on the preferred trait, and the initial genetic parameters. Under some parameter combinations, preferential mating increased the heritability of the preferred trait, providing a possible resolution for the lek paradox. The Kirkpatrick–Barton approximation for rG proved to be biased downward, but the realized genetic correlations were also low, generally <0.2. Such low values of rG indicate that coevolution of the preference and preferred trait is likely to be very slow and subject to significant stochastic variation. Lande's model accurately predicted the incidence of runaway selection in the simulations, except where preferences were relative and the preferred trait was subject to natural selection. In these cases, runaways were over- or underestimated, depending on the number of males sampled. We conclude that rapid coevolution of preferences and preferred traits is unlikely in natural populations, but that the parameter combinations most conducive to it are most likely to occur in lekking species. PMID:25077025

Genome-wide associations for birth weight and correlations with adult disease

PubMed Central

Feenstra, Bjarke; van Zuydam, Natalie R; Gaulton, Kyle J; Grarup, Niels; Bradfield, Jonathan P; Strachan, David P; Li-Gao, Ruifang; Ahluwalia, Tarunveer S; Kreiner, Eskil; Rueedi, Rico; Lyytikäinen, Leo-Pekka; Cousminer, Diana L; Wu, Ying; Thiering, Elisabeth; Wang, Carol A; Have, Christian T; Hottenga, Jouke-Jan; Vilor-Tejedor, Natalia; Joshi, Peter K; Boh, Eileen Tai Hui; Ntalla, Ioanna; Pitkänen, Niina; Mahajan, Anubha; van Leeuwen, Elisabeth M; Joro, Raimo; Lagou, Vasiliki; Nodzenski, Michael; Diver, Louise A; Zondervan, Krina T; Bustamante, Mariona; Marques-Vidal, Pedro; Mercader, Josep M; Bennett, Amanda J; Rahmioglu, Nilufer; Nyholt, Dale R; Ma, Ronald Ching Wan; Tam, Claudia Ha Ting; Tam, Wing Hung; Ganesh, Santhi K; van Rooij, Frank JA; Jones, Samuel E; Loh, Po-Ru; Ruth, Katherine S; Tuke, Marcus A; Tyrrell, Jessica; Wood, Andrew R; Yaghootkar, Hanieh; Scholtens, Denise M; Paternoster, Lavinia; Prokopenko, Inga; Kovacs, Peter; Atalay, Mustafa; Willems, Sara M; Panoutsopoulou, Kalliope; Wang, Xu; Carstensen, Lisbeth; Geller, Frank; Schraut, Katharina E; Murcia, Mario; van Beijsterveldt, Catharina EM; Willemsen, Gonneke; Appel, Emil V R; Fonvig, Cilius E; Trier, Caecilie; Tiesler, Carla MT; Standl, Marie; Kutalik, Zoltán; Bonas-Guarch, Sílvia; Hougaard, David M; Sánchez, Friman; Torrents, David; Waage, Johannes; Hollegaard, Mads V; de Haan, Hugoline G; Rosendaal, Frits R; Medina-Gomez, Carolina; Ring, Susan M; Hemani, Gibran; McMahon, George; Robertson, Neil R; Groves, Christopher J; Langenberg, Claudia; Luan, Jian'an; Scott, Robert A; Zhao, Jing Hua; Mentch, Frank D; MacKenzie, Scott M; Reynolds, Rebecca M; Lowe, William L; Tönjes, Anke; Stumvoll, Michael; Lindi, Virpi; Lakka, Timo A; van Duijn, Cornelia M; Kiess, Wieland; Körner, Antje; Sørensen, Thorkild IA; Niinikoski, Harri; Pahkala, Katja; Raitakari, Olli T; Zeggini, Eleftheria; Dedoussis, George V; Teo, Yik-Ying; Saw, Seang-Mei; Melbye, Mads; Campbell, Harry; Wilson, James F; Vrijheid, Martine; de Geus, Eco JCN; Boomsma, Dorret I; Kadarmideen, Haja N; Holm, Jens-Christian; Hansen, Torben; Sebert, Sylvain; Hattersley, Andrew T; Beilin, Lawrence J; Newnham, John P; Pennell, Craig E; Heinrich, Joachim; Adair, Linda S; Borja, Judith B; Mohlke, Karen L; Eriksson, Johan G; Widén, Elisabeth E; Kähönen, Mika; Viikari, Jorma S; Lehtimäki, Terho; Vollenweider, Peter; Bønnelykke, Klaus; Bisgaard, Hans; Mook-Kanamori, Dennis O; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G; Pisinger, Charlotta; Pedersen, Oluf; Power, Christine; Hyppönen, Elina; Wareham, Nicholas J; Hakonarson, Hakon; Davies, Eleanor; Walker, Brian R; Jaddoe, Vincent WV; Jarvelin, Marjo-Riitta; Grant, Struan FA; Vaag, Allan A; Lawlor, Debbie A; Frayling, Timothy M; Davey Smith, George; Morris, Andrew P; Ong, Ken K; Felix, Janine F; Timpson, Nicholas J; Perry, John RB; Evans, David M; McCarthy, Mark I; Freathy, Rachel M

2016-01-01

Birth weight (BW) is influenced by both foetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease1. These lifecourse associations have often been attributed to the impact of an adverse early life environment. We performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where foetal genotype was associated with BW (P <5x10-8). Overall, ˜15% of variance in BW could be captured by assays of foetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (rg=-0.22, P =5.5x10-13), T2D (rg=-0.27, P =1.1x10-6) and coronary artery disease (rg=-0.30, P =6.5x10-9) and, in large cohort data sets, demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P =1.9x10-4). We have demonstrated that lifecourse associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and have highlighted some of the pathways through which these causal genetic effects are mediated. PMID:27680694

Genetic Risk Variants for Social Anxiety

PubMed Central

Stein, Murray B.; Chen, Chia-Yen; Jain, Sonia; Jensen, Kevin P.; He, Feng; Heeringa, Steven G.; Kessler, Ronald C.; Maihofer, Adam; Nock, Matthew K.; Ripke, Stephan; Sun, Xiaoying; Thomas, Michael L.; Ursano, Robert J.; Smoller, Jordan W.; Gelernter, Joel

2017-01-01

Social anxiety is a neurobehavioral trait characterized by fear and reticence in social situations. Twin studies have shown that social anxiety has a heritable basis, shared with neuroticism and extraversion, but genetic studies have yet to demonstrate robust risk variants. We conducted genomewide association analysis (GWAS) of subjects within the Army Study To Assess Risk and Resilience in Service members (Army STARRS) to (1) determine SNP-based heritability of social anxiety; (2) discern genetic risk loci for social anxiety; and (3) determine shared genetic risk with neuroticism and extraversion. GWAS were conducted within ancestral groups (EUR, AFR, LAT) using linear regression models for each of the 3 component studies in Army STARRS, and then meta-analyzed across studies. SNP-based heritability for social anxiety was significant (h2g=0.12, p=2.17×10-4 in EUR). One meta-analytically genomewide significant locus was seen in each of EUR (rs708012, Chr 6: BP 36965970, p = 1.55×10-8; beta = 0.073) and AFR (rs78924501, Chr 1: BP 88406905, p = 3.58×10-8; beta = 0.265) samples. Social anxiety in Army STARRS was significantly genetically correlated (negatively) with extraversion (rg = -0.52, se = 0.22, p = 0.02) but not with neuroticism (rg = 0.05, se = 0.22, p = 0.81) or with an anxiety disorder factor score (rg = 0.02, se = 0.32, p = 0.94) from external GWAS meta-analyses. This first GWAS of social anxiety confirms a genetic basis for social anxiety, shared with extraversion but possibly less so with neuroticism. PMID:28224735

Antioxidant properties of repaglinide and its protections against cyclosporine A-induced renal tubular injury

PubMed Central

Li, Dao; Li, Jin; Li, Hui; Wu, Qiong; Li, Qi-Xiong

2016-01-01

Objective(s): Repaglinide (RG) is an antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus. It has a good safety and efficacy profile in diabetic patients with complications in renal impairment and is an appropriate treatment choice, even for individuals with more severe degrees of renal malfunctions. The aim of the present study was to examine the protective effect of RG on cyclosporine A (CsA)-induced rat renal impairment and to evaluate the antioxidant mechanisms by which RG exerts its protective actions. Materials and Methods: Fifty male Sprague-Dawley rats weighing 250–300 g were randomly divided into five groups: administrations of olive oil (control, PO), RG (0.4 mg/kg, PO), CsA (30 mg/kg in olive oil, SC), RG (0.2 or 0.4 mg/kg, PO) plus CsA (30 mg/kg in olive oil SC) every day for 15 days. Results: SC administration of CsA (30 mg/kg) to rats produced marked elevations in the levels of renal impairment parameters such as urinary protein, N-acetyl-beta-D-glucosaminidase (NAG), serum creatinine (SCr), and blood urea nitrogen (BUN). It also caused histologic injury to the kidneys. Oral administration of RG (0.2 and 0.4 mg/kg) markedly decreased all the aforementioned changes. In addition, CsA caused increases in the levels of malondialdehyde (MDA) and decreases in superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSR), glutathione-S-transferase (GST), and glutathione in kidney homogenate, which were reversed significantly by both doses of RG. Conclusion: The findings of our study indicate that RG may play an important role in protecting the kidney from oxidative insult. PMID:27635199

Genetic Correlation Analysis Suggests Association between Increased Self-Reported Sleep Duration in Adults and Schizophrenia and Type 2 Diabetes.

PubMed

Byrne, Enda M; Gehrman, Philip R; Trzaskowski, Maciej; Tiemeier, Henning; Pack, Allan I

2016-10-01

We sought to examine how much of the heritability of self-report sleep duration is tagged by common genetic variation in populations of European ancestry and to test if the common variants contributing to sleep duration are also associated with other diseases and traits. We utilized linkage disequilibrium (LD)-score regression to estimate the heritability tagged by common single nucleotide polymorphisms (SNPs) in the CHARGE consortium genome-wide association study (GWAS) of self-report sleep duration. We also used bivariate LD-score regression to investigate the genetic correlation of sleep duration with other publicly available GWAS datasets. We show that 6% (SE = 1%) of the variance in self-report sleep duration in the CHARGE study is tagged by common SNPs in European populations. Furthermore, we find evidence of a positive genetic correlation (rG) between sleep duration and type 2 diabetes (rG = 0.26, P = 0.02), and between sleep duration and schizophrenia (rG = 0.19, P = 0.01). Our results show that increased sample sizes will identify more common variants for self-report sleep duration; however, the heritability tagged is small when compared to other traits and diseases. These results also suggest that those who carry variants that increase risk to type 2 diabetes and schizophrenia are more likely to report longer sleep duration. © 2016 Associated Professional Sleep Societies, LLC.

Modular Adder Designs Using Optimal Reversible and Fault Tolerant Gates in Field-Coupled QCA Nanocomputing

NASA Astrophysics Data System (ADS)

Bilal, Bisma; Ahmed, Suhaib; Kakkar, Vipan

2018-02-01

The challenges which the CMOS technology is facing toward the end of the technology roadmap calls for an investigation of various logical and technological solutions to CMOS at the nano scale. Two such paradigms which are considered in this paper are the reversible logic and the quantum-dot cellular automata (QCA) nanotechnology. Firstly, a new 3 × 3 reversible and universal gate, RG-QCA, is proposed and implemented in QCA technology using conventional 3-input majority voter based logic. Further the gate is optimized by using explicit interaction of cells and this optimized gate is then used to design an optimized modular full adder in QCA. Another configuration of RG-QCA gate, CRG-QCA, is then proposed which is a 4 × 4 gate and includes the fault tolerant characteristics and parity preserving nature. The proposed CRG-QCA gate is then tested to design a fault tolerant full adder circuit. Extensive comparisons of gate and adder circuits are drawn with the existing literature and it is envisaged that our proposed designs perform better and are cost efficient in QCA technology.

A novel pathogenic mechanism of highly pathogenic avian influenza H5N1 viruses involves hemagglutinin mediated resistance to serum innate inhibitors.

PubMed

Panaampon, Jutatip; Ngaosuwankul, Nathamon; Suptawiwat, Ornpreya; Noisumdaeng, Pirom; Sangsiriwut, Kantima; Siridechadilok, Bunpote; Lerdsamran, Hatairat; Auewarakul, Prasert; Pooruk, Phisanu; Puthavathana, Pilaipan

2012-01-01

In this study, the effect of innate serum inhibitors on influenza virus infection was addressed. Seasonal influenza A(H1N1) and A(H3N2), 2009 pandemic A(H1N1) (H1N1pdm) and highly pathogenic avian influenza (HPAI) A(H5N1) viruses were tested with guinea pig sera negative for antibodies against all of these viruses as evaluated by hemagglutination-inhibition and microneutralization assays. In the presence of serum inhibitors, the infection by each virus was inhibited differently as measured by the amount of viral nucleoprotein produced in Madin-Darby canine kidney cells. The serum inhibitors inhibited seasonal influenza A(H3N2) virus the most, while the effect was less in seasonal influenza A(H1N1) and H1N1pdm viruses. The suppression by serum inhibitors could be reduced by heat inactivation or treatment with receptor destroying enzyme. In contrast, all H5N1 strains tested were resistant to serum inhibitors. To determine which structure (hemagglutinin (HA) and/or neuraminidase (NA)) on the virus particles that provided the resistance, reverse genetics (rg) was applied to construct chimeric recombinant viruses from A/Puerto Rico/8/1934(H1N1) (PR8) plasmid vectors. rgPR8-H5 HA and rgPR8-H5 HANA were resistant to serum inhibitors while rgPR8-H5 NA and PR8 A(H1N1) parental viruses were sensitive, suggesting that HA of HPAI H5N1 viruses bestowed viral resistance to serum inhibition. These results suggested that the ability to resist serum inhibition might enable the viremic H5N1 viruses to disseminate to distal end organs. The present study also analyzed for correlation between susceptibility to serum inhibitors and number of glycosylation sites present on the globular heads of HA and NA. H3N2 viruses, the subtype with highest susceptibility to serum inhibitors, harbored the highest number of glycosylation sites on the HA globular head. However, this positive correlation cannot be drawn for the other influenza subtypes.

Pivotal Roles of Ginsenoside Rg3 in Tumor Apoptosis Through Regulation of Reactive Oxygen Species.

PubMed

Sun, Hwa Yeon; Lee, Jun Hee; Han, Yong-Seok; Yoon, Yeo Min; Yun, Chul Won; Kim, Jae Heon; Song, Yun Seob; Lee, Sang Hun

2016-09-01

Elevated production of reactive oxygen species (ROS) is observed in various cancer types and pathophysiological conditions. In cancer cells, ROS induce cell proliferation, genetic instability, and a malignant phenotype. Ginsenoside Rg3 is the main pharmacologically active component in ginseng and has been reported to have an antioxidant effect. To overcome lung cancer by regulating the ROS level, we investigated the antitumor effect and mechanism of Rg3 and its antioxidative property on Lewis lung carcinoma (LLC) cells. Inhibition of ROS was suppressed in LLC cells by Rg3 treatment, and these cells were used to investigate the antioxidant, antiproliferative, and antitumor effects in LLC cells. ROS production was increased in cells grown in serum-containing media (conditioned media) compared to those grown in serum-free media. The high level of ROS induced LLC cell proliferation, but treatment with Rg3 (200 ng/ml) resulted in reduction of ROS, leading to inhibition of cell proliferation. Treatment with Rg3 significantly reduced cyclin and cyclin-dependent kinase expression in LLC cells. Additionally, Rg3 treatment significantly suppressed activation of mitogen-activated protein kinases and induced LLC cell apoptosis through activation of pro-apoptotic proteins and suppression of anti-apoptotic proteins. Taken together, these findings demonstrate the role of Rg3 in reduction of the intracellular ROS level, attenuation of proliferation via augmentation of cell cycle- and cell proliferation-associated proteins, and activation of apoptosis through regulation of apoptosis-associated proteins in LLC. These findings suggest that Rg3 could be used as a therapeutic agent in lung cancer. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117)

PubMed Central

Clarke, T-K; Adams, M J; Davies, G; Howard, D M; Hall, L S; Padmanabhan, S; Murray, A D; Smith, B H; Campbell, A; Hayward, C; Porteous, D J; Deary, I J; McIntosh, A M

2017-01-01

Alcohol consumption has been linked to over 200 diseases and is responsible for over 5% of the global disease burden. Well-known genetic variants in alcohol metabolizing genes, for example, ALDH2 and ADH1B, are strongly associated with alcohol consumption but have limited impact in European populations where they are found at low frequency. We performed a genome-wide association study (GWAS) of self-reported alcohol consumption in 112 117 individuals in the UK Biobank (UKB) sample of white British individuals. We report significant genome-wide associations at 14 loci. These include single-nucleotide polymorphisms (SNPs) in alcohol metabolizing genes (ADH1B/ADH1C/ADH5) and two loci in KLB, a gene recently associated with alcohol consumption. We also identify SNPs at novel loci including GCKR, CADM2 and FAM69C. Gene-based analyses found significant associations with genes implicated in the neurobiology of substance use (DRD2, PDE4B). GCTA analyses found a significant SNP-based heritability of self-reported alcohol consumption of 13% (se=0.01). Sex-specific analyses found largely overlapping GWAS loci and the genetic correlation (rG) between male and female alcohol consumption was 0.90 (s.e.=0.09, P-value=7.16 × 10−23). Using LD score regression, genetic overlap was found between alcohol consumption and years of schooling (rG=0.18, s.e.=0.03), high-density lipoprotein cholesterol (rG=0.28, s.e.=0.05), smoking (rG=0.40, s.e.=0.06) and various anthropometric traits (for example, overweight, rG=−0.19, s.e.=0.05). This study replicates the association between alcohol consumption and alcohol metabolizing genes and KLB, and identifies novel gene associations that should be the focus of future studies investigating the neurobiology of alcohol consumption. PMID:28937693

Mechanisms of Bunyavirus Virulence: A Genetic Approach.

DTIC Science & Technology

1984-12-01

of canine parvovirus Type-2, feline panleukopenia virus and mink enteritis virus. Virology 129,401-414. Partner A., Webster, R. G., and Bean W. J...CM, and Webster RG. Procedures for the characterization of the genetic material of candidate vaccine strains. Develop Biol Standard 39:15-24, 1977

Effect of enzyme on extraction of ginsenoside Rb1 and Rg3 from Panax notoginseng roots

NASA Astrophysics Data System (ADS)

Phuong, Nguyen Tran Xuan; Thy, Lu Thi Mong; Khang, Nguyen Luu Vinh; My, Huynh Thi Kieu; Tam, Nguyen Le Phuong; Hieu, Nguyen Huu

2018-04-01

Panax notoginseng is distributed throughout the north and northwest of Vietnam, especially Ha Giang, Lao Cai, and Cao Bang provinces. The root of this plant contains ginsenosides (Rb1, Rb2, Rd, Rg3), flavonoids, polyacetylene, polysaccharides, amino acids, fatty acids, and peptides. In this study, the ratios of enzyme (Viscozyme, Termamyl, Cellulase), solvent of components, and time extraction were investigated. The results showed that the highest contents of Rb1 and Rg3 were achieved in the sample extracted with the ratio of enzymes V:C:T = 1:0:0, ethanol:water (60:40, v/v) as extracting solvent in 45 minutes. Then, conditions of high performance liquid chromatography with diode array detector method to determine the content of ginsenosides Rb1 and Rg3 in the roots of Panax notoginseng were studied, including wavelength, mobile phase, and flow rate. The separation was subjected on a reversed-phase C18 column using acetonitrile (A) and water (B) as mobile phase. The gradient elution was set as follow: 0-10 min, 15-25% A; 10-20 min, 25-30% A; 20-40 min, 30-60% A; 40-60 min, 60-80% A; and 60-65 min back to 15% A before the next injection, at a flow rate of 0.5 mL/min, and the wavelength was set at 202 nm. The linear range was from 298.59 to 696.72 µg/mL for Rb1 and from 8.19 to 19.10 µg/L for Rg3. The limits of detection for Rb1 and Rg3 obtained were 0.31 µg/mL and 0.33 µg/mL, respectively. The limits of quantification were 0.95 µg/mL and 1.01 µg/mL for Rb1 and Rg3, respectively. Consequently, the high performance liquid chromatography demonstrated the highly sensitive and accurate method for determination of Rb1 and Rg3 in Panax notoginseng.

Investigating genetic correlations and causal effects between caffeine consumption and sleep behaviours.

PubMed

Treur, Jorien L; Gibson, Mark; Taylor, Amy E; Rogers, Peter J; Munafò, Marcus R

2018-04-22

Observationally, higher caffeine consumption is associated with poorer sleep and insomnia. We investigated whether these associations are a result of shared genetic risk factors and/or (possibly bidirectional) causal effects. Summary-level data were available from genome-wide association studies on caffeine intake (n = 91 462), plasma caffeine and caffeine metabolic rate (n = 9876), sleep duration and chronotype (being a "morning" versus an "evening" person) (n = 128 266), and insomnia complaints (n = 113 006). First, genetic correlations were calculated, reflecting the extent to which genetic variants influencing caffeine consumption and those influencing sleep overlap. Next, causal effects were estimated with bidirectional, two-sample Mendelian randomization. This approach utilizes the genetic variants most robustly associated with an exposure variable as an "instrument" to test causal effects. Estimates from individual variants were combined using inverse-variance weighted meta-analysis, weighted median regression and MR-Egger regression. We found no clear evidence for a genetic correlation between caffeine intake and sleep duration (rg = 0.000, p = .998), chronotype (rg = 0.086, p = .192) or insomnia complaints (rg = -0.034, p = .700). For plasma caffeine and caffeine metabolic rate, genetic correlations could not be calculated because of the small sample size. Mendelian randomization did not support causal effects of caffeine intake on sleep, or vice versa. There was weak evidence that higher plasma caffeine levels causally decrease the odds of being a morning person. Although caffeine may acutely affect sleep when taken shortly before bedtime, our findings suggest that a sustained pattern of high caffeine consumption is more likely to be associated with poorer sleep through shared environmental factors. Future research should identify such environments, which could aid the development of interventions to improve sleep. © 2018 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.

Genetic evaluation of calf and heifer survival in Iranian Holstein cattle using linear and threshold models.

PubMed

Forutan, M; Ansari Mahyari, S; Sargolzaei, M

2015-02-01

Calf and heifer survival are important traits in dairy cattle affecting profitability. This study was carried out to estimate genetic parameters of survival traits in female calves at different age periods, until nearly the first calving. Records of 49,583 female calves born during 1998 and 2009 were considered in five age periods as days 1-30, 31-180, 181-365, 366-760 and full period (day 1-760). Genetic components were estimated based on linear and threshold sire models and linear animal models. The models included both fixed effects (month of birth, dam's parity number, calving ease and twin/single) and random effects (herd-year, genetic effect of sire or animal and residual). Rates of death were 2.21, 3.37, 1.97, 4.14 and 12.4% for the above periods, respectively. Heritability estimates were very low ranging from 0.48 to 3.04, 0.62 to 3.51 and 0.50 to 4.24% for linear sire model, animal model and threshold sire model, respectively. Rank correlations between random effects of sires obtained with linear and threshold sire models and with linear animal and sire models were 0.82-0.95 and 0.61-0.83, respectively. The estimated genetic correlations between the five different periods were moderate and only significant for 31-180 and 181-365 (r(g) = 0.59), 31-180 and 366-760 (r(g) = 0.52), and 181-365 and 366-760 (r(g) = 0.42). The low genetic correlations in current study would suggest that survival at different periods may be affected by the same genes with different expression or by different genes. Even though the additive genetic variations of survival traits were small, it might be possible to improve these traits by traditional or genomic selection. © 2014 Blackwell Verlag GmbH.

Genetic loci associated with heart rate variability and their effects on cardiac disease risk

PubMed Central

Nolte, Ilja M.; Munoz, M. Loretto; Tragante, Vinicius; Amare, Azmeraw T.; Jansen, Rick; Vaez, Ahmad; von der Heyde, Benedikt; Avery, Christy L.; Bis, Joshua C.; Dierckx, Bram; van Dongen, Jenny; Gogarten, Stephanie M.; Goyette, Philippe; Hernesniemi, Jussi; Huikari, Ville; Hwang, Shih-Jen; Jaju, Deepali; Kerr, Kathleen F.; Kluttig, Alexander; Krijthe, Bouwe P.; Kumar, Jitender; van der Laan, Sander W.; Lyytikäinen, Leo-Pekka; Maihofer, Adam X.; Minassian, Arpi; van der Most, Peter J.; Müller-Nurasyid, Martina; Nivard, Michel; Salvi, Erika; Stewart, James D.; Thayer, Julian F.; Verweij, Niek; Wong, Andrew; Zabaneh, Delilah; Zafarmand, Mohammad H.; Abdellaoui, Abdel; Albarwani, Sulayma; Albert, Christine; Alonso, Alvaro; Ashar, Foram; Auvinen, Juha; Axelsson, Tomas; Baker, Dewleen G.; de Bakker, Paul I. W.; Barcella, Matteo; Bayoumi, Riad; Bieringa, Rob J.; Boomsma, Dorret; Boucher, Gabrielle; Britton, Annie R.; Christophersen, Ingrid; Dietrich, Andrea; Ehret, George B.; Ellinor, Patrick T.; Eskola, Markku; Felix, Janine F.; Floras, John S.; Franco, Oscar H.; Friberg, Peter; Gademan, Maaike G. J.; Geyer, Mark A.; Giedraitis, Vilmantas; Hartman, Catharina A.; Hemerich, Daiane; Hofman, Albert; Hottenga, Jouke-Jan; Huikuri, Heikki; Hutri-Kähönen, Nina; Jouven, Xavier; Junttila, Juhani; Juonala, Markus; Kiviniemi, Antti M.; Kors, Jan A.; Kumari, Meena; Kuznetsova, Tatiana; Laurie, Cathy C.; Lefrandt, Joop D.; Li, Yong; Li, Yun; Liao, Duanping; Limacher, Marian C.; Lin, Henry J.; Lindgren, Cecilia M.; Lubitz, Steven A.; Mahajan, Anubha; McKnight, Barbara; zu Schwabedissen, Henriette Meyer; Milaneschi, Yuri; Mononen, Nina; Morris, Andrew P.; Nalls, Mike A.; Navis, Gerjan; Neijts, Melanie; Nikus, Kjell; North, Kari E.; O'Connor, Daniel T.; Ormel, Johan; Perz, Siegfried; Peters, Annette; Psaty, Bruce M.; Raitakari, Olli T.; Risbrough, Victoria B.; Sinner, Moritz F.; Siscovick, David; Smit, Johannes H.; Smith, Nicholas L.; Soliman, Elsayed Z.; Sotoodehnia, Nona; Staessen, Jan A.; Stein, Phyllis K.; Stilp, Adrienne M.; Stolarz-Skrzypek, Katarzyna; Strauch, Konstantin; Sundström, Johan; Swenne, Cees A.; Syvänen, Ann-Christine; Tardif, Jean-Claude; Taylor, Kent D.; Teumer, Alexander; Thornton, Timothy A.; Tinker, Lesley E.; Uitterlinden, André G.; van Setten, Jessica; Voss, Andreas; Waldenberger, Melanie; Wilhelmsen, Kirk C.; Willemsen, Gonneke; Wong, Quenna; Zhang, Zhu-Ming; Zonderman, Alan B.; Cusi, Daniele; Evans, Michele K.; Greiser, Halina K.; van der Harst, Pim; Hassan, Mohammad; Ingelsson, Erik; Järvelin, Marjo-Riitta; Kääb, Stefan; Kähönen, Mika; Kivimaki, Mika; Kooperberg, Charles; Kuh, Diana; Lehtimäki, Terho; Lind, Lars; Nievergelt, Caroline M.; O'Donnell, Chris J.; Oldehinkel, Albertine J.; Penninx, Brenda; Reiner, Alexander P.; Riese, Harriëtte; van Roon, Arie M.; Rioux, John D.; Rotter, Jerome I.; Sofer, Tamar; Stricker, Bruno H.; Tiemeier, Henning; Vrijkotte, Tanja G. M.; Asselbergs, Folkert W.; Brundel, Bianca J. J. M.; Heckbert, Susan R.; Whitsel, Eric A.; den Hoed, Marcel; Snieder, Harold; de Geus, Eco J. C.

2017-01-01

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (−0.74

A free VP3 C-terminus is essential for the replication of infectious bursal disease virus.

PubMed

Mosley, Yung-Yi C; Wu, Ching Ching; Lin, Tsang Long

2017-03-15

Green fluorescent protein (GFP) has been successfully incorporated into the viral-like particles of infectious bursal disease virus (IBDV) with a linker at the C-terminus of VP3 in a baculovirus system. However, when the same locus in segment A was used to express GFP by a reverse genetic (RG) system, no viable GFP-expressing IBDV was recovered. To elucidate the underlying mechanism, cDNA construct of segment A with only the linker sequence (9 amino acids) was applied to generate RG IBDV virus (rIBDV). Similarly, no rIBDV was recovered. Moreover, when the incubation after transfection was extended, wildtype rIBDV without the linker was recovered suggesting a free C-terminus of VP3 might be necessary for IBDV replication. On the other hand, rIBDV could be recovered when additional sequence (up to 40 nucleotides) were inserted at the 3' noncoding region (NCR) adjacent to the stop codon of VP3, suggesting that the burden of the linker sequence was not in the stretched genome size but the disruption of the VP3 function. Finally, when the stop codon of VP3 was deleted in segment A to extend the translation into the 3' NCR without introducing additional genomic sequence, no rIBDV was recovered. Our data suggest that a free VP3 C-terminus is essential for IBDV replication. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetic parameters for yearling weight, carcass traits, and primal-cut yields of Hanwoo cattle.

PubMed

Choi, T J; Alam, M; Cho, C I; Lee, J G; Park, B; Kim, S; Koo, Y; Roh, S H

2015-04-01

Genetic parameters associated with yearling weight, carcass traits, and primal-cut yields of male Hanwoo cattle were investigated using univariate and bivariate animal models. The mean yearling weight (YWT), carcass weight (CWT), longissimus muscle area (LMA), backfat thickness (BFT), and marbling score (MS) were 352.47 ± 0.40 kg, 337.39 ± 0.64 kg, 78.28 ± 0.13 cm2, 8.45 ± 0.05 mm, and 3.25 ± 0.03, respectively. Total primal-cut yield (TPC) was 78.95 ± 0.10% of CWT, of which 42.3% was contributed by the forequarters (chuck, CHK; shoulder, SLD; ribs, RIB; and brisket and flank, BAF). Loins, top round (TRND), and round (RND) were associated with yields of 13.57%, 5.45 ± 0.01%, and 8.87 ± 0.02%, respectively. The largest cut studied was ribs (15.67 ± 0.03%). The estimated heritabilities (h2) of YWT, CWT, LMA, BFT, and MS were 0.18 ± 0.02, 0.29 ± 0.04, 0.38 ± 0.05, 0.45 ± 0.05, and 0.62 ± 0.07, respectively. Shoulder yield was highly heritable in Hanwoo steers (0.83 ± 0.13), followed by the yields of round (0.66 ± 0.12), striploin (0.64 ± 0.12), top round (0.62 ± 0.12), sirloin (0.60 ± 0.12), and total primal-cut yield (0.52 ± 0.11). The h2 values of CHK, BAF, RIB, and tenderloin (TLN) ranged from 0.19 ± 0.09 to 0.41 ± 0.11. Generally, the genetic CV was low for most traits (2.33%-6.15%), except for CHK, BFT, and MS. The genetic correlation (rg) was strong between YWT and CWT (0.77 ± 0.06). The greatest positive and negative rg among carcass traits were those between LMA and CWT (0.52 ± 0.08) and between LMA and BFT (-0.30 ± 0.09), respectively. The correlation between CHK and SLD (0.81 ± 0.14), and those between SLD, TLN, TRND, and RND, were mostly strong (0.77-0.87), but the rg between RIB and other traits were strongly negative. The TPC yield showed moderate to high rg with most primal cuts. The YWT, CWT, and LMA correlated notably with CHK, SLD, and loin yields, especially LMA. However, BFT and MS were negatively correlated with many primal cuts but RIB. Those rg estimates were also opposite of that of LMA and CWT with primal cuts. Phenotypic correlations (rp) were generally weaker than rg estimates. The rp of YWT, CWT, and LMA were either zero or moderately negative compared to those of the BFT and MS with primal cuts. Most primal cuts yielded positive rp estimates among them, except for RIB. Our results suggest that direct selection for YWT, various carcass traits, and primal-cut yields may increase the carcass value of Hanwoo males.

The anti-diabetic effects of ethanol extract from two variants of Artemisia princeps Pampanini in C57BL/KsJ-db/db mice.

PubMed

Jung, U J; Baek, N-I; Chung, H-G; Bang, M-H; Yoo, J-S; Jeong, T S; Lee, K-T; Kang, Y J; Lee, M K; Kim, H J; Yeo, J Y; Choi, M S

2007-10-01

The anti-diabetic effects of two variants of Artemisia princeps Pampanini, sajabalssuk (SB) and sajuarissuk (SS), were investigated in type 2 diabetic animal using their ethanol extracts. Male C57BL/KsJ-db/db (db/db) mice were divided into control, SB ethanol extract (SBE), SS ethanol extract (SSE), or rosiglitazone (RG) groups and their age-matched littermates (db/+) were used. Supplementation of the SBE (0.171 g/100g diet), SSE (0.154 g/100g diet), and RG (0.005 g/100g diet) improved glucose and insulin tolerance and significantly lowered blood glycosylated hemoglobin levels, as compared to the control group. Plasma insulin, C-peptide and glucagon levels in db/db mice were higher in the db/+ mice, however these values were significantly lowered by SBE, SSE or RG-supplement. Hepatic GK activity was significantly lower in the db/db mice than in the db/+ mice, while hepatic G6Pase activity was vice versa. Supplementation of SBE, SSE and RG reversed these hepatic glucose-regulating enzyme activities. In addition, SBE and SSE markedly increased the hepatic glycogen content and muscle ratio as compared to the control group, but they did not alter the food intake, body weight and plasma leptin level. The RG group, however, showed a significant increase in the food intake, body weight and plasma leptin. These results suggest that SBE and SSE exert an anti-diabetic effect in type 2 diabetic mice.

The DcpS inhibitor RG3039 improves motor function in SMA mice

PubMed Central

Van Meerbeke, James P.; Gibbs, Rebecca M.; Plasterer, Heather L.; Miao, Wenyan; Feng, Zhihua; Lin, Ming-Yi; Rucki, Agnieszka A.; Wee, Claribel D.; Xia, Bing; Sharma, Shefali; Jacques, Vincent; Li, Darrick K.; Pellizzoni, Livio; Rusche, James R.; Ko, Chien-Ping; Sumner, Charlotte J.

2013-01-01

Spinal muscular atrophy (SMA) is caused by mutations of the survival motor neuron 1 (SMN1) gene, retention of the survival motor neuron 2 (SMN2) gene and insufficient expression of full-length survival motor neuron (SMN) protein. Quinazolines increase SMN2 promoter activity and inhibit the ribonucleic acid scavenger enzyme DcpS. The quinazoline derivative RG3039 has advanced to early phase clinical trials. In preparation for efficacy studies in SMA patients, we investigated the effects of RG3039 in severe SMA mice. Here, we show that RG3039 distributed to central nervous system tissues where it robustly inhibited DcpS enzyme activity, but minimally activated SMN expression or the assembly of small nuclear ribonucleoproteins. Nonetheless, treated SMA mice showed a dose-dependent increase in survival, weight and motor function. This was associated with improved motor neuron somal and neuromuscular junction synaptic innervation and function and increased muscle size. RG3039 also enhanced survival of conditional SMA mice in which SMN had been genetically restored to motor neurons. As this systemically delivered drug may have therapeutic benefits that extend beyond motor neurons, it could act additively with SMN-restoring therapies delivered directly to the central nervous system such as antisense oligonucleotides or gene therapy. PMID:23727836

Genetics Home Reference: idiopathic inflammatory myopathy

MedlinePlus

... MYOSITIS MYOSITIS Sources for This Page Chinoy H, Lamb JA, Ollier WE, Cooper RG. An update on ... Review. Citation on PubMed Chinoy H, Platt H, Lamb JA, Betteridge Z, Gunawardena H, Fertig N, Varsani ...

Reaction norm of fertility traits adjusted for protein and fat production level across lactations in Holstein cattle.

PubMed

Menendez-Buxadera, A; Carabaño, M J; Gonzalez-Recio, O; Cue, R I; Ugarte, E; Alenda, R

2013-07-01

A total of 304,001 artificial insemination outcomes in up to 7 lactations from 142,389 Holstein cows, daughters of 5,349 sires and 101,433 dams, calving between January 1995 and December 2007 in 1,347 herds were studied by a reaction norm model. The (co)variance components for days to first service (DFS), days open, nonreturn rate in the first service (NRFS), and number of services per conception were estimated by 6 models: 3 Legendre polynomial degrees for the genetic effects and adjustment or not for the level of fat plus protein (FP) production recorded at day closest to DFS. For all traits and type of FP adjustment, a second degree polynomial showed the best fit. The use of the adjusted FP model did not increase the level of genetic (co)variance components except for DFS. The heritability for each of the traits was low in general (0.03-0.10) and increased from the first to fourth calving; nevertheless, very important variability was found for the estimated breeding value (EBV) of the sires. The genetic correlations (rg) were close to unity between adjacent calvings, but decreased for most distant parities, ranging from rg=0.36 (for DFS) to rg=0.63 (for NRFS), confirming the existence of heterogeneous genetic (co)variance components and EBV across lactations. The results of the eigen decomposition of rg shows that the first eigenvalue explained between 82 to 92% and the second between 8 to 14% of the genetic variance for all traits; therefore, a deformation of the overall mean trajectory for reproductive performance across the trajectory of the different calving could be expected if selection favored these eigenfunctions. The results of EBV for the 50 best sires showed a substantial reranking and variation in the shape of response across lactations. The more important aspect to highlight, however, is the difference between the EBV of the same sires in different calvings, a characteristic known as plasticity, which is particularly important for DFS and NRFS. This component of fertility adds another dimension to selection for fertility that can be used to change the negative genetic progress of reproductive performance presented in this population of Holstein cows. The use of a reaction norm model should allow producers to obtain more robust cows for maintenance of fertility levels along the whole productive life of the cows. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Protective effects of geniposide and ginsenoside Rg1 combination treatment on rats following cerebral ischemia are mediated via microglial microRNA‑155‑5p inhibition.

PubMed

Wang, Jun; Li, Dan; Hou, Jincai; Lei, Hongtao

2018-02-01

Geniposide, an active component of Gardenia, has been reported to protect against cerebral ischemia in animals. Ginsenoside Rg1, a component of Panax notoginseng, is usually administered in combination with Gardenia for the treatment of acute ischemic stroke; however, there are unknown effects of ginsenoside Rg1 that require further investigation. In the present study, the effects of geniposide and ginsensoide Rg1 combination treatment on focal cerebral ischemic stroke were investigated. For in vivo analysis, male rats were separated into three groups, including the (control), model and geniposide + ginsenoside Rg1 groups (n=8 per group). A middle cerebral artery occlusion model was established as the model group. The treatment group was treated with geniposide (30 mg/kg, tail vein injection) + ginsenoside Rg1 (6 mg/kg, tail vein injection), and the model group received saline instead. Neurobehavioral deficits, infarct volume, brain edema, and the expression of microRNA (miR)‑155‑5p and CD11b by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and immunohistochemistry, were assessed following 24 h of ischemia. For in vitro analysis, BV2 mouse microglial cells were cultured and exposed to geniposide (40 µg/ml) + ginsenoside Rg1 (8 µg/ml) during various durations of oxygen‑glucose deprivation (OGD). The expression levels of miR‑155‑5p, pri‑miR‑155 and pre‑miR‑155 were detected by RT‑qPCR. The results demonstrated that increases in brain infarct volume, edema volume, CD11b‑positive cells and miR‑155‑5p levels were alleviated following geniposide + ginsenoside administration in rats exposed to ischemia. Furthermore, geniposide + ginsenoside Rg1 treatment suppressed the miR‑155‑5p, pri‑miR‑155 and pre‑miR‑155 expression levels in OGD‑injured BV2 microglial cells. The results of the present study demonstrated that tail vein administration of geniposide in combination with ginsenoside Rg1 protected against focal cerebral ischemia in rats through inhibition of microglial miR‑155‑5p following ischemic injury, which may serve as a novel therapeutic agent for the treatment of strokes.

Joint genomic evaluation of French dairy cattle breeds using multiple-trait models.

PubMed

Karoui, Sofiene; Carabaño, María Jesús; Díaz, Clara; Legarra, Andrés

2012-12-07

Using a multi-breed reference population might be a way of increasing the accuracy of genomic breeding values in small breeds. Models involving mixed-breed data do not take into account the fact that marker effects may differ among breeds. This study was aimed at investigating the impact on accuracy of increasing the number of genotyped candidates in the training set by using a multi-breed reference population, in contrast to single-breed genomic evaluations. Three traits (milk production, fat content and female fertility) were analyzed by genomic mixed linear models and Bayesian methodology. Three breeds of French dairy cattle were used: Holstein, Montbéliarde and Normande with 2976, 950 and 970 bulls in the training population, respectively and 964, 222 and 248 bulls in the validation population, respectively. All animals were genotyped with the Illumina Bovine SNP50 array. Accuracy of genomic breeding values was evaluated under three scenarios for the correlation of genomic breeding values between breeds (r(g)): uncorrelated (1), r(g) = 0; estimated r(g) (2); high, r(g) = 0.95 (3). Accuracy and bias of predictions obtained in the validation population with the multi-breed training set were assessed by the coefficient of determination (R(2)) and by the regression coefficient of daughter yield deviations of validation bulls on their predicted genomic breeding values, respectively. The genetic variation captured by the markers for each trait was similar to that estimated for routine pedigree-based genetic evaluation. Posterior means for rg ranged from -0.01 for fertility between Montbéliarde and Normande to 0.79 for milk yield between Montbéliarde and Holstein. Differences in R(2) between the three scenarios were notable only for fat content in the Montbéliarde breed: from 0.27 in scenario (1) to 0.33 in scenarios (2) and (3). Accuracies for fertility were lower than for other traits. Using a multi-breed reference population resulted in small or no increases in accuracy. Only the breed with a small data set and large genetic correlation with the breed with a large data set showed increased accuracy for the traits with moderate (milk) to high (fat content) heritability. No benefit was observed for fertility, a lowly heritable trait.

Joint genomic evaluation of French dairy cattle breeds using multiple-trait models

PubMed Central

2012-01-01

Background Using a multi-breed reference population might be a way of increasing the accuracy of genomic breeding values in small breeds. Models involving mixed-breed data do not take into account the fact that marker effects may differ among breeds. This study was aimed at investigating the impact on accuracy of increasing the number of genotyped candidates in the training set by using a multi-breed reference population, in contrast to single-breed genomic evaluations. Methods Three traits (milk production, fat content and female fertility) were analyzed by genomic mixed linear models and Bayesian methodology. Three breeds of French dairy cattle were used: Holstein, Montbéliarde and Normande with 2976, 950 and 970 bulls in the training population, respectively and 964, 222 and 248 bulls in the validation population, respectively. All animals were genotyped with the Illumina Bovine SNP50 array. Accuracy of genomic breeding values was evaluated under three scenarios for the correlation of genomic breeding values between breeds (rg): uncorrelated (1), rg = 0; estimated rg (2); high, rg = 0.95 (3). Accuracy and bias of predictions obtained in the validation population with the multi-breed training set were assessed by the coefficient of determination (R2) and by the regression coefficient of daughter yield deviations of validation bulls on their predicted genomic breeding values, respectively. Results The genetic variation captured by the markers for each trait was similar to that estimated for routine pedigree-based genetic evaluation. Posterior means for rg ranged from −0.01 for fertility between Montbéliarde and Normande to 0.79 for milk yield between Montbéliarde and Holstein. Differences in R2 between the three scenarios were notable only for fat content in the Montbéliarde breed: from 0.27 in scenario (1) to 0.33 in scenarios (2) and (3). Accuracies for fertility were lower than for other traits. Conclusions Using a multi-breed reference population resulted in small or no increases in accuracy. Only the breed with a small data set and large genetic correlation with the breed with a large data set showed increased accuracy for the traits with moderate (milk) to high (fat content) heritability. No benefit was observed for fertility, a lowly heritable trait. PMID:23216664

Dietary flavonoids from modified apple reduce inflammation markers and modulate gut microbiota in mice.

PubMed

Espley, Richard V; Butts, Christine A; Laing, William A; Martell, Sheridan; Smith, Hannah; McGhie, Tony K; Zhang, Jingli; Paturi, Gunaranjan; Hedderley, Duncan; Bovy, Arnaud; Schouten, Henk J; Putterill, Joanna; Allan, Andrew C; Hellens, Roger P

2014-02-01

Apples are rich in polyphenols, which provide antioxidant properties, mediation of cellular processes such as inflammation, and modulation of gut microbiota. In this study we compared genetically engineered apples with increased flavonoids [myeloblastis transcription factor 10 (MYB10)] with nontransformed apples from the same genotype, "Royal Gala" (RG), and a control diet with no apple. Compared with the RG diet, the MYB10 diet contained elevated concentrations of the flavonoid subclasses anthocyanins, flavanol monomers (epicatechin) and oligomers (procyanidin B2), and flavonols (quercetin glycosides), but other plant secondary metabolites were largely unaltered. We used these apples to investigate the effects of dietary flavonoids on inflammation and gut microbiota in 2 mouse feeding trials. In trial 1, male mice were fed a control diet or diets supplemented with 20% MYB10 apple flesh and peel (MYB-FP) or RG apple flesh and peel (RG-FP) for 7 d. In trial 2, male mice were fed MYB-FP or RG-FP diets or diets supplemented with 20% MYB10 apple flesh or RG apple flesh for 7 or 21 d. In trial 1, the transcription levels of inflammation-linked genes in mice showed decreases of >2-fold for interleukin-2 receptor (Il2rb), chemokine receptor 2 (Ccr2), chemokine ligand 10 (Cxcl10), and chemokine receptor 10 (Ccr10) at 7 d for the MYB-FP diet compared with the RG-FP diet (P < 0.05). In trial 2, the inflammation marker prostaglandin E(2) (PGE(2)) in the plasma of mice fed the MYB-FP diet at 21 d was reduced by 10-fold (P < 0.01) compared with the RG-FP diet. In colonic microbiota, the number of total bacteria for mice fed the MYB-FP diet was 6% higher than for mice fed the control diet at 21 d (P = 0.01). In summary, high-flavonoid apple was associated with decreases in some inflammation markers and changes in gut microbiota when fed to healthy mice.

PPAR agonists reduce steatosis in oleic acid-overloaded HepaRG cells

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

Rogue, Alexandra; Université de Rennes 1, Faculté des Sciences Pharmaceutiques et Biologiques, 35043 Rennes Cedex; Biologie Servier, Gidy

2014-04-01

Although non-alcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease there is no pharmacological agent approved for its treatment. Since peroxisome proliferator-activated receptors (PPARs) are closely associated with hepatic lipid metabolism, they seem to play important roles in NAFLD. However, the effects of PPAR agonists on steatosis that is a common pathology associated with NAFLD, remain largely controversial. In this study, the effects of various PPAR agonists, i.e. fenofibrate, bezafibrate, troglitazone, rosiglitazone, muraglitazar and tesaglitazar on oleic acid-induced steatotic HepaRG cells were investigated after a single 24-hour or 2-week repeat treatment. Lipid vesicles stainedmore » by Oil-Red O and triglycerides accumulation caused by oleic acid overload, were decreased, by up to 50%, while fatty acid oxidation was induced after 2-week co-treatment with PPAR agonists. The greatest effects on reduction of steatosis were obtained with the dual PPARα/γ agonist muraglitazar. Such improvement of steatosis was associated with up-regulation of genes related to fatty acid oxidation activity and down-regulation of many genes involved in lipogenesis. Moreover, modulation of expression of some nuclear receptor genes, such as FXR, LXRα and CAR, which are potent actors in the control of lipogenesis, was observed and might explain repression of de novo lipogenesis. Conclusion: Altogether, our in vitro data on steatotic HepaRG cells treated with PPAR agonists correlated well with clinical investigations, bringing a proof of concept that drug-induced reversal of steatosis in human can be evaluated in in vitro before conducting long-term and costly in vivo studies in animals and patients. - Highlights: • There is no pharmacological agent approved for the treatment of NAFLD. • This study demonstrates that PPAR agonists can reduce fatty acid-induced steatosis. • Some nuclear receptors appear to be potent actors in the control of lipogenesis. • A proof of concept that reversal of steatosis can be evaluated in human HepaRG cells.« less

Genetics of animal temperament: aggressive behaviour at mixing is genetically associated with the response to handling in pigs.

PubMed

D'Eath, R B; Roehe, R; Turner, S P; Ison, S H; Farish, M; Jack, M C; Lawrence, A B

2009-11-01

Aggression when pigs are mixed into new social groups has negative impacts on welfare and production. Aggressive behaviour is moderately heritable and could be reduced by genetic selection. The possible wider impacts of selection for reduced aggressiveness on handling traits and activity in the home pen were investigated using 1663 male and female pedigree pigs (898 purebred Yorkshire and 765 Yorkshire × Landrace). Aggressive behaviour was observed over 24 h after pigs were mixed at 10 weeks of age into groups balanced for unfamiliarity and weight. Aggression was highly heritable (duration of involvement in reciprocal fighting h2 = 0.47 ± 0.03, and duration of delivering one-sided aggression h2 = 0.34 ± 0.03). Three weeks after mixing, home pen inactivity (indicated by the frequency of lying) was observed over 24 h. Inactivity was weakly heritable (h2 = 0.05 ± 0.01) but showed no significant genetic association with aggression. Pigs' behaviour during handling by humans was assessed on entry to, whilst inside and on exit from a weigh crate at both mixing and end of test at 22 weeks. Pigs were generally easy to handle, moving easily into and out of the crate. Scores indicating 'very difficult to move' were rare. Handling scores at weighing were weakly heritable (h2 = 0.03 to 0.17), and moderately correlated across the two weighings (rg = 0.28 to 0.76). Aggressive behaviour at mixing was genetically associated with handling at the end of test weighing: pigs that fought and delivered one-sided aggression had handling scores indicating more active behaviour at weighing (e.g. moving quickly into the crate v. fighting rg = 0.41 ± 0.05 and v. bullying rg = 0.60 ± 0.04). Also, there was a genetic association between receiving one-side aggression at mixing and producing high-pitched vocalisations in the weigh crate (rg = 0.78 ± 0.08). Correlated behavioural responses occurring across different challenging situations (e.g. social mixing and human handling) have been described by the concept of animal temperament (also known as coping styles, personality or behavioural syndromes), but this has rarely been demonstrated at the genetic level in farm animals. These findings may have practical implications for the development of breeding programmes aimed at altering animal temperament. Breeding to reduce aggression could result in some reduction in activity at weighing. This would have consequences for animal production, because pigs which are inactive at weighing take longer to move into and out of the weigh crate, and perhaps also for animal welfare.

Oral vaccination of wildlife using a vaccinia-rabies-glycoprotein recombinant virus vaccine (RABORAL V-RG®): a global review.

PubMed

Maki, Joanne; Guiot, Anne-Laure; Aubert, Michel; Brochier, Bernard; Cliquet, Florence; Hanlon, Cathleen A; King, Roni; Oertli, Ernest H; Rupprecht, Charles E; Schumacher, Caroline; Slate, Dennis; Yakobson, Boris; Wohlers, Anne; Lankau, Emily W

2017-09-22

RABORAL V-RG ® is an oral rabies vaccine bait that contains an attenuated ("modified-live") recombinant vaccinia virus vector vaccine expressing the rabies virus glycoprotein gene (V-RG). Approximately 250 million doses have been distributed globally since 1987 without any reports of adverse reactions in wildlife or domestic animals since the first licensed recombinant oral rabies vaccine (ORV) was released into the environment to immunize wildlife populations against rabies. V-RG is genetically stable, is not detected in the oral cavity beyond 48 h after ingestion, is not shed by vaccinates into the environment, and has been tested for thermostability under a range of laboratory and field conditions. Safety of V-RG has been evaluated in over 50 vertebrate species, including non-human primates, with no adverse effects observed regardless of route or dose. Immunogenicity and efficacy have been demonstrated under laboratory and field conditions in multiple target species (including fox, raccoon, coyote, skunk, raccoon dog, and jackal). The liquid vaccine is packaged inside edible baits (i.e., RABORAL V-RG, the vaccine-bait product) which are distributed into wildlife habitats for consumption by target species. Field application of RABORAL V-RG has contributed to the elimination of wildlife rabies from three European countries (Belgium, France and Luxembourg) and of the dog/coyote rabies virus variant from the United States of America (USA). An oral rabies vaccination program in west-central Texas has essentially eliminated the gray fox rabies virus variant from Texas with the last case reported in a cow during 2009. A long-term ORV barrier program in the USA using RABORAL V-RG is preventing substantial geographic expansion of the raccoon rabies virus variant. RABORAL V-RG has also been used to control wildlife rabies in Israel for more than a decade. This paper: (1) reviews the development and historical use of RABORAL V-RG; (2) highlights wildlife rabies control programs using the vaccine in multiple species and countries; and (3) discusses current and future challenges faced by programs seeking to control or eliminate wildlife rabies.

Genetics Home Reference: Cornelia de Lange syndrome

MedlinePlus

... Rampuria A, Rossier E, Spranger S, Van Maldergem L, Lynch SA, Gillessen-Kaesbach G, Lüdecke HJ, Ramsay RG, ... Kline AD, Krumina Z, Lee H, Leppig K, Lynch SA, Mallozzi MB, Mannini L, McKee S, Mehta SG, ...

Heritabilities and phenotypic and genetic correlations for bovine postrigor calpastatin activity, intramuscular fat content, Warner-Bratzler shear force, retail product yield, and growth rate.

PubMed

Shackelford, S D; Koohmaraie, M; Cundiff, L V; Gregory, K E; Rohrer, G A; Savell, J W

1994-04-01

To estimate the heritability (h2) of postrigor calpastatin activity (CA), 555 steers were reared and processed conventionally. Breed-types included purebreds (Angus [A], Braunvieh [B], Charolais [C], Gelbvieh [G], Hereford [H], Limousin [L], Pinzgauer [P], Red Poll [RP], and Simmental [S]), composite populations (MARC I [1/4 C, 1/4 B, 1/4 L, 1/8 H, 1/8 A], MARC II [1/4 S, 1/4 G, 1/4 H, 1/4 A], and MARC III [1/4 RP, 1/4 H, 1/4 P, 1/4 A]), and F1 crosses (H, A, C, G, P, Shorthorn, Galloway, Longhorn, Nellore, Piedmontese, or Salers x H or A). Steers were serially slaughtered on an age-constant (across breed groups) basis. Heritability estimates for CA, i.m. fat content (IMF), Warner-Bratzler shear (WBS) force, retail product yield (RPY), and ADG were .65 +/- .19, .93 +/- .02, .53 +/- .15, .45 +/- .18, and .32 +/- .26, respectively. The genetic correlations (rg) of CA with WBS, RPY, and ADG were .50 +/- .22, .44 +/- .25, and -.52 +/- .37, respectively. The rg of IMF with WBS, RPY, and ADG were -.57 +/- .16, -.63 +/- .15, and -.04 +/- .11, respectively. These h2 and rg estimates indicate that it should be possible to select for improvements in CA, IMF, and WBS. However, selection against CA may be a more suitable approach for improving meat tenderness than selection for increased IMF because the level of genetic antagonism between CA and RPY was not as great as that between IMF and RPY.

Ginsenoside 20(S)-Rg3 Inhibits the Warburg Effect Via Modulating DNMT3A/ MiR-532-3p/HK2 Pathway in Ovarian Cancer Cells.

PubMed

Zhou, Yuanyuan; Zheng, Xia; Lu, Jiaojiao; Chen, Wei; Li, Xu; Zhao, Le

2018-01-01

The Warburg effect is one of the main energy metabolism features supporting cancer cell growth. 20(S)-Rg3 exerts anti-tumor effect on ovarian cancer partly by inhibiting the Warburg effect. microRNAs are important regulators of the Warburg effect. However, the microRNA regulatory network mediating the anti-Warburg effect of 20(S)-Rg3 was largely unknown. microRNA deep sequencing was performed to identify the 20(S)-Rg3-influenced microRNAs in SKOV3 ovarian cancer cells. miR-532-3p was overexpressed by mimic532-3p transfection in SKOV3 and A2780 cells or inhibited by inhibitor532-3p transfection in 20(S)-Rg3-treated cells to examine the changes in HK2 and PKM2 expression, glucose consumption, lactate production and cell growth. Dual-luciferase reporter assay was conducted to verify the direct binding of miR-532-3p to HK2. The methylation status in the promoter region of pre-miR-532-3p gene was examined by methylation-specific PCR. Expression changes of key molecules controlling DNA methylation including DNMT1, DNMT3A, DNMT3B, and TET1-3 were examined in 20(S)-Rg3-treated cells. DNMT3A was overexpressed in 20(S)-Rg3-treated cells to examine its influence on miR-532-3p level, HK2 and PKM2 expression, glucose consumption and lactate production. Deep sequencing results showed that 11 microRNAs were increased and 9 microRNAs were decreased by 20(S)-Rg3 in SKOV3 cells, which were verified by qPCR. More than 2-fold increase of miR-532-3p was found in 20(S)-Rg3-treated SKOV3 cells. Forced expression of miR-532-3p reduced HK2 and PKM2 expression, glucose consumption and lactate production in SKOV3 and A2780 ovarian cancer cells. Inhibition of miR-532-3p antagonized the suppressive effect of 20(S)-Rg3 on HK2 and PKM2 expression, glucose consumption and lactate production in ovarian cancer cells. Dual-luciferase reporter assay showed that miR-532-3p directly suppressed HK2 rather than PKM2. miR-532-3p level was controlled by the methylation in the promoter region of its host gene. 20(S)-Rg3 inhibited DNMT3A expression while exerted insignificant effect on DNMT1, DNMT3B and TET1-3. 20(S)-Rg3 reversed DNMT3A-mediated methylation in the promoter of the host gene of miR-532-3p, and thus elevated miR-532-3p level followed by suppression of HK2 and PKM2 expression, glucose consumption and lactate production. 20(S)-Rg3 modulated microRNAs to exert the anti-tumor effect in ovarian cancer. 20(S)-Rg3 lessened the DNMT3A-mediated methylation and promoted the suppression of miR-532-3p on HK2 to antagonize the Warburg effect of ovarian cancer cells. © 2018 The Author(s). Published by S. Karger AG, Basel.

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

Dumont, Marie; Lehner, Arnaud; Bardor, Muriel

Screening of commercially available fluoro monosaccharides as putative growth inhibitors in Arabidopsis thaliana revealed that 2-fluoro 2-l-fucose (2F-Fuc) reduces root growth at micromolar concentrations. The inability of 2F-Fuc to affect an Atfkgp mutant that is defective in the fucose salvage pathway indicates that 2F-Fuc must be converted to its cognate GDP nucleotide sugar in order to inhibit root growth. Chemical analysis of cell wall polysaccharides and glycoproteins demonstrated that fucosylation of xyloglucans and of N-linked glycans is fully inhibited by 10 μm 2F-Fuc in Arabidopsis seedling roots, but genetic evidence indicates that these alterations are not responsible for the inhibitionmore » of root development by 2F-Fuc. Inhibition of fucosylation of cell wall polysaccharides also affected pectic rhamnogalacturonan-II (RG-II). At low concentrations, 2F-Fuc induced a decrease in RG-II dimerization. Both RG-II dimerization and root growth were partially restored in 2F-Fuc-treated seedlings by addition of boric acid, suggesting that the growth phenotype caused by 2F-Fuc was due to a deficiency of RG-II dimerization. Closer investigation of the 2F-Fuc-induced growth phenotype demonstrated that cell division is not affected by 2F-Fuc treatments. In contrast, the inhibitor suppressed elongation of root cells and promoted the emergence of adventitious roots. This study further emphasizes the importance of RG-II in cell elongation and the utility of glycosyltransferase inhibitors as new tools for studying the functions of cell wall polysaccharides in plant development. Moreover, supplementation experiments with borate suggest that the function of boron in plants might not be restricted to RG-II cross-linking, but that it might also be a signal molecule in the cell wall integrity-sensing mechanism.« less

Phenotypic Dissection of Bone Mineral Density Reveals Skeletal Site Specificity and Facilitates the Identification of Novel Loci in the Genetic Regulation of Bone Mass Attainment

PubMed Central

Estrada, Karol; St Pourcain, Beate; Heppe, Denise H. M.; Warrington, Nicole M.; Oei, Ling; Ring, Susan M.; Kruithof, Claudia J.; Timpson, Nicholas J.; Wolber, Lisa E.; Reppe, Sjur; Gautvik, Kaare; Grundberg, Elin; Ge, Bing; van der Eerden, Bram; van de Peppel, Jeroen; Hibbs, Matthew A.; Ackert-Bicknell, Cheryl L.; Choi, Kwangbom; Koller, Daniel L.; Econs, Michael J.; Williams, Frances M. K.; Foroud, Tatiana; Carola Zillikens, M.; Ohlsson, Claes; Hofman, Albert; Uitterlinden, André G.; Davey Smith, George; Jaddoe, Vincent W. V.; Tobias, Jonathan H.; Rivadeneira, Fernando; Evans, David M.

2014-01-01

Heritability of bone mineral density (BMD) varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we estimated the genetic (rg) and residual (re) correlations between BMD measured at the upper limbs (UL-BMD), lower limbs (LL-BMD) and skull (SK-BMD), using total-body DXA scans of ∼4,890 participants recruited by the Avon Longitudinal Study of Parents and their Children (ALSPAC). Point estimates of rg indicated that appendicular sites have a greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.78) between them, than with the skull (UL-/SK-BMD rg = 0.58 and LL-/SK-BMD rg = 0.43). Likewise, the residual correlation between BMD at appendicular sites (re = 0.55) was higher than the residual correlation between SK-BMD and BMD at appendicular sites (re = 0.20–0.24). To explore the basis for the observed differences in rg and re, genome-wide association meta-analyses were performed (n∼9,395), combining data from ALSPAC and the Generation R Study identifying 15 independent signals from 13 loci associated at genome-wide significant level across different skeletal regions. Results suggested that previously identified BMD-associated variants may exert site-specific effects (i.e. differ in the strength of their association and magnitude of effect across different skeletal sites). In particular, variants at CPED1 exerted a larger influence on SK-BMD and UL-BMD when compared to LL-BMD (P = 2.01×10−37), whilst variants at WNT16 influenced UL-BMD to a greater degree when compared to SK- and LL-BMD (P = 2.31×10−14). In addition, we report a novel association between RIN3 (previously associated with Paget's disease) and LL-BMD (rs754388: β = 0.13, SE = 0.02, P = 1.4×10−10). Our results suggest that BMD at different skeletal sites is under a mixture of shared and specific genetic and environmental influences. Allowing for these differences by performing genome-wide association at different skeletal sites may help uncover new genetic influences on BMD. PMID:24945404

Vaccination of small Asian mongoose (Herpestes javanicus) against rabies.

PubMed

Blanton, Jesse D; Meadows, Anastasia; Murphy, Staci M; Manangan, Jamie; Hanlon, Cathleen A; Faber, Marie-Luise; Dietzschold, Bernhard; Rupprecht, Charles E

2006-07-01

Oral vaccination of free-ranging wildlife is a promising technique in rabies control. The small Asian mongoose (Herpestes javanicus) is an important reservoir of rabies on several Caribbean islands, but no vaccines have been evaluated for this species. Captive mongooses were used to test the safety and efficacy of the commercially licensed vaccinia-rabies glycoprotein (V-RG) recombinant vaccine and a newly developed genetically engineered oral rabies virus vaccine (SPBNGA-S). In one study using V-RG, no vaccinated animals developed detectable rabies virus-neutralizing antibodies, and all but one died after experimental challenge with rabies virus. In contrast, all animals given SPBNGA-S demonstrated seroconversion within 7 to 14 days after vaccination and survived rabies virus challenge. On the basis of these preliminary results indicating the greater efficacy of SPBNGA-S vs. V-RG vaccine, additional investigations will be necessary to determine the optimal dose and duration of vaccination, as well as incorporation of the SPBNGA-S vaccine into edible bait.

Heritability of volumetric brain changes and height in children entering puberty.

PubMed

van Soelen, Inge L C; Brouwer, Rachel M; van Baal, G Caroline M; Schnack, Hugo G; Peper, Jiska S; Chen, Lei; Kahn, René S; Boomsma, Dorret I; Hulshoff Pol, Hilleke E

2013-03-01

The human brain undergoes structural changes in children entering puberty, while simultaneously children increase in height. It is not known if brain changes are under genetic control, and whether they are related to genetic factors influencing the amount of overall increase in height. Twins underwent magnetic resonance imaging brain scans at age 9 (N = 190) and 12 (N = 125). High heritability estimates were found at both ages for height and brain volumes (49-96%), and high genetic correlation between ages were observed (r(g) > 0.89). With increasing age, whole brain (+1.1%), cerebellum (+4.2%), cerebral white matter (+5.1%), and lateral ventricle (+9.4%) volumes increased, and third ventricle (-4.0%) and cerebral gray matter (-1.6%) volumes decreased. Children increased on average 13.8 cm in height (9.9%). Genetic influences on individual difference in volumetric brain and height changes were estimated, both within and across traits. The same genetic factors influenced both cerebral (20% heritable) and cerebellar volumetric changes (45%). Thus, the extent to which changes in cerebral and cerebellar volumes are heritable in children entering puberty are due to the same genes that influence change in both structures. The increase in height was heritable (73%), and not associated with cerebral volumetric change, but positively associated with cerebellar volume change (r(p) = 0.24). This association was explained by a genetic correlation (r(g) = 0.48) between height and cerebellar change. Brain and body each expand at their own pace and through separate genetic pathways. There are distinct genetic processes acting on structural brain development, which cannot be explained by genetic increase in height. Copyright © 2011 Wiley Periodicals, Inc.

Itinerant fermions on a triangular lattice: Unconventional magnetism and other ordered states

NASA Astrophysics Data System (ADS)

Ye, Mengxing; Chubukov, Andrey V.

2018-06-01

We consider a system of 2D fermions on a triangular lattice with well separated electron and hole pockets of similar sizes, centered at certain high-symmetry points in the Brillouin zone. We first analyze Stoner-type spin-density-wave (SDW) magnetism. We show that SDW order is degenerate at the mean-field level. Beyond mean-field, the degeneracy is lifted and is either 120∘ "triangular" order (same as for localized spins), or a collinear order with antiferromagnetic spin arrangement on two-thirds of sites, and nonmagnetic on the rest of sites. We also study a time-reversal symmetric directional spin bond order, which emerges when some interactions are repulsive and some are attractive. We show that this order is also degenerate at a mean-field level, but beyond mean-field the degeneracy is again lifted. We next consider the evolution of a magnetic order in a magnetic field starting from an SDW state in zero field. We show that a field gives rise to a canting of an SDW spin configuration. In addition, it necessarily triggers the directional bond order, which, we argue, is linearly coupled to the SDW order in a finite field. We derive the corresponding term in the free energy. Finally, we consider the interplay between an SDW order and superconductivity and charge order. For this, we analyze the flow of the couplings within parquet renormalization group (pRG) scheme. We show that magnetism wins if all interactions are repulsive and there is little energy space for pRG to develop. However, if system parameters are such that pRG runs over a wide range of energies, the system may develop either superconductivity or an unconventional charge order, which breaks time-reversal symmetry.

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

Westbrook, JW; Walker, AR; Neves, LG

Genetically improving constitutive resin canal development in Pinus stems may enhance the capacity to synthesize terpenes for bark beetle resistance, chemical feedstocks, and biofuels. To discover genes that potentially regulate axial resin canal number (RCN), single nucleotide polymorphisms (SNPs) in 4027 genes were tested for association with RCN in two growth rings and three environments in a complex pedigree of 520 Pinus taeda individuals (CCLONES). The map locations of associated genes were compared with RCN quantitative trait loci (QTLs) in a (P.taedaxPinuselliottii)xP.elliottii pseudo-backcross of 345 full-sibs (BC1). Resin canal number was heritable (h(2)0.12-0.21) and positively genetically correlated with xylem growthmore » (r(g)0.32-0.72) and oleoresin flow (r(g)0.15-0.51). Sixteen well-supported candidate regulators of RCN were discovered in CCLONES, including genes associated across sites and ages, unidirectionally associated with oleoresin flow and xylem growth, and mapped to RCN QTLs in BC1. Breeding is predicted to increase RCN 11% in one generation and could be accelerated with genomic selection at accuracies of 0.45-0.52 across environments. There is significant genetic variation for RCN in loblolly pine, which can be exploited in breeding for elevated terpene content.« less

Localization of QTLs for in vitro plant regeneration in tomato

PubMed Central

2011-01-01

Background Low regeneration ability limits biotechnological breeding approaches. The influence of genotype in the regeneration response is high in both tomato and other important crops. Despite the various studies that have been carried out on regeneration genetics, little is known about the key genes involved in this process. The aim of this study was to localize the genetic factors affecting regeneration in tomato. Results We developed two mapping populations (F2 and BC1) derived from a previously selected tomato cultivar (cv. Anl27) with low regeneration ability and a high regeneration accession of the wild species Solanum pennellii (PE-47). The phenotypic assay indicated dominance for bud induction and additive effects for both the percentage of explants with shoots and the number of regenerated shoots per explant. Two linkage maps were developed and six QTLs were identified on five chromosomes (1, 3, 4, 7 and 8) in the BC1 population by means of the Interval Mapping and restricted Multiple QTL Mapping methods. These QTLs came from S. pennellii, with the exception of the minor QTL located on chromosome 8, which was provided by cv. Anl27. The main QTLs correspond to those detected on chromosomes 1 and 7. In the F2 population, a QTL on chromosome 7 was identified on a similar region as that detected in the BC1 population. Marker segregation distortion was observed in this population in those areas where the QTLs of BC1 were detected. Furthermore, we located two tomato candidate genes using a marker linked to the high regeneration gene: Rg-2 (a putative allele of Rg-1) and LESK1, which encodes a serine/threonine kinase and was proposed as a marker for regeneration competence. As a result, we located a putative allele of Rg-2 in the QTL detected on chromosome 3 that we named Rg-3. LESK1, which is also situated on chromosome 3, is outside Rg-3. In a preliminary exploration of the detected QTL peaks, we found several genes that may be related to regeneration. Conclusions In this study we have identified new QTLs related to the complex process of regeneration from tissue culture. We have also located two candidate genes, discovering a putative allele of the high regeneration gene Rg-1 in the QTL on chromosome 3. The identified QTLs could represent a significant step toward the understanding of this process and the identification of other related candidate genes. It will also most likely facilitate the development of molecular markers for use in gene isolation. PMID:22014149

Localization of QTLs for in vitro plant regeneration in tomato.

PubMed

Trujillo-Moya, Carlos; Gisbert, Carmina; Vilanova, Santiago; Nuez, Fernando

2011-10-20

Low regeneration ability limits biotechnological breeding approaches. The influence of genotype in the regeneration response is high in both tomato and other important crops. Despite the various studies that have been carried out on regeneration genetics, little is known about the key genes involved in this process. The aim of this study was to localize the genetic factors affecting regeneration in tomato. We developed two mapping populations (F2 and BC1) derived from a previously selected tomato cultivar (cv. Anl27) with low regeneration ability and a high regeneration accession of the wild species Solanum pennellii (PE-47). The phenotypic assay indicated dominance for bud induction and additive effects for both the percentage of explants with shoots and the number of regenerated shoots per explant. Two linkage maps were developed and six QTLs were identified on five chromosomes (1, 3, 4, 7 and 8) in the BC1 population by means of the Interval Mapping and restricted Multiple QTL Mapping methods. These QTLs came from S. pennellii, with the exception of the minor QTL located on chromosome 8, which was provided by cv. Anl27. The main QTLs correspond to those detected on chromosomes 1 and 7. In the F2 population, a QTL on chromosome 7 was identified on a similar region as that detected in the BC1 population. Marker segregation distortion was observed in this population in those areas where the QTLs of BC1 were detected. Furthermore, we located two tomato candidate genes using a marker linked to the high regeneration gene: Rg-2 (a putative allele of Rg-1) and LESK1, which encodes a serine/threonine kinase and was proposed as a marker for regeneration competence. As a result, we located a putative allele of Rg-2 in the QTL detected on chromosome 3 that we named Rg-3. LESK1, which is also situated on chromosome 3, is outside Rg-3. In a preliminary exploration of the detected QTL peaks, we found several genes that may be related to regeneration. In this study we have identified new QTLs related to the complex process of regeneration from tissue culture. We have also located two candidate genes, discovering a putative allele of the high regeneration gene Rg-1 in the QTL on chromosome 3. The identified QTLs could represent a significant step toward the understanding of this process and the identification of other related candidate genes. It will also most likely facilitate the development of molecular markers for use in gene isolation.

Boron-bridged RG-II and calcium are required to maintain the pectin network of the Arabidopsis seed mucilage ultrastructure.

PubMed

Shi, Da-Chuan; Wang, Juan; Hu, Rui-Bo; Zhou, Gong-Ke; O'Neill, Malcolm A; Kong, Ying-Zhen

2017-06-01

The structure of a pectin network requires both calcium (Ca 2+ ) and boron (B). Ca 2+ is involved in crosslinking pectic polysaccharides and arbitrarily induces the formation of an "egg-box" structure among pectin molecules, while B crosslinks rhamnogalacturonan II (RG-II) side chain A apiosyl residues in primary cell walls to generate a borate-dimeric-rhamnogalacturonan II (dRG-II-B) complex through a boron-bridge bond, leading to the formation of a pectin network. Based on recent studies of dRG-II-B structures, a hypothesis has been proposed suggesting that Ca 2+ is a common component of the dRG-II-B complex. However, no in vivo evidence has addressed whether B affects the stability of Ca 2+ crosslinks. Here, we investigated the L-fucose-deficient dwarf mutant mur1, which was previously shown to require exogenous B treatment for phenotypic reversion. Imbibed Arabidopsis thaliana seeds release hydrated polysaccharides to form a halo of seed mucilage covering the seed surface, which consists of a water-soluble outer layer and an adherent inner layer. Our study of mur1 seed mucilage has revealed that the pectin in the outer layer of mucilage was relocated to the inner layer. Nevertheless, the mur1 inner mucilage was more vulnerable to rough shaking or ethylene diamine tetraacetic acid (EDTA) extraction than that of the wild type. Immunolabeling analysis suggested that dRG-II-B was severely decreased in mur1 inner mucilage. Moreover, non-methylesterified homogalacturonan (HG) exhibited obvious reassembly in the mur1 inner layer compared with the wild type, which may imply a possible connection between dRG-II-B deficiency and pectin network transformation in the seed mucilage. As expected, the concentration of B in the mur1 inner mucilage was reduced, whereas the distribution and concentration of Ca 2+ in the inner mucilage increased significantly, which could be the reason why pectin relocates from the outer mucilage to the inner mucilage. Consequently, the disruption of B bridges appears to result in the extreme sensitivity of the mur1 mucilage pectin complex to EDTA extraction, despite the reinforcement of the pectin network by excessive Ca 2+ . Therefore, we propose a hypothesis that B, in the form of dRG-II-B, works together with Ca 2+ to maintain pectin network crosslinks and ultimately the mucilage ultrastructure in seed mucilage. This work may serve to complement our current understanding of mucilage configuration.

Evidence of Common Genetic Overlap Between Schizophrenia and Cognition.

PubMed

Hubbard, Leon; Tansey, Katherine E; Rai, Dheeraj; Jones, Peter; Ripke, Stephan; Chambert, Kimberly D; Moran, Jennifer L; McCarroll, Steven A; Linden, David E J; Owen, Michael J; O'Donovan, Michael C; Walters, James T R; Zammit, Stanley

2016-05-01

Cognitive impairment is a core feature of schizophrenia but there is limited understanding of the genetic relationship between cognition in the general population and schizophrenia. We examine how common variants associated with schizophreniaen massecontribute to childhood cognitive ability in a population-based sample, and the extent to which common genetic variants associated with childhood cognition explain variation in schizophrenia. Schizophrenia polygenic risk scores were derived from the Psychiatric Genomics Consortium (n= 69 516) and tested for association with IQ, attention, processing speed, working memory, problem solving, and social cognition in over 5000 children aged 8 from the Avon Longitudinal Study of Parents and Children birth cohort. Polygenic scores for these cognitive domains were tested for association with schizophrenia in a large UK schizophrenia sample (n= 11 853). Bivariate genome-wide complex trait analysis (GCTA) estimated the amount of shared genetic factors between schizophrenia and cognitive domains. Schizophrenia polygenic risk score was associated with lower performance IQ (P= .001) and lower full IQ (P= .013). Polygenic score for performance IQ was associated with increased risk for schizophrenia (P= 3.56E-04). Bivariate GCTA revealed moderate genetic correlation between schizophrenia and both performance IQ (rG= -.379,P= 6.62E-05) and full IQ (rG= -.202,P= 5.00E-03), with approximately 14% of the genetic component of schizophrenia shared with that for performance IQ. Our results support the presence of shared common genetic factors between schizophrenia and childhood cognitive ability. We observe a genetic relationship between schizophrenia and performance IQ but not verbal IQ or other cognitive variables, which may have implications for studies utilizing cognitive endophenotypes for psychosis. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Evolution of mating system and the genetic covariance between male and female investment in Clarkia (onagraceae): selfing opposes the evolution of trade-offs.

PubMed

Mazer, Susan J; Delesalle, Véronique A; Paz, Horacio

2007-01-01

Sex allocation theory has assumed that hermaphroditic species exhibit strong genetically based trade-offs between investment in male and female function. The potential effects of mating system on the evolution of this genetic covariance, however, have not been explored. We have challenged the assumption of a ubiquitous trade-off between male and female investment by arguing that in highly self-fertilizing species, stabilizing natural selection should favor highly efficient ratios of male to female gametes. In flowering plants, the result of such selection would be similar pollen:ovule (P:O) ratios across selfing genotypes, precluding a negative genetic correlation (r(g)) between pollen and ovule production per flower. Moreover, if selfing genotypes with similar P:O ratios differ in total gametic investment per flower, a positive r(g) between pollen and ovule production would be observed. In outcrossers, by contrast, male- and female-biased flowers and genotypes may have equal fitness and coexist at evolutionary equilibrium. In the absence of strong stabilizing selection on the P:O ratio, selection on this trait will be relaxed, resulting in independence or resource-based trade-offs between male and female investment. To test this prediction, we conducted artificial selection on pollen and ovule production per flower in two sister species with contrasting mating systems. The predominantly self-fertilizing species (Clarkia exilis) consistently exhibited a significant positive r(g) between pollen and ovule production while the outcrossing species (C. unguiculata) exhibited either a trade-off or independence between these traits. Clarkia exilis also exhibited much more highly canalized gender expression than C. unguiculata. Selection on pollen and ovule production resulted in little correlated change in the P:O ratio in the selfing exilis, while dramatic changes in the P:O ratio were observed in unguiculata. To test the common prediction that floral attractiveness should be positively genetically correlated with investment in male function, we examined the response of petal area to selection on pollen and ovule production and found that petal area was not consistently genetically correlated with gender expression in either species. Our results suggest that the joint evolutionary trajectory of primary sexual traits in hermaphroditic species will be affected by their mating systems; this should be taken into account in future theoretical and comparative empirical investigations.

Genetic overlap between diagnostic subtypes of ischemic stroke.

PubMed

Holliday, Elizabeth G; Traylor, Matthew; Malik, Rainer; Bevan, Steve; Falcone, Guido; Hopewell, Jemma C; Cheng, Yu-Ching; Cotlarciuc, Ioana; Bis, Joshua C; Boerwinkle, Eric; Boncoraglio, Giorgio B; Clarke, Robert; Cole, John W; Fornage, Myriam; Furie, Karen L; Ikram, M Arfan; Jannes, Jim; Kittner, Steven J; Lincz, Lisa F; Maguire, Jane M; Meschia, James F; Mosley, Thomas H; Nalls, Mike A; Oldmeadow, Christopher; Parati, Eugenio A; Psaty, Bruce M; Rothwell, Peter M; Seshadri, Sudha; Scott, Rodney J; Sharma, Pankaj; Sudlow, Cathie; Wiggins, Kerri L; Worrall, Bradford B; Rosand, Jonathan; Mitchell, Braxton D; Dichgans, Martin; Markus, Hugh S; Levi, Christopher; Attia, John; Wray, Naomi R

2015-03-01

Despite moderate heritability, the phenotypic heterogeneity of ischemic stroke has hampered gene discovery, motivating analyses of diagnostic subtypes with reduced sample sizes. We assessed evidence for a shared genetic basis among the 3 major subtypes: large artery atherosclerosis (LAA), cardioembolism, and small vessel disease (SVD), to inform potential cross-subtype analyses. Analyses used genome-wide summary data for 12 389 ischemic stroke cases (including 2167 LAA, 2405 cardioembolism, and 1854 SVD) and 62 004 controls from the Metastroke consortium. For 4561 cases and 7094 controls, individual-level genotype data were also available. Genetic correlations between subtypes were estimated using linear mixed models and polygenic profile scores. Meta-analysis of a combined LAA-SVD phenotype (4021 cases and 51 976 controls) was performed to identify shared risk alleles. High genetic correlation was identified between LAA and SVD using linear mixed models (rg=0.96, SE=0.47, P=9×10(-4)) and profile scores (rg=0.72; 95% confidence interval, 0.52-0.93). Between LAA and cardioembolism and SVD and cardioembolism, correlation was moderate using linear mixed models but not significantly different from zero for profile scoring. Joint meta-analysis of LAA and SVD identified strong association (P=1×10(-7)) for single nucleotide polymorphisms near the opioid receptor μ1 (OPRM1) gene. Our results suggest that LAA and SVD, which have been hitherto treated as genetically distinct, may share a substantial genetic component. Combined analyses of LAA and SVD may increase power to identify small-effect alleles influencing shared pathophysiological processes. © 2015 American Heart Association, Inc.

Mutual exacerbation of peroxisome proliferator-activated receptor γ coactivator 1α deregulation and α-synuclein oligomerization.

PubMed

Eschbach, Judith; von Einem, Björn; Müller, Kathrin; Bayer, Hanna; Scheffold, Annika; Morrison, Bradley E; Rudolph, K Lenhard; Thal, Dietmar R; Witting, Anke; Weydt, Patrick; Otto, Markus; Fauler, Michael; Liss, Birgit; McLean, Pamela J; Spada, Albert R La; Ludolph, Albert C; Weishaupt, Jochen H; Danzer, Karin M

2015-01-01

Aggregation of α-synuclein (α-syn) and α-syn cytotoxicity are hallmarks of sporadic and familial Parkinson disease (PD), with accumulating evidence that prefibrillar oligomers and protofibrils are the pathogenic species in PD and related synucleinopathies. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a key regulator of mitochondrial biogenesis and cellular energy metabolism, has recently been associated with the pathophysiology of PD. Despite extensive effort on studying the function of PGC-1α in mitochondria, no studies have addressed whether PGC-1α directly influences oligomerization of α-syn or whether α-syn oligomers impact PGC-1α expression. We tested whether pharmacological or genetic activation of PGC-1α or PGC-11α knockdown could modulate the oligomerization of α-syn in vitro by using an α-syn -fragment complementation assay. In this study, we found that both PGC-1α reference gene (RG-PGC-1α) and the central nervous system (CNS)-specific PGC-1α (CNS-PGC-1α) are downregulated in human PD brain, in A30P α-syn transgenic animals, and in a cell culture model for α-syn oligomerization. Importantly, downregulation of both RG-PGC-1α and CNS-PGC-1α in cell culture or neurons from RG-PGC-1α-deficient mice leads to a strong induction of α-syn oligomerization and toxicity. In contrast, pharmacological activation or genetic overexpression of RG-PGC-1α reduced α-syn oligomerization and rescued α-syn-mediated toxicity. Based on our results, we propose that PGC-1α downregulation and α-syn oligomerization form a vicious circle, thereby influencing and/or potentiating each other. Our data indicate that restoration of PGC-1α is a promising approach for development of effective drugs for the treatment of PD and related synucleinopathies. © 2014 American Neurological Association.

Genetic relationship between cyclic ovarian activity in heifers and cows and beef traits in males

PubMed Central

Mialon, Marie-Madeleine; Renand, Gilles; Krauss, Daniel; Ménissier, François

2001-01-01

Records were collected in an experimental herd over an 11-year period from purebred Charolais heifers (n = 351), cows (n = 615) and young entire bulls (n = 383). The objective of the study was to estimate the genetic relationship between the components of female ovarian activity (age at puberty and postpartum anoestrus length), their growth rate and body condition score and beef traits measured on related bulls. Two methods were used to estimate age at puberty and postpartum anoestrus length: the detection of oestrous behaviour and a test of cyclicity based on plasmatic progesterone assay. This study shows the existence of significant heritability estimates for the different cyclicity traits (h2 between 0.11 and 0.38). Most of the genetic correlation coefficients between ovarian activity and growth rate of females and males are negative and favourable (rg between -0.43 and 0.06). Cyclicity is also favourably related with body condition score in young or adult females (rg between -0.65 and -0.22). The genetic relationship between female ovarian activity and proportion of adipose tissue in the male carcass is, however, close to zero. These results show that an antagonism between male beef traits measured in this study and female ovarian activity is unlikely to be a cause for concern in the short term. PMID:11403748

Genetic Parameters of Pre-adjusted Body Weight Growth and Ultrasound Measures of Body Tissue Development in Three Seedstock Pig Breed Populations in Korea

PubMed Central

Choy, Yun Ho; Mahboob, Alam; Cho, Chung Il; Choi, Jae Gwan; Choi, Im Soo; Choi, Tae Jeong; Cho, Kwang Hyun; Park, Byoung Ho

2015-01-01

The objective of this study was to compare the effects of body weight growth adjustment methods on genetic parameters of body growth and tissue among three pig breeds. Data collected on 101,820 Landrace, 281,411 Yorkshire, and 78,068 Duroc pigs, born in Korean swine breeder farms since 2000, were analyzed. Records included body weights on test day and amplitude (A)-mode ultrasound carcass measures of backfat thickness (BF), eye muscle area (EMA), and retail cut percentage (RCP). Days to 90 kg body weight (DAYS90), through an adjustment of the age based on the body weight at the test day, were obtained. Ultrasound measures were also pre-adjusted (ABF, EMA, AEMA, ARCP) based on their test day measures. The (co)variance components were obtained with 3 multi-trait animal models using the REMLF90 software package. Model I included DAYS90 and ultrasound traits, whereas model II and III accounted DAYS90 and pre-adjusted ultrasound traits. Fixed factors were sex (sex) and contemporary groups (herd-year-month of birth) for all traits among the models. Additionally, model I and II considered a linear covariate of final weight on the ultrasound measure traits. Heritability (h2) estimates for DAYS90, BF, EMA, and RCP ranged from 0.36 to 0.42, 0.34 to 0.43, 0.20 to 0.22, and 0.39 to 0.45, respectively, among the models. The h2 estimates of DAYS90 from model II and III were also somewhat similar. The h2 for ABF, AEMA, and ARCP were 0.35 to 0.44, 0.20 to 0.25, and 0.41 to 0.46, respectively. Our heritability estimates varied mostly among the breeds. The genetic correlations (rG) were moderately negative between DAYS90 and BF (−0.29 to −0.38), and between DAYS90 and EMA (−0.16 to −0.26). BF had strong rG with RCP (−0.87 to −0.93). Moderately positive rG existed between DAYS90 and RCP (0.20 to 0.28) and between EMA and RCP (0.35 to 0.44) among the breeds. For DAYS90, model II and III, its correlations with ABF, AEMA, and ARCP were mostly low or negligible except the rG between DAYS90 and AEMA from model III (0.27 to 0.30). The rG between AEMA and ABF and between AEMA and ARCP were moderate but with negative and positive signs, respectively; also reflected influence of pre-adjustments. However, the rG between BF and RCP remained non-influential to trait pre-adjustments or covariable fits. Therefore, we conclude that ultrasound measures taken at a body weight of about 90 kg as the test final should be adjusted for body weight growth. Our adjustment formulas, particularly those for BF and EMA, should be revised further to accommodate the added variation due to different performance testing endpoints with regard to differential growth in body composition. PMID:26580436

Genetic Parameters of Pre-adjusted Body Weight Growth and Ultrasound Measures of Body Tissue Development in Three Seedstock Pig Breed Populations in Korea.

PubMed

Choy, Yun Ho; Mahboob, Alam; Cho, Chung Il; Choi, Jae Gwan; Choi, Im Soo; Choi, Tae Jeong; Cho, Kwang Hyun; Park, Byoung Ho

2015-12-01

The objective of this study was to compare the effects of body weight growth adjustment methods on genetic parameters of body growth and tissue among three pig breeds. Data collected on 101,820 Landrace, 281,411 Yorkshire, and 78,068 Duroc pigs, born in Korean swine breeder farms since 2000, were analyzed. Records included body weights on test day and amplitude (A)-mode ultrasound carcass measures of backfat thickness (BF), eye muscle area (EMA), and retail cut percentage (RCP). Days to 90 kg body weight (DAYS90), through an adjustment of the age based on the body weight at the test day, were obtained. Ultrasound measures were also pre-adjusted (ABF, EMA, AEMA, ARCP) based on their test day measures. The (co)variance components were obtained with 3 multi-trait animal models using the REMLF90 software package. Model I included DAYS90 and ultrasound traits, whereas model II and III accounted DAYS90 and pre-adjusted ultrasound traits. Fixed factors were sex (sex) and contemporary groups (herd-year-month of birth) for all traits among the models. Additionally, model I and II considered a linear covariate of final weight on the ultrasound measure traits. Heritability (h(2)) estimates for DAYS90, BF, EMA, and RCP ranged from 0.36 to 0.42, 0.34 to 0.43, 0.20 to 0.22, and 0.39 to 0.45, respectively, among the models. The h(2) estimates of DAYS90 from model II and III were also somewhat similar. The h(2) for ABF, AEMA, and ARCP were 0.35 to 0.44, 0.20 to 0.25, and 0.41 to 0.46, respectively. Our heritability estimates varied mostly among the breeds. The genetic correlations (rG) were moderately negative between DAYS90 and BF (-0.29 to -0.38), and between DAYS90 and EMA (-0.16 to -0.26). BF had strong rG with RCP (-0.87 to -0.93). Moderately positive rG existed between DAYS90 and RCP (0.20 to 0.28) and between EMA and RCP (0.35 to 0.44) among the breeds. For DAYS90, model II and III, its correlations with ABF, AEMA, and ARCP were mostly low or negligible except the rG between DAYS90 and AEMA from model III (0.27 to 0.30). The rG between AEMA and ABF and between AEMA and ARCP were moderate but with negative and positive signs, respectively; also reflected influence of pre-adjustments. However, the rG between BF and RCP remained non-influential to trait pre-adjustments or covariable fits. Therefore, we conclude that ultrasound measures taken at a body weight of about 90 kg as the test final should be adjusted for body weight growth. Our adjustment formulas, particularly those for BF and EMA, should be revised further to accommodate the added variation due to different performance testing endpoints with regard to differential growth in body composition.

Inhibition of fucosylation of cell wall components by 2-fluoro 2-deoxy-L-fucose induces defects in root cell elongation.

PubMed

Dumont, Marie; Lehner, Arnaud; Bardor, Muriel; Burel, Carole; Vauzeilles, Boris; Lerouxel, Olivier; Anderson, Charles T; Mollet, Jean-Claude; Lerouge, Patrice

2015-12-01

Screening of commercially available fluoro monosaccharides as putative growth inhibitors in Arabidopsis thaliana revealed that 2-fluoro 2-l-fucose (2F-Fuc) reduces root growth at micromolar concentrations. The inability of 2F-Fuc to affect an Atfkgp mutant that is defective in the fucose salvage pathway indicates that 2F-Fuc must be converted to its cognate GDP nucleotide sugar in order to inhibit root growth. Chemical analysis of cell wall polysaccharides and glycoproteins demonstrated that fucosylation of xyloglucans and of N-linked glycans is fully inhibited by 10 μm 2F-Fuc in Arabidopsis seedling roots, but genetic evidence indicates that these alterations are not responsible for the inhibition of root development by 2F-Fuc. Inhibition of fucosylation of cell wall polysaccharides also affected pectic rhamnogalacturonan-II (RG-II). At low concentrations, 2F-Fuc induced a decrease in RG-II dimerization. Both RG-II dimerization and root growth were partially restored in 2F-Fuc-treated seedlings by addition of boric acid, suggesting that the growth phenotype caused by 2F-Fuc was due to a deficiency of RG-II dimerization. Closer investigation of the 2F-Fuc-induced growth phenotype demonstrated that cell division is not affected by 2F-Fuc treatments. In contrast, the inhibitor suppressed elongation of root cells and promoted the emergence of adventitious roots. This study further emphasizes the importance of RG-II in cell elongation and the utility of glycosyltransferase inhibitors as new tools for studying the functions of cell wall polysaccharides in plant development. Moreover, supplementation experiments with borate suggest that the function of boron in plants might not be restricted to RG-II cross-linking, but that it might also be a signal molecule in the cell wall integrity-sensing mechanism. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

Preclinical efficacy of the MDM2 inhibitor RG7112 in MDM2 amplified and TP53 wild-type glioblastomas

PubMed Central

Verreault, Maite; Schmitt, Charlotte; Goldwirt, Lauriane; Pelton, Kristine; Haidar, Samer; Levasseur, Camille; Guehennec, Jeremy; Knoff, David; Labussiere, Marianne; Marie, Yannick; Ligon, Azra H.; Mokhtari, Karima; Hoang-Xuan, Khe; Sanson, Marc; Alexander, Brian M; Wen, Patrick Y.; Delattre, Jean-Yves; Ligon, Keith L.; Idbaih, Ahmed

2016-01-01

Rationale p53 pathway alterations are key molecular events in glioblastoma (GBM). MDM2 inhibitors increase expression and stability of p53 and are presumed to be most efficacious in patients with TP53 wild-type and MDM2-amplified cancers. However, this biomarker hypothesis has not been tested in patients or patient-derived models for GBM. Methods We performed a preclinical evaluation of RG7112 MDM2 inhibitor, across a panel of 36 patient-derived GBM cell lines (PDCLs), each genetically characterized according to their P53 pathway status. We then performed a pharmacokinetic (PK) profiling of RG7112 distribution in mice and evaluated the therapeutic activity of RG7112 in orthotopic and subcutaneous GBM models. Results MDM2-amplified PDCLs were 44 times more sensitive than TP53 mutated lines that showed complete resistance at therapeutically attainable concentrations (avg. IC50 of 0.52 μM vs 21.9 μM). MDM4 amplified PDCLs were highly sensitive but showed intermediate response (avg. IC50 of 1.2 μM), whereas response was heterogeneous in TP53 wild-type PDCLs with normal MDM2/4 levels (avg. IC50 of 7.7 μM). In MDM2-amplified lines, RG7112 restored p53 activity inducing robust p21 expression and apoptosis. PK profiling of RG7112-treated PDCL intracranial xenografts demonstrated that the compound significantly crosses the blood-brain and the blood-tumor barriers. Most importantly, treatment of MDM2-amplified/TP53 wild-type PDCL-derived model (subcutaneous and orthotopic) reduced tumor growth, was cytotoxic, and significantly increased survival. Conclusion These data strongly support development of MDM2 inhibitors for clinical testing in MDM2-amplified GBM patients. Moreover, significant efficacy in a subset of non-MDM2 amplified models suggests that additional markers of response to MDM2 inhibitors must be identified. PMID:26482041

Pedigrees or markers: Which are better in estimating relatedness and inbreeding coefficient?

PubMed

Wang, Jinliang

2016-02-01

Individual inbreeding coefficient (F) and pairwise relatedness (r) are fundamental parameters in population genetics and have important applications in diverse fields such as human medicine, forensics, plant and animal breeding, conservation and evolutionary biology. Traditionally, both parameters are calculated from pedigrees, but are now increasingly estimated from genetic marker data. Conceptually, a pedigree gives the expected F and r values, FP and rP, with the expectations being taken (hypothetically) over an infinite number of individuals with the same pedigree. In contrast, markers give the realised (actual) F and r values at the particular marker loci of the particular individuals, FM and rM. Both pedigree (FP, rP) and marker (FM, rM) estimates can be used as inferences of genomic inbreeding coefficients FG and genomic relatedness rG, which are the underlying quantities relevant to most applications (such as estimating inbreeding depression and heritability) of F and r. In the pre-genomic era, it was widely accepted that pedigrees are much better than markers in delineating FG and rG, and markers should better be used to validate, amend and construct pedigrees rather than to replace them. Is this still true in the genomic era when genome-wide dense SNPs are available? In this simulation study, I showed that genomic markers can yield much better estimates of FG and rG than pedigrees when they are numerous (say, 10(4) SNPs) under realistic situations (e.g. genome and population sizes). Pedigree estimates are especially poor for species with a small genome, where FG and rG are determined to a large extent by Mendelian segregations and may thus deviate substantially from their expectations (FP and rP). Simulations also confirmed that FM, when estimated from many SNPs, can be much more powerful than FP for detecting inbreeding depression in viability. However, I argue that pedigrees cannot be replaced completely by genomic SNPs, because the former allows for the calculation of more complicated IBD coefficients (involving more than 2 individuals, more than one locus, and more than 2 genes at a locus) for which the latter may have reduced capacity or limited power, and because the former has social and other significance for remote relationships which have little genetic significance and cannot be inferred reliably from markers. Copyright © 2015 Elsevier Inc. All rights reserved.

Apparent Explosion Moments from Rg Waves Recorded on SPE: Implications for the Late-Time Damage Source Model

NASA Astrophysics Data System (ADS)

Patton, H. J.; Larmat, C. S.; Rougier, E.

2016-12-01

Seismic moments for chemical shots making up Phase I of the Source Physics Experiments (SPE) are estimated from 6 Hz Rg waves under the assumption that the shots are pure explosions. These apparent explosion moments are compared to moments determined using the Reduced Displacement Potential (RDP) method applied to free field data. LIDAR/photogrammetry observations, strong ground motions on the free surface near ground zero, and moment tensor inversion results are evidence in support of the fourth shot SPE-4P being essentially a pure explosion. The apparent moment for SPE-4P is 9 × 1010 Nm in good agreement with the RDP moment 8 × 1010 Nm. In stark contrast, apparent moments for the first three shots are three to four times smaller than RDP moments. Data show that spallation occurred on these shots, as well as permanent deformations detected with ground-based LIDAR. As such, the source medium suffered late-time damage. The late-time damage source model predicts destructive interference between Rg waves radiated by explosion and damage sources, which reduces amplitudes and explains why apparent moments are smaller than RDP moments based on compressional energy emitted directly from the source. SPE-5 was conducted at roughly the same yield-scaled burial depth as SPE-2 and -3, but with five times the yield. As such, the damage source model predicts less reduction of apparent moment. At this writing, preliminary results from Rg interferometry and RDP moments confirm this prediction. SPE-6 is scheduled for the fall of 2016, and it should have the strongest damage source of all SPE shots. The damage model predicts that the polarity of Rg waves could be reversed. Realization of this prediction will be strong confirmation of the late-time damage source model. This abstract has a Los Alamos National Laboratory Unlimited Release Number LA-UR-16-25709.

Shared genetic factors underlie migraine and depression

PubMed Central

Yang, Yuanhao; Zhao, Huiying; Heath, Andrew C; Madden, Pamela AF; Martin, Nicholas G; Nyholt, Dale R

2017-01-01

Migraine frequently co-occurs with depression. Using a large sample of Australian twin pairs, we aimed to characterise the extent to which shared genetic factors underlie these two disorders. Migraine was classified using three diagnostic measures, including self-reported migraine, the ID migraine™ screening tool, or migraine without aura (MO) and migraine with aura (MA) based on International Headache Society (IHS) diagnostic criteria. Major depressive disorder (MDD) and minor depressive disorder (MiDD) were classified using the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria. Univariate and bivariate twin models, with and without sex-limitation, were constructed to estimate the univariate and bivariate variance components and genetic correlation for migraine and depression. The univariate heritability of broad migraine (self-reported, ID migraine or IHS MO/MA) and broad depression (MiDD or MDD) was estimated at 56% (95% confidence interval [CI]: 53–60%) and 42% (95% CI: 37–46%), respectively. A significant additive genetic correlation (rG=0.36, 95% CI: 0.29–0.43) and bivariate heritability (h2=5.5%, 95% CI: 3.6–7.8%) was observed between broad migraine and depression using the bivariate Cholesky model. Notably, both the bivariate h2 (13.3%, 95% CI: 7.0–24.5%) and rG (0.51, 95% CI: 0.37–0.69) estimates significantly increased when analysing the more narrow clinically-accepted diagnoses of IHS MO/MA and MDD. Our results indicate that for both broad and narrow definitions, the observed comorbidity between migraine and depression can be explained almost entirely by shared underlying genetically determined disease mechanisms. PMID:27302564

The Genetic Architecture of Oral Language, Reading Fluency, and Reading Comprehension: A Twin Study From 7 to 16 Years

PubMed Central

2017-01-01

This study examines the genetic and environmental etiology underlying the development of oral language and reading skills, and the relationship between them, over a long period of developmental time spanning middle childhood and adolescence. It focuses particularly on the differential relationship between language and two different aspects of reading: reading fluency and reading comprehension. Structural equation models were applied to language and reading data at 7, 12, and 16 years from the large-scale TEDS twin study. A series of multivariate twin models show a clear patterning of oral language with reading comprehension, as distinct from reading fluency: significant but moderate genetic overlap between oral language and reading fluency (genetic correlation rg = .46–.58 at 7, 12, and 16) contrasts with very substantial genetic overlap between oral language and reading comprehension (rg = .81–.87, at 12 and 16). This pattern is even clearer in a latent factors model, fit to the data aggregated across ages, in which a single factor representing oral language and reading comprehension is correlated with—but distinct from—a second factor representing reading fluency. A distinction between oral language and reading fluency is also apparent in different developmental trajectories: While the heritability of oral language increases over the period from 7 to 12 to 16 years (from h2 = .27 to .47 to .55), the heritability of reading fluency is high and largely stable over the same period of time (h2 = .73 to .71 to .64). PMID:28541066

A quantitative genetic analysis of hibernation emergence date in a wild population of Columbian ground squirrels.

PubMed

Lane, J E; Kruuk, L E B; Charmantier, A; Murie, J O; Coltman, D W; Buoro, M; Raveh, S; Dobson, F S

2011-09-01

The life history schedules of wild organisms have long attracted scientific interest, and, in light of ongoing climate change, an understanding of their genetic and environmental underpinnings is increasingly becoming of applied concern. We used a multi-generation pedigree and detailed phenotypic records, spanning 18 years, to estimate the quantitative genetic influences on the timing of hibernation emergence in a wild population of Columbian ground squirrels (Urocitellus columbianus). Emergence date was significantly heritable [h(2) = 0.22 ± 0.05 (in females) and 0.34 ± 0.14 (in males)], and there was a positive genetic correlation (r(G) = 0.76 ± 0.22) between male and female emergence dates. In adult females, the heritabilities of body mass at emergence and oestrous date were h(2) = 0.23 ± 0.09 and h(2) = 0.18 ± 0.12, respectively. The date of hibernation emergence has been hypothesized to have evolved so as to synchronize subsequent reproduction with upcoming peaks in vegetation abundance. In support of this hypothesis, although levels of phenotypic variance in emergence date were higher than oestrous date, there was a highly significant genetic correlation between the two (r(G) = 0.98 ± 0.01). Hibernation is a prominent feature in the annual cycle of many small mammals, but our understanding of its influences lags behind that for phenological traits in many other taxa. Our results provide the first insight into its quantitative genetic influences and thus help contribute to a more general understanding of its evolutionary significance. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

Genetic and phenotypic relationships between and within support and demand tissues in a single line of broiler chicken.

PubMed

Rance, K A; McEntee, G M; McDevitt, R M

2002-09-01

1. With commercial selection for increased broiler performance there has been a correlated increase in the incidence of several metabolic disorders. A study was undertaken to investigate the balance between the unselected support tissues (including the heart, liver, spleen and the components of the gastrointestinal tract (GIT)) which drive growth in the selected demand tissues (eviscerated body mass) by assessing the genetic correlations between these traits. 2. Data were collected on 483 broiler birds taken from a commercial male broiler line with pedigree information. 3. Genetic parameters were estimated by restricted maximum likelihood with an individual animal model. Heritability estimates for the production traits ranged between h2 = 0.48 and 0.59 for leg and breast mass, respectively. The support tissues were generally associated with low to moderate heritabilities ranging between h2 = 0.19 for proventriculus to h2 = 0.38 for duodenum mass, although moderately high heritability estimates (h2 = 0.51 to 0.54) were associated with the spleen and gizzard. 4. The genetic correlations between production traits and support organs were generally low, however, heart mass was positively correlated with all carcase components of the lean tissue mass; the genetic correlations ranged between r(g) = 0.55 with breast mass to r(g) = 0.64 with eviscerated body mass. 5. In general, there were strong positive genetic correlations between the different components of the GIT. Organs that have been implicated in the development of metabolic disorders such as ascites (for example, the heart) could theoretically be used in commercial selection indices due to moderate heritabilities (heart: h2 = 0.30) and favourable correlations with commercially important traits.

Reversing Melanoma Cross-Resistance to BRAF and MEK Inhibitors by Co-Targeting the AKT/mTOR Pathway

PubMed Central

Attar, Narsis; Ng, Charles; Chu, Connie; Guo, Deliang; Nazarian, Ramin; Chmielowski, Bartosz; Glaspy, John A.; Comin-Anduix, Begonya; Mischel, Paul S.; Lo, Roger S.; Ribas, Antoni

2011-01-01

Background The sustained clinical activity of the BRAF inhibitor vemurafenib (PLX4032/RG7204) in patients with BRAFV600 mutant melanoma is limited primarily by the development of acquired resistance leading to tumor progression. Clinical trials are in progress using MEK inhibitors following disease progression in patients receiving BRAF inhibitors. However, the PI3K/AKT pathway can also induce resistance to the inhibitors of MAPK pathway. Methodology/Principal Findings The sensitivity to vemurafenib or the MEK inhibitor AZD6244 was tested in sensitive and resistant human melanoma cell lines exploring differences in activation-associated phosphorylation levels of major signaling molecules, leading to the testing of co-inhibition of the AKT/mTOR pathway genetically and pharmacologically. There was a high degree of cross-resistance to vemurafenib and AZD6244, except in two vemurafenib-resistant cell lines that acquired a secondary mutation in NRAS. In other cell lines, acquired resistance to both drugs was associated with persistence or increase in activity of AKT pathway. siRNA-mediated gene silencing and combination therapy with an AKT inhibitor or rapamycin partially or completely reversed the resistance. Conclusions/Significance Primary and acquired resistance to vemurafenib in these in vitro models results in frequent cross resistance to MEK inhibitors, except when the resistance is the result of a secondary NRAS mutation. Resistance to BRAF or MEK inhibitors is associated with the induction or persistence of activity within the AKT pathway in the presence of these drugs. This resistance can be potentially reversed by the combination of a RAF or MEK inhibitor with an AKT or mTOR inhibitor. These combinations should be available for clinical testing in patients progressing on BRAF inhibitors. PMID:22194965

Disease resistance in Atlantic salmon (Salmo salar): coinfection of the intracellular bacterial pathogen Piscirickettsia salmonis and the sea louse Caligus rogercresseyi.

PubMed

Lhorente, Jean Paul; Gallardo, José A; Villanueva, Beatriz; Carabaño, María J; Neira, Roberto

2014-01-01

Naturally occurring coinfections of pathogens have been reported in salmonids, but their consequences on disease resistance are unclear. We hypothesized that 1) coinfection of Caligus rogercresseyi reduces the resistance of Atlantic salmon to Piscirickettsia salmonis; and 2) coinfection resistance is a heritable trait that does not correlate with resistance to a single infection. In total, 1,634 pedigreed Atlantic salmon were exposed to a single infection (SI) of P. salmonis (primary pathogen) or coinfection with C. rogercresseyi (secondary pathogen). Low and high level of coinfection were evaluated (LC = 44 copepodites per fish; HC = 88 copepodites per fish). Survival and quantitative genetic analyses were performed to determine the resistance to the single infection and coinfections. C. rogercresseyi significantly increased the mortality in fish infected with P. salmonis (SI mortality = 251/545; LC mortality = 544/544 and HC mortality = 545/545). Heritability estimates for resistance to P. salmonis were similar and of medium magnitude in all treatments (h2SI = 0.23 ± 0.07; h2LC = 0.17 ± 0.08; h2HC = 0.24 ± 0.07). A large and significant genetic correlation with regard to resistance was observed between coinfection treatments (rg LC-HC = 0.99 ± 0.01) but not between the single and coinfection treatments (rg SI-LC = -0.14 ± 0.33; rg SI-HC = 0.32 ± 0.34). C. rogercresseyi, as a secondary pathogen, reduces the resistance of Atlantic salmon to the pathogen P. salmonis. Resistance to coinfection of Piscirickettsia salmonis and Caligus rogercresseyi in Atlantic salmon is a heritable trait. The absence of a genetic correlation between resistance to a single infection and resistance to coinfection indicates that different genes control these processes. Coinfection of different pathogens and resistance to coinfection needs to be considered in future research on salmon farming, selective breeding and conservation.

Genetic basis of semen traits and their relationship with growth rate in rabbits.

PubMed

Tusell, L; Legarra, A; García-Tomás, M; Rafel, O; Ramon, J; Piles, M

2012-05-01

This work aims to estimate the genetic parameters of seminal and production traits in a paternal line of rabbits selected for ADG during the fattening period. The considered traits were male libido (Lib) defined as successful mounting of an artificial vagina; presence of urine (Ur) and calcium carbonate deposits (Ca) in the ejaculate; semen pH; individual sperm motility (IM); the suitability for AI of the ejaculate (Sui), which involves the subjective combination of several quality traits; the average ejaculate volume (Vol); sperm concentration (Conc); and the average sperm production per ejaculate (Prod = Vol × Conc). The genetic relationship between all of these traits with ADG is also provided. Male libido and seminal data came either from routine evaluations of the ejaculates in an AI center or from 2 experiments in which bucks from the same population were used. Two consecutive ejaculates per male and per week were collected, leaving 7 d within weekly collections. A linear tri-trait model was used to analyze Conc, Vol, and ADG, whereas linear and threshold-linear 2-trait models were used to analyze male libido and the remaining seminal traits with ADG. A Bayesian approach was adopted for inference. Approximately 38% of ejaculates were rejected for AI primarily due to low IM scores. Variables related to the quality of the ejaculate (Ur, Ca, pH, IM, Sui) and Lib were found to be lowly heritable (h(2) ranged from 0.04 to 0.11), but repeatable. This indicates performance of bucks for seminal quality traits and libido in AI centers would be more strongly affected by management practices rather than genetic selection. Semen production traits exhibited moderate values of h(2) (0.22, 0.27, and 0.23 for Conc, Vol, and Prod, respectively), suggesting the possibility of effective selection for these traits. A moderate to high negative genetic correlation (r(g); posterior mean; highest posterior density at 95%, HPD(95%)) was estimated between Conc and Vol (-0.53, HPD(95%) = -0.76, -0.27). The ADG was estimated to have an h(2) of 0.16, to have a low, positive r(g) with Conc (0.21, HPD(95%) = -0.03, 0.48), to have a low, negative r(g) with Vol (-0.19, HPD(95%) = -0.47, 0.08), and to be genetically uncorrelated with all remaining traits analyzed. Therefore, selection for increasing ADG in paternal lines is expected to have no detrimental effects on Ur, Ca, pH, IM, Sui, and Lib and little to no effect on Conc, Vol, and Prod.

Endogenous Reference Genes and Their Quantitative Real-Time PCR Assays for Genetically Modified Bread Wheat (Triticum aestivum L.) Detection.

PubMed

Yang, Litao; Quan, Sheng; Zhang, Dabing

2017-01-01

Endogenous reference genes (ERG) and their derivate analytical methods are standard requirements for analysis of genetically modified organisms (GMOs). Development and validation of suitable ERGs is the primary step for establishing assays that monitoring the genetically modified (GM) contents in food/feed samples. Herein, we give a review of the ERGs currently used for GM wheat analysis, such as ACC1, PKABA1, ALMT1, and Waxy-D1, as well as their performances in GM wheat analysis. Also, we discussed one model for developing and validating one ideal RG for one plant species based on our previous research work.

CRISPR: a Versatile Tool for Both Forward and Reverse Genetics Research

PubMed Central

Gurumurthy, Channabasavaiah B.; Grati, M'hamed; Ohtsuka, Masato; Schilit, Samantha L.P.; Quadros, Rolen M.; Liu, Xue Zhong

2016-01-01

Human genetics research employs the two opposing approaches of forward and reverse genetics. While forward genetics identifies and links a mutation to an observed disease etiology, reverse genetics induces mutations in model organisms to study their role in disease. In most cases, causality for mutations identified by forward genetics is confirmed by reverse genetics through the development of genetically engineered animal models and an assessment of whether the model can recapitulate the disease. While many technological advances have helped improve these approaches, some gaps still remain. CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated) system, which has emerged as a revolutionary genetic engineering tool, holds great promise for closing such gaps. By combining the benefits of forward and reverse genetics, it has dramatically expedited human genetics research. We provide a perspective on the power of CRISPR-based forward and reverse genetics tools in human genetics and discuss its applications using some disease examples. PMID:27384229

Ginsenoside Rb1 inhibits fibrillation and toxicity of alpha-synuclein and disaggregates preformed fibrils.

PubMed

Ardah, Mustafa T; Paleologou, Katerina E; Lv, Guohua; Menon, Sindhu A; Abul Khair, Salema B; Lu, Jia-Hong; Safieh-Garabedian, Bared; Al-Hayani, Abdulmonem A; Eliezer, David; Li, Min; El-Agnaf, Omar M A

2015-02-01

Compelling evidence indicates that α-synuclein (α-syn) aggregation plays a central role in the pathogenesis of Parkinson's disease (PD) and other synucleinopathies. Identification of compounds that inhibit or reverse the aggregation process may thus represent a viable therapeutic strategy against PD and related disorders. Ginseng is a well-known medicinal plant that has been used in East Asia for more than two thousand years to treat several conditions. It is now understood that the pharmacological properties of ginseng can be attributed to its biologically active components, the ginsenosides, which in turn have been shown to have neuroprotective properties. We therefore sought to determine for the first time, the potential of the most frequently used and studied ginsenosides, namely Rg1, Rg3 and Rb1, as anti-amyloidogenic agents. The effect of Rg1, Rg3 and Rb1 on α-syn aggregation and toxicity was determined by an array of biophysical, biochemical and cell-culture-based techniques. Among the screened ginsenosides, only Rb1 was shown to be a potent inhibitor of α-syn fibrillation and toxicity. Additionally, Rb1 exhibited a strong ability to disaggregate preformed fibrils and to inhibit the seeded polymerization of α-syn. Interestingly, Rb1 was found to stabilize soluble non-toxic oligomers with no β-sheet content, that were susceptible to proteinase K digestion, and the binding of Rb1 to those oligomers may represent a potential mechanism of action. Thus, Rb1 could represent the starting point for designing new molecules that could be utilized as drugs for the treatment of PD and related disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

Field theory of the inverse cascade in two-dimensional turbulence

NASA Astrophysics Data System (ADS)

Mayo, Jackson R.

2005-11-01

A two-dimensional fluid, stirred at high wave numbers and damped by both viscosity and linear friction, is modeled by a statistical field theory. The fluid’s long-distance behavior is studied using renormalization-group (RG) methods, as begun by Forster, Nelson, and Stephen [Phys. Rev. A 16, 732 (1977)]. With friction, which dissipates energy at low wave numbers, one expects a stationary inverse energy cascade for strong enough stirring. While such developed turbulence is beyond the quantitative reach of perturbation theory, a combination of exact and perturbative results suggests a coherent picture of the inverse cascade. The zero-friction fluctuation-dissipation theorem (FDT) is derived from a generalized time-reversal symmetry and implies zero anomalous dimension for the velocity even when friction is present. Thus the Kolmogorov scaling of the inverse cascade cannot be explained by any RG fixed point. The β function for the dimensionless coupling ĝ is computed through two loops; the ĝ3 term is positive, as already known, but the ĝ5 term is negative. An ideal cascade requires a linear β function for large ĝ , consistent with a Padé approximant to the Borel transform. The conjecture that the Kolmogorov spectrum arises from an RG flow through large ĝ is compatible with other results, but the accurate k-5/3 scaling is not explained and the Kolmogorov constant is not estimated. The lack of scale invariance should produce intermittency in high-order structure functions, as observed in some but not all numerical simulations of the inverse cascade. When analogous RG methods are applied to the one-dimensional Burgers equation using an FDT-preserving dimensional continuation, equipartition is obtained instead of a cascade—in agreement with simulations.

Applications of the discrete Enskog-Boltzmann approach

NASA Astrophysics Data System (ADS)

Chu, Kwang-Hua Rainer

1998-08-01

The continuous progress of micromachining technology has led to a growing interest in MicroElectroMechanical System (MEMS) for applications ranging from simple microsensors and microactuators to sophisticated microsystems. The characteristic length scale of these microdevices will be of the order of sub-microns so that the gas flow in this environment is within the rarified gas (RG) regime. In this PhD work, the mass/momentum/energy transport of the monatomic gases along the microchannel and the dispersion/attenuation of 1-D ultrasound propagation (plane wave) of RG are investigated by using the Discrete Enskog-Boltzmann approaches. We applied the 4-velocity coplanar model to plane Poiseuille flow of RG in microchannels. Firstly we reported a steady-state solution for this flow with a final-stage uniform density distribution. Then, we modified the model by introducing a density ratio to accomodate the density variations along the microchannel and to include the grazing-collision effects. We also borrowed thee idea from the Extended Irreversible/Reversible Thermodynamics to derive the pressure-gradient for the dimensional velocity field. Our results show the Knudsen minimum of the non- dimensional volume flow rate for Knudsen number (Kn) around 1.5. Using the macroscopic velocity fields, with Cercignani's comments for the 'Kinetic Temperature', we can calculate the related temperature distribution across the microchannel. We also checked the thermodynamic or equilibrium properties of 4-, 6-, and 8-velocity models, by calculating the dispersion relation of 1-D plane ultrasound wave propagation in the RG regime which has large Kn of O(1). The results (after comparison with the measurements) confirmed that the 4-velocity model is the most suitable model for our applications.

Genetic parameters and genome-wide association study of hyperpigmentation of the visceral peritoneum in chickens.

PubMed

Luo, Chenglong; Qu, Hao; Wang, Jie; Wang, Yan; Ma, Jie; Li, Chunyu; Yang, Chunfen; Hu, Xiaoxiang; Li, Ning; Shu, Dingming

2013-05-16

Hyperpigmentation of the visceral peritoneum (HVP) has recently garnered much attention in the poultry industry because of the possible risk to the health of affected animals and the damage it causes to the appearance of commercial chicken carcasses. However, the heritable characters of HVP remain unclear. The objective of this study was to investigate the genetic parameters of HVP by genome-wide association study (GWAS) in chickens. HVP was found to be influenced by genetic factors, with a heritability score of 0.33. HVP had positive genetic correlations with growth and carcass traits, such as leg muscle weight (rg = 0.34), but had negative genetic correlations with immune traits, such as the antibody response to Newcastle disease virus (rg = -0.42). The GWAS for HVP using 39,833 single nucleotide polymorphisms indicated the genetic factors associated with HVP displayed an additive effect rather than a dominance effect. In addition, we determined that three genomic regions, involving the 50.5-54.0 Mb region of chicken (Gallus gallus) chromosome 1 (GGA1), the 58.5-60.5 Mb region of GGA1, and the 10.5-12.0 Mb region of GGA20, were strongly associated (P < 6.28 × 10-7) with HVP in chickens. Variants in these regions explained >50% of additive genetic variance for HVP. This study also confirmed that expression of BMP7, which codes for a bone morphogenetic protein and is located in one of the candidate regions, was significantly higher in the visceral peritoneum of Huiyang Beard chickens with HVP than in that of chickens without pigmentation (P < 0.05). HVP is a quantitative trait with moderate heritability. Genomic variants resulting in HVP were identified on GGA1 and GGA20, and expression of the BMP7 gene appears to be upregulated in HVP-affected chickens. Findings from this study should be used as a basis for further functional validation of candidate genes involved in HVP.

Bioinformatics approach for choosing the correct reference genes when studying gene expression in human keratinocytes.

PubMed

Beer, Lucian; Mlitz, Veronika; Gschwandtner, Maria; Berger, Tanja; Narzt, Marie-Sophie; Gruber, Florian; Brunner, Patrick M; Tschachler, Erwin; Mildner, Michael

2015-10-01

Reverse transcription polymerase chain reaction (qRT-PCR) has become a mainstay in many areas of skin research. To enable quantitative analysis, it is necessary to analyse expression of reference genes (RGs) for normalization of target gene expression. The selection of reliable RGs therefore has an important impact on the experimental outcome. In this study, we aimed to identify and validate the best suited RGs for qRT-PCR in human primary keratinocytes (KCs) over a broad range of experimental conditions using the novel bioinformatics tool 'RefGenes', which is based on a manually curated database of published microarray data. Expression of 6 RGs identified by RefGenes software and 12 commonly used RGs were validated by qRT-PCR. We assessed whether these 18 markers fulfilled the requirements for a valid RG by the comprehensive ranking of four bioinformatics tools and the coefficient of variation (CV). In an overall ranking, we found GUSB to be the most stably expressed RG, whereas the expression values of the commonly used RGs, GAPDH and B2M were significantly affected by varying experimental conditions. Our results identify RefGenes as a powerful tool for the identification of valid RGs and suggest GUSB as the most reliable RG for KCs. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Generation of Human Liver Chimeric Mice with Hepatocytes from Familial Hypercholesterolemia Induced Pluripotent Stem Cells.

PubMed

Yang, Jiayin; Wang, Yu; Zhou, Ting; Wong, Lai-Yung; Tian, Xiao-Yu; Hong, Xueyu; Lai, Wing-Hon; Au, Ka-Wing; Wei, Rui; Liu, Yuqing; Cheng, Lai-Hung; Liang, Guichan; Huang, Zhijian; Fan, Wenxia; Zhao, Ping; Wang, Xiwei; Ibañez, David P; Luo, Zhiwei; Li, Yingying; Zhong, Xiaofen; Chen, Shuhan; Wang, Dongye; Li, Li; Lai, Liangxue; Qin, Baoming; Bao, Xichen; Hutchins, Andrew P; Siu, Chung-Wah; Huang, Yu; Esteban, Miguel A; Tse, Hung-Fat

2017-03-14

Familial hypercholesterolemia (FH) causes elevation of low-density lipoprotein cholesterol (LDL-C) in blood and carries an increased risk of early-onset cardiovascular disease. A caveat for exploration of new therapies for FH is the lack of adequate experimental models. We have created a comprehensive FH stem cell model with differentiated hepatocytes (iHeps) from human induced pluripotent stem cells (iPSCs), including genetically engineered iPSCs, for testing therapies for FH. We used FH iHeps to assess the effect of simvastatin and proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies on LDL-C uptake and cholesterol lowering in vitro. In addition, we engrafted FH iHeps into the liver of Ldlr -/- /Rag2 -/- /Il2rg -/- mice, and assessed the effect of these same medications on LDL-C clearance and endothelium-dependent vasodilation in vivo. Our iHep models recapitulate clinical observations of higher potency of PCSK9 antibodies compared with statins for reversing the consequences of FH, demonstrating the utility for preclinical testing of new therapies for FH patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of acupuncturing Pishu combined with Ginsenoside Rg3 on the immune function of rats with chronic fatigue.

PubMed

Zhang, Wenjing; Zhang, Yue; Ma, Xiande; Chen, Yiguo

2015-01-01

This study was designed to investigate the effects of acupuncturing Pishu combined with Ginsenoside Rg3 on the immune function of rats with chronic fatigue. Forty male SD rats were equally randomized into control group, chronic fatigue system group (CFS), Ginsenoside Rg3 (Rg3) group, acupuncture group and acupuncture combined with Ginsenoside Rg3 (A+Rg3) group. Rats with chronic fatigue were established by bounding and forced swimming in cold water once daily for 21 days except control group, then the rats in the acupuncture and A+Rg3 group were treated by manual acupuncture stimulation of bilateral "Pishu" once daily for 7 days. Ginsenoside Rg3 was administered by intravenous to the rats of the A+Rg3 and Rg3 group for 7 days in dosages of 2 mg/kg body weight, and two markers of physical fatigue were evaluated: body weight and blood lactic acid (LA). The percentages of CD3(+) lymphocytes, CD4(+) lymphocytes, and CD8(+) lymphocytes in the spleens of the rats were evaluated using flow cytometric analysis. Serum IFN-gamma (IFN-γ) and IL-4 contents were detected by ELISA. Increased body weight and reduced blood LA concentrations were found in the rat of Rg3 group and A+Rg3 group than that in CFS group. The rat of Rg3 group and A+Rg3 group also showed a significant increase in the percentage of CD4(+) lymphocytes and a significant decrease in the percentage of CD8(+) lymphocytes and correct CD4(+)/CD8(+) ratio. Compared with the CFS group, the level of IFN-γ in the Rg3, acupuncture and A+Rg3 groups was reduced and IL-4 was increased. Acupuncture and Rg3 can improve the immune system activity of CFS rats and acupuncturing Pishu combined with Rg3 was significantly superior compared with Rg3 and acupuncture, respectively.

Public Awareness and Practice of Responsible Gambling in Macao.

PubMed

Tong, Kwok-Kit; Hung, Eva P W; Lei, Caren M W; Wu, Anise M S

2018-01-30

Responsible gambling (RG) is a relatively new concept to the Macao gambling industry. Although recent studies reported a heightened public awareness of RG, the prevalence of disordered gambling is still high. This discrepancy may suggest an existing gap between RG awareness and gambling practices, pinpointing aspects that need to be improved by different RG stakeholders. The gap may be attributable to people's limited knowledge toward practices favoring RG. To explore means for enhancing the RG campaign, we studied Macao residents' interpretation and adoption of RG practices. In Study 1, a random community sample was collected to assess the extent to which common RG practices were adopted. Results suggested that there was a fair proportion of gamblers not adhering to them and gambling disorder tendency was related to the adoption of RG practices. It implied a successful promotion of RG practices may reduce gambling problems. In Study 2, focus group discussions were conducted to explore how RG was conceptualized. Twenty-five participants (including 11 casino employees) took part in four focus group interviews. All participants were aware of RG but their knowledge of RG practices was limited. Very few of them were able to identify major practices such as putting constraints on gambling amount and time and the application for self-exclusion. We argue that future RG promotion needs to be more specific and behavior-oriented and it should also address various procedural concerns on how RG practices can be implemented.

Genetic Factors Influencing Coagulation Factor XIII B-Subunit Contribute to Risk of Ischemic Stroke.

PubMed

Hanscombe, Ken B; Traylor, Matthew; Hysi, Pirro G; Bevan, Stephen; Dichgans, Martin; Rothwell, Peter M; Worrall, Bradford B; Seshadri, Sudha; Sudlow, Cathie; Williams, Frances M K; Markus, Hugh S; Lewis, Cathryn M

2015-08-01

Abnormal coagulation has been implicated in the pathogenesis of ischemic stroke, but how this association is mediated and whether it differs between ischemic stroke subtypes is unknown. We determined the shared genetic risk between 14 coagulation factors and ischemic stroke and its subtypes. Using genome-wide association study results for 14 coagulation factors from the population-based TwinsUK sample (N≈2000 for each factor), meta-analysis results from the METASTROKE consortium ischemic stroke genome-wide association study (12 389 cases, 62 004 controls), and genotype data for 9520 individuals from the WTCCC2 ischemic stroke study (3548 cases, 5972 controls-the largest METASTROKE subsample), we explored shared genetic risk for coagulation and stroke. We performed three analyses: (1) a test for excess concordance (or discordance) in single nucleotide polymorphism effect direction across coagulation and stroke, (2) an estimation of the joint effect of multiple coagulation-associated single nucleotide polymorphisms in stroke, and (3) an evaluation of common genetic risk between coagulation and stroke. One coagulation factor, factor XIII subunit B (FXIIIB), showed consistent effects in the concordance analysis, the estimation of polygenic risk, and the validation with genotype data, with associations specific to the cardioembolic stroke subtype. Effect directions for FXIIIB-associated single nucleotide polymorphisms were significantly discordant with cardioembolic disease (smallest P=5.7×10(-04)); the joint effect of FXIIIB-associated single nucleotide polymorphisms was significantly predictive of ischemic stroke (smallest P=1.8×10(-04)) and the cardioembolic subtype (smallest P=1.7×10(-04)). We found substantial negative genetic covariation between FXIIIB and ischemic stroke (rG=-0.71, P=0.01) and the cardioembolic subtype (rG=-0.80, P=0.03). Genetic markers associated with low FXIIIB levels increase risk of ischemic stroke cardioembolic subtype. © 2015 The Authors.

Results from six generations of selection for intramuscular fat in Duroc swine using real-time ultrasound. II. Genetic parameters and trends.

PubMed

Schwab, C R; Baas, T J; Stalder, K J

2010-01-01

Design of breeding programs requires knowledge of variance components that exist for traits included in specific breeding goals and the genetic relationships that exist among traits of economic importance. A study was conducted to evaluate direct and correlated genetic responses to selection for intramuscular fat (IMF) and to estimate genetic parameters for economically important traits in Duroc swine. Forty gilts were purchased from US breeders and randomly mated for 2 generations to boars available in regional boar studs to develop a base population of 56 litters. Littermate pairs of gilts from this population were randomly assigned to a select line (SL) or control line (CL) and mated to the same boar to establish genetic ties between lines. In the SL, the top 10 boars and 75 gilts were selected based on IMF EBV obtained from a bivariate animal model that included IMF evaluated on the carcass and IMF predicted via ultrasound. One boar from each sire family and 50 to 60 gilts representing all sire families were randomly selected to maintain the CL. Carcass and ultrasound IMF were both moderately heritable (0.31 and 0.38, respectively). Moderate to high genetic relationships were estimated among carcass backfat and meat quality measures of IMF, Instron tenderness, and objective loin muscle color. Based on estimates obtained in this study, more desirable genetic merit for pH is associated with greater genetic value for loin color, tenderness, and sensory characteristics. Intramuscular fat measures obtained on the carcass and predicted using ultrasound technology were highly correlated (r(g) = 0.86 from a 12-trait analysis; r(g) = 0.90 from a 5-trait analysis). Estimated genetic relationships among IMF measures and other traits evaluated were generally consistent. Intramuscular fat measures were also genetically associated with Instron tenderness and flavor score in a desirable direction. Direct genetic response in IMF measures observed in the SL corresponded to a significant decrease in EBV for carcass loin muscle area (-0.90 cm(2) per generation) and an increase in carcass backfat EBV (0.98 mm per generation). Selection for IMF has led to more desirable EBV for objective tenderness and has had an adverse effect on additive genetic merit for objective loin color.

Disease Resistance in Atlantic Salmon (Salmo salar): Coinfection of the Intracellular Bacterial Pathogen Piscirickettsia salmonis and the Sea Louse Caligus rogercresseyi

PubMed Central

Lhorente, Jean Paul; Gallardo, José A.; Villanueva, Beatriz; Carabaño, María J.; Neira, Roberto

2014-01-01

Background Naturally occurring coinfections of pathogens have been reported in salmonids, but their consequences on disease resistance are unclear. We hypothesized that 1) coinfection of Caligus rogercresseyi reduces the resistance of Atlantic salmon to Piscirickettsia salmonis; and 2) coinfection resistance is a heritable trait that does not correlate with resistance to a single infection. Methodology In total, 1,634 pedigreed Atlantic salmon were exposed to a single infection (SI) of P. salmonis (primary pathogen) or coinfection with C. rogercresseyi (secondary pathogen). Low and high level of coinfection were evaluated (LC = 44 copepodites per fish; HC = 88 copepodites per fish). Survival and quantitative genetic analyses were performed to determine the resistance to the single infection and coinfections. Main Findings C. rogercresseyi significantly increased the mortality in fish infected with P. salmonis (SI mortality = 251/545; LC mortality = 544/544 and HC mortality = 545/545). Heritability estimates for resistance to P. salmonis were similar and of medium magnitude in all treatments (h 2 SI = 0.23±0.07; h 2 LC = 0.17±0.08; h 2 HC = 0.24±0.07). A large and significant genetic correlation with regard to resistance was observed between coinfection treatments (rg LC-HC = 0.99±0.01) but not between the single and coinfection treatments (rg SI-LC = −0.14±0.33; rg SI-HC = 0.32±0.34). Conclusions/Significance C. rogercresseyi, as a secondary pathogen, reduces the resistance of Atlantic salmon to the pathogen P. salmonis. Resistance to coinfection of Piscirickettsia salmonis and Caligus rogercresseyi in Atlantic salmon is a heritable trait. The absence of a genetic correlation between resistance to a single infection and resistance to coinfection indicates that different genes control these processes. Coinfection of different pathogens and resistance to coinfection needs to be considered in future research on salmon farming, selective breeding and conservation. PMID:24736323

Reverse Genetics for Mammalian Orthoreovirus.

PubMed

Stuart, Johnasha D; Phillips, Matthew B; Boehme, Karl W

2017-01-01

Reverse genetics allows introduction of specific alterations into a viral genome. Studies performed with mutant viruses generated using reverse genetics approaches have contributed immeasurably to our understanding of viral replication and pathogenesis, and also have led to development of novel vaccines and virus-based vectors. Here, we describe the reverse genetics system that allows for production and recovery of mammalian orthoreovirus, a double-stranded (ds) RNA virus, from plasmids that encode the viral genome.

Archaeal Genome Organization and Stress Responses: Implications for the Origin and Evolution of Cellular Life

NASA Astrophysics Data System (ADS)

Musgrave, David; Zhang, Xiaoying; Dinger, Marcel

2002-08-01

For DNA to be used as an informational molecule it must exist in the cell on the edge of stability because all genomic processes require local controlled melting. This presents mechanistic opportunities and problems for genomic DNA from hyperthermophilic organisms, whose unpackaged DNA could melt at optimal temperatures for growth. Hyperthermophiles are suggested to employ the novel positively supercoiling topoisomerase enzyme reverse gyrase (RG) to form positively supercoiled DNA that is intrinsically resistant to thermal denaturation. RG is presently the only archaeal gene that is uniquely found in hyperthermophiles and therefore is central to hypotheses suggesting a hypothermophilic origin of life. However, the suggestion that RG has evolved by the fusion of two pre-existing enzymes has led to hypotheses for a lower temperature for the origin of life. In addition to the action of topoisomerases, DNA packaging and the intracellular ionic environment can also manipulate DNA topology significantly. In the Euryarchaeota, nucleosomes containing minimal histones can adopt two alternate DNA topologies in a salt-dependent manner. From this we hypothesize that since internal salt concentrations are increased following an increase in temperature, the genomic effects of temperature fluctuations could also be accommodated by changes in nucleosome organization. In addition, stress-induced changes in the nucleoid proteins could also play a role in maintaining the genome in the optimal topological state in changing environments. The function of these systems could therefore be central to temperature adaptation and thus be implicated in origin of life scenarios involving hyperthermophiles.

An Approach to the Design of a Particulate System for Oral Protein Delivery .II. Preparation and Stability Study of rhGH-Loaded Microspheres in Simulated Gastrointestinal Fluids

PubMed Central

Nafissi Varcheh, Nastaran; Aboofazeli, Reza

2011-01-01

The delivery of therapeutic proteins has gained momentum with development of biotechnology. However, large molecular weight, hydrophilic nature and susceptibility to harsh environment of gastrointestinal tract (GIT) resulted in low absorption. The main objective of this work was the design of a particulate system for oral delivery of recombinant human growth hormone (rhGH) on the basis of particle uptake mechanism in GIT. Biodegradable protein-loaded microspheres were prepared using Resomers (RG207, RG756 and RG505) by double emulsion methods. Aqueous solution of protein and freshly prepared rhGH-zinc complex were used for loading process. Various analytical methods, including fluorescence spectroscopy, SDS-PAGE electrophoresis and reversed-phase chromatography, were set up for the quantification and qualification of rhGH before and after the formulation and fabrication procedures. At the optimum conditions, microspheres were mostly below 10 μm with relatively high protein loading (> 50%). Obtained data showed that the stability of protein did not change during the formulation and microencapsulation processes. Results also showed that the encapsulation process in the presence of zinc caused no detectable change in the protein chemical stability. In-vitro stability study of microspheres in different simulated GI media indicated that the entrapped protein was physically stable. Less than 20% of rhGH was released from the microspheres incubated in both simulated stomach and intestine fluids for 3 and 6 h, respectively. PMID:24250342

Formation of Rhamnogalacturonan II-Borate Dimer in Pectin Determines Cell Wall Thickness of Pumpkin Tissue1

PubMed Central

Ishii, Tadashi; Matsunaga, Toshiro; Hayashi, Noriko

2001-01-01

Boron (B) deficiency results in inhibition of pumpkin (Cucurbia moschata Duchesne) growth that is accompanied by swelling of the cell walls. Monomeric rhamnogalacturonan II (mRG-II) accounted for 80% to 90% of the total RG-II in B-deficient walls, whereas the borate ester cross-linked RG-II dimer (dRG-II-B) accounted for more than 80% of the RG-II in control plants. The results of glycosyl residue and glycosyl linkage composition analyses of the RG-II from control and B-deficient plants were similar. Thus, B deficiency does not alter the primary structure of RG-II. The addition of 10B-enriched boric acid to B-deficient plants resulted within 5 h in the conversion of mRG-II to dRG-II-10B. The wall thickness of the 10B-treated plants and control plants was similar. The formation and possible functions of a borate ester cross-linked RG-II in the cell walls are discussed. PMID:11500567

The genetic architecture of pediatric cognitive abilities in the Philadelphia Neurodevelopmental Cohort

PubMed Central

Robinson, Elise B.; Kirby, Andrew; Ruparel, Kosha; Yang, Jian; McGrath, Lauren; Anttila, Verneri; Neale, Benjamin M.; Merikangas, Kathleen; Lehner, Thomas; Sleiman, Patrick M.A.; Daly, Mark J.; Gur, Ruben; Gur, Raquel; Hakonarson, Hakon

2014-01-01

The objective of this analysis was to examine the genetic architecture of diverse cognitive abilities in children and adolescents, including the magnitude of common genetic effects and patterns of shared and unique genetic influences. Subjects included 3,689 members of the Philadelphia Neurodevelopmental Cohort, a general population sample of ages 8-21 years who completed an extensive battery of cognitive tests. We used genome-wide complex trait analysis (GCTA) to estimate the SNP-based heritability of each domain, as well as the genetic correlation between all domains that showed significant genetic influence. Several of the individual domains suggested strong influence of common genetic variants (e.g. reading ability, h2g=0.43, p=4e-06; emotion identification, h2g=0.36, p=1e-05; verbal memory, h2g=0.24, p=0.005). The genetic correlations highlighted trait domains that are candidates for joint interrogation in future genetic studies (e.g. language reasoning and spatial reasoning, r(g)=0.72, p=0.007). These results can be used to structure future genetic and neuropsychiatric investigations of diverse cognitive abilities. PMID:25023143

Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia

PubMed Central

Kiel, Mark J.; Velusamy, Thirunavukkarasu; Rolland, Delphine; Sahasrabuddhe, Anagh A.; Chung, Fuzon; Bailey, Nathanael G.; Schrader, Alexandra; Li, Bo; Li, Jun Z.; Ozel, Ayse B.; Betz, Bryan L.; Miranda, Roberto N.; Medeiros, L. Jeffrey; Zhao, Lili; Herling, Marco

2014-01-01

The comprehensive genetic alterations underlying the pathogenesis of T-cell prolymphocytic leukemia (T-PLL) are unknown. To address this, we performed whole-genome sequencing (WGS), whole-exome sequencing (WES), high-resolution copy-number analysis, and Sanger resequencing of a large cohort of T-PLL. WGS and WES identified novel mutations in recurrently altered genes not previously implicated in T-PLL including EZH2, FBXW10, and CHEK2. Strikingly, WGS and/or WES showed largely mutually exclusive mutations affecting IL2RG, JAK1, JAK3, or STAT5B in 38 of 50 T-PLL genomes (76.0%). Notably, gain-of-function IL2RG mutations are novel and have not been reported in any form of cancer. Further, high-frequency mutations in STAT5B have not been previously reported in T-PLL. Functionally, IL2RG-JAK1-JAK3-STAT5B mutations led to signal transducer and activator of transcription 5 (STAT5) hyperactivation, transformed Ba/F3 cells resulting in cytokine-independent growth, and/or enhanced colony formation in Jurkat T cells. Importantly, primary T-PLL cells exhibited constitutive activation of STAT5, and targeted pharmacologic inhibition of STAT5 with pimozide induced apoptosis in primary T-PLL cells. These results for the first time provide a portrait of the mutational landscape of T-PLL and implicate deregulation of DNA repair and epigenetic modulators as well as high-frequency mutational activation of the IL2RG-JAK1-JAK3-STAT5B axis in the pathogenesis of T-PLL. These findings offer opportunities for novel targeted therapies in this aggressive leukemia. PMID:24825865

Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia.

PubMed

Kiel, Mark J; Velusamy, Thirunavukkarasu; Rolland, Delphine; Sahasrabuddhe, Anagh A; Chung, Fuzon; Bailey, Nathanael G; Schrader, Alexandra; Li, Bo; Li, Jun Z; Ozel, Ayse B; Betz, Bryan L; Miranda, Roberto N; Medeiros, L Jeffrey; Zhao, Lili; Herling, Marco; Lim, Megan S; Elenitoba-Johnson, Kojo S J

2014-08-28

The comprehensive genetic alterations underlying the pathogenesis of T-cell prolymphocytic leukemia (T-PLL) are unknown. To address this, we performed whole-genome sequencing (WGS), whole-exome sequencing (WES), high-resolution copy-number analysis, and Sanger resequencing of a large cohort of T-PLL. WGS and WES identified novel mutations in recurrently altered genes not previously implicated in T-PLL including EZH2, FBXW10, and CHEK2. Strikingly, WGS and/or WES showed largely mutually exclusive mutations affecting IL2RG, JAK1, JAK3, or STAT5B in 38 of 50 T-PLL genomes (76.0%). Notably, gain-of-function IL2RG mutations are novel and have not been reported in any form of cancer. Further, high-frequency mutations in STAT5B have not been previously reported in T-PLL. Functionally, IL2RG-JAK1-JAK3-STAT5B mutations led to signal transducer and activator of transcription 5 (STAT5) hyperactivation, transformed Ba/F3 cells resulting in cytokine-independent growth, and/or enhanced colony formation in Jurkat T cells. Importantly, primary T-PLL cells exhibited constitutive activation of STAT5, and targeted pharmacologic inhibition of STAT5 with pimozide induced apoptosis in primary T-PLL cells. These results for the first time provide a portrait of the mutational landscape of T-PLL and implicate deregulation of DNA repair and epigenetic modulators as well as high-frequency mutational activation of the IL2RG-JAK1-JAK3-STAT5B axis in the pathogenesis of T-PLL. These findings offer opportunities for novel targeted therapies in this aggressive leukemia. © 2014 by The American Society of Hematology.

Identification of the molecular genetic basis of the low palmitic acid seed oil trait in soybean mutant line RG3 and association analysis of molecular markers with elevated seed stearic acid and reduced seed palmitic acid

USDA-ARS?s Scientific Manuscript database

The fatty acid composition of vegetable oil is becoming increasingly critical for the ultimate functionality and utilization in foods and industrial products. Partial chemical hydrogenation of soybean oil increases oxidative stability and shelf life but also results in the introduction of trans fats...

Germanium Does Not Substitute for Boron in Cross-Linking of Rhamnogalacturonan II in Pumpkin Cell Walls1

PubMed Central

Ishii, Tadashi; Matsunaga, Toshiro; Iwai, Hiroaki; Satoh, Shinobu; Taoshita, Junji

2002-01-01

Boron (B)-deficient pumpkin (Cucurbita moschata Duchesne) plants exhibit reduced growth, and their tissues are brittle. The leaf cell walls of these plants contain less than one-half the amount of borate cross-linked rhamnogalacturonan II (RG-II) dimer than normal plants. Supplying germanium (Ge), which has been reported to substitute for B, to B-deficient plants does not restore growth or reduce tissue brittleness. Nevertheless, the leaf cell walls of the Ge-treated plants accumulated considerable amounts of Ge. Dimeric RG-II (dRG-II) accounted for between 20% and 35% of the total RG-II in the cell walls of the second to fourth leaves from Ge-treated plants, but only 2% to 7% of the RG-II was cross-linked by germanate (dRG-II-Ge). The ability of RG-II to form a dimer is not reduced by Ge treatment because approximately 95% of the monomeric RG-II generated from the walls of Ge-treated plants is converted to dRG-II-Ge in vitro in the presence of germanium oxide and lead acetate. However, dRG-II-Ge is unstable and is converted to monomeric RG-II when the Ge is removed. Therefore, the content of dRG-II-Ge and dRG-II-B described above may not reflect the actual ratio of these in muro. 10B-Enriched boric acid and Ge are incorporated into the cell wall within 10 min after their foliar application to B-deficient plants. Foliar application of 10B but not Ge results in an increase in the proportion of dRG-II in the leaf cell wall. Taken together, our results suggest that Ge does not restore the growth of B-deficient plants. PMID:12481079

Adjuvant effects of protopanaxadiol and protopanaxatriol saponins from ginseng roots on the immune responses to ovalbumin in mice.

PubMed

Sun, Jianhua; Hu, Songhua; Song, Xiaoming

2007-01-22

Protopanaxadiol saponins (Rg3, Rd, Rc, Rb1 and Rb2) and protopanaxatriol saponins (Rg1, Re and Rg2) isolated from the root of Panax ginseng C.A. Meyer were evaluated for their adjuvant effects on the immune responses to ovalbumin (OVA) in mice. BALB/c mice were subcutaneously injected twice at a 3-week interval with 10 microg of ovalbumin or 10 microg of OVA plus 50 microg of ginsenosides Rg3, Rd, Rc, Rb1, Rb2, Rg1, Re or Rg2 or Quil A (n=5). Blood samples were collected for measuring specific total-IgG, IgG1 and IgG2a, and splenocytes were harvested for determining lymphocyte proliferation as well as IFN-gamma and IL-5 production 2 weeks after the boosting. The results indicated that OVA-specific antibody responses were significantly higher in mice immunized with OVA co-administered with Rg1, Re, Rg2, Rg3 and Rb1 but not with Rd, Rc and Rb2 when compared with the control (immunized with OVA only). Significantly enhanced splenocyte proliferative responses to Con A, LPS and OVA as well as the production of both IL-5 and IFN-gamma stimulated by OVA were also detected in mice immunized with OVA co-administered with Rg1 but not with Rb1, Re and Rg3. Of the ginsenosides studied, Rg1, Re, Rg2, Rg3 and Rb1 have more potent adjuvant properties than the others, indicating that they are the major constituents contributing to the adjuvant activities of total ginseng saponins. Varieties of ginsenosides in adjuvant activity might be attributed to the varieties of molecular conformations determined by the side sugar chains attaching to their dammarane skeleton.

Ginsenoside Rg3 regulates S-nitrosylation of the NLRP3 inflammasome via suppression of iNOS

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

Yoon, Sung-Jin; Park, Jun-Young; Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon

Ginsenoside Rg3, a specific biological effector, is well-known as a major bioactive ingredient of Panax ginseng. However, its role in the inflammasome activation process remains unclear. In this report, we demonstrate that ginsenosides 20(R)-Rg3 and 20(S)-Rg3 are capable of suppressing both lethal endotoxic shock and the S-nitrosylation of the NLRP3 inflammasome by inhibiting nitric oxide (NO) production through the regulation of inducible nitric oxide synthase (iNOS) expression. In response to lipopolysaccharide (LPS), the reducing effect of 20(S)-Rg3 and 20(R)-Rg3 on nitric oxide led to an increase in the survival time of mice after lethal endotoxin-induced shock, and excess levels ofmore » NO inhibited IL-1β production via the S-nitrosylation of the NLRP3 inflammasome. In addition, ginsenosides 20(R)-Rg3 and 20(S)-Rg3 had suppressive effects on the LPS- or UV-irradiation-induced reactive oxygen species (ROS) levels in macrophage and HaCaT cells and thereby prevented apoptosis of spleen cells in mice. Altogether, these results demonstrate that ginsenoside 20(R)-Rg3 and 20(S)-Rg3, a naturally occurring compound, might act as a dual therapeutic regulator for the treatment of inflammatory and oxidative stress-related diseases. - Highlights: • Ginsenosides Rg3 inhibits NO production through the regulation of iNOS expression. • Ginsenosides Rg3 inhibits the S-nitrosylation of the NLRP3 inflammasome. • Ginsenosides Rg3 suppress on the LPS- or UV-irradiation-induced ROS levels in cells.« less

Late Pleistocene granodiorite beneath Crater Lake caldera, Oregon, dated by ion microprobe

USGS Publications Warehouse

Bacon, C.R.; Persing, H.M.; Wooden, J.L.; Ireland, T.R.

2000-01-01

Variably melted granodiorite blocks ejected during the Holocene caldera-forming eruption of Mount Mazama were plucked from the walls of the climactic magma chamber ~15 km depth. Ion-microprobe U-Pb dating of zircons from two unmelted granodiorite blocks with SHRIMP RG (sensitive high-resolution ion microprobe-reverse geometry) gives a nominal 238U/206Pb age of 101+78-80 ka, or 174+89-115 ka when adjusted for an initial 230Th deficit. SHRIMP RG U-Th measurements on a subset of the zircons yield a 230Th/238U isochron age of 112 ?? 24 ka, considered to be the best estimate of the time of solidification of the pluton. These results suggest that the granodiorite is related to andesite and dacite of Mount Mazama and not to magmas of the climactic eruption. The unexposed granodiorite has an area of at least 28 km2. This young, shallow pluton was emplaced in virtually the same location where a similarly large magma body accumulated and powered violent explosive eruptions ~7700 yr ago, resulting in collapse of Crater Lake caldera.

Red-koji fermented red ginseng ameliorates high fat diet-induced metabolic disorders in mice.

PubMed

Kim, Chang Man; Yi, Seong Joon; Cho, Il Je; Ku, Sae Kwang

2013-10-30

Fermentation of medicinal herbs improves their pharmacological efficacy. In this study, we investigated the effects of red-koji fermented red ginseng (fRG) on high-fat diet (HFD)-mediated metabolic disorders, and those effects were compared to those of non-fermented red ginseng (RG). fRG (500, 250 or 125 mg/kg), RG (250 mg/kg), simvastatin (10 mg/kg), silymarin (100 mg/kg) and metformin (250 mg/kg) were orally administered from 1 week after initiation of HFD supply for 84 days. The diameter of adipocytes in periovarian and abdominal fat pads and the thickness of the abdominal fat were significantly decreased by fRG treatment, while HFD-mediated weight gain was partly alleviated by fRG in a dose-dependent manner. Moreover, biochemical and histomorphometrical analyses clearly indicated that fRG significantly inhibited HFD-induced metabolic disorders such as hyperglycemia, hyperlipidemia, hepatopathy and nephropathy in a dose-dependent manner. More favorable pharmacological effects on HFD-mediated metabolic disorders were also observed with fRG compared to an equal dose of RG. This finding provides direct evidence that the pharmacological activities of RG were enhanced by red-koji fermentation, and fRG could be a neutraceutical resource for the alleviation of obesity-mediated metabolic disorders.

Genetic Relations Among Procrastination, Impulsivity, and Goal-Management Ability: Implications for the Evolutionary Origin of Procrastination

PubMed Central

Gustavson, Daniel E.; Miyake, Akira; Hewitt, John K.; Friedman, Naomi P.

2014-01-01

Previous research has revealed a moderate positive correlation between procrastination and impulsivity. However, little is known about why these two constructs are related. This study used behavioral genetic methodology to test three predictions derived from an evolutionary account that postulates that procrastination arose as a by-product of impulsivity (Steel, 2010): (a) Procrastination is heritable; (b) the two traits share considerable genetic variation; and (c) goal-management ability is an important component of this shared variation. These predictions were confirmed. First, both procrastination and impulsivity were moderately heritable (46% and 49%, respectively). Second, although the two traits were separable at the phenotypic level (r=.65), they were not separable at the genetic level (rg=1.0). Finally, variation in goal-management ability accounted for much of this shared genetic variation. These results suggest that procrastination and impulsivity are linked primarily through genetic influences on the ability to use their high-priority goals effectively to regulate their action. PMID:24705635

Ginsenoside Rg1 improves fertility and reduces ovarian pathological damages in premature ovarian failure model of mice.

PubMed

He, Lianli; Ling, Li; Wei, Tianqin; Wang, Yaping; Xiong, Zhengai

2017-04-01

This study aims to investigate the effect as well as mechanism of ginsenoside Rg1 (Rg1) on premature ovarian failure (POF) induced by d-galactose (d-gal) in mice. C57BL/6 female mice were divided into four groups randomly, which were the saline group, the d-gal group, the d-gal + Rg1 group, and the Rg1 group. Body weight was recorded. Overall ovarian function including estrous cycles, sex hormone secretion, ovarian follicle development, and ovarian morphology was analyzed by H&E staining and ELISA. Effect of Rg1 on aging was determined by analyzing the activities of oxidation-associated biomarkers, pro-inflammatory cytokine secretion, expression of senescence-associated proteins, and fertility. Compared with the d-gal group, in Rg1 + d-gal group, body weight was increased significantly, estrous cycle block was released, and fertility and the morphology of ovaries were restored. And, Rg1 treatment after d-gal administration significantly reduced senescence-associated protein expression, increased the activity of total superoxide dismutase and glutathione peroxidase from bovine erythrocyte, and induced higher follicle stimulating hormone receptor protein expression. Additionally, the expression levels of malondialdehyde, interleukin-1β, tumor necrosis factor-α, and interleukin-6 were significantly decreased. Together, Rg1 improves mouse fertility and reduces ovarian pathological damage in d-gal-induced POF model possibly through enhancing anti-inflammatory and antioxidant capacities and reducing expression of senescence signal pathway proteins. Impact statement Ginsenoside Rg1 (Rg1) is a kind of natural estrogen and it has antioxidation and antiaging effects. However, whether Rg1 has effects on premature ovarian failure (POF) is still not clear. In this study, aging model induced by d-galactose was used to mimic POF. The effect and possible mechanism of Rg1 on ovary aging was investigated. We found that Rg1 treatment up-regulated the expression of follicle stimulating hormone receptor and down-regulated senescence-associated protein expression in granule cells of POF mice. Particularly, Rg1 improved fertility ability and reduced ovarian pathological damages by its antioxidative and anti-inflammation capacity. Thus, Rg1 enhances the antiaging ability of ovary and fertility ability of POF mice through enhancing the anti-inflammatory and antioxidant capacities of ovary.

Local Explosion Monitoring using Rg

NASA Astrophysics Data System (ADS)

O'Rourke, C. T.; Baker, G. E.

2016-12-01

Rg is the high-frequency fundamental-mode Rayleigh wave, which is only excited by near-surface events. As such, an Rg detection indicates that a seismic source is shallow, generally less than a few km depending on the velocity structure, and so likely man-made. Conversely, the absence of Rg can indicate that the source is deeper and so likely naturally occurring. We have developed a new automated method of detecting Rg arrivals from various explosion sources at local distances, and a process for estimating the likelihood that a source is not shallow when no Rg is detected. Our Rg detection method scans the spectrogram of a seismic signal for a characteristic frequency peak. We test this on the Bighorn Arch Seismic Experiment data, which includes earthquakes, active source explosions in boreholes, and mining explosions recorded on a dense network that spans the Bighorn Mountains and Powder River Basin. The Rg passbands used were 0.4-0.8 Hz for mining blasts and 0.8-1.2 Hz for borehole shots. We successfully detect Rg across the full network for most mining blasts. The lower-yield shots are detectable out to 50 km. We achieve <1% false-positive rate for the small-magnitude earthquakes in the region. Rg detections on known non-shallow earthquake seismograms indicates they are largely due to windowing leakage at very close distances or occasionally to cultural noise. We compare our results to existing methods that use cross-correlation to detect retrograde motion of the surface waves. Our method shows more complete detection across the network, especially in the Powder River Basin where Rg exhibits prograde motion that does not trigger the existing detector. We also estimate the likelihood that Rg would have been detected from a surface source, based on the measured P amplitude. For example, an event with a large P wave and no detectable Rg would have a high probability of being a deeper event, whereas we cannot confidently determine whether an event with a small P wave and no Rg detection is shallow or not. These results allow us to detect Rg arrivals, which indicate a shallow source, and to use the absence of Rg to estimate the likelihood that a source in a calibrated region is not shallow enough to be man-made.

Radial glia in the proliferative ventricular zone of the embryonic and adult turtle, Trachemys scripta elegans.

PubMed

Clinton, Brian K; Cunningham, Christopher L; Kriegstein, Arnold R; Noctor, Stephen C; Martínez-Cerdeño, Verónica

2014-01-01

To better understand the role of radial glial (RG) cells in the evolution of the mammalian cerebral cortex, we investigated the role of RG cells in the dorsal cortex and dorsal ventricular ridge of the turtle, Trachemys scripta elegans. Unlike mammals, the glial architecture of adult reptile consists mainly of ependymoradial glia, which share features with mammalian RG cells, and which may contribute to neurogenesis that continues throughout the lifespan of the turtle. To evaluate the morphology and proliferative capacity of ependymoradial glia (here referred to as RG cells) in the dorsal cortex of embryonic and adult turtle, we adapted the cortical electroporation technique, commonly used in rodents, to the turtle telencephalon. Here, we demonstrate the morphological and functional characteristics of RG cells in the developing turtle dorsal cortex. We show that cell division occurs both at the ventricle and away from the ventricle, that RG cells undergo division at the ventricle during neurogenic stages of development, and that mitotic Tbr2+ precursor cells, a hallmark of the mammalian SVZ, are present in the turtle cortex. In the adult turtle, we show that RG cells encompass a morphologically heterogeneous population, particularly in the subpallium where proliferation is most prevalent. One RG subtype is similar to RG cells in the developing mammalian cortex, while 2 other RG subtypes appear to be distinct from those seen in mammal. We propose that the different subtypes of RG cells in the adult turtle perform distinct functions.

Radial glia in the proliferative ventricular zone of the embryonic and adult turtle, Trachemys scripta elegans

PubMed Central

Clinton, Brian K; Cunningham, Christopher L; Kriegstein, Arnold R; Noctor, Stephen C; Martínez-Cerdeño, Verónica

2014-01-01

To better understand the role of radial glial (RG) cells in the evolution of the mammalian cerebral cortex, we investigated the role of RG cells in the dorsal cortex and dorsal ventricular ridge of the turtle, Trachemys scripta elegans. Unlike mammals, the glial architecture of adult reptile consists mainly of ependymoradial glia, which share features with mammalian RG cells, and which may contribute to neurogenesis that continues throughout the lifespan of the turtle. To evaluate the morphology and proliferative capacity of ependymoradial glia (here referred to as RG cells) in the dorsal cortex of embryonic and adult turtle, we adapted the cortical electroporation technique, commonly used in rodents, to the turtle telencephalon. Here, we demonstrate the morphological and functional characteristics of RG cells in the developing turtle dorsal cortex. We show that cell division occurs both at the ventricle and away from the ventricle, that RG cells undergo division at the ventricle during neurogenic stages of development, and that mitotic Tbr2+ precursor cells, a hallmark of the mammalian SVZ, are present in the turtle cortex. In the adult turtle, we show that RG cells encompass a morphologically heterogeneous population, particularly in the subpallium where proliferation is most prevalent. One RG subtype is similar to RG cells in the developing mammalian cortex, while 2 other RG subtypes appear to be distinct from those seen in mammal. We propose that the different subtypes of RG cells in the adult turtle perform distinct functions. PMID:27504470

The Synthesis and Origin of the Pectic Polysaccharide Rhamnogalacturonan II – Insights from Nucleotide Sugar Formation and Diversity

PubMed Central

Bar-Peled, Maor; Urbanowicz, Breeanna R.; O’Neill, Malcolm A.

2012-01-01

There is compelling evidence showing that the structurally complex pectic polysaccharide rhamnogalacturonan II (RG-II) exists in the primary cell wall as a borate cross-linked dimer and that this dimer is required for the assembly of a functional wall and for normal plant growth and development. The results of several studies have also established that RG-II structure and cross-linking is conserved in vascular plants and that RG-II likely appeared early in the evolution of land plants. Two features that distinguish RG-II from other plant polysaccharides are that RG-II is composed of 13 different glycoses linked to each other by up to 22 different glycosidic linkages and that RG-II is the only polysaccharide known to contain both apiose and aceric acid. Thus, one key event in land plant evolution was the emergence of genes encoding nucleotide sugar biosynthetic enzymes that generate the activated forms of apiose and aceric acid required for RG-II synthesis. Many of the genes involved in the generation of the nucleotide sugars used for RG-II synthesis have been functionally characterized. By contrast, only one glycosyltransferase involved in the assembly of RG-II has been identified. Here we provide an overview of the formation of the activated sugars required for RG-II synthesis and point to the possible cellular and metabolic processes that could be involved in assembling and controlling the formation of a borate cross-linked RG-II molecule. We discuss how nucleotide sugar synthesis is compartmentalized and how this may control the flux of precursors to facilitate and regulate the formation of RG-II. PMID:22639675

Protective effects of ginsenoside Rg1 against lipopolysaccharide/d-galactosamine-induced acute liver injury in mice through inhibiting toll-like receptor 4 signaling pathway.

PubMed

Ning, Chenqing; Gao, Xiaoguang; Wang, Changyuan; Huo, Xiaokui; Liu, Zhihao; Sun, Huijun; Yang, Xiaobo; Sun, Pengyuan; Ma, Xiaodong; Meng, Qiang; Liu, Kexin

2018-06-11

Acute liver injury (ALI) is a dramatic liver disease characterized by large areas of inflammation in the liver. This study aimed to investigate the protective effects of ginsenoside Rg1 (Rg1), a biologically active component in Panax ginseng, on lipopolysaccharide/d-galactosamine (LPS/D-GalN)-induced ALI in mice, and meanwhile explore the molecular mechanism in vivo and in vitro. Mice were pretreated with Rg1 for three days prior to LPS (40 μg/kg)/D-GalN (700 mg/kg) administration. The results showed that Rg1 improved the survival rate and reduced the liver to body weight ratios in mice. Rg1 also reduced the production of oxidative markers such as MDA and MPO induced by LPS/D-GalN. In addition, Rg1 significantly decreased the production of inflammatory cytokines including TNF-α, IL-6, IL-1β, Mip-2, Mcp-1, iNOS, and increased the activity of anti-inflammatory cytokine IL-10. Moreover, Rg1 inhibited the protein expression of TLR4 and its downstream genes including NF-κB and MAPKs, which are involved in inflammatory response. Rg1 dramatically reduced oxidative stress by regulating the expression of efflux transporters Mrp2 and various enzymes including GCLC, GCLM, HO-1 and NQO1. However, the changes in these genes and protein induced by Rg1 were abrogated by TLR4 antagonist TAK-242 in vitro. In conclusion, Rg1 had hepatoprotective effect on LPS/D-GalN-induced ALI in mice. The protection may be associated with the inhibition of TLR4. These findings suggest that Rg1 may be a promising agent for prevention against ALI. Copyright © 2018 Elsevier B.V. All rights reserved.

Ginsenoside Rg3 improves cardiac mitochondrial population quality: Mimetic exercise training

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

Sun, Mengwei; Huang, Chenglin; Wang, Cheng

Highlights: •Rg3 is an ergogenic aid. •Rg3 improves mitochondrial antioxidant capacity. •Rg3 regulates mitochondria dynamic remodeling. •Rg3 alone matches some the benefits of aerobic exercise. -- Abstract: Emerging evidence indicates exercise training could mediate mitochondrial quality control through the improvement of mitochondrial dynamics. Ginsenoside Rg3 (Rg3), one of the active ingredients in Panax ginseng, is well known in herbal medicine as a tonic and restorative agent. However, the molecular mechanism underlying the beneficial effects of Rg3 has been elusive. In the present study, we compared the effects of Rg3 administration with aerobic exercise on mitochondrial adaptation in cardiac muscle tissuemore » of Sprague–Dawley (SD) rats. Three groups of SD rats were studied: (1) sedentary control, (2) Rg3-treated and (3) aerobic exercise trained. Both aerobic exercise training and Rg3 supplementation enhanced peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1α) and nuclear factor-E2-related factor 2 (Nrf2) protein levels in cardiac muscle. The activation of PGC-1α led to increased mRNA levels of mitochondrial transcription factor A (Tfam) and nuclear related factor 1(Nrf1), these changes were accompanied by increases in mitochondrial DNA copy number and complex protein levels, while activation of Nrf2 increased levels of phase II detoxifying enzymes, including nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1(NQO1), superoxide dismutase (MnSOD) and catalase. Aerobic exercise also enhanced mitochondrial autophagy pathway activity, including increased conversion of LC3-I to LC3-II and greater expression of beclin1 and autophagy-related protein 7 (ATG7), these effects of aerobic exercise are comparable to that of Rg3. These results demonstrate that Rg3 mimics improved cardiac adaptations to exercise by regulating mitochondria dynamic remodeling and enhancing the quantity and quality of mitochondria.« less

Actinomycin D enhances killing of cancer cells by immunotoxin RG7787 through activation of the extrinsic pathway of apoptosis

PubMed Central

Liu, Xiu Fen; Xiang, Laiman; Zhou, Qi; Carralot, Jean-Philippe; Prunotto, Marco; Niederfellner, Gerhard; Pastan, Ira

2016-01-01

RG7787 is a mesothelin-targeted immunotoxin designed to have low-immunogenicity, high-cytotoxic activity and fewer side effects. RG7787 kills many types of mesothelin-expressing cancer cells lines and causes tumor regressions in mice. Safety and immunogenicity of RG7787 is now being assessed in a phase I trial. To enhance the antitumor activity of RG7787, we screened for clinically used drugs that can synergize with RG7787. Actinomycin D is a potent transcription inhibitor that is used for treating several cancers. We report here that actinomycin D and RG7787 act synergistically to kill many mesothelin-positive cancer cell lines and produce major regressions of pancreatic and stomach cancer xenografts. Analyses of RNA expression show that RG7787 or actinomycin D alone and together increase levels of TNF/TNFR family members and NF-κB–regulated genes. Western blots revealed the combination changed apoptotic protein levels and enhanced cleavage of Caspases and PARP. PMID:27601652

Evaluation of the Immune Responses to and Cross-Protective Efficacy of Eurasian H7 Avian Influenza Viruses

PubMed Central

Kwon, Hyeok-Il; Kim, Young-Il; Park, Su-Jin; Song, Min-Suk; Kim, Eun-Ha; Kim, Se Mi; Si, Young-Jae; Lee, In-Won; Song, Byung-Min; Lee, Youn-Jeong; Yun, Seok Joong; Kim, Wun-Jae

2017-01-01

ABSTRACT Due to increasing concerns about human infection by various H7 influenza viruses, including recent H7N9 viruses, we evaluated the genetic relationships and cross-protective efficacies of three different Eurasian H7 avian influenza viruses. Phylogenic and molecular analyses revealed that recent Eurasian H7 viruses can be separated into two different lineages, with relatively high amino acid identities within groups (94.8 to 98.8%) and low amino acid identities between groups (90.3 to 92.6%). In vivo immunization with representatives of each group revealed that while group-specific cross-reactivity was induced, cross-reactive hemagglutination inhibition (HI) titers were approximately 4-fold lower against heterologous group viruses than against homologous group viruses. Moreover, the group I (RgW109/06) vaccine protected 100% of immunized mice from various group I viruses, while only 20 to 40% of immunized mice survived lethal challenge with heterologous group II viruses and exhibited high viral titers in the lung. Moreover, while the group II (RgW478/14) vaccine also protected mice from lethal challenge with group II viruses, it failed to elicit cross-protection against group I viruses. However, it is noteworthy that vaccination with RgAnhui1/13, a virus of a sublineage of group I, cross-protected immunized mice against lethal challenge with both group I and II viruses and significantly attenuated lung viral titers. Interestingly, immune sera from RgAnhui1/13-vaccinated mice showed a broad neutralizing spectrum rather than the group-specific pattern observed with the other viruses. These results suggest that the recent human-infective H7N9 strain may be a candidate broad cross-protective vaccine for Eurasian H7 viruses. IMPORTANCE Genetic and phylogenic analyses have demonstrated that the Eurasian H7 viruses can be separated into at least two different lineages, both of which contain human-infective fatal H7 viruses, including the recent novel H7N9 viruses isolated in China since 2013. Due to the increasing concerns regarding the global public health risk posed by H7 viruses, we evaluated the genetic relationships between Eurasian H7 avian influenza viruses and the cross-protective efficacies of three different H7 viruses: W109/06 (group I), W478/14 (group II), and Anhui1/13 (a sublineage of group I). While each vaccine induced group-specific antibody responses and cross-protective efficacy, only Anhui1/13 was able to cross-protect immunized hosts against lethal challenge across groups. In fact, the Anhui1/13 virus induced not only cross-protection but also broad serum neutralizing antibody responses against both groups of viruses. This suggests that Anhui1/13-like H7N9 viruses may be viable vaccine candidates for broad protection against Eurasian H7 viruses. PMID:28331080

Evaluation of the Immune Responses to and Cross-Protective Efficacy of Eurasian H7 Avian Influenza Viruses.

PubMed

Kwon, Hyeok-Il; Kim, Young-Il; Park, Su-Jin; Song, Min-Suk; Kim, Eun-Ha; Kim, Se Mi; Si, Young-Jae; Lee, In-Won; Song, Byung-Min; Lee, Youn-Jeong; Yun, Seok Joong; Kim, Wun-Jae; Choi, Young Ki

2017-06-01

Due to increasing concerns about human infection by various H7 influenza viruses, including recent H7N9 viruses, we evaluated the genetic relationships and cross-protective efficacies of three different Eurasian H7 avian influenza viruses. Phylogenic and molecular analyses revealed that recent Eurasian H7 viruses can be separated into two different lineages, with relatively high amino acid identities within groups (94.8 to 98.8%) and low amino acid identities between groups (90.3 to 92.6%). In vivo immunization with representatives of each group revealed that while group-specific cross-reactivity was induced, cross-reactive hemagglutination inhibition (HI) titers were approximately 4-fold lower against heterologous group viruses than against homologous group viruses. Moreover, the group I (RgW109/06) vaccine protected 100% of immunized mice from various group I viruses, while only 20 to 40% of immunized mice survived lethal challenge with heterologous group II viruses and exhibited high viral titers in the lung. Moreover, while the group II (RgW478/14) vaccine also protected mice from lethal challenge with group II viruses, it failed to elicit cross-protection against group I viruses. However, it is noteworthy that vaccination with RgAnhui1/13, a virus of a sublineage of group I, cross-protected immunized mice against lethal challenge with both group I and II viruses and significantly attenuated lung viral titers. Interestingly, immune sera from RgAnhui1/13-vaccinated mice showed a broad neutralizing spectrum rather than the group-specific pattern observed with the other viruses. These results suggest that the recent human-infective H7N9 strain may be a candidate broad cross-protective vaccine for Eurasian H7 viruses. IMPORTANCE Genetic and phylogenic analyses have demonstrated that the Eurasian H7 viruses can be separated into at least two different lineages, both of which contain human-infective fatal H7 viruses, including the recent novel H7N9 viruses isolated in China since 2013. Due to the increasing concerns regarding the global public health risk posed by H7 viruses, we evaluated the genetic relationships between Eurasian H7 avian influenza viruses and the cross-protective efficacies of three different H7 viruses: W109/06 (group I), W478/14 (group II), and Anhui1/13 (a sublineage of group I). While each vaccine induced group-specific antibody responses and cross-protective efficacy, only Anhui1/13 was able to cross-protect immunized hosts against lethal challenge across groups. In fact, the Anhui1/13 virus induced not only cross-protection but also broad serum neutralizing antibody responses against both groups of viruses. This suggests that Anhui1/13-like H7N9 viruses may be viable vaccine candidates for broad protection against Eurasian H7 viruses. Copyright © 2017 American Society for Microbiology.

The effect of recycled Natural Rubber Glove (rRG) Plasticizers to Deflection and Flexural Strength Properties of PP/MMt/rRG Smart Composites and Its Inflammability

NASA Astrophysics Data System (ADS)

Suharty, N. S.; Ismail, H.; Diharjo, K.; Handayani, D. S.; Saputri, L. N. M. Z.; Ariesta, N.

2018-03-01

Had been synthesized PP/rRG/MMt+ZB smart material composite in solution reactive processes with various rRG concentration. The addition of rRG plasticizers will improve the deflection properties and increase the filler capacity MMt loading to reach the optimum concentration. The addition of 3% rRG is capable of loading filler capacity MMt to 23% as the optimum condition. At the optimum conditions it can increase the deflection (Defl) and flexural strength (FS) up to 16% and 15% respectively compared to that of the composites without rRG. The rRG plasticizer serves as a bio-compatibilizer that can reduce surface tension of the mixture and leads to decrease the Defl., follow by the increase of loading filler capacity and well interaction finally can increase the FS properties. The increase of loading filler MMt up to 23% can also improve the inflammability of the composites. Time to Ignition (TTI) increase by 5% and Burning Rate (BR) decrease by 4.5% compared to that of the composites which is containing MMt 20% without rRG.

Ginsenoside Rg1 exerts synergistic anti-inflammatory effects with low doses of glucocorticoids in vitro.

PubMed

Song, Yanqin; Zhao, Feng; Zhang, Leiming; Du, Yuan; Wang, Tian; Fu, Fenghua

2013-12-01

Glucocorticoids (GCs) are usually used to treat inflammatory diseases. However, they cause severe and irreversible side effects, which limit the use of these compounds. Ginsenoside Rg1 had been demonstrated to possess anti-inflammatory and anti-cancer effects. The present study was designed to investigate whether Rg1 exhibits synergistic anti-inflammatory effects when combined with glucocorticoids. After stimulated by lipopolysaccharide (LPS), murine macrophagic RAW264.7 cells were treated with Rg1, corticosterone (Cort) or Rg1 and Cort. Then nitric oxide (NO), tumor necrosis factor-α (TNF-α) and glucocorticoid receptor (GR) expression were measured. The results showed that Rg1 or Cort could reduce the production of NO and TNF-α, and Rg1 dose-dependently up-regulated GR expression, while Cort dose-dependently down-regulated GR expression. The combination of low concentrations of Rg1 with Cort, which alone could not markedly inhibit the release of inflammatory factors, inhibited the secretion of NO and TNF-α in LPS-stimulated RAW264.7 macrophage cells, and up-regulated the expression of GR. The findings suggested Rg1 can synergize with glucocorticoid to enhance its anti-inflammatory effect. © 2013.

Burst noise in the HAWAII-1RG multiplexer

NASA Astrophysics Data System (ADS)

Bacon, Candice M.; McMurtry, Craig W.; Pipher, Judith L.; Forrest, William J.; Garnett, James D.

2005-08-01

Burst noise (also known as popcorn noise and random telegraph signal/noise) is a phenomenon that is understood to be a result of defects in the vicinity of a p-n junction. It is characterized by rapid level shifts in both positive and negative directions and can have varying magnitudes. This noise has been seen in both HAWAII-1RG and HAWAII-2RG multiplexers and is under investigation. We have done extensive burst noise testing on a HAWAII-1RG multiplexer, where we have determined a significant percentage of pixels exhibit the phenomenon. In addition, the prevalence of small magnitude transitions make sensitivity of detection the main limiting factor. Since this is a noise source for the HAWAII-1RG multiplexer, its elimination would make the HAWAII-1RG and the HAWAII-2RG even lower noise multiplexers.

Gambling Responsibly: Who Does It and To What End?

PubMed

Hing, Nerilee; Sproston, Kerry; Tran, Katherine; Russell, Alex M T

2017-03-01

Numerous responsible gambling (RG) strategies are promoted to assist consumers to "gamble responsibly". However, consumer adoption of RG strategies, how this varies by gambler risk group, and whether usage is associated with non-problematic gambling are largely unknown. This study aimed to (1) determine how use of RG-related strategies differs amongst regular gamblers by gambler risk group; and (2) identify RG-related strategies whose usage predicts non-problem/low risk gambling. Regular Australian gamblers on high-risk products (N = 860), recruited through gambling venues and an online wagering operator, were surveyed about their use of RG strategies promoted on the website of their jurisdiction's main RG agency. Knowledge of RG strategies was reasonably high amongst all gambler risk groups, but lower-risk groups were more likely to use RG strategies. A logistic regression correctly predicted 82.1 % of lower-risk gamblers and 77.2 % of higher-risk gamblers. Predictors of lower-risk gambling included: greater confidence in their understanding of RG; endorsement of lower gambling expenditure and frequency limits; fewer erroneous gambling beliefs; being less likely to gamble to win money, challenge their skills/beat the odds, or forget about worries and stresses; and being more likely to gamble for pleasure/entertainment. Lower-risk gamblers were more likely to set a money limit in advance of gambling and to balance their gambling with other activities. These findings contribute to understanding which strategies are favoured by different risk groups, and which are associated with safer levels of gambling. They can guide consumer information aimed at enhancing RG consumption and future research on RG consumption.

An efficient and rapid influenza gene cloning strategy for reverse genetics system.

PubMed

Shao, Hongxia; Fan, Zhonglei; Wan, Zhimin; Tian, Xiaoyan; Chen, Hongjun; Perez, Daniel R; Qin, Aijian; Ye, Jianqiang

2015-09-15

Influenza reverse genetics plays vital roles in understanding influenza molecular characteristics and vaccine development. However, current influenza reverse genetics heavily depends on restriction enzyme and ligation for gene cloning. The traditional cloning process of influenza eight fragments for virus rescuing generally requires considerable work. To simplify and increase the pace of gene cloning for influenza reverse genetics system, we developed a rapid restriction enzyme-free ExnaseTM II-based in vitro recombination approach for influenza gene cloning. We used this strategy rapidly and successfully to clone influenza eight genes both from viruses PR8 and H9N2 for virus rescuing. Our data demonstrate that the strategy developed here can accelerate the process of influenza gene cloning into reverse genetics system, and shows high potential for applications in both influenza basic and applied research. Copyright © 2015 Elsevier B.V. All rights reserved.

Theoretical Study of Decomposition Pathways for HArF and HKrF

NASA Technical Reports Server (NTRS)

Chaban, Galina M.; Lundell, Jan; Gerber, R. Benny; Kwak, Donchan (Technical Monitor)

2002-01-01

To provide theoretical insights into the stability and dynamics of the new rare gas compounds HArF and HKrF, reaction paths for decomposition processes HRgF to Rg + HF and HRgF to H + Rg + F (Rg = Ar, Kr) are calculated using ab initio electronic structure methods. The bending channels, HRgF to Rg + HF, are described by single-configurational MP2 and CCSD(T) electronic structure methods, while the linear decomposition paths, HRgF to H + Rg + F, require the use of multi-configurational wave functions that include dynamic correlation and are size extensive. HArF and HKrF molecules are found to be energetically stable with respect to atomic dissociation products (H + Rg + F) and separated by substantial energy barriers from Rg + HF products, which ensure their kinetic stability. The results are compatible with experimental data on these systems.

New Threats from H7N9 Influenza Virus: Spread and Evolution of High- and Low-Pathogenicity Variants with High Genomic Diversity in Wave Five.

PubMed

Quan, Chuansong; Shi, Weifeng; Yang, Yang; Yang, Yongchun; Liu, Xiaoqing; Xu, Wen; Li, Hong; Li, Juan; Wang, Qianli; Tong, Zhou; Wong, Gary; Zhang, Cheng; Ma, Sufang; Ma, Zhenghai; Fu, Guanghua; Zhang, Zewu; Huang, Yu; Song, Houhui; Yang, Liuqing; Liu, William J; Liu, Yingxia; Liu, Wenjun; Gao, George F; Bi, Yuhai

2018-06-01

H7N9 virus has caused five infection waves since it emerged in 2013. The highest number of human cases was seen in wave 5; however, the underlying reasons have not been thoroughly elucidated. In this study, the geographical distribution, phylogeny, and genetic evolution of 240 H7N9 viruses in wave 5, including 35 new isolates from patients and poultry in nine provinces, were comprehensively analyzed together with strains from first four waves. Geographical distribution analysis indicated that the newly emerging highly pathogenic (HP) and low-pathogenicity (LP) H7N9 viruses were cocirculating, causing human and poultry infections across China. Genetic analysis indicated that dynamic reassortment of the internal genes among LP-H7N9/H9N2/H6Ny and HP-H7N9, as well as of the surface genes, between the Yangtze and Pearl River Delta lineages resulted in at least 36 genotypes, with three major genotypes (G1 [A/chicken/Jiangsu/SC537/2013-like], G3 [A/Chicken/Zhongshan/ZS/2017-like], and G11 [A/Anhui/40094/2015-like]). The HP-H7N9 genotype likely evolved from G1 LP-H7N9 by the insertion of a KRTA motif at the cleavage site (CS) and then evolved into 15 genotypes with four different CS motifs, including PKG KRTA R/G, PKG KRIA R/G, PKR KRAA R/G, and PKR KRTA R/G. Approximately 46% (28/61) of HP strains belonged to G3. Importantly, neuraminidase (NA) inhibitor (NAI) resistance (R292K in NA) and mammalian adaptation (e.g., E627K and A588V in PB2) mutations were found in a few non-human-derived HP-H7N9 strains. In summary, the enhanced prevalence and diverse genetic characteristics that occurred with mammalian-adapted and NAI-resistant mutations may have contributed to increased numbers of human infections in wave 5. IMPORTANCE The highest numbers of human H7N9 infections were observed during wave 5 from October 2016 to September 2017. Our results showed that HP-H7N9 and LP-H7N9 had spread virtually throughout China and underwent dynamic reassortment with different subtypes (H7N9/H9N2 and H6Ny) and lineages (Yangtze and Pearl River Delta lineages), resulting in totals of 36 and 3 major genotypes, respectively. Notably, the NAI drug-resistant (R292K in NA) and mammalian-adapted (e.g., E627K in PB2) mutations were found in HP-H7N9 not only from human isolates but also from poultry and environmental isolates, indicating increased risks for human infections. The broad dissemination of LP- and HP-H7N9 with high levels of genetic diversity and host adaptation and drug-resistant mutations likely accounted for the sharp increases in the number of human infections during wave 5. Therefore, more strategies are needed against the further spread and damage of H7N9 in the world. Copyright © 2018 American Society for Microbiology.

Performance of the first HAWAII 4RG-15 arrays in the laboratory and at the telescope

NASA Astrophysics Data System (ADS)

Hall, Donald N. B.; Atkinson, Dani; Beletic, James W.; Blank, Richard; Farris, Mark; Hodapp, Klaus W.; Jacobson, Shane M.; Loose, Markus; Luppino, Gerard

2012-07-01

The primary goal of the HAWAII 4RG-15 (H4RG-15) development is to provide a 16 megapixel 4096x4096 format at significantly reduced price per pixel while maintaining the superb low background performance of the HAWAII 2RG (H2RG). The H4RG-15 design incorporates several new features, notably clocked reference output and interleaved reference pixel readout, that promise to significantly improve noise performance while the reduction in pixel pitch from 18 to 15 microns should improve transimpedance gain although at the expense of some degradation in full well and crosstalk. During the Phase-1 development, Teledyne has produced and screen tested six hybrid arrays. In preparation for Phase-2, the most promising of these are being extensively characterized in the University of Hawaii’s (UH) ULBCam test facility originally developed for the JWST H2RG program. The end-to-end performance of the most promising array has been directly established through astronomical imaging observations at the UH 88-inch telescope on Mauna Kea. We report the performance of these Phase-1 H4RG-15s within the context of established H2RG performance for key parameters (primarily CDS read noise), also highlighting the improvements from the new readout modes.

Comparison of particle morphology between commercial- and research-grade calcium hydroxide in endodontics.

PubMed

Komabayashi, Takashi; Ahn, Chul; Spears, Robert; Zhu, Qiang

2014-09-01

Ca(OH)2 aqueous slurry is widely used as an inter-appointment antimicrobial dressing in root canal treatment. The aim of this study was to quantify the particle size and shape of commercial-grade UltraCal XS (UC) and to compare it with that of research-grade Ca(OH)2 (RG) using a flow particle image analyzer (FPIA). The morphology and penetration inside the dentin tubules of the UC and RG particles were examined using a scanning electron microscope (SEM). UC and RG (10 mg) were mixed with 15 mL of alcohol, and were sonicated. Five milliliters of the dispersion was subjected to FPIA, and particle length, width, perimeter and aspect ratio were analyzed. In addition, UC paste and RG aqueous slurry were agitated on dentin discs and were prepared for SEM examination. There were significant differences between UC and RG with regard to the frequency of different length groups (P < 0.0001). UC contained smaller particles than RG (P < 0.0001). Under SEM, the agitated UC and RG particles occluded the opening of dentin tubules and penetrated inside the dentin tubules. The size of UC particles is smaller than those of RG. Both UC and RG particles were able to penetrate into open dentin tubules.

Comparison of particle morphology between commercial- and research-grade calcium hydroxide in endodontics

PubMed Central

Komabayashi, Takashi; Ahn, Chul; Spears, Robert; Zhu, Qiang

2014-01-01

Ca(OH)2 aqueous slurry is widely used as an inter-appointment antimicrobial dressing in root canal treatment. The aim of this study was to quantify the particle size and shape of commercial-grade UltraCal XS (UC) and to compare it with that of research-grade Ca(OH)2 (RG) using a flow particle image analyzer (FPIA). The morphology and penetration inside the dentin tubules of the UC and RG particles were examined using a scanning electron microscope (SEM). UC and RG (10 mg) were mixed with 15 mL of alcohol, and were sonicated. Five milliliters of the dispersion was subjected to FPIA, and particle length, width, perimeter and aspect ratio were analyzed. In addition, UC paste and RG aqueous slurry were agitated on dentin discs and were prepared for SEM examination. There were significant differences between UC and RG with regard to the frequency of different length groups (P < 0.0001). UC contained smaller particles than RG (P < 0.0001). Under SEM, the agitated UC and RG particles occluded the opening of dentin tubules and penetrated inside the dentin tubules. The size of UC particles is smaller than those of RG. Both UC and RG particles were able to penetrate into open dentin tubules. PMID:25231145

Collapse kinetics of vibrated granular chains

NASA Astrophysics Data System (ADS)

Jeng, Pei-Ren; Chen, Kuan Hua; Hwang, Gwo-jen; Lien, Chenhsin; To, Kiwing; Chou, Y. C.

2011-12-01

The kinetics of the collapse of the coil state into condensed states is studied with vibrated granular chain composed of N metal beads partially immersed in water. The radius of gyration of the chain, Rg is measured. For short chains (N < 140), disk-like condensed state is formed and Rg decreases with time such that the function ΔRg2 (≡ Rg2 - Rg2(∞)) = A e-t/τ, where the relaxation time τ follows a power-law dependence on the chain length N with an exponent γ = 1.9 ± 0.2. For the chains with length N ≥ 300, rod-like clusters are observed during the initial stage of collapse and Rg2 = Rg2(0) - Btβ, with β = 0.6 ± 0.1. In the coarsening stage, the exponential dependence of ΔRg2 on time still holds, however, the relaxation time τ fluctuates and has no simple dependence on N. Furthermore, the time dependence of the averaged radius of gyration of the individual clusters, Rg,cl can be described by the theory of Lifshitz and Slyozov. A peak in the structure function of long chains is observed in the initial stage of the collapse transition. The collapse transition in the bead chains is a first order phase transition. However, features of the spinodal decomposition are also observed.

High growth rate hydride vapor phase epitaxy at low temperature through use of uncracked hydrides

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

Schulte, Kevin L.; Braun, Anna; Simon, John

We demonstrate hydride vapor phase epitaxy (HVPE) of GaAs with unusually high growth rates (RG) at low temperature and atmospheric pressure by employing a hydride-enhanced growth mechanism. Under traditional HVPE growth conditions that involve growth from Asx species, RG exhibits a strong temperature dependence due to slow kinetics at the surface, and growth temperatures >750 degrees C are required to obtain RG > 60 um/h. We demonstrate that when the group V element reaches the surface in a hydride, the kinetic barrier is dramatically reduced and surface kinetics no longer limit RG. In this regime, RG is dependent on massmore » transport of uncracked AsH3 to the surface. By controlling the AsH3 velocity and temperature profile of the reactor, which both affect the degree of AsH3 decomposition, we demonstrate tuning of RG. We achieve RG above 60 um/h at temperatures as low as 560 degrees C and up to 110 um/h at 650 degrees C. We incorporate high-RG GaAs into solar cell devices to verify that the electronic quality does not deteriorate as RG is increased. The open circuit voltage (VOC), which is a strong function of non-radiative recombination in the bulk material, exhibits negligible variance in a series of devices grown at 650 degrees C with RG = 55-110 um/h. The implications of low temperature growth for the formation of complex heterostructure devices by HVPE are discussed.« less

High growth rate hydride vapor phase epitaxy at low temperature through use of uncracked hydrides

DOE PAGES

Schulte, Kevin L.; Braun, Anna; Simon, John; ...

2018-01-22

We demonstrate hydride vapor phase epitaxy (HVPE) of GaAs with unusually high growth rates (RG) at low temperature and atmospheric pressure by employing a hydride-enhanced growth mechanism. Under traditional HVPE growth conditions that involve growth from Asx species, RG exhibits a strong temperature dependence due to slow kinetics at the surface, and growth temperatures >750 degrees C are required to obtain RG > 60 um/h. We demonstrate that when the group V element reaches the surface in a hydride, the kinetic barrier is dramatically reduced and surface kinetics no longer limit RG. In this regime, RG is dependent on massmore » transport of uncracked AsH3 to the surface. By controlling the AsH3 velocity and temperature profile of the reactor, which both affect the degree of AsH3 decomposition, we demonstrate tuning of RG. We achieve RG above 60 um/h at temperatures as low as 560 degrees C and up to 110 um/h at 650 degrees C. We incorporate high-RG GaAs into solar cell devices to verify that the electronic quality does not deteriorate as RG is increased. The open circuit voltage (VOC), which is a strong function of non-radiative recombination in the bulk material, exhibits negligible variance in a series of devices grown at 650 degrees C with RG = 55-110 um/h. The implications of low temperature growth for the formation of complex heterostructure devices by HVPE are discussed.« less

Mechanism-based site-directed mutagenesis to shift the optimum pH of the phenylalanine ammonia-lyase from Rhodotorula glutinis JN-1.

PubMed

Zhu, Longbao; Zhou, Li; Cui, Wenjing; Liu, Zhongmei; Zhou, Zhemin

2014-09-01

Phenylalanine ammonia-lyase ( Rg PAL) from Rhodotorula glutinis JN-1 stereoselectively catalyzes the conversion of the l-phenylalanine into trans -cinnamic acid and ammonia, and was used in chiral resolution of dl-phenylalanine to produce the d-phenylalanine under acidic condition. However, the optimum pH of Rg PAL is 9 and the Rg PAL exhibits low catalytic efficiency at acidic side. Therefore, a mutant Rg PAL with a lower optimum pH is expected. Based on catalytic mechanism and structure analysis, we constructed a mutant Rg PAL-Q137E by site-directed mutagenesis, and found that this mutant had an extended optimum pH 7-9 with activity of 1.8-fold higher than that of the wild type at pH 7. As revealed by Friedel-Crafts-type mechanism of Rg PAL, the improvement of the Rg PAL-Q137E might be due to the negative charge of Glu137 which could stabilize the intermediate transition states through electrostatic interaction. The Rg PAL-Q137E mutant was used to resolve the racemic dl-phenylalanine, and the conversion rate and the ee D value of d-phenylalanine using Rg PAL-Q137E at pH 7 were increased by 29% and 48%, and achieved 93% and 86%, respectively. This work provides an effective strategy to shift the optimum pH which is favorable to further applications of Rg PAL.

Contextualizing Hepatocyte Functionality of Cryopreserved HepaRG Cell Cultures

PubMed Central

Jackson, Jonathan P.; Li, Linhou; Chamberlain, Erica D.; Wang, Hongbing

2016-01-01

Over the last decade HepaRG cells have emerged as a promising alternative to primary human hepatocytes (PHH) and have been featured in over 300 research publications. Most of these reports employed freshly differentiated HepaRG cells that require time-consuming culture (∼28 days) for full differentiation. Recently, a cryopreserved, predifferentiated format of HepaRG cells (termed here “cryo-HepaRG”) has emerged as a new model that improves global availability and experimental flexibility; however, it is largely unknown whether HepaRG cells in this format fully retain their hepatic characteristics. Therefore, we systematically investigated the hepatocyte functionality of cryo-HepaRG cultures in context with the range of interindividual variation observed with PHH in both sandwich-culture and suspension formats. These evaluations uncovered a novel adaptation period for the cryo-HepaRG format and demonstrated the impact of extracellular matrix on cryo-HepaRG functionality. Pharmacologically important drug-metabolizing alleles were genotyped in HepaRG cells and poor metabolizer alleles for CYP2D6, CYP2C9, and CYP3A5 were identified and consistent with higher frequency alleles found in individuals of Caucasian decent. We observed liver enzyme inducibility with aryl hydrocarbon receptor, constitutive androstane receptor (CAR), and pregnane X receptor activators comparable to that of sandwich-cultured PHH. Finally, we show for the first time that cryo-HepaRG supports proper CAR cytosolic sequestration and translocation to hepatocyte nuclei in response to phenobarbital treatment. Taken together, these data reveal important considerations for the use of this cell model and demonstrate that cryo-HepaRG are suitable for metabolism and toxicology screening. PMID:27338863

Phospholipid complex enriched micelles: A novel drug delivery approach for promoting the antidiabetic effect of repaglinide.

PubMed

Kassem, Ahmed Alaa; Abd El-Alim, Sameh Hosam; Basha, Mona; Salama, Abeer

2017-03-01

To enhance the oral antidiabetic effect of repaglinide (RG), a newly emerging approach, based on the combination of phospholipid complexation and micelle techniques, was employed. Repaglinide-phospholipid complex (RG-PLC) was prepared by the solvent-evaporation method then characterized using Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and X-ray powder diffraction (XPRD). The results revealed obvious disappearance of the characteristic peaks of the prepared RG-PLCs confirming the formation of drug-phospholipid complex. RG-PLC enriched micelles (RG-PLC-Ms) were prepared by the solvent-evaporation technique employing poloxamer 188 as surfactant. The prepared RG-PLC-Ms showed high drug encapsulation efficiencies (93.81-99.38%), with nanometric particle diameters (500.61-665.32nm) of monodisperse distribution and high stability (Zeta potential < -29.8mV). The in vitro release of RG from RG-PLC-Ms was pH-dependant according to the release media. A higher release pattern was reported in pH=1.2 compared to a more retarded release in pH=6.8 owing to two different kinetics of drug release. Oral antidiabetic effect of two optimized RG-PLC-M formulations was evaluated in an alloxan-induced diabetic rat model for 7-day treatment protocol. The two investigated formulations depicted normal blood glucose, serum malondialdehyde and insulin levels as well as an improved lipid profile, at the end of daily oral treatment, in contrast to RG marketed tablets implying enhanced antidiabetic effect of the drug. Hence, phospholipid-complex enriched micelles approach holds a promising potential for promoting the antidiabetic effect of RG. Copyright © 2016 Elsevier B.V. All rights reserved.

A VARI-Based Relative Greenness from MODIS Data for Computing the Fire Potential Index

NASA Technical Reports Server (NTRS)

Schneider, P.; Roberts, D. A.; Kyriakidis, P. C.

2008-01-01

The Fire Potential Index (FPI) relies on relative greenness (RG) estimates from remote sensing data. The Normalized Difference Vegetation index (NDVI), derived from NOAA Advanced Very High Resolution Radiometer (AVHRR) imagery is currently used to calculate RG operationally. Here we evaluated an alternate measure of RG using the Visible Atmospheric Resistant Index (VARI) derived from Moderate Resolution Imaging Spectrometer (MODIS) data. VARI was chosen because it has previously been shown to have the strongest relationship with Live Fuel Moisture (LFM) out of a wide selection of MODIS-derived indices in southern California shrublands. To compare MODIS-based NDVI-FPI and VARI-FPI, RG was calculated from a 6-year time series of MODIS composites and validated against in-situ observations of LFM as a surrogate for vegetation greenness. RG from both indices was then compared in terms of its performance for computing the FPI using historical wildfire data. Computed RG values were regressed against ground-sampled LFM at 14 sites within Los Angeles County. The results indicate the VARI-based RG consistently shows a stronger relationship with observed LFM than NDVI-based RG. With an average R2 of 0.727 compared to a value of only 0.622 for NDVI-RG, VARI-RG showed stronger relationships at 13 out of 14 sites. Based on these results, daily FPI maps were computed for the years 2001 through 2005 using both NDVI-RG and VARI-RG. These were then validated against 12,490 fire detections from the MODIS active fire product using logistic regression. Deviance of the logistic regression model was 408.8 for NDVI-FPI and 176.2 for VARI-FPI. The c-index was found to be 0.69 and 0.78, respectively. The results show that VARI-FP outperforms NDVI-FPI in distinguishing between fire and no-fire events for historical wildfire data in southern California for the given time period.

Factors associated with canine resource guarding behaviour in the presence of dogs: A cross-sectional survey of dog owners.

PubMed

Jacobs, Jacquelyn A; Coe, Jason B; Pearl, David L; Widowski, Tina M; Niel, Lee

2017-02-20

Resource guarding (RG) involves the use of specific behaviour patterns to control access to an item of potential "value" (as perceived by the dog), and can be expressed in the presence of various animals, including other dogs. The current study aimed to identify factors associated with RG patterns expressed around other dogs. Dog owners (n=3068) were recruited through social media to answer questions regarding dog- and household-related factors, as well as their dog's current and past behaviour around resources in the presence of other dogs. Participants were screened for their ability to identify different forms of resource guarding from video, and were removed from the study if they incorrectly identified any of the videos provided. This resulted in a final sample of 2207 participants (n=3589 dogs). Multiple multi-level logistic regression models were developed to determine the association between independent variables of interest and RG patterns (i.e., RG aggression, avoidance, and rapid ingestion) when in the presence of other dogs. Namely, dogs living in multi-dog households were more likely to display RG aggression, avoidance, and rapid ingestion (p<0.01) compared to dogs that live without other dogs. Dogs with higher levels of impulsivity and fear were more likely to display RG aggression (p<0.001). Neutered males (p<0.01) were more likely to be RG aggressive compared to dogs of other sexes and neuter statuses. Teaching dogs to reliably "drop" items when requested was associated with a reduced likelihood of biting RG aggression (p<0.05). Distinct associative relationships between the patterns of RG in the presence of other dogs were identified. Dogs that express RG aggression were less likely to express RG avoidance or RG rapid ingestion; however, the latter two types were likely to co-occur, perhaps dependent on the type of resource involved. This suggests that dogs may be relatively more fixed in their action around items in the presence of dogs. However, a longitudinal study is important to determine the exact nature of relationships between RG patterns. The results identified in this study can be used as a basis for further investigation on factors influencing RG behaviour in the presence of other dogs. Copyright © 2017 Elsevier B.V. All rights reserved.

The relationship between genetic and chemotypic diversity in American ginseng (Panax quinquefolius L.).

PubMed

Schlag, Erin M; McIntosh, Marla S

2013-09-01

Ginseng is one of the world's most important herbals used as an adaptogen and a cure for an impressively large range of ailments. Differences in the medicinal properties of ginseng roots have been attributed to variation in ginsenoside composition. In this study, the association between genetic and chemotypic profiles of wild and cultivated American ginseng (Panax quinquefolius L.) roots grown in Maryland was investigated. Ginseng roots were classified into chemotypes based on their relative composition of Re and Rg1. Genetic profiles of these roots were determined from the analysis of 38 polymorphic RAPD markers and used for a cluster analysis of genetic similarities. The close correspondence between chemotype and genetic cluster provides the first DNA-based evidence for the genetic basis of ginsenoside composition. Results of this research are significant for plant breeding and conservation, phytochemical research, and clinical and pharmacological studies. Also, the correlation between RAPD markers and chemotype indicates the potential to use RAPD markers as a reliable and practical method for identification and certification of ginseng roots. Copyright © 2013 Elsevier Ltd. All rights reserved.

SHRIMP-RG U-Pb isotopic systematics of zircon from the Angel Lake orthogneiss, East Humboldt Range, Nevada: Is this really archean crust?

USGS Publications Warehouse

Premo, Wayne R.; Castineiras, Pedro; Wooden, Joseph L.

2008-01-01

New SHRIMP-RG (sensitive high-resolution ion microprobe-reverse geometry) data confirm the existence of Archean components within zircon grains of a sample from the orthogneiss of Angel Lake, Nevada, United States, previously interpreted as a nappe of Archean crust. However, the combined evidence strongly suggests that this orthogneiss is a highly deformed, Late Cretaceous monzogranite derived from melting of a sedimentary source dominated by Archean detritus. Zircon grains from the same sample used previously for isotope dilution-thermal ionization mass spectrometry (ID-TIMS) isotopic work were analyzed using the SHRIMP-RG to better define the age and origin of the orthogneiss. Prior to analysis, imaging revealed a morphological variability and intragrain, polyphase nature of the zircon population. The SHRIMP-RG yielded 207Pb/206Pb ages between ca. 2430 and 2580 Ma (a best-fit mean 207Pb/206Pb age of 2531 ± 19 Ma; 95% confidence) from mostly rounded to subrounded zircons and zircon components (cores). In addition, several analyses from rounded to subrounded cores or grains yielded discordant 207Pb/206Pb ages between ca. 1460 and ca. 2170 Ma, consistent with known regional magmatic events. All cores of Proterozoic to latest Archean age were encased within clear, typically low Th/U (206Pb/238U ages between 72 and 91 Ma, consistent with magmatic ages from Lamoille Canyon to the south. An age of ca. 90 Ma is suggested, the younger 206Pb/238U ages resulting from Pb loss. The Cretaceous and Precambrian zircon components also have distinct trace element characteristics, indicating that these age groups are not related to the same igneous source. These results support recent geophysical interpretations and negate the contention that the Archean-Proterozoic boundary extends into the central Great Basin area. They further suggest that the world-class gold deposits along the Carlin Trend are not underlain by Archean cratonal crust, but rather by the Proterozoic Mojave province and Neoproterozoic and Paleozoic metasedimentary sequences dominated by detritus derived from Late Archean sources rather than Proterozoic sources, as is evident farther to the south in the Ruby Mountains.

Genetic Study of White Matter Integrity in UK Biobank (N=8448) and the Overlap With Stroke, Depression, and Dementia.

PubMed

Rutten-Jacobs, Loes C A; Tozer, Daniel J; Duering, Marco; Malik, Rainer; Dichgans, Martin; Markus, Hugh S; Traylor, Matthew

2018-06-01

Structural integrity of the white matter is a marker of cerebral small vessel disease, which is the major cause of vascular dementia and a quarter of all strokes. Genetic studies provide a way to obtain novel insights in the disease mechanism underlying cerebral small vessel disease. The aim was to identify common variants associated with microstructural integrity of the white matter and to elucidate the relationships of white matter structural integrity with stroke, major depressive disorder, and Alzheimer disease. This genome-wide association analysis included 8448 individuals from UK Biobank-a population-based cohort study that recruited individuals from across the United Kingdom between 2006 and 2010, aged 40 to 69 years. Microstructural integrity was measured as fractional anisotropy- (FA) and mean diffusivity (MD)-derived parameters on diffusion tensor images. White matter hyperintensity volumes (WMHV) were assessed on T2-weighted fluid-attenuated inversion recovery images. We identified 1 novel locus at genome-wide significance ( VCAN [versican]: rs13164785; P =3.7×10 -18 for MD and rs67827860; P =1.3×10 -14 for FA). LD score regression showed a significant genome-wide correlation between FA, MD, and WMHV (FA-WMHV rG 0.39 [SE, 0.15]; MD-WMHV rG 0.56 [SE, 0.19]). In polygenic risk score analysis, FA, MD, and WMHV were significantly associated with lacunar stroke, MD with major depressive disorder, and WMHV with Alzheimer disease. Genetic variants within the VCAN gene may play a role in the mechanisms underlying microstructural integrity of the white matter in the brain measured as FA and MD. Mechanisms underlying white matter alterations are shared with cerebrovascular disease, and inherited differences in white matter microstructure impact on Alzheimer disease and major depressive disorder. © 2018 The Authors.

The Effectiveness of Pemetrexed Monotherapy Depending on Polymorphisms in TS and MTHFR Genes as Well as Clinical Factors in Advanced NSCLC Patients.

PubMed

Kucharczyk, Tomasz; Krawczyk, Paweł; Powrózek, Tomasz; Kowalski, Dariusz M; Ramlau, Rodryg; Kalinka-Warzocha, Ewa; Knetki-Wróblewska, Magdalena; Winiarczyk, Kinga; Krzakowski, Maciej; Milanowski, Janusz

2016-01-01

In NSCLC, second-line chemotherapy using pemetrexed or docetaxel has limited efficacy and should be dedicated to selected groups of patients. Pemetrexed is an antifolate compound with the ability to inhibit enzymes (TS, DHFR and GARFT) involved in pyrimidine and purine synthesis. The objective of this study was to evaluate the association between polymorphisms of TS and MHFR genes and clinical outcomes in NSCLC patients treated with pemetrexed monotherapy. DNA was isolated from peripheral blood of 72 non-squamous NSCLC patients treated with pemetrexed. Using PCR and RFLP methods, the variable number of tandem repeats (VNTR), the G > C SNP in these repeats and insertion/deletion polymorphism of TS gene as well as 677C > T SNP in MTHFR gene were analyzed and correlated with disease control rate, progression-free survival and overall survival (OS) of NSCLC patients. Carriers of 2R/3R(G), 3R(C)/3R(G), 3R(G)/3R(G) genotypes showed significantly more frequent early progression than carriers of 2R/2R, 2R/3R(C), 3R(C)/3R(C) genotypes of TS gene (p < 0.05). Among carriers of triple 28 bp tandem repeats (3R) in TS gene and C/C genotype of MTHFR gene a significantly shorter OS was observed (HR = 3.07; p = 0.003). In multivariate analysis, significantly higher risk of death was observed in carriers of both 3R/3R genotype in TS and C/C genotype in 677C > T SNP in MTHFR (HR = 3.85; p < 0.005) as well as in patients with short duration of response to first-line chemotherapy (HR = 2.09; p < 0.005). Results of our study suggested that genetic factors may have a high predictive and prognostic value (even greater than clinical factors) for patients treated with pemetrexed monotherapy.

Characterization of Metarhizium species and varieties based on molecular analysis, heat tolerance and cold activity

USGS Publications Warehouse

Fernandes, E.K.K.; Keyser, C.A.; Chong, J.P.; Rangel, D.E.N.; Miller, M.P.; Roberts, D.W.

2010-01-01

Aims: The genetic relationships and conidial tolerances to high and low temperatures were determined for isolates of several Metarhizium species and varieties. Methods and Results: Molecular-based techniques [AFLP and rDNA (ITS1, ITS2 and 5??8S) gene sequencing] were used to characterize morphologically identified Metarhizium spp. isolates from a wide range of sources. Conidial suspensions of isolates were exposed to wet heat (45 ?? 0??2??C) and plated on potato dextrose agar plus yeast extract (PDAY) medium. After 8-h exposure, the isolates divided clearly into two groups: (i) all isolates of Metarhizium anisopliae var. anisopliae (Ma-an) and Metarhizium from the flavoviride complex (Mf) had virtually zero conidial relative germination (RG), (ii) Metarhizium anisopliae var. acridum (Ma-ac) isolates demonstrated high heat tolerance (c. 70-100% RG). Conidial suspensions also were plated on PDAY and incubated at 5??C for 15 days, during which time RGs for Ma-an and Ma-ac isolates were virtually zero, whereas the two Mf were highly cold active (100% RG). Conclusions: Heat and cold exposures can be used as rapid tools to tentatively identify some important Metarhizium species and varieties. Significance and Impact of the Study: Identification of Metarhizium spp. currently relies primarily on DNA-based methods; we suggest a simple temperature-based screen to quickly obtain tentative identification of isolates as to species or species complexes. ?? 2009 The Society for Applied Microbiology.

77 FR 47670 - RG Steel Sparrows Point LLC, Formerly Known as Severstal Sparrows Point LLC, a Subsidiary of RG...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-09

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-74,919] RG Steel Sparrows Point LLC, Formerly Known as Severstal Sparrows Point LLC, a Subsidiary of RG Steel LLC, Including All On-Site Leased Workers, Sparrows Point, MD; Amended Certification Regarding Eligibility To Apply for...

Teledyne H1RG, H2RG, and H4RG Noise Generator

NASA Technical Reports Server (NTRS)

Rauscher, Bernard J.

2015-01-01

This paper describes the near-infrared detector system noise generator (NG) that we wrote for the James Webb Space Telescope (JWST) Near Infrared Spectrograph (NIRSpec). NG simulates many important noise components including; (1) white "read noise", (2) residual bias drifts, (3) pink 1/f noise, (4) alternating column noise, and (5) picture frame noise. By adjusting the input parameters, NG can simulate noise for Teledyne's H1RG, H2RG, and H4RG detectors with and without Teledyne's SIDECAR ASIC IR array controller. NG can be used as a starting point for simulating astronomical scenes by adding dark current, scattered light, and astronomical sources into the results from NG. NG is written in Python-3.4.

ATM Heterozygosity and the Development of Radiation-Induced Erectile Dysfunction and Urinary Morbidity Following Radiotherapy for Prostate Cancer

DTIC Science & Technology

2009-02-01

mentors Richard Stock, M.D., and Barry Rosenstein,PhD., regarding the natural history of prostate cancer treated with brachytherapy and the genetics...Supplement 1, 1 November 2007, Page S630 Peters CA, Stone NN, Cesaretti JA and Stock RG “The Effect of Family History on Outcome in Patients Treated...Grimm PD, et al. Centralized multi- institutional postimplant analysis for interstitial prostate brachy- therapy. Int J Radiat Oncol Biol Phys 1998;41:921

Inventorying rock glaciers: The relevance of definitions, processes and base data

NASA Astrophysics Data System (ADS)

Kellerer-Pirklbauer, Andreas; Lieb, Gerhard Karl; Wagner, Thomas; Winkler, Gerfried

2017-04-01

Rock glacier inventories have been elaborated for many mountain regions during the last decades. Such inventories have been used for instance to determine the current (using intact rock glaciers) or the past extent (using relict ones) of mountain permafrost and its change over time. However, the recognition and delineation of a rock glacier is not always a trivial task in particular in cases where the "typical" rock glacier surface morphology with longitudinal and transversal ridges and furrows is missing. A further inventorying restriction is based on which genetic model for rock glacier formation is used or favored by the elaborator, i.e. glacier-derived rock glaciers (with massive sedimentary or "glacier" ice), talus-derived rock glaciers (dominated by congelation ice), or a mix thereof. In addition to that, relict rock glaciers are commonly more difficult to recognize and to delineate due to the decay of morphological features or the coverage by vegetation. In this regard the geomorphic concept of equifinality plays an important role because similar looking landforms might have been formed as a result of quite different sets of processes and time periods. Two examples illustrating this problem are as follows: (i) relict embryonal rock glaciers or protalus ramparts look very similar to pronival ramparts although the acting process was substantial different; (ii) multiple ridges at a presumed rock glacier front might have been formed by several phases of glacier advance forming a set of terminal moraines. Therefore, the elaboration of a rock glacier inventory is certainly influenced by subjectivity related to the expertise and field knowledge of the mapping person. A further crucial mapping restriction is based upon the used terrain (digital elevation models/DEM and maps) and optical (airborne, spaceborne) data. Under the assumption that improved data bases help to solve the problems mentioned above the authors of this abstract elaborated three generations of rock glacier inventories for the Federal Province of Styria (16,400 km2), Austria, during the last two decades - each time using the best data sources available. The first Styrian rock glacier inventory (StRGI1) was elaborated in the mid-1990s using official maps, aerial photographs, and field verification. The second Styrian rock glacier inventory (StRG2) was elaborated in 2010-2011 using the StRG1, airborne orthophotographs, and photogrammetrically-derived DEMs with a 10m-grid resolution. Finally, the third Styrian rock glacier inventory (StRG3) was elaborated in 2014-2016 using the StRG2, airborne and spaceborne orthophotographs, and an airborne laser scanning-derived DEM with a 1m-grid resolution. The number of mapped rock glaciers increased from less than 400 listed in StRG1, slightly more than 400 in StRG2 to 710 in StRG3. The substantial increase in the number of rock glaciers in StRG3 is particularly related to the used laser scanning-based DEM because relict rock glaciers located at lower elevations in densely vegetated areas and forests have not been detected earlier. This contribution will present examples of inventoried rock glaciers and how their delineation and interpretation changed during the different inventory generations and hence contributes to the ongoing discussion about how to delineate and interpret rock glaciers.

Generation of recombinant rotaviruses expressing fluorescent proteins using an optimized reverse genetics system.

PubMed

Komoto, Satoshi; Fukuda, Saori; Ide, Tomihiko; Ito, Naoto; Sugiyama, Makoto; Yoshikawa, Tetsushi; Murata, Takayuki; Taniguchi, Koki

2018-04-18

An entirely plasmid-based reverse genetics system for rotaviruses was established very recently. We improved the reverse genetics system to generate recombinant rotavirus by transfecting only 11 cDNA plasmids for its 11 gene segments under the condition of increasing the ratio of the cDNA plasmids for NSP2 and NSP5 genes. Utilizing this highly efficient system, we then engineered infectious recombinant rotaviruses expressing bioluminescent (NanoLuc luciferase) and fluorescent (EGFP and mCherry) reporters. These recombinant rotaviruses expressing reporters remained genetically stable during serial passages. Our reverse genetics approach and recombinant rotaviruses carrying reporter genes will be great additions to the tool kit for studying the molecular virology of rotavirus, and for developing future next-generation vaccines and expression vectors. IMPORTANCE Rotavirus is one of the most important pathogens causing severe gastroenteritis in young children worldwide. In this paper, we describe a robust and simple reverse genetics system based on only rotavirus cDNAs, and its application for engineering infectious recombinant rotaviruses harboring bioluminescent (NanoLuc) and fluorescent (EGFP and mCherry) protein genes. This highly efficient reverse genetics system and recombinant RVAs expressing reporters could be powerful tools for the study of different aspects of rotavirus replication. Furthermore, they may be useful for next-generation vaccine production for this medically important virus. Copyright © 2018 American Society for Microbiology.

Isolation, structural determination, and evaluation of the biological activity of 20(S)-25-methoxyl-dammarane-3beta, 12beta, 20-triol [20(S)-25-OCH3-PPD], a novel natural product from Panax notoginseng.

PubMed

Zhao, Y; Wang, W; Han, L; Rayburn, E R; Hill, D L; Wang, H; Zhang, R

2007-01-01

Ginseng has been used extensively for medicinal purposes, with suggested utility for indications as diverse as diabetes, cardiovascular disease and cancer. Herein we report the discovery and characterization of 20(S)-25-OCH3-PPD, a ginsenoside that inhibits growth and survival of cancer cells. The novel dammarane triterpene sapogenin (C31H56O4; molecular weight 492) was isolated from the total hydrolyzed saponins extracted from the leaves of Panax notoginseng using conventional and reverse-phase silica gel chromatography. Based on physicochemical characteristics and NMR data, the compound was identified as 20(S)-25-OCH3-PPD. The biological activities of 20(S)-25-OCH3-PPD and its known analogs, 20(S)-PPD and Rg3, were evaluated in 12 human cancer cell lines. In all cell lines, the order of cytotoxicity of the test compounds was 20(S)-25-OCH3-PPD > 20(S)-PPD > Rg3. 20(S)-25-OCH3-PPD also induced apoptosis and cell cycle arrest in the G1 phase, and inhibited proliferation in breast cancer cell lines, demonstrating its potent biological effects. In regard to cytotoxicity, the IC50 values of 20(S)-25-OCH3-PPD for most cell lines were in the lower microM range, a 5-15-fold greater cytotoxicity relative to 20(S)-PPD and a 10-100-fold increase over Rg3. These findings suggest a structure-activity relationship among dammarane-type sapogenins. The data presented here may provide a basis for the future development of 20(S)-25-OCH3-PPD as a novel anti-cancer agent.

Relationship among performance, carcass, and feed efficiency characteristics, and their ability to predict economic value in the feedlot.

PubMed

Retallick, K M; Faulkner, D B; Rodriguez-Zas, S L; Nkrumah, J D; Shike, D W

2013-12-01

A 4-yr study was conducted using 736 steers of known Angus, Simmental, or Simmental × Angus genetics to determine performance, carcass, and feed efficiency factors that explained variation in economic performance. Steers were pen fed and individual DMI was recorded using a GrowSafe automated feeding system (GrowSafe Systems Ltd., Airdrie, Alberta, Canada). Steers consumed a similar diet and received similar management each year. The objectives of this study were to: 1) determine current economic value of feed efficiency and 2) identify performance, carcass, and feed efficiency characteristics that predict: carcass value, profit, cost of gain, and feed costs. Economic data used were from 2011 values. Feed efficiency values investigated were: feed conversion ratio (FCR; feed to gain), residual feed intake (RFI), residual BW gain (RG), and residual intake and BW gain (RIG). Dependent variables were carcass value ($/steer), profit ($/steer), feed costs ($/steer • d(-1)), and cost of gain ($/kg). Independent variables were year, DMI, ADG, HCW, LM area, marbling, yield grade, dam breed, and sire breed. A 10% improvement in RG (P < 0.05) yielded the lowest cost of gain at $0.09/kg and highest carcass value at $17.92/steer. Carcass value increased (P < 0.05) as feed efficiency improved for FCR, RG, and RIG. Profit increased with a 10% improvement in feed efficiency (P < 0.05) with FCR at $34.65/steer, RG at $31.21/steer, RIG at $21.66/steer, and RFI at $11.47/steer. The carcass value prediction model explained 96% of the variation among carcasses and included HCW, marbling score, and yield grade. Average daily gain, marbling score, yield grade, DMI, HCW, and year born constituted 81% of the variation for prediction of profit. Eighty-five percent of the variation in cost of gain was explained by ADG, DMI, HCW, and year. Prediction equations were developed that excluded ADG and DMI, and included feed efficiency values. Using these equations, cost of gain was explained primarily by FCR (R(2) = 0.71). Seventy-three percent of profitability was explained, with 55% being accounted for by RG and marbling. These prediction equations represent the relative importance of factors contributing to economic success in feedlot cattle based on current prices.

Reverse genetics of Newcastle disease virus

USDA-ARS?s Scientific Manuscript database

Reverse genetics allows the generation of recombinant viruses or vectors used in functional studies, vaccine development, and gene therapy. This technique allows genetic manipulation and cloning of viral genomes, mutation through site-directed mutagenesis, and gene insertion or deletion, among othe...

Protective Effect of Ginsenosides Rg1 and Re on Lipopolysaccharide-Induced Sepsis by Competitive Binding to Toll-Like Receptor 4

PubMed Central

Su, Fei; Xue, Yin; Wang, Yuemin; Zhang, Lili; Chen, Wangxue

2015-01-01

We previously demonstrated that ginsenosides Rg1 and Re enhanced the immune response in C3H/HeB mice but not in C3H/HeJ mice carrying a mutation in the Tlr4 gene. The results of the present study showed that both Rg1 and Re inhibited mRNA expression and production of proinflammatory mediators that included tumor necrosis factor α, interleukin-1β, interleukin-6, cyclooxygenase-2, and inducible nitric oxide synthase from lipopolysaccharide (LPS)-stimulated macrophages. Rg1 was found to be distributed both extracellularly and intracellularly but Re was located only extracellularly to compete with LPS for binding to Toll-like receptor 4. Preinjection of Rg1 and Re into rats suppressed LPS-induced increases in body temperature, white blood cell counts, and levels of serum proinflammatory mediators. Preinjection of Rg1 and Re into mice prevented the LPS-induced decreases in total white blood cell counts and neutrophil counts, inhibited excessive expression of multiple proinflammatory mediators, and successfully rescued 100% of the mice from sepsis-associated death. More significantly, when administered after lethal LPS inoculation, Rg1, but not Re, still showed a potent antisepsis effect and protected 90% of the mice from death. The better protection efficacy of Rg1 could result from its intracellular distribution, suggesting that Rg1 may be an ideal antisepsis agent. PMID:26149990

Combined Salvianolic Acid B and Ginsenoside Rg1 Exerts Cardioprotection against Ischemia/Reperfusion Injury in Rats

PubMed Central

Deng, Yanping; Yang, Min; Xu, Feng; Zhang, Qian; Zhao, Qun; Yu, Haitao; Li, Defang; Zhang, Ge; Lu, Aiping; Cho, Kenka; Teng, Fukang; Wu, Peng; Wang, Linlin; Wu, Wanying; Liu, Xuan; Guo, De-an; Jiang, Baohong

2015-01-01

Lack of pharmacological strategies in clinics restricts the patient prognosis with myocardial ischemia/reperfusion (I/R) injury. The aim of this study was to evaluate the cardioprotection of combined salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1) against myocardial I/R injury and further investigate the underlying mechanism. I/R injury was induced by coronary artery ligation for Wistar male rats and hypoxia/reoxygenation injury was induced on H9c2 cells. Firstly, the best ratio between SalB and Rg1was set as 2:5 based on their effects on heart function detected by hemodynamic measurement. Then SalB-Rg1 (2:5) was found to maintain mitochondrial membrane potential and resist apoptosis and necrosis in H9c2 cell with hypoxia/reoxygenation injury. Companying with same dose of SalB or Rg1 only, SalB-Rg1 showed more significant effects on down-regulation of myocardial infarct size, maintenance of myocardium structure, improvement on cardiac function, decrease of cytokine secretion including TNF-α, IL-1β, RANTES and sVCAM-1. Finally, the SalB-Rg1 improved the viability of cardiac myocytes other than cardiac fibroblasts in rats with I/R injury using flow cytometry. Our results revealed that SalB-Rg1 was a promising strategy to prevent myocardial I/R injury. PMID:26280455

Ginsenoside Rg1 enhances lymphatic transport of intrapulmonary silica via VEGF-C/VEGFR-3 signaling in silicotic rats.

PubMed

Yu, Jie; Mao, Lijun; Guan, Li; Zhang, Yanlin; Zhao, Jinyuan

2016-03-25

Ginsenoside Rg1, extracted mainly from Panax ginseng, has been shown to exert strong pro-angiogenic activities in vivo. But it is unclear whether ginsenoside Rg1 could promote lung lymphangiogenesis to improve lymphatic transport of intrapulmonary silica in silicotic rats. Here we investigated the effect of ginsenoside Rg1 on lymphatic transport of silica during experimental silicosis, and found that ginsenoside Rg1 treatment significantly raised the silicon content in tracheobronchial lymph nodes and serum to reduce the silicon level in lung interstitium, meanwhile increased pulmonary lymphatic vessel density by enhancing the protein and mRNA expressions of vascular endothelial growth factor-C (VEGF-C) and vascular endothelial growth factor receptor-3 (VEGFR-3). The stimulative effect of ginsenoside Rg1 on lymphatic transport of silica was actively correlated with its pro-lymphangiogenic identity. And VEGFR-3 inhibitor SAR131675 blocked these above effects of ginsenoside Rg1. These findings suggest that ginsenoside Rg1 exhibits good protective effect against lung burden of silica during experimental silicosis through improving lymphatic transport of intrapulmonary silica, which is potentially associated with the activation of VEGF-C/VEGFR-3 signaling pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

Ginsenoside Rg1 and platelet-rich fibrin enhance human breast adipose-derived stem cells function for soft tissue regeneration

PubMed Central

Li, Hong-Mian; Peng, Qi-Liu; Huang, Min-Hong; Li, De-Quan; Liang, Yi-Dan; Chi, Gang-Yi; Li, De-Hui; Yu, Bing-Chao; Huang, Ji-Rong

2016-01-01

Adipose-derived stem cells (ASCs) can be used to repair soft tissue defects, wounds, burns, and scars and to regenerate various damaged tissues. The cell differentiation capacity of ASCs is crucial for engineered adipose tissue regeneration in reconstructive and plastic surgery. We previously reported that ginsenoside Rg1 (G-Rg1 or Rg1) promotes proliferation and differentiation of ASCs in vitro and in vivio. Here we show that both G-Rg1 and platelet-rich fibrin (PRF) improve the proliferation, differentiation, and soft tissue regeneration capacity of human breast adipose-derived stem cells (HBASCs) on collagen type I sponge scaffolds in vitro and in vivo. Three months after transplantation, tissue wet weight, adipocyte number, intracellular lipid, microvessel density, and gene and protein expression of VEGF, HIF-1α, and PPARγ were higher in both G-Rg1- and PRF-treated HBASCs than in control grafts. More extensive new adipose tissue formation was evident after treatment with G-Rg1 or PRF. In summary, G-Rg1 and/or PRF co-administration improves the function of HBASCs for soft tissue regeneration engineering. PMID:27191987

Red Ginseng (Panax ginseng) Decreases Isoproterenol-Induced Cardiac Injury via Antioxidant Properties in Porcine

PubMed Central

Lim, Kyu Hee; Cho, Jae Youl; Kim, Bumseok; Bae, Bong-Seuk

2014-01-01

Abstract Red ginseng (RG, Panax ginseng) has been shown to possess various ginsenosides. These ginsenosides are widely used for treating cardiovascular diseases in Asian communities. The present study was designed to evaluate the cardioprotective potential of RG against isoproterenol (ISO)-induced myocardial infarction (MI), by assessing electrocardiographic, hemodynamic, and biochemical parameters. Male porcines were orally administered with RG (250 and 500 mg/kg) or with vehicle for 9 days, with concurrent intraperitoneal injections of ISO (20 mg/kg) on the 8th and 9th day. RG significantly attenuated ISO-induced cardiac dysfunctions as evidenced by improved ventricular hemodynamic functions and reduced ST segment and QRS complex intervals. Also, RG significantly ameliorated myocardial injury parameters such as antioxidants. Malonaldialdehyde formation was also inhibited by RG. Based on the results, it is concluded that RG possesses significant cardioprotective potential through the inhibition of oxidative stress and may serve as an adjunct in the treatment and prophylaxis of MI. PMID:24456361

RNA Virus Reverse Genetics and Vaccine Design

PubMed Central

Stobart, Christopher C.; Moore, Martin L.

2014-01-01

RNA viruses are capable of rapid spread and severe or potentially lethal disease in both animals and humans. The development of reverse genetics systems for manipulation and study of RNA virus genomes has provided platforms for designing and optimizing viral mutants for vaccine development. Here, we review the impact of RNA virus reverse genetics systems on past and current efforts to design effective and safe viral therapeutics and vaccines. PMID:24967693

Intrinsically disordered RGG/RG domains mediate degenerate specificity in RNA binding

PubMed Central

Ozdilek, Bagdeser A.; Thompson, Valery F.; Ahmed, Nasiha S.; White, Connor I.

2017-01-01

Abstract RGG/RG domains are the second most common RNA binding domain in the human genome, yet their RNA-binding properties remain poorly understood. Here, we report a detailed analysis of the RNA binding characteristics of intrinsically disordered RGG/RG domains from Fused in Sarcoma (FUS), FMRP and hnRNPU. For FUS, previous studies defined RNA binding as mediated by its well-folded domains; however, we show that RGG/RG domains are the primary mediators of binding. RGG/RG domains coupled to adjacent folded domains can achieve affinities approaching that of full-length FUS. Analysis of RGG/RG domains from FUS, FMRP and hnRNPU against a spectrum of contrasting RNAs reveals that each display degenerate binding specificity, while still displaying different degrees of preference for RNA. PMID:28575444

Generation of EMS-Mutagenized Populations of Arabidopsis thaliana for Polyamine Genetics.

PubMed

Atanasov, Kostadin E; Liu, Changxin; Tiburcio, Antonio F; Alcázar, Rubén

2018-01-01

In the recent years, genetic engineering of polyamine biosynthetic genes has provided evidence for their involvement in plant stress responses and different aspects of plant development. Such approaches are being complemented with the use of reverse genetics, in which mutants affected on a particular trait, tightly associated with polyamines, are isolated and the causal genes mapped. Reverse genetics enables the identification of novel genes in the polyamine pathway, which may be involved in downstream signaling, transport, homeostasis, or perception. Here, we describe a basic protocol for the generation of ethyl methanesulfonate (EMS) mutagenized populations of Arabidopsis thaliana for its use in reverse genetics applied to polyamines.

Ginsenoside-Rg{sub 1} induces angiogenesis by the inverse regulation of MET tyrosine kinase receptor expression through miR-23a

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

Kwok, Hoi-Hin; Chan, Lai-Sheung; Poon, Po-Ying

2015-09-15

Therapeutic angiogenesis has been implicated in ischemic diseases and wound healing. Ginsenoside-Rg{sub 1} (Rg{sub 1}), one of the most abundant active components of ginseng, has been demonstrated as an angiogenesis-stimulating compound in different models. There is increasing evidence implicating microRNAs (miRNAs), a group of non-coding RNAs, as important regulators of angiogenesis, but the role of microRNAs in Rg{sub 1}-induced angiogenesis has not been fully explored. In this report, we found that stimulating endothelial cells with Rg{sub 1} could reduce miR-23a expression. In silico experiments predicted hepatocyte growth factor receptor (MET), a well-established mediator of angiogenesis, as the target of miR-23a.more » Transfection of the miR-23a precursor or inhibitor oligonucleotides validated the inverse relationship of miR-23a and MET expression. Luciferase reporter assays further confirmed the interaction between miR-23a and the MET mRNA 3′-UTR. Intriguingly, ginsenoside-Rg{sub 1} was found to increase MET protein expression in a time-dependent manner. We further demonstrated that ginsenoside-Rg{sub 1}-induced angiogenic activities were indeed mediated through the down-regulation of miR-23a and subsequent up-regulation of MET protein expression, as confirmed by gain- and loss-of-function angiogenic experiments. In summary, our results demonstrated that ginsenoside-Rg{sub 1} could induce angiogenesis by the inverse regulation of MET tyrosine kinase receptor expression through miR-23a. This study has broadened our understanding of the non-genomic effects of ginsenoside-Rg{sub 1,} and provided molecular evidence that warrant further development of natural compound as novel angiogenesis-promoting therapy. - Highlights: • Therapeutic angiogenesis has been implicated in ischemic diseases and wound healing. • Ginsenoside-Rg{sub 1} (Rg{sub 1}) has been demonstrated as an angiogenesis-stimulating compound. • We found that Rg{sub 1} induces angiogenesis by decreasing miR-23a expression. • Hepatocyte growth factor receptor (MET) is a direct regulatory target of miR-23a. • Rg{sub 1} could induce angiogenesis by the inverse regulation of MET through miR-23a.« less

Insertion of rare gas atoms into BF3 and AlF3 molecules: An ab initio investigation

NASA Astrophysics Data System (ADS)

Jayasekharan, T.; Ghanty, T. K.

2006-12-01

The structure, stability, charge redistribution, and harmonic vibrational frequencies of rare gas inserted group III-B fluorides with the general formula F -Rg-MF2 (where M =B and Al; Rg =Ar, Kr, and Xe) have been investigated using ab initio quantum chemical methods. The Rg atom is inserted in one of the M -F bond of MF3 molecules, and the geometries are optimized for ground as well as transition states using the MP2 method. It has been found that Rg inserted F -Rg-M portion is linear in both F -Rg-BF2 and F -Rg-AlF2 species. The binding energies corresponding to the lowest energy fragmentation products MF3+Rg (two-body dissociation) have been computed to be -670.4, -598.8, -530.7, -617.0, -562.1, and -494.0kJ /mol for F -Ar-BF2, F -Kr-BF2, F -Xe-BF2, F -Ar-AlF2, F -Kr-AlF2, and F -Xe-AlF2 species, respectively. The dissociation energies corresponding to MF2+Rg +F fragments (three-body dissociation) are found to be positive with respect to F -Rg-MF2 species, and the computed values are 56.3, 127.8, and 196.0kJ/mol for F -Ar-BF2, F -Kr-BF2, and F -Xe-BF2 species, respectively. The corresponding values for F -Ar-AlF2, F -Kr-AlF2, and F -Xe-AlF2 species are also found to be positive. The decomposition of F -Rg-MF2 species into the MF3+Rg (two-body dissociation) channel typically proceeds via a transition state involving F -Rg-M out-of-plane bending mode. The transition state barrier heights are 35.5, 62.7, 89.8, 22.0, 45.6, and 75.3kJ/mol for F -Ar-BF2, F -Kr-BF2, F -Xe-BF2, F -Ar-AlF2, F -Kr-AlF2, and F -Xe-AlF2 species, respectively. The calculated geometrical parameters and the energy values suggest that these species are metastable and may be prepared and characterized using low temperature matrix isolation techniques, and are possibly the next new candidates for gas phase or matrix experiments.

77 FR 70478 - RG Steel Wheeling, LLC, Wheeling Office, A Division Of RG Steel, LLC, Including On-Site Leased...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-26

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-81,880: TA-A-81,880A] RG Steel Wheeling, LLC, Wheeling Office, A Division Of RG Steel, LLC, Including On-Site Leased Workers From Pro Unlimited and Green Energy Initiatives LLC, Including Workers Whose Wages Were Reported Through Severstal Wheeling, Wheeling, WV: Mountain State...

Novel genetic loci associated with hippocampal volume

PubMed Central

Hibar, Derrek P.; Adams, Hieab H. H.; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L.; Hofer, Edith; Renteria, Miguel E.; Bis, Joshua C.; Arias-Vasquez, Alejandro; Ikram, M. Kamran; Desrivières, Sylvane; Vernooij, Meike W.; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S.; Armstrong, Nicola J.; Athanasiu, Lavinia; Axelsson, Tomas; Beecham, Ashley H.; Beiser, Alexa; Bernard, Manon; Blanton, Susan H.; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brickman, Adam M.; Carmichael, Owen; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Chouraki, Vincent; Cuellar-Partida, Gabriel; Crivello, Fabrice; Den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Giddaluru, Sudheer; Goldman, Aaron L.; Gottesman, Rebecca F.; Grimm, Oliver; Griswold, Michael E.; Guadalupe, Tulio; Gutman, Boris A.; Hass, Johanna; Haukvik, Unn K.; Hoehn, David; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Jørgensen, Kjetil N.; Karbalai, Nazanin; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Liewald, David C. M.; Lopez, Lorna M.; Luciano, Michelle; Macare, Christine; Marquand, Andre F.; Matarin, Mar; Mather, Karen A.; Mattheisen, Manuel; McKay, David R.; Milaneschi, Yuri; Muñoz Maniega, Susana; Nho, Kwangsik; Nugent, Allison C.; Nyquist, Paul; Loohuis, Loes M. Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pirpamer, Lukas; Pütz, Benno; Ramasamy, Adaikalavan; Richards, Jennifer S.; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rommelse, Nanda; Ropele, Stefan; Rose, Emma J.; Royle, Natalie A.; Rundek, Tatjana; Sämann, Philipp G.; Saremi, Arvin; Satizabal, Claudia L.; Schmaal, Lianne; Schork, Andrew J.; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V.; Sprooten, Emma; Strike, Lachlan T.; Teumer, Alexander; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Trompet, Stella; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Lee, Sven J.; Van der Meer, Dennis; Van Donkelaar, Marjolein M. J.; Van Eijk, Kristel R.; Van Erp, Theo G. M.; Van Rooij, Daan; Walton, Esther; Westlye, Lars T.; Whelan, Christopher D.; Windham, Beverly G.; Winkler, Anderson M.; Wittfeld, Katharina; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Yanek, Lisa R.; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P.; Agartz, Ingrid; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A.; Arepalli, Sampath; Assareh, Amelia A.; Barral, Sandra; Bastin, Mark E.; Becker, Diane M.; Becker, James T.; Bennett, David A.; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I.; Brodaty, Henry; Brouwer, Rachel M.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Bulayeva, Kazima B.; Cahn, Wiepke; Calhoun, Vince D.; Cannon, Dara M.; Cavalleri, Gianpiero L.; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R.; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E.; Czisch, Michael; Dale, Anders M.; Davies, Gareth E.; De Craen, Anton J. M.; De Geus, Eco J. C.; De Jager, Philip L.; De Zubicaray, Greig I.; Deary, Ian J.; Debette, Stéphanie; DeCarli, Charles; Delanty, Norman; Depondt, Chantal; DeStefano, Anita; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C.; Duggirala, Ravi; Dyer, Thomas D.; Enzinger, Christian; Erk, Susanne; Espeseth, Thomas; Fedko, Iryna O.; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E.; Fleischman, Debra A.; Ford, Ian; Fornage, Myriam; Foroud, Tatiana M.; Fox, Peter T.; Francks, Clyde; Fukunaga, Masaki; Gibbs, J. Raphael; Glahn, David C.; Gollub, Randy L.; Göring, Harald H. H.; Green, Robert C.; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Håberg, Asta K.; Hansell, Narelle K.; Hardy, John; Hartman, Catharina A.; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G.; Heslenfeld, Dirk J.; Ho, Beng-Choon; Hoekstra, Pieter J.; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Huentelman, Matthew; Pol, Hilleke E. Hulshoff; Ikeda, Masashi; Jack Jr, Clifford R.; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G.; Jukema, J. Wouter; Kahn, René S.; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L.; Lopez, Oscar L.; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S.; McDonald, Colm; McIntosh, Andrew M.; McMahon, Francis J.; McMahon, Katie L.; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W.; Morris, Derek W.; Mosley, Thomas H.; Mühleisen, Thomas W.; Müller-Myhsok, Bertram; Nalls, Michael A.; Nauck, Matthias; Nichols, Thomas E.; Niessen, Wiro J.; Nöthen, Markus M.; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L.; Ophoff, Roel A.; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W. J. H.; Pike, G. Bruce; Potkin, Steven G.; Psaty, Bruce M.; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L.; Romanczuk-Seiferth, Nina; Rotter, Jerome I.; Ryten, Mina; Sacco, Ralph L.; Sachdev, Perminder S.; Saykin, Andrew J.; Schmidt, Reinhold; Schmidt, Helena; Schofield, Peter R.; Sigursson, Sigurdur; Simmons, Andrew; Singleton, Andrew; Sisodiya, Sanjay M.; Smith, Colin; Smoller, Jordan W.; Soininen, Hilkka; Steen, Vidar M.; Stott, David J.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Tsolaki, Magda; Tzourio, Christophe; Uitterlinden, Andre G.; Hernández, Maria C. Valdés; Van der Brug, Marcel; van der Lugt, Aad; van der Wee, Nic J. A.; Van Haren, Neeltje E. M.; van 't Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N.; Vellas, Bruno; Veltman, Dick J.; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M.; Wassink, Thomas H.; Weale, Michael E.; Weinberger, Daniel R.; Weiner, Michael W.; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y.; Wright, Clinton B.; Zielke, Ronald H.; Zonderman, Alan B.; Martin, Nicholas G.; Van Duijn, Cornelia M.; Wright, Margaret J.; Longstreth, W. T.; Schumann, Gunter; Grabe, Hans J.; Franke, Barbara; Launer, Lenore J.; Medland, Sarah E.; Seshadri, Sudha; Thompson, Paul M.; Ikram, M. Arfan

2017-01-01

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=−0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness. PMID:28098162

Monitoring changes in the demographic and genealogical structure of the main Spanish local beef breeds.

PubMed

Cañas-Álvarez, J J; Gónzalez-Rodríguez, A; Martín-Collado, D; Avilés, C; Altarriba, J; Baro, J A; De la Fuente, L F; Díaz, C; Molina, A; Varona, L; Piedrafita, J

2014-10-01

Demographic and pedigree analyses describe the structure and dynamics of livestock populations. We studied information recorded in the herdbooks of Asturiana de los Valles (AV; N = 458,806), Avileña-Negra Ibérica (ANI; N = 204,623), Bruna dels Pirineus (BP; N = 62,138), Morucha (Mo; N = 65,350), Pirenaica (Pi; N = 217,428), Retinta (Re; N = 135,300), and Rubia Gallega (RG; N = 235,511) beef breeds from their creation until 2009. All breeds have increased in the number of registered cows in recent years. In all breeds, herds do not behave as isolated entities and a high rate of exchange of breeding males between herds exists. A percentage of herds (12-52%) make some type of selection and sell bulls to other herds. There were large differences in average number of progeny per bull, ranging from 15.6 (AV) to 373.7 animals (RG, with a high incidence of AI). Generation interval estimates ranged from 4.7 (AV) to 7.6 (RG) yr in the sire pathway and from 5.95 (AV) to 7.8 (Mo) yr in the dam pathway. Density of pedigrees varied among breeds, with Pi, ANI, and Re having the more dense pedigrees, with average completeness indexes of more than 96% in the first generation and 80% when 6 generations were considered. A general increase in average inbreeding was observed in all breeds in the years analyzed. For animals born in 2009, average inbreeding coefficients ranged from 0.6 (BP) to 7.2% (Re) when all animals were considered and from 3.6 (Pi) to 17.6% (BP) when only inbred animals were considered. Due to the lack of completeness of pedigrees in most populations, inbreeding coefficients may be considered as a lower bound of the true parameters. The proportion of inbred animals tended to increase in the periods analyzed in all breeds. Differences between inbreeding and coancestry rates (except in RG) suggest the presence of population structure. Effective population size (Ne) based on the inbreeding rate estimated by regression ranged from 43 to 378 for Re and BP, whereas Ne estimates based on coancestry were greater, with a range of 100 for RG to 9,985 for BP. These facts suggest that an adequate mating policy can help to monitor inbreeding so as not to lose genetic variability. Effective number of ancestors in 2009 for 6 of the breeds ranged from 42 (RG) to 220 (AV), with BP having much a greater value, and was lower than was the effective number of founders in all breeds, suggesting the existence of bottlenecks.

Boron bridging of rhamnogalacturonan-II, monitored by gel electrophoresis, occurs during polysaccharide synthesis and secretion but not post-secretion

PubMed Central

Chormova, Dimitra; Messenger, David J; Fry, Stephen C

2014-01-01

The cell-wall pectic domain rhamnogalacturonan-II (RG-II) is cross-linked via borate diester bridges, which influence the expansion, thickness and porosity of the wall. Previously, little was known about the mechanism or subcellular site of this cross-linking. Using polyacrylamide gel electrophoresis (PAGE) to separate monomeric from dimeric (boron-bridged) RG-II, we confirmed that Pb2+ promotes H3BO3-dependent dimerisation in vitro. H3BO3 concentrations as high as 50 mm did not prevent cross-linking. For in-vivo experiments, we successfully cultured ‘Paul's Scarlet’ rose (Rosa sp.) cells in boron-free medium: their wall-bound pectin contained monomeric RG-II domains but no detectable dimers. Thus pectins containing RG-II domains can be held in the wall other than via boron bridges. Re-addition of H3BO3 to 3.3 μm triggered a gradual appearance of RG-II dimer over 24 h but without detectable loss of existing monomers, suggesting that only newly synthesised RG-II was amenable to boron bridging. In agreement with this, Rosa cultures whose polysaccharide biosynthetic machinery had been compromised (by carbon starvation, respiratory inhibitors, anaerobiosis, freezing or boiling) lost the ability to generate RG-II dimers. We conclude that RG-II normally becomes boron-bridged during synthesis or secretion but not post-secretion. Supporting this conclusion, exogenous [3H]RG-II was neither dimerised in the medium nor cross-linked to existing wall-associated RG-II domains when added to Rosa cultures. In conclusion, in cultured Rosa cells RG-II domains have a brief window of opportunity for boron-bridging intraprotoplasmically or during secretion, but secretion into the apoplast is a point of no return beyond which additional boron-bridging does not readily occur. PMID:24320597

Ginsenoside Rg3 attenuates sepsis-induced injury and mitochondrial dysfunction in liver via AMPK-mediated autophagy flux.

PubMed

Xing, Wei; Yang, Lei; Peng, Yue; Wang, Qianlu; Gao, Min; Yang, Mingshi; Xiao, Xianzhong

2017-08-31

Sepsis-led mitochondrial dysfunction has become a critical pathophysiological procedure in sepsis. Since ginsenosides have been applied in the treatment of mitochondrial dysfunction, ginsenoside Rg3 was employed to study its effects on the mitochondrial dysfunction induced by sepsis. The apoptosis rate, oxygen consumption rate (OCR), reactive oxygen species (ROS), antioxidant glutathione (GSH) pools, and mitochondrial transmembrane potential (MTP) were determined in LPS-induced sepsis hepatocytes treated with different concentrations of Rg3. Then, the protein expression levels of mitochondrial biogenesis related transcription factors, autophagy-related proteins, and AMP-activated protein kinase (AMPK) signal pathway related proteins were determined by Western blotting in both in vitro and in vivo sepsis models. Rg3 shows functions of promotion of OCR, attenuation of ROS, and maintenance of GSH pools, and its conjugating activity in the in vitro sepsis models. Rg3-treated cells were observed to have a higher MTP value compared with the LPS only induced cells. Moreover, Rg3 treatment can inhibit mitochondrial dysfunction via increasing the protein expression levels of mitochondrial biogenesis related transcription factors. Rg3 treatment has the function of inhibitor of apoptosis of human primary hepatocytes, and Rg3 can up-regulate the autophagy-related proteins and activate AMPK signal pathway in sepsis models. Meanwhile, the mitochondrial protective function exerted by Rg3 decreased after the autophagy inhibitors or AMPK inhibitor treatment in LPS-induced human primary hepatocytes. Rg3 can improve mitochondrial dysfunction by regulating autophagy in mitochondria via activating the AMPK signal pathway, thus protecting cell and organ injuries caused by sepsis. © 2017 The Author(s).

Molecular characterization of a Penicillium chrysogenum exo-rhamnogalacturonan lyase that is structurally distinct from other polysaccharide lyase family proteins.

PubMed

Iwai, Marin; Kawakami, Takuya; Ikemoto, Takeshi; Fujiwara, Daisuke; Takenaka, Shigeo; Nakazawa, Masami; Ueda, Mitsuhiro; Sakamoto, Tatsuji

2015-10-01

We previously described an endo-acting rhamnogalacturonan (RG) lyase, termed PcRGL4A, of Penicillium chrysogenum 31B. Here, we describe a second RG lyase, called PcRGLX. We determined the cDNA sequence of the Pcrglx gene, which encodes PcRGLX. Based on analyses using a BLAST search and a conserved domain search, PcRGLX was found to be structurally distinct from known RG lyases and might belong to a new polysaccharide lyase family together with uncharacterized fungal proteins of Nectria haematococca, Aspergillus oryzae, and Fusarium oxysporum. The Pcrglx cDNA gene product (rPcRGLX) expressed in Escherichia coli demonstrated specific activity against RG but not against homogalacturonan. Divalent cations were not essential for the enzymatic activity of rPcRGLX. rPcRGLX mainly released unsaturated galacturonosyl rhamnose (ΔGR) from RG backbones used as the substrate from the initial stage of the reaction, indicating that the enzyme can be classified as an exo-acting RG lyase (EC 4.2.2.24). This is the first report of an RG lyase with this mode of action in Eukaryota. rPcRGLX acted synergistically with PcRGL4A to degrade soybean RG and released ΔGR. This ΔGR was partially decorated with galactose (Gal) residues, indicating that rPcRGLX preferred oligomeric RGs to polymeric RGs, that the enzyme did not require Gal decoration of RG backbones for degradation, and that the enzyme bypassed the Gal side chains of RG backbones. These characteristics of rPcRGLX might be useful in the determination of complex structures of pectins.

Adipocytokine and ghrelin levels in relation to bone mineral density in prepubertal rhythmic gymnasts entering puberty: a 3-year follow-up study.

PubMed

Võsoberg, Kristel; Tillmann, Vallo; Tamm, Anna-Liisa; Jürimäe, Toivo; Maasalu, Katre; Jürimäe, Jaak

2016-04-01

To investigate changes in bone mineral density (BMD) in rhythmic gymnasts (RG) entering puberty and their age-matched untrained controls (UC) over the 36-month period, and associations with leptin, adiponectin and ghrelin over this period. Whole body (WB), lumbar spine (LS) and femoral neck (FN) BMD, WB bone mineral content (BMC), and leptin, adiponectin and ghrelin were measured in 35 RG and 33 UC girls at baseline and at 12-month intervals over the next 3 years. The change over the 36 months was calculated (∆ score). The pubertal development over the next 36 months was slower in RG compard to UC, while there was no difference in bone age development between the groups. BMD at all sites was higher in RG in comparison with UC at every measurement point. ∆LS BMD and ∆FN BMD, but not ∆WB BMD and ∆WB BMC, were higher in RG compared with UC. None of the measured hormones at baseline or their ∆ scores correlated with ∆BMD and ∆BMC in RG. Baseline fat free mass correlated with ∆WB BMD and ∆WB BMC in RG, while baseline leptin was related to ∆WB BMC, ∆WB BMD and ∆LS BMD in UC. Measured baseline hormones and their ∆ scores did not correlate with increases in bone mineral values in RG entering puberty. Although the pubertal development in RG was slower than in UC, high-intensity training appeared to increase BMD growth and counterbalance negative effects of slow pubertal develpment, lower fat mass and leptin in RG.

20(R)-ginsenoside Rg3, a rare saponin from red ginseng, ameliorates acetaminophen-induced hepatotoxicity by suppressing PI3K/AKT pathway-mediated inflammation and apoptosis.

PubMed

Zhou, Yan-Dan; Hou, Jin-Gang; Liu, Wei; Ren, Shen; Wang, Ying-Ping; Zhang, Rui; Chen, Chen; Wang, Zi; Li, Wei

2018-06-01

Although ginsenoside Rg3 was isolated as a major component of Korea red ginseng and confirmed to exert potential hepatoprotective effect on acetaminophen (APAP)-induced liver injury via induction of glutathione S-transferase (GST) in vitro, thein vivo hepatoprotective effect of Rg3 and the underlying molecular mechanism of action remain unclear. The current study was aimed to explore whether 20(R)-Ginsenoside Rg3 (20(R)-Rg3) could alleviate acetaminophen-induced liver injury in mice and to determine the involvement of PI3K/AKT signaling pathway. Our findings demonstrated that a single injection of APAP (250 mg/kg) increased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β); such increases were attenuated by pretreatment of mice with 20(R)-Rg3 for seven days. The depletion of glutathione (GSH), generation of malondialdehyde (MDA) and the over expression of cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) caused by APAP exposure were also inhibited by 20(R)-Rg3 pretreatment. Moreover, 20(R)-Rg3 pretreatment significantly alleviated APAP-induced apoptosis, necrosis, and inflammatory infiltration in liver tissues. Importantly, 20(R)-Rg3 effectively attenuated APAP-induced liver injury in part via activating PI3K/AKT signaling pathway. In summary, 20(R)-Rg3 exerted liver protection against APAP-caused hepatotoxicity evidenced by inhibition of oxidative stress and inflammatory response, alleviation of hepatocellular necrosis and apoptosis via activation of PI3K/AKT signaling pathway, showing potential as a novel therapeutic agent to prevent liver damage. Copyright © 2018 Elsevier B.V. All rights reserved.

The inhibitory effects of a rhamnogalacturonan I (RG-I) domain from ginseng pectin on galectin-3 and its structure-activity relationship.

PubMed

Gao, Xiaoge; Zhi, Yuan; Sun, Lin; Peng, Xiaoxia; Zhang, Tao; Xue, Huiting; Tai, Guihua; Zhou, Yifa

2013-11-22

Pectin has been shown to inhibit the actions of galectin-3, a β-galactoside-binding protein associated with cancer progression. The structural features of pectin involved in this activity remain unclear. We investigated the effects of different ginseng pectins on galectin-3 action. The rhamnogalacturonan I-rich pectin fragment, RG-I-4, potently inhibited galectin-3-mediated hemagglutination, cancer cell adhesion and homotypic aggregation, and binding of galectin-3 to T-cells. RG-I-4 specifically bound to the carbohydrate recognition domain of galectin-3 with a dissociation constant of 22.2 nm, which was determined by surface plasmon resonance analysis. The structure-activity relationship of RG-I-4 was investigated by modifying the structure through various enzymatic and chemical methods followed by activity tests. The results showed that (a) galactan side chains were essential to the activity of RG-I-4, whereas arabinan side chains positively or negatively regulated the activity depending on their location within the RG-I-4 molecule. (b) The activity of galactan chain was proportional to its length up to 4 Gal residues and largely unchanged thereafter. (c) The majority of galactan side chains in RG-I-4 were short with low activities. (d) The high activity of RG-I-4 resulted from the cooperative action of these side chains. (e) The backbone of the molecule was very important to RG-I-4 activity, possibly by maintaining a structural conformation of the whole molecule. (f) The isolated backbone could bind galectin-3, which was insensitive to lactose treatment. The novel discovery that the side chains and backbone play distinct roles in regulating RG-I-4 activity is valuable for producing highly active pectin-based galectin-3 inhibitors.

Exact renormalization group in Batalin-Vilkovisky theory

NASA Astrophysics Data System (ADS)

Zucchini, Roberto

2018-03-01

In this paper, inspired by the Costello's seminal work [11], we present a general formulation of exact renormalization group (RG) within the Batalin-Vilkovisky (BV) quantization scheme. In the spirit of effective field theory, the BV bracket and Laplacian structure as well as the BV effective action (EA) depend on an effective energy scale. The BV EA at a certain scale satisfies the BV quantum master equation at that scale. The RG flow of the EA is implemented by BV canonical maps intertwining the BV structures at different scales. Infinitesimally, this generates the BV exact renormalization group equation (RGE). We show that BV RG theory can be extended by augmenting the scale parameter space R to its shifted tangent bundle T [1]ℝ. The extra odd direction in scale space allows for a BV RG supersymmetry that constrains the structure of the BV RGE bringing it to Polchinski's form [6]. We investigate the implications of BV RG supersymmetry in perturbation theory. Finally, we illustrate our findings by constructing free models of BV RG flow and EA exhibiting RG supersymmetry in the degree -1 symplectic framework and studying the perturbation theory thereof. We find in particular that the odd partner of effective action describes perturbatively the deviation of the interacting RG flow from its free counterpart.

Counting RG flows

DOE PAGES

Gukov, Sergei

2016-01-05

Here, interpreting renormalization group flows as solitons interpolating between different fixed points, we ask various questions that are normally asked in soliton physics but not in renormalization theory. Can one count RG flows? Are there different "topological sectors" for RG flows? What is the moduli space of an RG flow, and how does it compare to familiar moduli spaces of (supersymmetric) dowain walls? Analyzing these questions in a wide variety of contexts -- from counting RG walls to AdS/CFT correspondence -- will not only provide favorable answers, but will also lead us to a unified general framework that is powerfulmore » enough to account for peculiar RG flows and predict new physical phenomena. Namely, using Bott's version of Morse theory we relate the topology of conformal manifolds to certain properties of RG flows that can be used as precise diagnostics and "topological obstructions" for the strong form of the C-theorem in any dimension. Moreover, this framework suggests a precise mechanism for how the violation of the strong C-theorem happens and predicts "phase transitions" along the RG flow when the topological obstruction is non-trivial. Along the way, we also find new conformal manifolds in well-known 4d CFT's and point out connections with the superconformal index and classifying spaces of global symmetry groups.« less

A novel reverse genetics system for production of infectious West Nile virus using homologous recombination in mammalian cells.

PubMed

Kobayashi, Shintaro; Yoshii, Kentaro; Hirano, Minato; Muto, Memi; Kariwa, Hiroaki

2017-02-01

Reverse genetics systems facilitate investigation of many aspects of the life cycle and pathogenesis of viruses. However, genetic instability in Escherichia coli has hampered development of a reverse genetics system for West Nile virus (WNV). In this study, we developed a novel reverse genetics system for WNV based on homologous recombination in mammalian cells. Introduction of the DNA fragment coding for the WNV structural protein together with a DNA-based replicon resulted in the release of infectious WNV. The growth rate and plaque size of the recombinant virus were almost identical to those of the parent WNV. Furthermore, chimeric WNV was produced by introducing the DNA fragment coding for the structural protein and replicon plasmid derived from various strains. Here, we report development of a novel system that will facilitate research into WNV infection. Copyright © 2016 Elsevier B.V. All rights reserved.

Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus.

PubMed

Owen, C David; Tailford, Louise E; Monaco, Serena; Šuligoj, Tanja; Vaux, Laura; Lallement, Romane; Khedri, Zahra; Yu, Hai; Lecointe, Karine; Walshaw, John; Tribolo, Sandra; Horrex, Marc; Bell, Andrew; Chen, Xi; Taylor, Gary L; Varki, Ajit; Angulo, Jesus; Juge, Nathalie

2017-12-19

Ruminococcus gnavus is a human gut symbiont wherein the ability to degrade mucins is mediated by an intramolecular trans-sialidase (RgNanH). RgNanH comprises a GH33 catalytic domain and a sialic acid-binding carbohydrate-binding module (CBM40). Here we used glycan arrays, STD NMR, X-ray crystallography, mutagenesis and binding assays to determine the structure and function of RgNanH_CBM40 (RgCBM40). RgCBM40 displays the canonical CBM40 β-sandwich fold and broad specificity towards sialoglycans with millimolar binding affinity towards α2,3- or α2,6-sialyllactose. RgCBM40 binds to mucus produced by goblet cells and to purified mucins, providing direct evidence for a CBM40 as a novel bacterial mucus adhesin. Bioinformatics data show that RgCBM40 canonical type domains are widespread among Firmicutes. Furthermore, binding of R. gnavus ATCC 29149 to intestinal mucus is sialic acid mediated. Together, this study reveals novel features of CBMs which may contribute to the biogeography of symbiotic bacteria in the gut.

Nitrogen-doped hollow carbon spheres wrapped with graphene nanostructure for highly sensitive electrochemical sensing of parachlorophenol.

PubMed

Yi, Yinhui; Zhu, Gangbing; Sun, Heng; Sun, Jianfan; Wu, Xiangyang

2016-12-15

Owing to awfully harmful to the environment and human health, the qualitative and quantitative determination of parachlorophenol (PCP) is of great significance. In this paper, by using silica@polydopamine as template, nitrogen-doped hollow carbon spheres wrapped with reduced graphene oxide (NHCNS@RG) nanostructure was prepared successfully via a self-assembly approach due to the electrostatic interaction, and the obtained NHCNS@RG could exhibit the unique properties of NHCNS and RG: the NHCNS could impede the aggregation tendency of RG and possess high electrocatalytic activity; the RG enlarges the contacting area and offers many area-normalized edge-plane structures and active sites. Scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, X-ray diffraction and electrochemical method were used to characterize the morphology and structure of NHCNS@RG. Then, the NHCNS@RG hybrids were applied for the electrochemical sensing of PCP, under the optimized conditions, the detection limit of PCP obtained in this work is 0.01μM and the linear range is 0.03-38.00μM. Copyright © 2016 Elsevier B.V. All rights reserved.

Further analysis of the structure and immunological activity of an RG-I type pectin from Panax ginseng.

PubMed

Zhang, Xu; Li, Shanshan; Sun, Lin; Ji, Li; Zhu, Jingjing; Fan, Yuying; Tai, Guihua; Zhou, Yifa

2012-06-20

In this paper, we further analysed the structure of a type I rhamnogalacturonan (RG-I) pectin (WGPA-2-RG) fractionated from ginseng polysaccharides. Methylation and periodate oxidation analyses showed that WGPA-2-RG has a backbone consisting of alternating rhamnose (Rha) and galacturonic acid (GalA) residues and side chains consisting of type II arabinogalactan (AG-II). Partial acidic hydrolysis for 6h completely removed arabinose (Ara), partial galactose (Gal), but little GalA and Rha. During partial hydrolysis, the molecular weight of WGPA-2-RG decreased smoothly, suggesting that the Ara and cleavable Gal residues exist on the surface of the molecule, while GalA and Rha residues exist in the core of the molecule. The bioactivity assay showed that the arabinogalactan side chains of WGPA-2-RG are essential structures for stimulating NO secretion and lymphocyte proliferation. However, removal of the Ara and Gal residues through hydrolysis did not appreciably affect the ability of WGPA-2-RG to enhance macrophage phagocytosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Critical asymmetry in renormalization group theory for fluids.

PubMed

Zhao, Wei; Wu, Liang; Wang, Long; Li, Liyan; Cai, Jun

2013-06-21

The renormalization-group (RG) approaches for fluids are employed to investigate critical asymmetry of vapour-liquid equilibrium (VLE) of fluids. Three different approaches based on RG theory for fluids are reviewed and compared. RG approaches are applied to various fluid systems: hard-core square-well fluids of variable ranges, hard-core Yukawa fluids, and square-well dimer fluids and modelling VLE of n-alkane molecules. Phase diagrams of simple model fluids and alkanes described by RG approaches are analyzed to assess the capability of describing the VLE critical asymmetry which is suggested in complete scaling theory. Results of thermodynamic properties obtained by RG theory for fluids agree with the simulation and experimental data. Coexistence diameters, which are smaller than the critical densities, are found in the RG descriptions of critical asymmetries of several fluids. Our calculation and analysis show that the approach coupling local free energy with White's RG iteration which aims to incorporate density fluctuations into free energy is not adequate for VLE critical asymmetry due to the inadequate order parameter and the local free energy functional used in the partition function.

Yang Baxter and anisotropic sigma and lambda models, cyclic RG and exact S-matrices

NASA Astrophysics Data System (ADS)

Appadu, Calan; Hollowood, Timothy J.; Price, Dafydd; Thompson, Daniel C.

2017-09-01

Integrable deformation of SU(2) sigma and lambda models are considered at the classical and quantum levels. These are the Yang-Baxter and XXZ-type anisotropic deformations. The XXZ type deformations are UV safe in one regime, while in another regime, like the Yang-Baxter deformations, they exhibit cyclic RG behaviour. The associ-ated affine quantum group symmetry, realized classically at the Poisson bracket level, has q a complex phase in the UV safe regime and q real in the cyclic RG regime, where q is an RG invariant. Based on the symmetries and RG flow we propose exact factorizable S-matrices to describe the scattering of states in the lambda models, from which the sigma models follow by taking a limit and non-abelian T-duality. In the cyclic RG regimes, the S-matrices are periodic functions of rapidity, at large rapidity, and in the Yang-Baxter case violate parity.

Comparative study of Korean White Ginseng and Korean Red Ginseng on efficacies of OVA-induced asthma model in mice.

PubMed

Lim, Chi-Yeon; Moon, Jeong-Min; Kim, Bu-Yeo; Lim, Se-Hyun; Lee, Guem-San; Yu, Hak-Sun; Cho, Su-In

2015-01-01

Korean ginseng is a well-known medicinal herb that has been widely used in traditional medicine to treat various diseases, including asthma. Ginseng can be classified as white ginseng (WG) or red ginseng (RG), according to processing conditions. In this study, the authors compared the efficacies of these two ginseng types in a mouse model of acute asthma. To produce the acute asthma model, BALB/c mice were sensitized with ovalbumin (OVA) and aluminum hydroxide, and then challenged with OVA. WG and RG extracts were administered to mice orally. The influences of WG and RG on airway hyperresponsiveness (AHR), immune cell distributions in bronchoalveolar lavage fluid (BALF), and OVA-specific immunoglobulin E (IgE), IgG1, and IgG2a in serum were investigated. Cytokine production by lymphocytes isolated from peribronchial lymph nodes and histopathological changes was also examined. In OVA-sensitized mice, both WG and RG reduced AHR and suppressed immune cell infiltration in bronchoalveolar regions. BALF OVA-specific IgE levels were significantly lower in RG-treated OVA-sensitized mice than in the OVA-sensitized control group. WG and RG also suppressed inflammatory cytokine production by peribronchial lymphocytes. Histopathological findings showed reduced inflammatory cell infiltration and airway remodeling (e.g., epithelial hyperplasia) in WG- and RG-treated OVA mice compared with OVA controls. In this study, WG and RG showed antiasthmatic effects in an OVA-sensitized mouse model, and the efficacies of RG were found to be better than those of WG.

Digestibility of new dietary fibre materials, resistant glucan and hydrogenated resistant glucan in rats and humans, and the physical effects in rats.

PubMed

Oku, Tsuneyuki; Tanabe, Kenichi; Morita, Shigeki; Hamaguchi, Norihisa; Shimura, Fumio; Nakamura, Sadako

2015-11-28

Resistant glucan (RG) and hydrogenated resistant glucan (HRG) are newly developed non-digestible carbohydrate materials that decrease lifestyle-related diseases. The bioavailability of RG and HRG was investigated by in vitro experiments using human and rat small intestinal enzymes and by in vivo experiments using rats in the present study. Oligosaccharides, which are minor components of RG and HRG, were hydrolysed slightly by small intestinal enzymes of humans and rats, and the hydrolysing activity was slightly higher in rats than in humans. The amount of glucose released from HRG was greater than that from RG. However, the high-molecular-weight carbohydrates of the main components were hardly hydrolysed. Furthermore, neither RG nor HRG inhibited disaccharidase activity. When rats were raised on a diet containing 5 % of RG, HRG, resistant maltodextrin or fructo-oligosaccharide (FOS) for 4 weeks, all rats developed loose stools and did not recover during the experiment, except for the FOS group. Body weight gain was normal in all groups and was not significantly different compared with the control group. Caecal tissue and content weights were significantly increased by feeding RG or HRG, although other organ and tissue weights were not significantly different among the groups. In conclusion, RG and HRG consist of small amounts of glucose and digestible and non-digestible oligosaccharides, and large amounts of glucose polymers, which were hardly hydrolysed by α-amylase and small intestinal enzymes. RG and HRG, which were developed newly as dietary fibre materials, had no harmful effects on the growth and development of rats.

Photoionisation study of Xe.CF{sub 4} and Kr.CF{sub 4} van-der-Waals molecules

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

Alekseev, V. A., E-mail: alekseev@va3474.spb.edu; Kevorkyants, R.; Garcia, G. A.

2016-05-14

We report on photoionization studies of Xe.CF{sub 4} and Kr.CF{sub 4} van-der-Waals complexes produced in a supersonic expansion and detected using synchrotron radiation and photoelectron-photoion coincidence techniques. The ionization potential of CF{sub 4} is larger than those of the Xe and Kr atoms and the ground state of the Rg.CF{sub 4}{sup +} ion correlates with Rg{sup +} ({sup 2}P{sub 3/2}) + CF{sub 4}. The onset of the Rg.CF{sub 4}{sup +} signals was found to be only ∼0.2 eV below the Rg ionization potential. In agreement with experiment, complementary ab initio calculations show that vertical transitions originating from the potential minimummore » of the ground state of Rg.CF{sub 4} terminate at a part of the potential energy surfaces of Rg.CF{sub 4}{sup +}, which are approximately 0.05 eV below the Rg{sup +} ({sup 2}P{sub 3/2}) + CF{sub 4} dissociation limit. In contrast to the neutral complexes, which are most stable in the face geometry, for the Rg.CF{sub 4}{sup +} ions, the calculations show that the minimum of the potential energy surface is in the vertex geometry. Experiments which have been performed only with Xe.CF{sub 4} revealed no Xe.CF{sub 4}{sup +} signal above the first ionization threshold of Xe, suggesting that the Rg.CF{sub 4}{sup +} ions are not stable above the first dissociation limit.« less

Strains and stressors: an analysis of touchscreen learning in genetically diverse mouse strains.

PubMed

Graybeal, Carolyn; Bachu, Munisa; Mozhui, Khyobeni; Saksida, Lisa M; Bussey, Timothy J; Sagalyn, Erica; Williams, Robert W; Holmes, Andrew

2014-01-01

Touchscreen-based systems are growing in popularity as a tractable, translational approach for studying learning and cognition in rodents. However, while mouse strains are well known to differ in learning across various settings, performance variation between strains in touchscreen learning has not been well described. The selection of appropriate genetic strains and backgrounds is critical to the design of touchscreen-based studies and provides a basis for elucidating genetic factors moderating behavior. Here we provide a quantitative foundation for visual discrimination and reversal learning using touchscreen assays across a total of 35 genotypes. We found significant differences in operant performance and learning, including faster reversal learning in DBA/2J compared to C57BL/6J mice. We then assessed DBA/2J and C57BL/6J for differential sensitivity to an environmental insult by testing for alterations in reversal learning following exposure to repeated swim stress. Stress facilitated reversal learning (selectively during the late stage of reversal) in C57BL/6J, but did not affect learning in DBA/2J. To dissect genetic factors underlying these differences, we phenotyped a family of 27 BXD strains generated by crossing C57BL/6J and DBA/2J. There was marked variation in discrimination, reversal and extinction learning across the BXD strains, suggesting this task may be useful for identifying underlying genetic differences. Moreover, different measures of touchscreen learning were only modestly correlated in the BXD strains, indicating that these processes are comparatively independent at both genetic and phenotypic levels. Finally, we examined the behavioral structure of learning via principal component analysis of the current data, plus an archival dataset, totaling 765 mice. This revealed 5 independent factors suggestive of "reversal learning," "motivation-related late reversal learning," "discrimination learning," "speed to respond," and "motivation during discrimination." Together, these findings provide a valuable reference to inform the choice of strains and genetic backgrounds in future studies using touchscreen-based tasks.

Rg to Lg Scattering Observations and Modeling

NASA Astrophysics Data System (ADS)

Baker, G. E.; Stevens, J. L.; Xu, H.

2005-12-01

Lg is important to explosion yield estimation and earthquake/explosion discrimination, but the source of explosion generated Lg is still an area of active investigation. We investigate the contribution of Rg scattering to Lg. Common spectral nulls in vertical component Rg and Lg have been interpreted as evidence that scattered Rg is the dominant source of Lg in some areas. The nulls are assumed to result from non-spherical components of the explosion source, modeled as a CLVD located above the explosion. We compare Rg with 3-component Sg and Lg spectra in different source areas. Wavenumber synthetics and nonlinear source calculations constrain the predicted source spectra of Rg and directly generated Lg. Modal scattering calculations place bounds on the contribution of Rg to Lg relative to pS, S*, and directly generated S-waves. Rg recorded east and west of the Quartz 3 Deep Seismic Sounding explosion have persistent spectral nulls, but at different frequencies. The azimuthal dependence of the source spectra suggests that it may not be simply related to a CLVD source. The spectral nulls of Sg, Lg, and Lg coda do not correspond to the Rg spectral nulls, so for this overburied source, the spectral observations do not indicate that Rg scattering is a dominant contributor to Lg. Preliminary comparisons of Rg with Lg spectra for events from the Semipalatinsk Test Site yield a similar result. We compare Rg at 20-100 km with Lg at 650 km for Balapan and Degelen explosions with known yield and source depth. The events range from 130 to 50 percent of theoretical containment depth, so relative contributions from a CLVD are expected to vary significantly. For studied previously NTS and Kazakh depth of burial data, the use of 3-components provides further insight into scattering between components. In a complementary analysis, to assess whether S-wave generation is affected by source depth or scaled depth, we have examined regional phase amplitudes of 13 Degelen explosions with known yields and source depths. Initial Pn, the entire P wavetrain, Sn, Lg, and Lg coda have similar log amplitude vs. log yield curves. The slope of those curves varies with frequency, from approximately 0.84 at 0.6 Hz to 0.65 at 6 Hz. We will complement these results with similar observations of Balapan explosion records.

Manipulations in Maternal Environment Reverse Periodontitis in Genetically Predisposed Rats

PubMed Central

Sluyter, Frans; Breivik, Torbjørn; Cools, Alexander

2002-01-01

The predisposition to develop periodontitis is partly genetically determined in humans as well as in animals. Here we demonstrate, however, that early manipulations in the maternal environment of an animal (rat) model of periodontitis can fully reverse the genetic predisposition to develop periodontitis at adult age. PMID:12093700

The behavioural consequences of sex reversal in dragons

PubMed Central

Li, Hong; Holleley, Clare E.; Elphick, Melanie; Georges, Arthur

2016-01-01

Sex differences in morphology, physiology, and behaviour are caused by sex-linked genes, as well as by circulating sex-steroid levels. Thus, a shift from genotypic to environmental sex determination may create an organism that exhibits a mixture of male-like and female-like traits. We studied a lizard species (Central Bearded Dragon, Pogona vitticeps), in which the high-temperature incubation of eggs transforms genetically male individuals into functional females. Although they are reproductively female, sex-reversed dragons (individuals with ZZ genotype reversed to female phenotype) resemble genetic males rather than females in morphology (relative tail length), general behaviour (boldness and activity level), and thermoregulatory tactics. Indeed, sex-reversed ‘females’ are more male-like in some behavioural traits than are genetic males. This novel phenotype may impose strong selection on the frequency of sex reversal within natural populations, facilitating rapid shifts in sex-determining systems. A single period of high incubation temperatures (generating thermally induced sex reversal) can produce functionally female individuals with male-like (or novel) traits that enhance individual fitness, allowing the new temperature-dependent sex-determining system to rapidly replace the previous genetically based one.

Protective Effects of Processed Ginseng and Its Active Ginsenosides on Cisplatin-Induced Nephrotoxicity: In Vitro and in Vivo Studies.

PubMed

Park, Jun Yeon; Choi, Pilju; Kim, Taejung; Ko, Hyeonseok; Kim, Ho-kyong; Kang, Ki Sung; Ham, Jungyeob

2015-07-01

Although cisplatin can dramatically improve the survival rate in cancer patients, its use is limited by its nephrotoxicity. Previous investigations showed that Panax ginseng contains components that exhibit protective activity against cisplatin-induced nephropathy. The aim of the present study is to investigate the effect of microwave-assisted processing on the protective effect of ginseng and identify ginsenosides that are active against cisplatin-induced kidney damage to evaluate the potential of using ginseng in the management of nephrotoxicity. The LLC-PK1 cell damage by cisplatin was significantly decreased by treatment with microwave-processed ginseng (MG) and ginsenosides Rg3, Rg5, and Rk1. Reduced expression of p53 and c-Jun N-terminal kinase proteins by cisplatin in LLC-PK1 cells was markedly ameliorated after Rg3 and Rg5/Rk1 treatment. Additionally, elevated expression of cleaved caspase-3 was significantly reduced by ginsenosides Rg5, Rk1, and with even greater potency, Rg3. Moreover, MG and its fraction containing active ginsenosides showed protective effects against cisplatin-induced nephropathy in mice. We found that ginsenosides Rg3, Rg5, and Rk1 generated during the heat treatment of ginseng ameliorate renal damage by regulating inflammation and apoptosis. Results of current experiments provide evidence of the renoprotective effects and therapeutic potential of MG and its active ginsenosides, both in vitro and in vivo.

HM{sup +}–RG complexes (M = group 2 metal; RG = rare gas): Physical vs. chemical interactions

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

Harris, Joe P.; Dodson, Hannah; Wright, Timothy G., E-mail: Tim.Wright@nottingham.ac.uk

2015-04-21

Previous work on the HM{sup +}–He complexes (M = Be–Ra) has been extended to the cases of the heavier rare gas atoms, HM{sup +}–RG (RG = Ne–Rn). Optimized geometries and harmonic vibrational frequencies have been calculated using MP2 theory and quadruple-ζ quality basis sets. Dissociation energies for the loss of the rare gas atom have been calculated at these optimized geometries using coupled cluster with single and double excitations and perturbative triples, CCSD(T)theory, extrapolating interaction energies to the basis set limit. Comparisons are made between the present data and the previously obtained helium results, as well as to those ofmore » the bare HM{sup +} molecules; furthermore, comparisons are made to the related M{sup +}–RG and M{sup 2+}–RG complexes. Partial atomic charge analyses have also been undertaken, and these used to test a simple charge-induced dipole model. Molecular orbital diagrams are presented together with contour plots of the natural orbitals from the quadratic configuration with single and double excitations (QCISD) density. The conclusion is that the majority of these complexes are physically bound, with very little sharing of electron density; however, for M = Be, and to a lesser extent M = Mg, some evidence for chemical effects is seen in HM{sup +}–RG complexes involving RG atoms with the higher atomic numbers.« less

Chronic treatment with ginsenoside Rg1 promotes memory and hippocampal long-term potentiation in middle-aged mice.

PubMed

Zhu, G; Wang, Y; Li, J; Wang, J

2015-04-30

Ginseng serves as a potential candidate for the treatment of aging-related memory decline or memory loss. However, the related mechanism is not fully understood. In this study, we applied an intraperitoneal injection of ginsenoside Rg1, an active compound from ginseng in middle-aged mice and detected memory improvement and the underlying mechanisms. Our results showed that a period of 30-day administration of ginsenoside Rg1 enhanced long-term memory in the middle-aged animals. Consistent with the memory improvement, ginsenoside Rg1 administration facilitated weak theta-burst stimulation (TBS)-induced long-term potentiation (LTP) in acute hippocampal slices from middle-aged animals. Ginsenoside Rg1 administration increased the dendritic apical spine numbers and area in the CA1 region. In addition, ginsenoside Rg1 administration up-regulated the expression of hippocampal p-AKT, brain-derived neurotrophic factor (BDNF), proBDNF and glutamate receptor 1 (GluR1), but not p-ERK. Interestingly, the phosphatase and tensin homolog deleted on chromosome ten (PTEN) inhibitor (bpV) mimicked the ginsenoside Rg1 effects, including increasing p-AKT expression, promoting hippocampal basal synaptic transmission, LTP and memory. Taken together, our data suggest that ginsenoside Rg1 treatment improves memory in middle-aged mice possibly through regulating the PI3K/AKT pathway, altering apical spines and facilitating hippocampal LTP. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

DNA methylation enzyme inhibitor RG108 suppresses the radioresistance of esophageal cancer

PubMed Central

Ou, Yao; Zhang, Quan; Tang, Yiting; Lu, Zhonghua; Lu, Xujing; Zhou, Xifa; Liu, Changmin

2018-01-01

Esophageal cancer (EC) is the eighth most common highly aggressive cancer worldwide. The purpose of this study was to investigate the effect of the DNA methyltransferase inhibitor RG108 on the radiosensitivity of EC cells. MTT and clonogenic assays were performed to assess the effect of RG108 on the proliferation and radiosensitivity of Eca-109 and TE-1 human EC cells. The cell cycle progression and alterations in apoptosis were analyzed by flow cytometry. For the in vivo analysis, the Eca-109 cells were inoculated into nude mice to establish tumors. Tissues from xenografts were obtained to detect changes to microvessels and tumor growth by immunohistochemistry (IHC). RNA-seq was used to identify differentially expressed genes. We found that RG108 increased the radiosensitivity of EC cells. Apoptosis and G2/M-phase arrest were induced by X-ray irradiation and were significantly enhanced by RG108. In addition, growth of tumor xenografts from the Eca-109 cells was significantly inhibited by irradiation in combination with RG108. The RNA-seq analysis revealed that, compared with radiation alone, X-ray irradiation in combination with RG108 altered the expression of 121 genes in multiple pathways, including the TGF-β signaling pathway and the Epstein-Barr virus infection pathway. In conclusion, RG108 induced radiosensitivity in EC cells both in vitro and in vivo. PMID:29328411

Influence of poly (lactide-co-glycolide) type and gamma irradiation on the betamethasone acetate release from the in situ forming systems.

PubMed

Rafienia, Mohammad; Emami, Shahriar Hojjati; Mirzadeh, Hamid; Mobedi, Hamid; Karbasi, Saeed

2009-04-01

In situ forming biodegradable polymeric systems were prepared from Poly (DL-lactide-co-glycolide), RG504H (50:50, lactide:glycolide), RG756 (75:25) and mixture of them. They were dissolved in N-methyl-2-pyrrolidone (33% w/w) and mixed with betamethasone acetate (BTMA, 5 and 10% w/w) and ethyl heptanoate (5% w/w, as an additive). The effects of gamma irradiation, drug loading, type of polymers and solvent removal were evaluated on release profiles. Scanning electron microscopy (SEM) of RG756 samples loaded by BTMA did not show any degradation until two weeks. Differential scanning calorimeter (DSC) experiments confirmed insignificant decrease in T(g), and consequently release rate. Declining T(g) of RG504H and RG756 after gamma irradiation was about 0.4 and 1.46 degrees C, respectively. High performance liquid chromatography (HPLC) revealed that BTMA release is more rapid from the formulations prepared using the RG504H with lower molecular weight. The formulations prepared by RG756 had lower burst release (2.5-41%) than the samples based on RG504H (60-67%) and mixture of them (30-33%). Regarding this research three different kinds of steriled in situ forming systems were developed which can release BTMA for 24, 90 and 60 days.

Ginsenoside Rg1 prevents cerebral and cerebellar injury induced by obstructive jaundice in rats via inducing expression of TIPE-2.

PubMed

Zhou, Tingting; Zu, Guo; Zhou, Lu; Che, Ningwei; Guo, Jing; Liang, Zhanhua

2016-01-01

The aim of the study was to analyze the effect of Ginsenoside Rg1 (Rg1) on cerebral and cerebellar injury in experimental obstructive jaundice (OJ). OJ was done by ligature and section of extrahepatic biliary duct. Rg1 was injected intraperitoneally (10 mg kg(-1)d(-1) or 20 mg kg(-1) d(-1)). Comparison of serum total bile salts (TBA), total bilirubin (TBil), direct bilirubin (DBil), TNF-α, IL-6 and IL-1β among groups. Malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined, also apoptosis and mRNA and protein levels of TIPE2 (TNF-α-inducible protein 8-like 2) were tested in cerebrum and cerebellum. Our results showed that Rg1 reduced MDA and apoptosis in cerebrum and cerebellum induced by OJ, also GSH and antioxidant enzyme activity were raised obviously in rats treated with Rg1. Moreover, decreased mRNA and protein levels of TIPE2 in OJ rats and Rg1 could improve the decreased mRNA and protein levels of TIPE2 in OJ rats. In conclusion, Rg1 decreased oxidative stress and apoptosis, also recovered the antioxidant status and mRNA and protein levels of TIPE2 in the cerebrum and cerebellum of OJ rats. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Marburg Virus Reverse Genetics Systems

PubMed Central

Schmidt, Kristina Maria; Mühlberger, Elke

2016-01-01

The highly pathogenic Marburg virus (MARV) is a member of the Filoviridae family and belongs to the group of nonsegmented negative-strand RNA viruses. Reverse genetics systems established for MARV have been used to study various aspects of the viral replication cycle, analyze host responses, image viral infection, and screen for antivirals. This article provides an overview of the currently established MARV reverse genetic systems based on minigenomes, infectious virus-like particles and full-length clones, and the research that has been conducted using these systems. PMID:27338448

Marburg Virus Reverse Genetics Systems.

PubMed

Schmidt, Kristina Maria; Mühlberger, Elke

2016-06-22

The highly pathogenic Marburg virus (MARV) is a member of the Filoviridae family and belongs to the group of nonsegmented negative-strand RNA viruses. Reverse genetics systems established for MARV have been used to study various aspects of the viral replication cycle, analyze host responses, image viral infection, and screen for antivirals. This article provides an overview of the currently established MARV reverse genetic systems based on minigenomes, infectious virus-like particles and full-length clones, and the research that has been conducted using these systems.

Caspase-Mediated Anti-Apoptotic Effect of Ginsenoside Rg5, a Main Rare Ginsenoside, on Acetaminophen-Induced Hepatotoxicity in Mice.

PubMed

Wang, Zi; Hu, Jun-Nan; Yan, Meng-Han; Xing, Jing-Jing; Liu, Wen-Cong; Li, Wei

2017-10-25

Frequent overdose of acetaminophen (APAP) is one of the most common and important incentives of acute hepatotoxicity. Prior to this work, our research group confirmed that black ginseng (Panax ginseng, BG) showed powerful protective effects on APAP-induced ALI. However, it is not clear which kind of individual ginsenoside from BG plays such a liver protection effect. The objective of the current investigation was to evaluate whether ginsenoside Rg5 (G-Rg5) protected against APAP-induced hepatotoxicity and the involved action mechanisms. Mice were administrated with G-Rg5 at two dosages of 10 or 20 mg/kg for 7 consecutive days. After the last treatment, all of the animals that received a single intraperitoneal injection of APAP (250 mg/kg) showed severe liver toxicity after 24 h, and the liver protection effects of G-Rg5 were examined. The results clearly indicated that pretreatment with G-Rg5 remarkably inhibited the production of serum tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β) compared with the APAP group. Meanwhile, G-Rg5 decreased the hepatic malondialdehyde (MDA) content, the protein expression levels of 4-hydroxynonenal (4-HNE) and cytochrome P450 2E1 (CYP2E1) in the liver tissues. G-Rg5 decreased APAP caused the hepatic overexpression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Furthermore, analysis of immunohistochemistry and Western blotting also indicated that G-Rg5 pretreatment inhibited activation of apoptotic pathways mainly via increasing the expression of Bcl-2 protein, decreasing the expression of Bax protein, proliferating cell nuclear antigen (PCNA), cytochrome c, caspase-3, caspase-8, and caspase-9. Liver histopathological observation provided further evidence that pretreatment with G-Rg5 could significantly inhibit hepatocyte necrosis, inflammatory cell infiltration, and apoptosis caused by APAP. In conclusion, the present study clearly demonstrates that G-Rg5 exerts a liver protection effect against APAP-induced acute hepatotoxicity mainly via a caspase-mediated anti-apoptotic effect.

Ginsenoside Rg1 protects rat bone marrow mesenchymal stem cells against ischemia induced apoptosis through miR-494-3p and ROCK-1.

PubMed

Zheng, Hui-Zhen; Fu, Xue-Kun; Shang, Jiu-Long; Lu, Rong-Xi; Ou, Yong-Fang; Chen, Chun-Ling

2018-03-05

This study aimed to verify the cytoprotective effect of ginsenoside Rg1 in vivo, and to elucidate the mechanism of Rg1 in the ischemic microenvironment. Male rat bone marrow mesenchymal stem cells (rBMSCs) or rBMSCs treated with Rg1 were injected into ischemic region of the arterial embolism hind limb in female rats. Behavioral and histological data, obtained one-week post injection, showed that rBMSCs with Rg1 could improve the survival rate of BMSCs and enhance the therapeutic effects. rBMSCs treated with hypoxia and serum deprivation for 24h (H/SD-rBMSCs) showed the up-regulated expression of ras homolog family member A (RhoA), Rho associated coiled-coil containing protein kinase 1 (ROCK-1), myosin light chain 2 (MLC-2), Bcl2 associated agonist of cell death (Bad) and Bcl2 associated X, apoptosis regulator (Bax); while the expression of miR-148b-3p, miR-148b-5p and miR-494-3p was down-regulated. H/SD with Rg1 treatment (H/SD+Rg1-rBMSCs) inhibited the expression of ROCK-1, MLC-2, Bad and Bax, increased the expression of Bcl-2, miR-494-3p. After ROCK-1 knockout, the expression of Bad and Bax were downregulated and Bcl-2 upregulated, but Rg1 no longer altered their expression. Mir-494-3p functional study established that miR-494-3 mimic downregulated and miR-494-3 inhibitor upregulated ROCK-1 gene expression, Rg1 did not have the ability to change the ROCK gene expression after loss of function of miR-494-3p. Also, the function loss of mir-494-3p promoted apoptosis; otherwise reduced apoptosis. The anti-apoptotic effect of Rg1 disappeared after mir-494-3p loss or gain function. In conclusion, Ginsenoside Rg1 has shown to have protective effects on ischemic-induced rBMSCs apoptosis through mir-494-3p→ROCK-1→Bcl-2 signaling pathway. Copyright © 2018. Published by Elsevier B.V.

Influence of grazing and land use on stream-channel characteristics among small dairy farms in the Eastern United States

USGS Publications Warehouse

Brand, Genevieve; Vondracek, Bruce C.; Jordan, Nicholas R.

2015-01-01

Rotational grazing (RG) is a livestock management practice that rotates grazing cattle on a scale of hours to days among small pastures termed paddocks. It may beneficially affect stream channels, relative to other livestock management practices. Such effects and other beneficial effects on hydrology are important to RG's potential to provide a highly multifunctional mode of livestock farming. Previous comparisons of effects of RG and confinement dairy (CD) on adjoining streams have been restricted in scale and scope. We examined 11 stream-channel characteristics on a representative sample of 37 small dairy farms that used either RG or CD production methods. Our objectives were: (1) to compare channel characteristics on RG and CD farms, as these production methods are implemented in practice, in New York, Pennsylvania and Wisconsin, USA; and (2) to examine land use on these farms that may affect stream-channel characteristics. To help interpret channel characteristic findings, we examined on-farm land use in riparian areas 50 m in width along both sides of stream reaches and whole-farm land use. In all states, stream-channel characteristics on RG and CD farms did not differ. Whole-farm land use differed significantly between farm types; CD farms allocated more land to annual row crops, whereas RG farms allocated more land to pasture and grassland. However, land cover in 50 m riparian areas was not different between farm types within states; in particular, many RG and CD farms had continuously grazed pastures in riparian areas, typically occupied by juvenile and non-lactating cows, which may have contributed sediment and nutrients to streams. This similarity in riparian management practices may explain the observed similarity of farm types with respect to stream-channel characteristics. To realize the potential benefits of RG on streams, best management practices that affect stream-channel characteristics, such as protection of riparian areas, may improve aggregate effects of RG on stream quality and also enhance other environment, economic and social benefits of RG.

77 FR 64148 - Advisory Committee on Reactor Safeguards (ACRS) Meeting of the ACRS Subcommittee on Regulatory...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-18

... Regulatory Guides (RG) RG 1.79, ````Preoperational Testing of Emergency Core Cooling Systems for Pressurized Water Reactors,'' Revision 2 and RG 1.79.1, ``Initial Test Program of Emergency Core Cooling Systems for...

Feasibility of deep-inspiration breath-hold PET/CT with short-time acquisition: detectability for pulmonary lesions compared with respiratory-gated PET/CT.

PubMed

Yamashita, Shozo; Yokoyama, Kunihiko; Onoguchi, Masahisa; Yamamoto, Haruki; Hiko, Shigeaki; Horita, Akihiro; Nakajima, Kenichi

2014-01-01

Deep-inspiration breath-hold (DIBH) PET/CT with short-time acquisition and respiratory-gated (RG) PET/CT are performed for pulmonary lesions to reduce the respiratory motion artifacts, and to obtain more accurate standardized uptake value (SUV). DIBH PET/CT demonstrates significant advantages in terms of rapid examination, good quality of CT images and low radiation exposure. On the other hand, the image quality of DIBH PET is generally inferior to that of RG PET because of short-time acquisition resulting in poor signal-to-noise ratio. In this study, RG PET has been regarded as a gold standard, and its detectability between DIBH and RG PET studies was compared using each of the most optimal reconstruction parameters. In the phantom study, the most optimal reconstruction parameters for DIBH and RG PET were determined. In the clinical study, 19 cases were examined using each of the most optimal reconstruction parameters. In the phantom study, the most optimal reconstruction parameters for DIBH and RG PET were different. Reconstruction parameters of DIBH PET could be obtained by reducing the number of subsets for those of RG PET in the state of fixing the number of iterations. In the clinical study, high correlation in the maximum SUV was observed between DIBH and RG PET studies. The clinical result was consistent with that of the phantom study surrounded by air since most of the lesions were located in the low pulmonary radioactivity. DIBH PET/CT may be the most practical method which can be the first choice to reduce respiratory motion artifacts if the detectability of DIBH PET is equivalent with that of RG PET. Although DIBH PET may have limitations in suboptimal signal-to-noise ratio, most of the lesions surrounded by low background radioactivity could provide nearly equivalent image quality between DIBH and RG PET studies when each of the most optimal reconstruction parameters was used.

Physiological Expression of AMPKγ2RG Mutation Causes Wolff-Parkinson-White Syndrome and Induces Kidney Injury in Mice*

PubMed Central

Yang, Xiaodong; Mudgett, John; Bou-About, Ghina; Champy, Marie-France; Jacobs, Hugues; Monassier, Laurent; Pavlovic, Guillaume; Sorg, Tania; Herault, Yann; Petit-Demoulière, Benoit; Lu, Ku; Feng, Wen; Wang, Hongwu; Ma, Li-Jun; Askew, Roger; Erion, Mark D.; Kelley, David E.; Myers, Robert W.; Li, Cai

2016-01-01

Mutations of the AMP-activated kinase gamma 2 subunit (AMPKγ2), N488I (AMPKγ2NI) and R531G (AMPKγ2RG), are associated with Wolff-Parkinson-White (WPW) syndrome, a cardiac disorder characterized by ventricular pre-excitation in humans. Cardiac-specific transgenic overexpression of human AMPKγ2NI or AMPKγ2RG leads to constitutive AMPK activation and the WPW phenotype in mice. However, overexpression of these mutant proteins also caused profound, non-physiological increase in cardiac glycogen, which might abnormally alter the true phenotype. To investigate whether physiological levels of AMPKγ2NI or AMPKγ2RG mutation cause WPW syndrome and metabolic changes in other organs, we generated two knock-in mouse lines on the C57BL/6N background harboring mutations of human AMPKγ2NI and AMPKγ2RG, respectively. Similar to the reported phenotypes of mice overexpressing AMPKγ2NI or AMPKγ2RG in the heart, both lines developed WPW syndrome and cardiac hypertrophy; however, these effects were independent of cardiac glycogen accumulation. Compared with AMPKγ2WT mice, AMPKγ2NI and AMPKγ2RG mice exhibited reduced body weight, fat mass, and liver steatosis when fed with a high fat diet (HFD). Surprisingly, AMPKγ2RG but not AMPKγ2NI mice fed with an HFD exhibited severe kidney injury characterized by glycogen accumulation, inflammation, apoptosis, cyst formation, and impaired renal function. These results demonstrate that expression of AMPKγ2NI and AMPKγ2RG mutations at physiological levels can induce beneficial metabolic effects but that this is accompanied by WPW syndrome. Our data also reveal an unexpected effect of AMPKγ2RG in the kidney, linking lifelong constitutive activation of AMPK to a potential risk for kidney dysfunction in the context of an HFD. PMID:27621313

Physiological Expression of AMPKγ2RG Mutation Causes Wolff-Parkinson-White Syndrome and Induces Kidney Injury in Mice.

PubMed

Yang, Xiaodong; Mudgett, John; Bou-About, Ghina; Champy, Marie-France; Jacobs, Hugues; Monassier, Laurent; Pavlovic, Guillaume; Sorg, Tania; Herault, Yann; Petit-Demoulière, Benoit; Lu, Ku; Feng, Wen; Wang, Hongwu; Ma, Li-Jun; Askew, Roger; Erion, Mark D; Kelley, David E; Myers, Robert W; Li, Cai; Guan, Hong-Ping

2016-11-04

Mutations of the AMP-activated kinase gamma 2 subunit (AMPKγ2), N488I (AMPKγ2 NI ) and R531G (AMPKγ2 RG ), are associated with Wolff-Parkinson-White (WPW) syndrome, a cardiac disorder characterized by ventricular pre-excitation in humans. Cardiac-specific transgenic overexpression of human AMPKγ2 NI or AMPKγ2 RG leads to constitutive AMPK activation and the WPW phenotype in mice. However, overexpression of these mutant proteins also caused profound, non-physiological increase in cardiac glycogen, which might abnormally alter the true phenotype. To investigate whether physiological levels of AMPKγ2 NI or AMPKγ2 RG mutation cause WPW syndrome and metabolic changes in other organs, we generated two knock-in mouse lines on the C57BL/6N background harboring mutations of human AMPKγ2 NI and AMPKγ2 RG , respectively. Similar to the reported phenotypes of mice overexpressing AMPKγ2 NI or AMPKγ2 RG in the heart, both lines developed WPW syndrome and cardiac hypertrophy; however, these effects were independent of cardiac glycogen accumulation. Compared with AMPKγ2 WT mice, AMPKγ2 NI and AMPKγ2 RG mice exhibited reduced body weight, fat mass, and liver steatosis when fed with a high fat diet (HFD). Surprisingly, AMPKγ2 RG but not AMPKγ2 NI mice fed with an HFD exhibited severe kidney injury characterized by glycogen accumulation, inflammation, apoptosis, cyst formation, and impaired renal function. These results demonstrate that expression of AMPKγ2 NI and AMPKγ2 RG mutations at physiological levels can induce beneficial metabolic effects but that this is accompanied by WPW syndrome. Our data also reveal an unexpected effect of AMPKγ2 RG in the kidney, linking lifelong constitutive activation of AMPK to a potential risk for kidney dysfunction in the context of an HFD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Comparative investigation of pure and mixed rare gas atoms on coronene molecules.

PubMed

Rodríguez-Cantano, Rocío; Bartolomei, Massimiliano; Hernández, Marta I; Campos-Martínez, José; González-Lezana, Tomás; Villarreal, Pablo; Pérez de Tudela, Ricardo; Pirani, Fernando; Hernández-Rojas, Javier; Bretón, José

2017-01-21

Clusters formed by the combination of rare gas (RG) atoms of He, Ne, Ar, and Kr on coronene have been investigated by means of a basin-hopping algorithm and path integral Monte Carlo calculations at T = 2 K. Energies and geometries have been obtained and the role played by the specific RG-RG and RG-coronene interactions on the final results is analysed in detail. Signatures of diffuse behavior of the He atoms on the surface of the coronene are in contrast with the localization of the heavier species, Ar and Kr. The observed coexistence of various geometries for Ne suggests the motion of the RG atoms on the multi-well potential energy surface landscape offered by the coronene. Therefore, the investigation of different clusters enables a comparative analysis of localized versus non-localized features. Mixed Ar-He-coronene clusters have also been considered and the competition of the RG atoms to occupy the docking sites on the molecule is discussed. All the obtained information is crucial to assess the behavior of coronene, a prototypical polycyclic aromatic hydrocarbon clustering with RG atoms at a temperature close to that of interstellar medium, which arises from the critical balance of the interactions involved.

The structurally effect of surface coated rhamnogalacturonan I on response of the osteoblast-like cell line SaOS-2.

PubMed

Svava, Rikke; Gurzawska, Katarzyna; Yihau, Yu; Haugshøj, Kenneth Brian; Dirscherl, Kai; Levery, Steven B; Jørgensen, Niklas Rye; Gotfredsen, Klaus; Damager, Iben; Ulvskov, Peter; Jørgensen, Bodil

2014-06-01

Osseointegration is important when implants are inserted into the bone and can be improved by biochemical surface coating of the implant. In this paper enzymatically modified rhamnogalacturonan I (RG-I) from apple and lupin was used for biochemical coating of aminated surfaces and the importance of the quality of RG-I, the nature of the binding, the fine structure of RG-I, and its effect on SaOS-2 cell line cultured on coated surfaces was investigated. SaOS-2 cells are osteoblast-like cells and a well-established in vitro model of bone-matrix forming osteoblasts. Purification by gel filtration could remove small fragments of galacturonic acid (GalA) and binding studies showed that the purity of the RG-I molecules was important for the quality of the coating. The structure of RG-I and osteoblast-like cells' viability were positively correlated so that high content of 1,4-linked galactose (Gal) and a low content of arabinose in the RG-I molecules favored cell viability. These results indicate that coating of implants with RG-I affect osseointegration positively. Copyright © 2013 Wiley Periodicals, Inc.

Enzymatic generation of galactose-rich oligosaccharides/oligomers from potato rhamnogalacturonan I pectic polysaccharides.

PubMed

Khodaei, Nastaran; Karboune, Salwa

2016-04-15

Potato pulp by-product rich in galactan-rich rhamnogalacturonan I (RG I) was investigated as a new source of oligosaccharides with potential prebiotic properties. The efficiency of selected monocomponent enzymes and multi-enzymatic preparations to generate oligosaccharides/oligomers from potato RG I was evaluated. These overall results of yield were dependent on the activity profile of the multi-enzymatic preparations. Highest oligo-RG I yield of 93.9% was achieved using multi-enzymatic preparation (Depol 670L) with higher hydrolytic activity toward side chains of RG I as compared to its backbone. Main oligo-RG I products were oligosaccharides with DP of 2-12 (79.8-100%), while the oligomers with DP of 13-70 comprised smaller proportion (0.0-20.2%). Galactose (58.9-91.2%, w/w) was the main monosaccharide of oligo-RG I, while arabinose represented 0.0-12.1%. An understanding of the relationship between the activity profile of multi-enzymatic preparations and the yield/DP of oligo-RG I was achieved. This is expected to provide the capability to generate galacto- and galacto(arabino) oligosaccharides and their corresponding oligomers from an abundant by-product. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genetic dissection of behavioral flexibility: reversal learning in mice.

PubMed

Laughlin, Rick E; Grant, Tara L; Williams, Robert W; Jentsch, J David

2011-06-01

Behavioral inflexibility is a feature of schizophrenia, attention-deficit/hyperactivity disorder, and behavior addictions that likely results from heritable deficits in the inhibitory control over behavior. Here, we investigate the genetic basis of individual differences in flexibility, measured using an operant reversal learning task. We quantified discrimination acquisition and subsequent reversal learning in a cohort of 51 BXD strains of mice (2-5 mice/strain, n = 176) for which we have matched data on sequence, gene expression in key central nervous system regions, and neuroreceptor levels. Strain variation in trials to criterion on acquisition and reversal was high, with moderate heritability (∼.3). Acquisition and reversal learning phenotypes did not covary at the strain level, suggesting that these traits are effectively under independent genetic control. Reversal performance did covary with dopamine D2 receptor levels in the ventral midbrain, consistent with a similar observed relationship between impulsivity and D2 receptors in humans. Reversal, but not acquisition, is linked to a locus on mouse chromosome 10 with a peak likelihood ratio statistic at 86.2 megabase (p < .05 genome-wide). Variance in messenger RNA levels of select transcripts expressed in neocortex, hippocampus, and striatum correlated with the reversal learning phenotype, including Syn3, Nt5dc3, and Hcfc2. This work demonstrates the clear trait independence between, and genetic control of, discrimination acquisition and reversal and illustrates how globally coherent data sets for a single panel of highly related strains can be interrogated and integrated to uncover genetic sources and molecular and neuropharmacological candidates of complex behavioral traits relevant to human psychopathology. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Assessment of brain reference genes for RT-qPCR studies in neurodegenerative diseases

PubMed Central

Rydbirk, Rasmus; Folke, Jonas; Winge, Kristian; Aznar, Susana; Pakkenberg, Bente; Brudek, Tomasz

2016-01-01

Evaluation of gene expression levels by reverse transcription quantitative real-time PCR (RT-qPCR) has for many years been the favourite approach for discovering disease-associated alterations. Normalization of results to stably expressed reference genes (RGs) is pivotal to obtain reliable results. This is especially important in relation to neurodegenerative diseases where disease-related structural changes may affect the most commonly used RGs. We analysed 15 candidate RGs in 98 brain samples from two brain regions from Alzheimer’s disease (AD), Parkinson’s disease (PD), Multiple System Atrophy, and Progressive Supranuclear Palsy patients. Using RefFinder, a web-based tool for evaluating RG stability, we identified the most stable RGs to be UBE2D2, CYC1, and RPL13 which we recommend for future RT-qPCR studies on human brain tissue from these patients. None of the investigated genes were affected by experimental variables such as RIN, PMI, or age. Findings were further validated by expression analyses of a target gene GSK3B, known to be affected by AD and PD. We obtained high variations in GSK3B levels when contrasting the results using different sets of common RG underlining the importance of a priori validation of RGs for RT-qPCR studies. PMID:27853238

Assessment of brain reference genes for RT-qPCR studies in neurodegenerative diseases.

PubMed

Rydbirk, Rasmus; Folke, Jonas; Winge, Kristian; Aznar, Susana; Pakkenberg, Bente; Brudek, Tomasz

2016-11-17

Evaluation of gene expression levels by reverse transcription quantitative real-time PCR (RT-qPCR) has for many years been the favourite approach for discovering disease-associated alterations. Normalization of results to stably expressed reference genes (RGs) is pivotal to obtain reliable results. This is especially important in relation to neurodegenerative diseases where disease-related structural changes may affect the most commonly used RGs. We analysed 15 candidate RGs in 98 brain samples from two brain regions from Alzheimer's disease (AD), Parkinson's disease (PD), Multiple System Atrophy, and Progressive Supranuclear Palsy patients. Using RefFinder, a web-based tool for evaluating RG stability, we identified the most stable RGs to be UBE2D2, CYC1, and RPL13 which we recommend for future RT-qPCR studies on human brain tissue from these patients. None of the investigated genes were affected by experimental variables such as RIN, PMI, or age. Findings were further validated by expression analyses of a target gene GSK3B, known to be affected by AD and PD. We obtained high variations in GSK3B levels when contrasting the results using different sets of common RG underlining the importance of a priori validation of RGs for RT-qPCR studies.

The Schwabe and Gleissberg Periods in the Wolf Sunspot Numbers and the Group Sunspot Numbers

NASA Astrophysics Data System (ADS)

Li, K. J.; Gao, P. X.; Su, T. W.

2005-06-01

Three wavelet functions: the Morlet wavelet, the Paul wavelet, and the DOG wavelet have been respectively performed on both the monthly Wolf sunspot numbers (Rz) from January 1749 to May 2004 and the monthly group sunspot numbers (Rg) from June 1795 to December 1995 to study the evolution of the Gleissberg and Schwabe periods of solar activity. The main results obtained are (1) the two most obvious periods in both the Rz and Rg are the Schwabe and Gleissberg periods. The Schwabe period oscillated during the second half of the eighteenth century and was steady from the 1850s onward. No obvious drifting trend of the Schwabe period exists. (2) The Gleissberg period obviously drifts to longer periods the whole consideration time, and the drifting speed of the Gleissberg period is larger for Rz than for Rg. (3) Although the Schwabe-period values for Rz and Rg are about 10.7 years, the value for Rz seems slightly larger than that for Rg. The Schwabe period of Rz is highly significant after the 1820s, and the Schwabe period of Rg is highly significant over almost the whole consideration time except for about 20 years around the 1800s. The evolution of the Schwabe period for both Rz and Rg in time is similar to each other. (4) The Gleissberg period in Rz and Rg is highly significant during the whole consideration time, but this result is unreliable at the two ends of each of the time series of the data. The evolution of the Gleissberg period in Rz is similar to that in Rg.

Ginsenoside Rg1 improves bone marrow haematopoietic activity via extramedullary haematopoiesis of the spleen

PubMed Central

Liu, Hua-Hsing; Chen, Fei-Peng; Liu, Rong-Kai; Lin, Chun-Lin; Chang, Ko-Tung

2015-01-01

Cyclophosphamide (CY) is a chemotherapeutic agent used for cancer and immunological diseases. It induces cytotoxicity of bone marrow and causes myelosuppression and extramedullary haematopoiesis (EMH) in treated patients. EMH is characterized with the emergence of multipotent haematopoietic progenitors most likely in the spleen and liver. Previous studies indicated that a Chinese medicine, ginsenoside Rg1, confers a significant effect to elevate the number of lineage (Lin−) Sca-1+ c-Kit+ haematopoietic stem and progenitor cells (HSPCs) and restore the function of bone marrow in CY-treated myelosuppressed mice. However, whether the amelioration of bone marrow by Rg1 accompanies an alleviation of EMH in the spleen was still unknown. In our study, the cellularity and weight of the spleen were significantly reduced after Rg1 treatment in CY-treated mice. Moreover, the number of c-Kit+ HSPCs was significantly decreased but not as a result of apoptosis, indicating that Rg1 alleviated EMH of the spleen induced by CY. Unexpectedly, the proliferation activity of c-Kit+ HSPCs was only up-regulated in the spleen, but not in the bone marrow, after Rg1 treatment in CY-treated mice. We also found that a fraction of c-Kit+/CD45+ HSPCs was simultaneously increased in the circulation after Rg1 treatment. Interestingly, the effects of Rg1 on the elevation of HSPCs in bone marrow and in the peripheral blood were suppressed in CY-treated splenectomized mice. These results demonstrated that Rg1 improves myelosuppression induced by CY through its action on the proliferation of HSPCs in EMH of the spleen and migration of HSPCs from the spleen to the bone marrow. PMID:26153045

Ginsenoside Rg1 improves bone marrow haematopoietic activity via extramedullary haematopoiesis of the spleen.

PubMed

Liu, Hua-Hsing; Chen, Fei-Peng; Liu, Rong-Kai; Lin, Chun-Lin; Chang, Ko-Tung

2015-11-01

Cyclophosphamide (CY) is a chemotherapeutic agent used for cancer and immunological diseases. It induces cytotoxicity of bone marrow and causes myelosuppression and extramedullary haematopoiesis (EMH) in treated patients. EMH is characterized with the emergence of multipotent haematopoietic progenitors most likely in the spleen and liver. Previous studies indicated that a Chinese medicine, ginsenoside Rg1, confers a significant effect to elevate the number of lineage (Lin(-) ) Sca-1(+) c-Kit(+) haematopoietic stem and progenitor cells (HSPCs) and restore the function of bone marrow in CY-treated myelosuppressed mice. However, whether the amelioration of bone marrow by Rg1 accompanies an alleviation of EMH in the spleen was still unknown. In our study, the cellularity and weight of the spleen were significantly reduced after Rg1 treatment in CY-treated mice. Moreover, the number of c-Kit(+) HSPCs was significantly decreased but not as a result of apoptosis, indicating that Rg1 alleviated EMH of the spleen induced by CY. Unexpectedly, the proliferation activity of c-Kit(+) HSPCs was only up-regulated in the spleen, but not in the bone marrow, after Rg1 treatment in CY-treated mice. We also found that a fraction of c-Kit(+) /CD45(+) HSPCs was simultaneously increased in the circulation after Rg1 treatment. Interestingly, the effects of Rg1 on the elevation of HSPCs in bone marrow and in the peripheral blood were suppressed in CY-treated splenectomized mice. These results demonstrated that Rg1 improves myelosuppression induced by CY through its action on the proliferation of HSPCs in EMH of the spleen and migration of HSPCs from the spleen to the bone marrow. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

The DcpS inhibitor RG3039 improves survival, function and motor unit pathologies in two SMA mouse models

PubMed Central

Gogliotti, Rocky G.; Cardona, Herminio; Singh, Jasbir; Bail, Sophie; Emery, Carina; Kuntz, Nancy; Jorgensen, Michael; Durens, Madel; Xia, Bing; Barlow, Courtenay; Heier, Christopher R.; Plasterer, Heather L.; Jacques, Vincent; Kiledjian, Megerditch; Jarecki, Jill; Rusche, James; DiDonato, Christine J.

2013-01-01

Spinal muscular atrophy (SMA) is caused by insufficient levels of the survival motor neuron (SMN) protein due to the functional loss of the SMN1 gene and the inability of its paralog, SMN2, to fully compensate due to reduced exon 7 splicing efficiency. Since SMA patients have at least one copy of SMN2, drug discovery campaigns have sought to identify SMN2 inducers. C5-substituted quinazolines increase SMN2 promoter activity in cell-based assays and a derivative, RG3039, has progressed to clinical testing. It is orally bioavailable, brain-penetrant and has been shown to be an inhibitor of the mRNA decapping enzyme, DcpS. Our pharmacological characterization of RG3039, reported here, demonstrates that RG3039 can extend survival and improve function in two SMA mouse models of varying disease severity (Taiwanese 5058 Hemi and 2B/− SMA mice), and positively impacts neuromuscular pathologies. In 2B/− SMA mice, RG3039 provided a >600% survival benefit (median 18 days to >112 days) when dosing began at P4, highlighting the importance of early intervention. We determined the minimum effective dose and the associated pharmacokinetic (PK) and exposure relationship of RG3039 and DcpS inhibition ex vivo. These data support the long PK half-life with extended pharmacodynamic outcome of RG3039 in 2B/− SMA mice. In motor neurons, RG3039 significantly increased both the average number of cells with gems and average number of gems per cell, which is used as an indirect measure of SMN levels. These studies contribute to dose selection and exposure estimates for the first studies with RG3039 in human subjects. PMID:23736298

Rg-Lg coupling as a Lg-wave excitation mechanism

NASA Astrophysics Data System (ADS)

Ge, Z.; Xie, X.

2003-12-01

Regional phase Lg is predominantly comprised of shear wave energy trapped in the crust. Explosion sources are expected to be less efficient for excitation of Lg phases than earthquakes to the extent that the source can be approximated as isotropic. Shallow explosions generate relatively large surface wave Rg compared to deeper earthquakes, and Rg is readily disrupted by crustal heterogeneity. Rg energy may thus scatter into trapped crustal S-waves near the source region and contribute to low-frequency Lg wave. In this study, a finite-difference modeling plus the slowness analysis are used for investigating the above mentioned Lg-wave excitation mechanism. The method allows us to investigate near source energy partitioning in multiple domains including frequency, slowness and time. The main advantage of this method is that it can be applied at close range, before Lg is actually formed, which allows us to use very fine near source velocity model to simulate the energy partitioning process. We use a layered velocity structure as the background model and add small near source random velocity patches to the model to generate the Rg to Lg coupling. Two types of simulations are conducted, (1) a fixed shallow explosion source vs. randomness at different depths and (2) a fixed shallow randomness vs. explosion sources at different depths. The results show apparent couplings between the Rg and Lg waves at lower frequencies (0.3-1.5 Hz). A shallow source combined with shallow randomness generates the maximum Lg-wave, which is consistent with the Rg energy distribution of a shallow explosion source. The Rg energy and excited Lg energy show a near linear relationship. The numerical simulation and slowness analysis suggest that the Rg to Lg coupling is an effective excitation mechanism for low frequency Lg-waves from a shallow explosion source.

[Research of anti-aging mechanism of ginsenoside Rg1 on brain].

PubMed

Li, Cheng-peng; Zhang, Meng-si; Liu, Jun; Geng, Shan; Li, Jing; Zhu, Jia-hong; Zhang, Yan-yan; Jia, Yan-yan; Wang, Lu; Wang, Shun-he; Wang, Ya-ping

2014-11-01

Neurodegenerative disease is common and frequently occurs in elderly patients. Previous studies have shown that ginsenoside Rg1 was able to inhibit senescent of brain, but the mechanism on the brain during the treatment remains elucidated. To study the mechanism of ginsenoside Rg1 in the process of anti-aging of brain, forty male SD rats were randomly divided into normal group, Rg1 normal group, brain aging model group and Rg1 brain aging model group, each group with 10 rats (brain aging model group: subcutaneous injection of D-galactose (120 mg kg(-1)), qd for 42 consecutive days; Rg1 brain aging model group: while copying the same test as that of brain aging model group, begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Rg1 normal group: subcutaneous injection of the same amount of saline; begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Normal: injected with an equal volume of saline within the same time. Perform the related experiment on the second day after finishing copying the model or the completion of the first two days of drug injections). Learning and memory abilities were measured by Morris water maze. The number of senescent cells was detected by SA-beta-Gal staining while the level of IL-1 and IL-6 proinflammatory cytokines in hippocampus were detected by ELISA. The activities of SOD, contents of GSH in hippo- campus were quantified by chromatometry. The change of telomerase activities and telomerase length were performed by TRAP-PCR and southern blotting assay, respectively. It is pointed that, in brain aging model group, the spatial learning and memory capacities were weaken, SA-beta-Gal positive granules increased in section of brain tissue, the activity of antioxidant enzyme SOD and the contents of GSH decreased in hippocampus, the level of IL-1 and IL-6 increased in hippocampus, while the length of telomere and the activity of telomerase decreased in hippocampus. Rats of Rg1 brain aging group had their spatial learning and memory capacities enhanced, SA-beta-Gal positive granules in section of brain tissue decreased, the activity of antioxidant enzyme SOD and the contents of GSH increased in hippocampus, the level of IL-1 and IL-6 in hippocampus decreased, the length contraction of telomere suppressed while the change of telomerase activity increased in hippocampus. Compared with that of normal group, the spatial learning and memory capacities were enhanced in Rg1 normal group, SA-beta-Gal positive granules in section of brain tissue decreased in Rg1 normal group, the level of IL-1 and IL-6 in hippocampus decreased in Rg1 normal group. The results indicated that improvement of antioxidant ability, regulating the level of proinflammatory cytokines and regulation of telomerase system may be the underlying anti-aging mechanism of Ginsenoside Rg1.

Static electric polarizabilities and first hyperpolarizabilities of molecular ions RgH + (Rg = He, Ne, Ar, Kr, Xe): ab initio study

NASA Astrophysics Data System (ADS)

Cukras, Janusz; Antušek, Andrej; Holka, Filip; Sadlej, Joanna

2009-06-01

Extensive ab initio calculations of static electric properties of molecular ions of general formula RgH + (Rg = He, Ne, Ar, Kr, Xe) involving the finite field method and coupled cluster CCSD(T) approach have been done. The relativistic effects were taken into account by Douglas-Kroll-Hess approximation. The numerical stability and reliability of calculated values have been tested using the systematic sequence of Dunning's cc-pVXZ-DK and ANO-RCC-VQZP basis sets. The influence of ZPE and pure vibrational contribution has been discussed. The component αzz has increasing trend in RgH + while the relativistic effect on αzz leads to a small increase of this molecular parameter.

WFIRST: Principal Components Analysis of H4RG-10 Near-IR Detector Data Cubes

NASA Astrophysics Data System (ADS)

Rauscher, Bernard

2018-01-01

The Wide Field Infrared Survey Telescope’s (WFIRST) Wide Field Instrument (WFI) incorporates an array of eighteen Teledyne H4RG-10 near-IR detector arrays. Because WFIRST’s science investigations require controlling systematic uncertainties to state-of-the-art levels, we conducted principal components analysis (PCA) of some H4RG-10 test data obtained in the NASA Goddard Space Flight Center Detector Characterization Laboratory (DCL). The PCA indicates that the Legendre polynomials provide a nearly orthogonal representation of up-the-ramp sampled illuminated data cubes, and suggests other representations that may provide an even more compact representation of the data in some circumstances. We hypothesize that by using orthogonal representations, such as those described here, it may be possible to control systematic errors better than has been achieved before for NASA missions. We believe that these findings are probably applicable to other H4RG, H2RG, and H1RG based systems.

Effect of gamma irradiation on the conversion of ginsenoside Rb1 to Rg3

NASA Astrophysics Data System (ADS)

Kim, Jae-Hun; Kwon, Sun-Kyu; Sung, Nak-Yun; Jung, Pil-Mun; Choi, Jong-il; Kim, Jae-Kyung; Sharma, Arun K.; Lee, Ju-Woon

2012-08-01

Ginsenosides, the most important secondary metabolites in ginseng, have various biological activities. Many studies have focused on the conversion of one of the major ginsenosides, Rb1, to the more active minor ginsenoside, Rg3. This study was carried out to investigate the effect of gamma irradiation on the conversion of Rb1 to Rg3. Rb1 solutions were gamma-irradiated at doses of 10 and 30 kGy and analyzed by high performance liquid chromatography (HPLC). HPLC chromatograms showed a decreased content of Rb1 with increasing irradiation dose, but the content of Rg3 was increased. The highest content of Rg3 was present in the 30 kGy-irradiated Rb1 sample. The cytotoxic effects tested in cancer cell lines were increased in the gamma-irradiated group. Therefore, these results suggest that gamma irradiation can be an effective method for the conversion of the ginsenoside Rb1 to Rg3.

DEVELOPMENT OF HFE SECTIONS OF DG-1145.

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

HIGGINS,J.C.; OHARA, J.M.; BONGARRA, J.

2007-03-26

For the licensing of the current fleet of commercial nuclear power plants (NPPs), the Nuclear Regulatory Commission (NRC) used two key documents, NUREG-0800 and Regulatory Guide (RG) 1.70. RG 1.70 provided guidance to applicants on the contents needed in their Safety Analysis Reports (SARs) submitted as part of their application to construct or operate an NPP. NUREG-0800, the NRC Standard Review Plan (SRP), provides guidance to the NRR staff reviewers on performing their safety reviews of these applications. As part of the preparation for a new wave of improved NPP designs the NRC is in the process of updating themore » SRP and is also developing a new RG designated as draft RG or DG-1145, ''Combined License Applications for Nuclear Power Plants (LWR Edition).'' This will eventually become RG 1.206 and will take the place of RG 1.70. This will provide guidance for combined license (COL) applicants, as well as for other 10CFR Part 52 variations that are permitted.« less

Enhancement of ginsenoside Rg(1) in Panax ginseng hairy root by overexpressing the α-L-rhamnosidase gene from Bifidobacterium breve.

PubMed

Zhang, Ru; Zhang, Bian-Ling; Li, Gu-Cai; Xie, Tao; Hu, Teng; Luo, Zhi-Yong

2015-10-01

To improve the production of ginsenoside Rg1 in Panax ginseng. The α-L-rhamnosidase gene from Bifidobacterium breve (BbRha) was overexpressed into hairy root culture system using Agrobacterium rhizogenes A4. Ginsenoside Rg1 in hairy roots was obtained following transformation via overexpressed gene representing 2.2-fold higher than those of control lines. Several overexpression transgenic hairy root lines were obtained exhibiting markedly increased levels of the corresponding α-L-rhamnosidase enzymatic activity relative to control. Ginsenoside Rg1 levels in the transgenic lines were higher (2.2-fold) than those of control after following 30 days culturing, while ginsenoside Re contents in tested transgenic lines were found to be lower. The transgenic hairy roots harboring α-L-rhamnosidase gene improved the accumulation of ginsenoside Rg1 up to 3.6 mg g(-1) dry weight. BbRha gene selectively enhances the production of ginsenoside Rg1 in P. ginseng hairy roots.

Phase structure of NJL model with weak renormalization group

NASA Astrophysics Data System (ADS)

Aoki, Ken-Ichi; Kumamoto, Shin-Ichiro; Yamada, Masatoshi

2018-06-01

We analyze the chiral phase structure of the Nambu-Jona-Lasinio model at finite temperature and density by using the functional renormalization group (FRG). The renormalization group (RG) equation for the fermionic effective potential V (σ ; t) is given as a partial differential equation, where σ : = ψ bar ψ and t is a dimensionless RG scale. When the dynamical chiral symmetry breaking (DχSB) occurs at a certain scale tc, V (σ ; t) has singularities originated from the phase transitions, and then one cannot follow RG flows after tc. In this study, we introduce the weak solution method to the RG equation in order to follow the RG flows after the DχSB and to evaluate the dynamical mass and the chiral condensate in low energy scales. It is shown that the weak solution of the RG equation correctly captures vacuum structures and critical phenomena within the pure fermionic system. We show the chiral phase diagram on temperature, chemical potential and the four-Fermi coupling constant.

Moment analysis method as applied to the 2S --> 2P transition in cryogenic alkali metal/rare gas matrices.

PubMed

Terrill Vosbein, Heidi A; Boatz, Jerry A; Kenney, John W

2005-12-22

The moment analysis method (MA) has been tested for the case of 2S --> 2P ([core]ns1 --> [core]np1) transitions of alkali metal atoms (M) doped into cryogenic rare gas (Rg) matrices using theoretically validated simulations. Theoretical/computational M/Rg system models are constructed with precisely defined parameters that closely mimic known M/Rg systems. Monte Carlo (MC) techniques are then employed to generate simulated absorption and magnetic circular dichroism (MCD) spectra of the 2S --> 2P M/Rg transition to which the MA method can be applied with the goal of seeing how effective the MA method is in re-extracting the M/Rg system parameters from these known simulated systems. The MA method is summarized in general, and an assessment is made of the use of the MA method in the rigid shift approximation typically used to evaluate M/Rg systems. The MC-MCD simulation technique is summarized, and validating evidence is presented. The simulation results and the assumptions used in applying MA to M/Rg systems are evaluated. The simulation results on Na/Ar demonstrate that the MA method does successfully re-extract the 2P spin-orbit coupling constant and Landé g-factor values initially used to build the simulations. However, assigning physical significance to the cubic and noncubic Jahn-Teller (JT) vibrational mode parameters in cryogenic M/Rg systems is not supported.

Efficacy of a Recombinant Turkey Herpesvirus H5 Vaccine Against Challenge With H5N1 Clades 1.1.2 and 2.3.2.1 Highly Pathogenic Avian Influenza Viruses in Domestic Ducks (Anas platyrhynchos domesticus).

PubMed

Pantin-Jackwood, Mary J; Kapczynski, Darrell R; DeJesus, Eric; Costa-Hurtado, Mar; Dauphin, Gwenaelle; Tripodi, Astrid; Dunn, John R; Swayne, David E

2016-03-01

Domestic ducks are the second most abundant poultry species in many Asian countries and have played a critical role in the epizootiology of H5N1 highly pathogenic avian influenza (HPAI).In this study, the protective efficacy of a live recombinant vector vaccine based on a turkey herpesvirus (HVT) expressing the H5 gene from a clade 2.2 H5N1 HPAI strain (A/Swan/Hungary/4999/ 2006) (rHVT-H5/2.2), given at 3 days of age, was examined in Pekin ducks (Anas platyrhynchos domesticus). The vaccine was given alone or in combination with an inactivated H5N1 clade 2.3.2.1 reverse genetic (rgGD/2.3.2.1) vaccine given at 16 days of age, either as a single vaccination or in a prime-boost regime. At 30 days of age, ducks were challenged with one of two H5N1 HPAI viruses: A/duck/Vietnam/NCVD-2721/2013 (clade 1.1.2) or A/duck/Vietnam/NCVD-1584/2012 (clade 2.3.2.1.C). These viruses produced 100% mortality in less than 5 days in nonvaccinated control ducks. Ducks vaccinated with the rgGD/2.3.2.1 vaccine, with or without the rHVT-H5/2.2 vaccine, were 90%-100% protected against mortality after challenge with either of the two H5N1 HPAI viruses. The rHVT-H5/2.2 vaccine alone, however, conferred only 30% protection against mortality after challenge with either H5N1 HPAI virus; the surviving ducks from these groups shed higher amount of virus and for longer than the single-vaccinated rgGD/2.3.2.1 group. Despite low protection, ducks vaccinated with the rHVT-H5/2.2 vaccine and challenged with the clade 1.1.2 Vietnam virus had a longer mean death time than nonvaccinated controls (P = 0.02). A booster effect was found on reduction of virus shedding when using both vaccines, with lower oropharyngeal viral titers at 4 days after challenge with either HPAI virus (P < 0.05). Neither rHVT-H5/2.2 nor standard HVT vaccine could be detected in samples collected from multiple tissues at different time points, indicting minimal levels of viral replication. In conclusion, although a minor effect on survival was observed, this study demonstrates the suboptimal protection with the rHVT-H5/2.2 vaccine given alone in Pekin ducks against H5N1 HPAI viruses and only a minor additive effect on virus shedding reduction when used with an inactivated vaccine in a prime-boost regime.

Selection for Duration of Fertility and Mule Duck White Plumage Colour in a Synthetic Strain of Ducks (Anas platyrhynchos).

PubMed

Liu, H C; Huang, J F; Lee, S R; Liu, H L; Hsieh, C H; Huang, C W; Huang, M C; Tai, C; Poivey, J P; Rouvier, R; Cheng, Y S

2015-05-01

A synthetic strain of ducks (Anas platyrhynchos) was developed by introducing genes for long duration of fertility to be used as mother of mule ducklings and a seven-generation selection experiment was conducted to increase the number of fertile eggs after a single artificial insemination (AI) with pooled Muscovy semen. Reciprocal crossbreeding between Brown Tsaiya LRI-2 (with long duration of fertility) and Pekin L-201 (with white plumage mule ducklings) ducks produced the G0. Then G1 were intercrossed to produce G2 and so on for the following generations. Each female duck was inseminated 3 times, at 26, 29, and 32 weeks of age. The eggs were collected for 14 days from day 2 after AI. Individual data regarding the number of incubated eggs (Ie), the number of fertile eggs at candling at day 7 of incubation (F), the total number of dead embryos (M), the maximum duration of fertility (Dm) and the number of hatched mule ducklings (H) with plumage colour were recorded. The selection criterion was the breeding values of the best linear unbiased prediction animal model for F. The results show high percentage of exhibited heterosis in G2 for traits to improve (19.1% for F and 12.9% for H); F with a value of 5.92 (vs 3.74 in the Pekin L-201) was improved in the G2. Heritabilities were found to be low for Ie (h (2) = 0.07±0.03) and M (h (2) = 0.07±0.01), moderately low for Dm (h (2) = 0.13±0.02), of medium values for H (h (2) = 0.20±0.03) and F (h (2) = 0.23±0.03). High and favourable genetic correlations existed between F and Dm (rg = 0.93), between F and H (rg = 0.97) and between Dm and H (rg = 0.90). The selection experiment showed a positive trend for phenotypic values of F (6.38 fertile eggs in G10 of synthetic strain vs 5.59 eggs in G4, and 3.74 eggs in Pekin L-201), with correlated response for increasing H (5.73 ducklings in G10 vs 4.86 in G4, and 3.09 ducklings in Pekin L-201) and maximum duration of the fertile period without increasing the embryo mortality rate. The average predicted genetic response for F was 40% of genetic standard deviation per generation of selection. The mule ducklings' feather colour also was improved. It was concluded that this study provided results for a better understanding of the genetics of the duration of fertility traits in the common female duck bred for mule and that the selection of a synthetic strain was effective method of improvement.

Rapid estimation of the electron correlation energy for van der Waals complexes RgX (Rg = Kr, Xe, X = Br, I)

NASA Astrophysics Data System (ADS)

Xinying, Li; Yongfang, Zhao; Xiaogong, Jing; Fengli, Liu; Fengyou, Hao

2006-01-01

We present the rules of electron correlation energies for RgX (Rg = Kr, Xe, X = Br, I) van der Waals (vdW) complex systems at CCSD(T) theoretical level with SDB-cc-pVQZ basis set by the Gaussian 98 program. A new method to derive the dispersion coefficient C6 by fitting the intermonomer electron correlation energies to C6R-6 function is introduced. The present C6 values are compared with the corresponding theoretical ones.

Anti-Inflammatory Effect of Ginsenoside Rg5 in Lipopolysaccharide-Stimulated BV2 Microglial Cells

PubMed Central

Lee, Yu Young; Park, Jin-Sun; Jung, Ji-Sun; Kim, Dong-Hyun; Kim, Hee-Sun

2013-01-01

Microglia are resident immune cells in the central nervous system. They play a role in normal brain development and neuronal recovery. However, overactivation of microglia causes neuronal death, which is associated with neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. Therefore, controlling microglial activation has been suggested as an important target for treatment of neurodegenerative diseases. In the present study, we investigated the anti-inflammatory effect of ginsenoside Rg5 in lipopolysaccharide (LPS)-stimulated BV2 microglial cells and rat primary microglia. The data showed that Rg5 suppressed LPS-induced nitric oxide (NO) production and proinflammatory TNF-α secretion. In addition, Rg5 inhibited the mRNA expressions of iNOS, TNF-α, IL-1β, COX-2 and MMP-9 induced by LPS. Further mechanistic studies revealed that Rg5 inhibited the phophorylations of PI3K/Akt and MAPKs and the DNA binding activities of NF-κB and AP-1, which are upstream molecules controlling inflammatory reactions. Moreover, Rg5 suppressed ROS production with upregulation of hemeoxygenase-1 (HO-1) expression in LPS-stimulated BV2 cells. Overall, microglial inactivation by ginsenoside Rg5 may provide a therapeutic potential for various neuroinflammatory disorders. PMID:23698769

Rg1 inhibits high glucose-induced mesenchymal activation and fibrosis via regulating miR-2113/RP11-982M15.8/Zeb1 pathway.

PubMed

Xue, Li-Ping; Fu, Xiao-Lin; Hu, Min; Zhang, Li-Wei; Li, Ya-Di; Peng, Ya-Li; Ding, Peng

2018-07-02

Recent study has showed that Ginsenoside Rg1, the mian active compound of Panax ginseng, could ameliorate oxidative stress and myocardial apoptosis in diabetes mellitus. However, the roles and mechanisms of Rg1 in proliferative diabetic retinopathy (PDR) are still unclear. In the present study, we aimed to investigate the effects of Rg1 on mesenchymal activation of high-glucose (HG) cultured müller cells. High glucose conditions up-regulate MMP-2, MMP-9 and down-regulate TIMP-2, and promote mesenchymal activation in Müller cells. And Rg1 inhibits the HG-induced mesenchymal activation and HG-increased MMP-2 and MMP-9 and HG-decreased TIMP-2 in Müller cells. HG up-regulates Zeb1 and lncRNA RP11-982M15.8, and down-regulates miR-2113, and Rg1 inhibits these effects of HG. Both inhibition of miR-2113 and over-expression of RP11-982M15.8 significantly restored the HG induced mesenchymal activasion. Taken together, our findings suggested that Rg1 inhibited HG-induced mesenchymal activation and fibrosis via regulating miR-2113/RP11-982M15.8/Zeb1 pathway. Copyright © 2018. Published by Elsevier Inc.

Information Foraging Across the Life Span: Search and Switch in Unknown Patches.

PubMed

Chin, Jessie; Payne, Brennan R; Fu, Wai-Tat; Morrow, Daniel G; Stine-Morrow, Elizabeth A L

2015-07-01

In this study, we used a word search puzzle paradigm to investigate age differences in the rate of information gain (RG; i.e., word gain as a function of time) and the cues used to make patch-departure decisions in information foraging. The likelihood of patch departure increased as the profitability of the patch decreased generally. Both younger and older adults persisted past the point of optimality as defined by the marginal value theorem (Charnov, 1976), which assumes perfect knowledge of the foraging ecology. Nevertheless, there was evidence that adults were rational in terms of being sensitive to the change in RG for making the patch-departure decisions. However, given the limitations in cognitive resources and knowledge about the ecology, the estimation of RG may not be accurate. Younger adults were more likely to leave the puzzle as the long-term RG incrementally decreased, whereas older adults were more likely to leave the puzzle as the local RG decreased. However, older adults with better executive control were more likely to adjust their likelihood of patch-departure decisions to the long-term change in RG. Thus, age-dependent reliance on the long-term or local change in RG to make patch-departure decisions might be due to individual differences in executive control. Copyright © 2015 Cognitive Science Society, Inc.

Ginsenoside Rg1 nanoparticle penetrating the blood-brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction.

PubMed

Shen, Junyi; Zhao, Zhiming; Shang, Wei; Liu, Chunli; Zhang, Beibei; Zhao, Lingjie; Cai, Hui

2017-01-01

Diabetic cerebral infarction is with poorer prognosis and high rates of mortality. Ginsenoside Rg1 (Rg1) has a wide variety of therapeutic values for central nervous system (CNS) diseases for the neuron protective effects. However, the blood-brain barrier (BBB) restricts Rg1 in reaching the CNS. In this study, we investigated the therapeutic effects of Rg1 nanoparticle (PHRO, fabricated with γ-PGA, L-PAE (H), Rg1, and OX26 antibody), targeting transferrin receptor, on the diabetes rats complicated with diabetic cerebral infarction in vitro and in vivo. Dynamic light scattering analysis shows the average particle size of PHRO was 79±18 nm and the polydispersity index =0.18. The transmission electron microscope images showed that all NPs were spherical in shape with diameters of 89±23 nm. PHRO released Rg1 with sustained release manner and could promote the migration of cerebrovascular endothelial cells and tube formation and even penetrated the BBB in vitro. PHRO could penetrate the BBB with high concentration in brain tissue to reduce the cerebral infarction volume and promote neuronal recovery in vivo. PHRO was promising to be a clinical treatment of diabetes mellitus with cerebral infarction.

Ginsenoside Rg1 nanoparticle penetrating the blood–brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction

PubMed Central

Shen, Junyi; Zhao, Zhiming; Shang, Wei; Liu, Chunli; Zhang, Beibei; Zhao, Lingjie; Cai, Hui

2017-01-01

Diabetic cerebral infarction is with poorer prognosis and high rates of mortality. Ginsenoside Rg1 (Rg1) has a wide variety of therapeutic values for central nervous system (CNS) diseases for the neuron protective effects. However, the blood–brain barrier (BBB) restricts Rg1 in reaching the CNS. In this study, we investigated the therapeutic effects of Rg1 nanoparticle (PHRO, fabricated with γ-PGA, L-PAE (H), Rg1, and OX26 antibody), targeting transferrin receptor, on the diabetes rats complicated with diabetic cerebral infarction in vitro and in vivo. Dynamic light scattering analysis shows the average particle size of PHRO was 79±18 nm and the polydispersity index =0.18. The transmission electron microscope images showed that all NPs were spherical in shape with diameters of 89±23 nm. PHRO released Rg1 with sustained release manner and could promote the migration of cerebrovascular endothelial cells and tube formation and even penetrated the BBB in vitro. PHRO could penetrate the BBB with high concentration in brain tissue to reduce the cerebral infarction volume and promote neuronal recovery in vivo. PHRO was promising to be a clinical treatment of diabetes mellitus with cerebral infarction. PMID:28919749

Comprehensive clinical evaluation of a large Spanish family with Anderson-Fabry disease, novel GLA mutation and severe cardiac phenotype.

PubMed

San Román-Monserrat, Irene; Moreno-Flores, Victoria; López-Cuenca, David; Rodríguez-González-Herrero, Elena; Guillén-Navarro, Encarna; Rodríguez-González-Herrero, Beatriz; Alegría-Fernández, Marisol; Poza-Cisneros, Gabriela; Piñero-Fernández, Juan A; Sornichero-Martínez, Javier; Gimeno-Blanes, Juan R

2014-06-06

Fabry disease is an X-linked multisystemic lysosomal-storage condition. We describe a large family with a novel GLA mutation: p.M187R/g7219 T>G. Anamnesis/physical-exam, blood/urine analysis, α-Gal-A activity and/or genetic study of at-risk individuals and multidisciplinary evaluation in confirmed cases. 4 males and 13 heterozygous-females displayed the mutation. Cardiac/renal/neurological disease was diagnosed at a mean age of 41/29/39 years in males and 51/56/46 years in females. Onset mean age was 20 years versus 42 years. 9/15 had cardiomyopathy. Delta wave suggestive of accessory pathway was identified in 1 male and 2 females. 1 female had cardiac arrest (ventricular fibrillation, 61 years). 2 females and 1 male died suddenly (63, 64 and 57 years). Cardiac-subscore of Mainz Severity-Score-Index was severe for males and females over 40 years. 4/15(26%) developed early renal disease. 2 males needed dialysis. 1 male died at 69 years in spite of kidney-heart transplant. We describe the largest genetically confirmed Spanish family using multidisciplinary evaluation and MSSI calculation. The novel mutation p.M187R/g7219 T>G is associated with a particularly malignant cardiac phenotype in males and females over 40 years. Severity was higher than that of the largest Spanish FOS-cohort. Short-PR with delta is being reported for the first time. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Strains and Stressors: An Analysis of Touchscreen Learning in Genetically Diverse Mouse Strains

PubMed Central

Graybeal, Carolyn; Bachu, Munisa; Mozhui, Khyobeni; Saksida, Lisa M.; Bussey, Timothy J.; Sagalyn, Erica; Williams, Robert W.; Holmes, Andrew

2014-01-01

Touchscreen-based systems are growing in popularity as a tractable, translational approach for studying learning and cognition in rodents. However, while mouse strains are well known to differ in learning across various settings, performance variation between strains in touchscreen learning has not been well described. The selection of appropriate genetic strains and backgrounds is critical to the design of touchscreen-based studies and provides a basis for elucidating genetic factors moderating behavior. Here we provide a quantitative foundation for visual discrimination and reversal learning using touchscreen assays across a total of 35 genotypes. We found significant differences in operant performance and learning, including faster reversal learning in DBA/2J compared to C57BL/6J mice. We then assessed DBA/2J and C57BL/6J for differential sensitivity to an environmental insult by testing for alterations in reversal learning following exposure to repeated swim stress. Stress facilitated reversal learning (selectively during the late stage of reversal) in C57BL/6J, but did not affect learning in DBA/2J. To dissect genetic factors underlying these differences, we phenotyped a family of 27 BXD strains generated by crossing C57BL/6J and DBA/2J. There was marked variation in discrimination, reversal and extinction learning across the BXD strains, suggesting this task may be useful for identifying underlying genetic differences. Moreover, different measures of touchscreen learning were only modestly correlated in the BXD strains, indicating that these processes are comparatively independent at both genetic and phenotypic levels. Finally, we examined the behavioral structure of learning via principal component analysis of the current data, plus an archival dataset, totaling 765 mice. This revealed 5 independent factors suggestive of “reversal learning,” “motivation-related late reversal learning,” “discrimination learning,” “speed to respond,” and “motivation during discrimination.” Together, these findings provide a valuable reference to inform the choice of strains and genetic backgrounds in future studies using touchscreen-based tasks. PMID:24586288

Neuroprotective effects of ginsenoside Rg1 against oxygen-glucose deprivation in cultured hippocampal neurons.

PubMed

He, Qing; Sun, Jianguo; Wang, Qin; Wang, Wei; He, Bin

2014-03-01

Ginsenoside Rg1 (Rg1) is believed to be one of the main active principles in ginseng, a traditional Chinese medicine extensively used to enhance stamina and deal with fatigue as well as physical stress. It has been reported that Rg1 performs multiple biological activities, including neuroprotective activity. In this study, we investigated the efficacy of ginsenoside Rg1 on ischemia-reperfusion injury in cultured hippocampal cells and also probed its possible mechanisms. To establish a model of oxygen-glucose deprivation (OGD) and reperfusion, cultured hippocampal neurons were exposed to OGD for 2.5 hours, followed by a 24-hour reoxygenation. Cultured hippocampal neurons were randomly divided into control group, model group (vehicle), and ginsenoside Rg1 treatment groups (5μM, 20μM, 60μM). At 24 hours post-OGD, the intracellular free calcium concentration was detected using Furo-3/AM-loaded hippocampal neurons deprived of oxygen and glucose. Neuronal nitric oxide synthase (nNOS) activity was measured by chemical colorimetry. Cell apoptosis was evaluated by Hoechst staining, and the neuron viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Excitotoxic neuronal injury of OGD was demonstrated by the increase of intracellular free calcium concentrations and elevated nNOS activity in the model group compared with the control group. The intracellular free calcium concentrations and the nNOS activity in the groups receiving intermediate and high dose of ginsenoside Rg1 were significantly lower than those of the control group (p < 0.05). In addition, intermediate and high dose of ginsenoside Rg1 administration could also attenuate the cell viability loss (p < 0.05) and cell apoptosis induced by OGD. Ginsenoside Rg1 has neuroprotective effect on ischemia-reperfusion injury in cultured hippocampal cells mediated by blocking calcium over-influx into neuronal cells and decreasing the nNOS activity after OGD exposure. We infer that ginsenoside Rg1 may serve as a potential therapeutic agent for cerebral ischemia injury. Copyright © 2014. Published by Elsevier B.V.

Interactions of C+(2PJ) with rare gas atoms: incipient chemical interactions, potentials and transport coefficients

NASA Astrophysics Data System (ADS)

Tuttle, William D.; Thorington, Rebecca L.; Viehland, Larry A.; Breckenridge, W. H.; Wright, Timothy G.

2018-03-01

Accurate interatomic potentials were calculated for the interaction of a singly charged carbon cation, C+, with a single rare gas atom, RG (RG = Ne-Xe). The RCCSD(T) method and basis sets of quadruple-ζ and quintuple-ζ quality were employed; each interaction energy was counterpoise corrected and extrapolated to the basis set limit. The lowest C+(2P) electronic term of the carbon cation was considered, and the interatomic potentials calculated for the diatomic terms that arise from these: 2Π and 2Σ+. Additionally, the interatomic potentials for the respective spin-orbit levels were calculated, and the effect on the spectroscopic parameters was examined. In doing this, anomalously large spin-orbit splittings for RG = Ar-Xe were found, and this was investigated using multi-reference configuration interaction calculations. The latter indicated a small amount of RG → C+ electron transfer and this was used to rationalize the observations. This is taken as evidence of an incipient chemical interaction, which was also examined via contour plots, Birge-Sponer plots and various population analyses across the C+-RG series (RG = He-Xe), with the latter showing unexpected results. Trends in several spectroscopic parameters were examined as a function of the increasing atomic number of the RG atom. Finally, each set of RCCSD(T) potentials was employed, including spin-orbit coupling to calculate the transport coefficients for C+ in RG, and the results were compared with the limited available data. This article is part of the theme issue `Modern theoretical chemistry'.

Elite level rhythmic gymnasts have significantly more and stronger pain than peers of similar age: a prospective study.

PubMed

Sabeti, Manuel; Jeremian, Lusine; Graf, Alexandra; Kandelhart, Robert

2015-01-01

Rhythmic gymnastics (RG) unites aesthetic, ballet-like motion, and all aspects of gymnastics. To reach elite level, girls begin at early age the intensive training. To date it is unclear if such demanding training influences the incidence and intensity of painful overuse injuries. The purpose of this study is to analyze anatomical painful regions and pain intensity in elite level rhythmic gymnasts (elRG) and compare results with an age-matched control group (CG). This prospective field study was carried out at the European Championship in RG 2013 (218 participating athletes, Vienna, Austria). Volunteering athletes were interviewed according to a preformed questionnaire. As CG secondary school pupils without any competitive sports experience were analyzed accordingly. Overall, 243 young females (144 elRG/66 % of all participants and 99 CG) were observed. ElRGs were significantly (s.) smaller, lighter, and had s. stronger pain (p < 0.001). A total of 72 % of athletes reported to have at least one painful body region compared with 52 % of CG (p < 0.001). ElRG had nearly three times more serious injuries than the CG. In all 23 % off all elRG reported to have had no access to professional medical care. ElRGs were s. more frequently (25 vs 9 %) affected at the lumbar spine and the ankle joint (17.4 vs 7 %). To our knowledge, this trial analyzes the largest cohort of elRG to date. Hence, it is clearly alluded that intensive training in RG is a significant factor causing more and stronger pain than in a CG.

78 FR 67206 - Qualification Tests for Safety-Related Actuators in Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-08

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0079] Qualification Tests for Safety-Related Actuators in..., ``Qualification Tests for Safety-Related Actuators in Nuclear Power Plants.'' This RG is being revised to provide... power plants. This RG is proposed Revision 1 of RG 1.73, ``Qualification Tests of Electric Valve...

78 FR 47011 - Software Unit Testing for Digital Computer Software Used in Safety Systems of Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-02

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0195] Software Unit Testing for Digital Computer Software... revised regulatory guide (RG), revision 1 of RG 1.171, ``Software Unit Testing for Digital Computer Software Used in Safety Systems of Nuclear Power Plants.'' This RG endorses American National Standards...

RG flows and bifurcations

DOE PAGES

Gukov, Sergei

2017-03-29

Interpreting RG flows as dynamical systems in the space of couplings we produce a variety of constraints, global (topological) as well as local. These constraints, in turn, rule out some of the proposed RG flows and also predict new phases and fixed points, surprisingly, even in familiar theories such as model, QED3, or QCD4.

Rare Gases Inserted into Biological Building Blocks: A Theoretical Study of Glycine - Rg Compounds (Rg-Xe, Kr, Ar)

NASA Technical Reports Server (NTRS)

Chaban, Galina M.

2005-01-01

Compounds formed by insertion of rare-gas atoms (Xe, Kr, and Ar) into glycine molecule are investigated using accurate ab initio computational methods. Identification of such insertion compounds may open new frontiers in the field of rare-gas chemistry, such as possible existence of biological molecules that include chemically bound rare gas atoms. The most stable glycine-Rg configuration is found to correspond to insertion of Rg atoms into the 0-H bond of glycine. These NH2CH2COORgH compounds are metastable , but separated by sizable potential barriers from the Rg + glycine dissociation products. Preliminary calculations show that NH2CH2COOXeH compound is energetically stable with respect to another (3-body) dissociation channel (NH2CH2COO + Rg + H), while the corresponding Ar species is not stable in this respect. The compound with the inserted Kr is a borderline case, with the 3-body dissociation products being close in energy to the NH2CH2COOKrH minimum.

Adsorption of rare gases on the C20 nanocage: a theoretical investigation

NASA Astrophysics Data System (ADS)

Rahimi, Rezvan; Kamalinahad, Saeedeh; Solimannejad, Mohammad

2018-03-01

The adsorption of rare gases (Rg) on the external surface of pristine and Sc-doped C20 (ScC19) nanocage is investigated using density functional theory (DFT). Also, time-dependent density functional theory (TD-DFT) and natural bond orbital (NBO) calculations are performed at the CAM-B3LYP/6-31G (d) level. The NBO analyses indicate that the adsorption of Rg molecules with studied nanocage significantly alters its electronic nature. Theoretical results have shown that Rg is weakly adsorbed on the pristine C20, so this nanocage cannot be a proper sensor for detecting and sensing rare gases. In order to improve properties of the nanocage as a promising sensor, Sc-doping process was investigated. The more negative adsorption energies (Eads) of Rg/ScC19 means that adsorption of Rg on the surface of ScC19 is energetically more favored than C20 and other nano-structures as reported in previous studies. It is expected that significant changes in the electronic properties caused by Rg may be used for designing new sensors for detection of rare gases.

Symposium on Electromagnetic Launcher Technology, 5th, Sandestin, FL, Apr. 3-5, 1990, Proceedings

NASA Astrophysics Data System (ADS)

Gooden, Clarence E.

1991-01-01

The present conference on electromagnetic accelerators (EMAs) and railguns (RGs) discusses active-current management for four-rail RGs, the design of a compulsator-drive 60-caliber RG, EMA studies with augmented rails, muzzle-shunt augmentation of conventional RGs, effect of in-bore gas on RG performance, the distributed-energy store RG, plasma diagnostics for high power ignitron development, a review of EMA armature research, RG hybrid armatures, a new solid-armature design concept, and the electrodynamics of RG plasma armatures. Also discussed is RG modeling at speed using three-dimensional finite elements, power supply technology for EMAs, rotating machine power supplies for next-generation EMAs, advanced EMA power supplies with magnetic-flux compression, metal-to-metal switches for large currents, lightweight high-effiency energy-storage transformers, hypervelocity projectile development for EMAs, structural design issues for EMA projectiles, stiff RGs, a reinforced Al conductor for cryogenic applications, mass-stabilized projectile designs for EMA launch, indictively-commutated coilguns, an actively switched pulsed induction accelerator, a plasma gun-augmented electrothermal accelerator, a symmetrical rail accelerator, and a travelling-wave synchronous coil gun.

A twin study of spatial and non-spatial delayed response performance in middle age.

PubMed

Kremen, William S; Mai, Tuan; Panizzon, Matthew S; Franz, Carol E; Blankfeld, Howard M; Xian, Hong; Eisen, Seth A; Tsuang, Ming T; Lyons, Michael J

2011-06-01

Delayed alternation and object alternation are classic spatial and non-spatial delayed response tasks. We tested 632 middle-aged male veteran twins on variants of these tasks in order to compare test difficulty, measure their inter-correlation, test order effects, and estimate heritabilities (proportion of observed variance due to genetic influences). Non-spatial alternation (NSA), which may involve greater reliance on processing of subgoals, was significantly more difficult than spatial alternation (SA). Despite their similarities, NSA and SA scores were uncorrelated. NSA performance was worse when administered second; there was no SA order effect. NSA scores were modestly heritable (h(2)=.25; 26); SA was not. There was shared genetic variance between NSA scores and general intellectual ability (r(g)=.55; .67), but this also suggests genetic influences specific to NSA. Compared with findings from small, selected control samples, high "failure" rates in this community-based sample raise concerns about interpretation of brain dysfunction in elderly or patient samples. Copyright © 2011 Elsevier Inc. All rights reserved.

Classification of pumpkin seed oils according to their species and genetic variety by attenuated total reflection Fourier-transform infrared spectroscopy.

PubMed

Saucedo-Hernández, Yanelis; Lerma-García, María Jesús; Herrero-Martínez, José Manuel; Ramis-Ramos, Guillermo; Jorge-Rodríguez, Elisa; Simí-Alfonso, Ernesto F

2011-04-27

Attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR), followed by multivariate treatment of the spectral data, was used to classify seed oils of the genus Cucurbita (pumpkins) according to their species as C. maxima, C. pepo, and C. moschata. Also, C. moschata seed oils were classified according to their genetic variety as RG, Inivit C-88, and Inivit C-2000. Up to 23 wavelength regions were selected on the spectra, each region corresponding to a peak or shoulder. The normalized absorbance peak areas within these regions were used as predictors. Using linear discriminant analysis (LDA), an excellent resolution among all categories concerning both Cucurbita species and C. moschata varieties was achieved. The proposed method was straightforward and quick and can be easily implemented. Quality control of pumpkin seed oils is important because Cucurbita species and genetic variety are both related to the pharmaceutical properties of the oils.

A Twin Study of Spatial and Non-Spatial Delayed Response Performance in Middle Age

PubMed Central

Kremen, William S.; Mai, Tuan; Panizzon, Matthew S.; Franz, Carol E.; Blankfeld, Howard M.; Xian, Hong; Eisen, Seth A.; Tsuang, Ming T.; Lyons, Michael J.

2011-01-01

Delayed alternation and object alternation are classic spatial and non-spatial delayed response tasks. We tested 632 middle-aged male veteran twins on variants of these tasks in order to compare test difficulty, measure their inter-correlation, test order effects, and estimate heritabilities (proportion of observed variance due to genetic influences). Non-spatial alternation (NSA), which may involve greater reliance on processing of subgoals, was significantly more difficult than spatial alternation (SA). Despite their similarities, NSA and SA scores were uncorrelated. NSA performance was worse when administered second; there was no SA order effect. NSA scores were modestly heritable (h2=.25; 26); SA was not. There was shared genetic variance between NSA scores and general intellectual ability (rg=.55; .67), but this also suggests genetic influences specific to NSA. Compared with findings from small, selected control samples, high “failure” rates in this community-based sample raise concerns about interpretation of brain dysfunction in elderly or patient samples. PMID:21477911

[Correlation of insulin-like growth factor-1 (IGF-1) to angiogenesis of breast cancer in IGF-1-deficient mice].

PubMed

Tang, Hong-Bo; Ren, Yu-Ping; Zhang, Jun; Ma, Shi-Hui; Gao, Feng; Wu, Yi-Ping

2007-11-01

Insulin-like growth factors (IGFs) play important roles in the development and progression of tumors. But the mechanism of tumorigenesis in relation to IGF-1 is unclear yet. This study was to explore the correlation of circulating IGF-1 level to the angiogenesis of breast cancer in IGF-1-deficient mice. The liver-specific IGF-1-deficient (LID) mice and control mice were injected with 7,12-dimethybenz(a)anthracene (DMBA) to develop breast cancer. Ginsenoside Rg3 was used to intervene tumor growth. The occurrence rates of breast cancer were compared. The expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) was detected by immunohistochemistry. The occurrence rate of breast cancer was 66.67% in untreated control mice, 33.33% in untreated LID mice, 36.00% in Rg3-treated control mice, and 12.00% in Rg3-treated LID mice. The tumor size was (0.79+/-0.20) cm in untreated control mice, (0.37+/-0.08) cm in untreated LID mice, (0.32+/-0.08) cm in Rg3-treated control mice, and (0.15+/-0.05) cm in Rg3-treated LID mice. The average light density and positive rate of VEGF were the highest in untreated control mice (0.34+/-0.10 and 0.04+/-0.02, P<0.05), and the lowest in Rg3-treated LID mice (0.13+/-0.03 and 0.01+/-0.00, P<0.05). The MVD was 31.9+/-5.3 in untreated control mice, 26.8+/-4.9 in untreated LID mice, 20.1+/-4.9 in Rg3-treated control mice, and 14.4+/-4.9 in Rg3-treated LID mice. Circulating IGF-1 plays a role in the onset and development of breast cancer. Degrading serum IGF-1 level could inhibit angiogenesis and growth of breast cancer. Rg3 could promote this effect.

Interaction Potentials for Br(2P) + Ar, Kr, Xe (1S) by the Crossed Molecular Beams Method.

DTIC Science & Technology

1981-03-01

recombination was significantly affected by eBr-RG" In their study, the interaction potential between Br and RG was assumed to be of the Lennard ... Jones (L-J) form with the following parameters: RG=Ar, c=1.0 kcal/mole, a=3.0 A; RG=Xe, e-1.0 kcal/mole, a=3.5 A. A slightly shallower Br-Ar potential ...AOA-A00 002 CALIFORNIA UNIV BERKELEY LAWRENCE BERKELEY LAB F/6 20/7 INTERACTION POTENTIALS FOR BR2P) + AR. KR. XE (IS) BY THE CROS--ETCfIU MAR 81 P

The effect of harvesting strategy of grass silage on digestion and nutrient supply in dairy cows.

PubMed

Kuoppala, K; Rinne, M; Ahvenjärvi, S; Nousiainen, J; Huhtanen, P

2010-07-01

This study examined the effects of primary growth (PG) and regrowth (RG) timothy-meadow fescue silages harvested at 2 stages of growth on feed intake, cell wall digestion and ruminal passage kinetics in lactating dairy cows. Four dairy cows equipped with rumen cannulas were used in a study designed as a 4 x 4 Latin square with 21-d periods. The experimental silages were offered ad libitum with 8 kg/d of concentrate. Ruminal digestion and passage kinetics were assessed by the rumen evacuation technique. Silages of PG were on average more digestible than RG silages. The concentration of neutral detergent fiber (NDF) and indigestible NDF (iNDF) increased and the concentration of digestible organic matter in dry matter (DM) of silages decreased with advancing maturity in PG and RG. Cows consumed more feed DM, energy, and protein and produced more milk when fed PG diets rather than RG diets. Delaying the harvest decreased DM intake and milk production in PG and RG. There were no differences between PG and RG in rumen pH, ammonia N, or total volatile fatty acid concentrations. The intake of N, omasal canal flow of total nonammonia N and microbial N, excretion of N in feces, and ruminal true digestibility of N were higher for PG than for RG diets. The efficiency of microbial N synthesis was not different between PG and RG. Intake and omasal canal flow of organic matter, NDF, and potentially digestible NDF (pdNDF) were higher in PG than in RG. Whole-diet digestibility of organic matter, NDF, or pdNDF in the rumen or in the total tract was not different between PG and RG despite the higher digestibility of PG silages measured in sheep. Rumen pool sizes of crude protein and iNDF were lower for PG diets, whereas the pool size of pdNDF was higher for PG diets than for RG diets. The rate of passage of iNDF was higher for PG diets than for RG diets, with no difference between them in rate of digestion or passage of pdNDF. The lower milk production in cows fed regrowth grass silages compared with primary growth silages could be attributed to the lower silage DM intake potential. Chemical composition of the silages, rumen fill, digestion and passage kinetics of NDF, or the ratio of protein to energy in absorbed nutrients could not explain the differences in DM intake between silages made from primary and regrowth grass. Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Localization of excitons by molecular layer formation in a polymer film

NASA Astrophysics Data System (ADS)

Chattopadhyay, S.; Datta, A.

2005-10-01

Spin coated films of atactic polystyrene of two different molecular weights have been studied with uv spectroscopy and x-ray reflectivity, the film thickness (d) varying from ˜2Rg to ˜12Rg where Rg is the unperturbed radius of gyration of the polymer. uv extinction due to the pure electronic singlet A1g1→E1u1 is seen to increase with d-1 for 4Rg⩽d⩽12Rg (region 1). This suggests excitonic interaction along d . The variation of total exciton energy (E) of the A1g→E1u singlet with d in region 1 can be well explained by formation of linear J -aggregates of polystyrene molecules, in a lattice with spacing “ a ” (in Å) Rg0 at d≃4Rg , where the exciton is still delocalized. Layering reduces the Hamaker constant (AH) , deciding the cohesive force, between the layers and this reduction, ΔAH , is found to be less than Ae at d⩾4Rg , where iAe/ℏ is the amplitude for exciton transfer between neighboring molecules in the excitonic lattice of region 1. On the other hand, ΔAH in region 2 starts from a value larger than Ae . This indicates that ΔAH acts as a barrier between the layer, which localizes the exciton within the layers.

Tailored liquid chromatography-mass spectrometry analysis improves the coverage of the intracellular metabolome of HepaRG cells.

PubMed

Cuykx, Matthias; Negreira, Noelia; Beirnaert, Charlie; Van den Eede, Nele; Rodrigues, Robim; Vanhaecke, Tamara; Laukens, Kris; Covaci, Adrian

2017-03-03

Metabolomics protocols are often combined with Liquid Chromatography-Mass Spectrometry (LC-MS) using mostly reversed phase chromatography coupled to accurate mass spectrometry, e.g. quadrupole time-of-flight (QTOF) mass spectrometers to measure as many metabolites as possible. In this study, we optimised the LC-MS separation of cell extracts after fractionation in polar and non-polar fractions. Both phases were analysed separately in a tailored approach in four different runs (two for the non-polar and two for the polar-fraction), each of them specifically adapted to improve the separation of the metabolites present in the extract. This approach improves the coverage of a broad range of the metabolome of the HepaRG cells and the separation of intra-class metabolites. The non-polar fraction was analysed using a C18-column with end-capping, mobile phase compositions were specifically adapted for each ionisation mode using different co-solvents and buffers. The polar extracts were analysed with a mixed mode Hydrophilic Interaction Liquid Chromatography (HILIC) system. Acidic metabolites from glycolysis and the Krebs cycle, together with phosphorylated compounds, were best detected with a method using ion pairing (IP) with tributylamine and separation on a phenyl-hexyl column. Accurate mass detection was performed with the QTOF in MS-mode only using an extended dynamic range to improve the quality of the dataset. Parameters with the greatest impact on the detection were the balance between mass accuracy and linear range, the fragmentor voltage, the capillary voltage, the nozzle voltage, and the nebuliser pressure. By using a tailored approach for the intracellular HepaRG metabolome, consisting of three different LC techniques, over 2200 metabolites can be measured with a high precision and acceptable linear range. The developed method is suited for qualitative untargeted LC-MS metabolomics studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of ginseng saponins on the recombinant serotonin type 3A receptor expressed in xenopus oocytes: implication of possible application as an antiemetic.

PubMed

Min, Kyeong T; Koo, Bon N; Kang, Jeong W; Bai, Sun Joon; Ko, Sung R; Cho, Zang-Hee

2003-08-01

Nausea and vomiting are the most frequently reported side-effects by patients who are given general anesthesia perioperatively and patients with cancer who undergo chemotherapy or radiotherapy. Serotonin (5-hydroxytryptamine, 5HT) type 3A receptor (5HT(3A) receptor) is known to mediate nausea and vomiting and its antagonists have been used effectively to prevent and/or reduce the incidence and severity of nausea and vomiting. However, the adverse effects on cardiac function, such as QT interval prolongation, limit their routine use by these patients. This study was designed to elucidate the effect of ginseng saponins on the recombinant 5HT(3A) receptor expressed in the xenopus oocyte. After in vitro transcription of the recombinant human 5HT(3A) receptor in the Xenopus laevis oocyte, we examined Panax ginseng saponins (total saponin [TS], panaxadiol saponin [PD] fraction, panaxatriol saponin [PT] fraction, and ginsenoside-Rb1 and -Rg1) for their ability to inhibit current flow through the 5HT(3A) receptor using the voltage-clamp technique. All saponin fractions (TS, PD, PT fraction, as well as ginsenoside-Rb1 and -Rg1) inhibited the peak current induced by the agonist 5HT on the 5HT(3A) receptor in a concentration-dependent, reversible, and voltage-independent manner. The PT fraction inhibited 5HT-induced currents in 5HT(3A) receptor more than the PD fraction; meanwhile, there was a similar degree of inhibition between ginsenoside-Rg1 and -Rb1, the main substitutes of PT fraction and PD saponin fractions, respectively. These results indicate that ginseng saponins, especially PT fraction, have substantial inhibitory effects on the recombinant 5HT(3A) receptor, suggesting that some of the specific types of ginsenoside might have an antagonistic action against 5HT(3A) receptor related to nausea and vomiting.

Structure and biological activity of protopanaxatriol-type saponins from the roots of Panax notoginseng.

PubMed

Sun, Hongxiang; Yang, Zhigang; Ye, Yiping

2006-01-01

The further purification of the total saponins from the roots of Panax notoginseng by using ordinary and reversed-phase silica-gel, as well as Sephadex LH-20 chromatography afford seven adjuvant active protopanaxatriol-type saponins (PTS), ginsenosides-Rh1 (Rh1),-Rh4 (Rh4),-Rg1 (Rg1),-Re (Re), notoginsenosides-R1 (R1),-R2 (R2),-U (U). These saponins were evaluated for their haemolytic activities and adjuvant potentials on the cellular and humoral immune responses of ICR mice against ovalbumin (OVA). The effect of the substitution pattern of these PTS on their biological activities was investigated and structure-activity relationships were established. Among seven PTS, the haemolytic activity of Rh1 was higher than that of other six compounds (p<0.001) The HD50 values of Rh4 and U were significantly bigger than those of R2, Rg1 and Re (p<0.05 or p<0.01). Seven PTS could significantly increase the concanavalin A (Con A)-, lipopolysaccharide (LPS)- and OVA-induced splenocyte proliferation in the OVA-immunized mice (p<0.01 or p<0.001). The OVA-specific IgG, IgG1, IgG2a and IgG2b antibody levels in serum were also significantly enhanced by seven PTS compared with OVA control group (p<0.01 or p<0.001). The structure-activity relationship studies suggested that the number, the length and the position of sugar side chains, and the type of glucosyl group in the structure of PTS could not only affect their haemolytic activities and adjuvant potentials, but have significant effects on the nature of the immune responses. The information about this structure/function relationship might be useful for developing semisynthetic tetracyclic triterpenoid saponin derivatives with immunological adjuvant activity, as well as a reference to the distribution of the functional groups composing the saponin molecule.

Biotransformation of ginsenosides F4 and Rg6 in zebrafish.

PubMed

Shen, Wen-Wen; Zhang, Hai-Xia; Qiu, Shou-Bei; Wei, Ying-Jie; Zhu, Fen-Xia; Wang, Jing; Wang, Dan-Dan; Jia, Xiao-Bin; Tang, Dao-Quan; Chen, Bin

2017-03-28

Ginsenosides F 4 and Rg 6 (GF 4 and GRg 6 ), two main active components of steamed notoginseng or red ginseng, are dehydrated disaccharide saponins. In this work, biotransformation of ginsenosides F 4 and Rg 6 in zebrafish was investigated by qualitatively identifying their metabolites and then proposing their possible metabolic pathways. The prediction of possible metabolism of ginsenosides F 4 and Rg 6 using zebrafish model which can effectively simulate existing mammals model was early and quickly performed. Metabolites of ginsenosides F 4 and Rg 6 after exposing to zebrafish for 24 h were identified by Ultraperformance Liquid Chromatography/Quadrupole-Time-of-Flight Mass Spectrometry. A total of 8 and 6 metabolites of ginsenosides F 4 and Rg 6 were identified in zebrafish, respectively. Of these, 7 and 5, including M1, M3-M5, M7-M9 and N1 (N5), N2, N4 (N9), N7-N8 were reported for the first time as far as we know. The mechanisms of their biotransformation involved were further deduced to be desugarization, glucuronidation, sulfation, dehydroxylation, loss of C-17 and/or C-23 residue pathways. It was concluded that loss of rhamnose at position C-6 and glucuronidation at position C-3 in zebrafish were considered as the main physiologic and metabolic processes of ginsenosides F 4 and ginsenosides Rg 6 , respectively.

Slowly switching between environments facilitates reverse evolution in small populations.

PubMed

Tan, Longzhi; Gore, Jeff

2012-10-01

Natural populations must constantly adapt to ever-changing environmental conditions. A particularly interesting question is whether such adaptations can be reversed by returning the population to an ancestral environment. Such evolutionary reversals have been observed in both natural and laboratory populations. However, the factors that determine the reversibility of evolution are still under debate. The time scales of environmental change vary over a wide range, but little is known about how the rate of environmental change influences the reversibility of evolution. Here, we demonstrate computationally that slowly switching between environments increases the reversibility of evolution for small populations that are subject to only modest clonal interference. For small populations, slow switching reduces the mean number of mutations acquired in a new environment and also increases the probability of reverse evolution at each of these "genetic distances." As the population size increases, slow switching no longer reduces the genetic distance, thus decreasing the evolutionary reversibility. We confirm this effect using both a phenomenological model of clonal interference and also a Wright-Fisher stochastic simulation that incorporates genetic diversity. Our results suggest that the rate of environmental change is a key determinant of the reversibility of evolution, and provides testable hypotheses for experimental evolution. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

NF-κB and JNK mediated apoptosis and G0/G1 arrest of HeLa cells induced by rubiarbonol G, an arborinane-type triterpenoid from Rubia yunnanensis.

PubMed

Zeng, Guang-Zhi; Wang, Zhe; Zhao, Li-Mei; Fan, Jun-Ting; Tan, Ning-Hua

2018-06-28

Rubia yunnanensis is a medicinal plant mainly grown in Yunnan province in Southwest China, and its root named "Xiaohongshen" has been used as a herb in Yunnan for the treatment of cancers. Three major types of chemical components, Rubiaceae-type cyclopeptides, quinones, and triterpenoids, were identified from R. yunnanensis, in which some of compounds including rubiarbonol G (RG), a unique arboriane-type triterpenoid, showed cytotoxicity on cancer cells. But the cytotoxic mechanism of RG has not been reported. To investigate the cytotoxic mechanism of RG on cancer cells. RG was evaluated its cytotoxicity on 7 cancer cell lines by the SRB assay, and detected the effect on apoptosis and cell cycle arrest by Annexin V-FITC/PI apoptosis assay and DNA contents analysis. The expression and activity of apoptosis and cell cycle related proteins were also investigated by western blot and caspase activity assay. Furthermore, the effect of RG on NF-κB signaling was also tested by luciferase assay, western blot, and immunofluorescence staining. RG showed potent cytotoxicity on 7 human cancer cell lines, whose activity was attributed to apoptosis induction and G 0 /G 1 arrest in HeLa cells. Results from the mechanism study showed that RG promoted the activation of ERK1/2 and JNK pathway in MAPK family, which in turn increased the expression of p53, thereby triggering the G 0 /G 1 arrest through p53/p21/cyclin D1 signaling. Moreover, RG-mediated JNK activation down-regulated the expression of the anti-apoptotic protein Bcl-2, which caused the release of cytochrome c to the cytosol and activated the cleavage of caspase cascade and poly(ADP-ribose) polymerase, thereby inducing apoptosis in HeLa cells. In addition, RG was also found to inhibit the activation of NF-κB signaling by down-regulating the expression and attenuating the translocation to nucleus of NF-κB p65, by which the down-stream p53, cyclin D1, Bcl-2, and caspases were regulated, thereby triggering apoptosis and G 0 /G 1 arrest in HeLa cells. These results indicated that RG induces mitochondria-mediated apoptosis and G 0 /G 1 cell cycle arrest by activation of JNK signaling as well as inactivation of NF-κB pathway in HeLa cells, which suggests that RG is one of the key active ingredients accounting for the anti-tumor effect of R. yunnanensis. Copyright © 2017 Elsevier B.V. All rights reserved.

Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci.

PubMed

Jones, Samuel E; Tyrrell, Jessica; Wood, Andrew R; Beaumont, Robin N; Ruth, Katherine S; Tuke, Marcus A; Yaghootkar, Hanieh; Hu, Youna; Teder-Laving, Maris; Hayward, Caroline; Roenneberg, Till; Wilson, James F; Del Greco, Fabiola; Hicks, Andrew A; Shin, Chol; Yun, Chang-Ho; Lee, Seung Ku; Metspalu, Andres; Byrne, Enda M; Gehrman, Philip R; Tiemeier, Henning; Allebrandt, Karla V; Freathy, Rachel M; Murray, Anna; Hinds, David A; Frayling, Timothy M; Weedon, Michael N

2016-08-01

Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases, particularly obesity and type 2 diabetes, but until recently, little was known about the genetic factors influencing these heritable traits. We performed genome-wide association studies of self-reported chronotype (morning/evening person) and self-reported sleep duration in 128,266 white British individuals from the UK Biobank study. Sixteen variants were associated with chronotype (P<5x10-8), including variants near the known circadian rhythm genes RGS16 (1.21 odds of morningness, 95% CI [1.15, 1.27], P = 3x10-12) and PER2 (1.09 odds of morningness, 95% CI [1.06, 1.12], P = 4x10-10). The PER2 signal has previously been associated with iris function. We sought replication using self-reported data from 89,283 23andMe participants; thirteen of the chronotype signals remained associated at P<5x10-8 on meta-analysis and eleven of these reached P<0.05 in the same direction in the 23andMe study. We also replicated 9 additional variants identified when the 23andMe study was used as a discovery GWAS of chronotype (all P<0.05 and meta-analysis P<5x10-8). For sleep duration, we replicated one known signal in PAX8 (2.6 minutes per allele, 95% CI [1.9, 3.2], P = 5.7x10-16) and identified and replicated two novel associations at VRK2 (2.0 minutes per allele, 95% CI [1.3, 2.7], P = 1.2x10-9; and 1.6 minutes per allele, 95% CI [1.1, 2.2], P = 7.6x10-9). Although we found genetic correlation between chronotype and BMI (rG = 0.056, P = 0.05); undersleeping and BMI (rG = 0.147, P = 1x10-5) and oversleeping and BMI (rG = 0.097, P = 0.04), Mendelian Randomisation analyses, with limited power, provided no consistent evidence of causal associations between BMI or type 2 diabetes and chronotype or sleep duration. Our study brings the total number of loci associated with chronotype to 22 and with sleep duration to three, and provides new insights into the biology of sleep and circadian rhythms in humans.

Influence of stimulus size on revealing non-cardinal color mechanisms.

PubMed

Gunther, Karen L; Downey, Colin O

2016-10-01

Multiple studies have shown that performance of subjects on a number of visual tasks is worse for non-cardinal than cardinal colors, especially in the red-green/luminance (RG/LUM) and tritan/luminance (TRIT/LUM) color planes. Inspired by neurophysiological evidence that suppressive surround input to receptive fields is particularly sensitive to luminance, we hypothesized that non-cardinal mechanisms in the RG/LUM and TRIT/LUM planes would be more sensitive to stimulus size than are isoluminant non-cardinal mechanisms. In Experiment 1 we tested 9-10 color-normal subjects in each of the three color planes (RG/TRIT, RG/LUM, and TRIT/LUM) on visual search at four bull's-eye dot sizes (0.5°/1°, 1°/2°, 2°/4°, and 3°/6° center/annulus dot diameter). This study yielded a significant main effect of dot size in each of the three color planes. In Experiment 2 we tested the same hypothesis using noise masking, at three stimulus sizes (3°, 6° and 9° diameter Gabors), again in all three color planes (5 subjects per color plane). This experiment yielded, in the RG/TRIT plane, a significant main effect of stimulus size; in the RG/LUM plane, significant evidence for non-cardinal mechanisms only for the 9° stimulus; but in the TRIT/LUM plane no evidence for non-cardinal mechanisms at any stimulus size. These results suggest that non-cardinal mechanisms, particularly in the RG/LUM color plane, are more sensitive to stimulus size than are non-cardinals in the RG/TRIT plane, supporting our hypothesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

D-Amino acid oxidase bio-functionalized platforms: Toward an enhanced enzymatic bio-activity

NASA Astrophysics Data System (ADS)

Herrera, Elisa; Valdez Taubas, Javier; Giacomelli, Carla E.

2015-11-01

The purpose of this work is to study the adsorption process and surface bio-activity of His-tagged D-amino acid oxidase (DAAO) from Rhodotorula gracilis (His6-RgDAAO) as the first step for the development of an electrochemical bio-functionalized platform. With such a purpose this work comprises: (a) the His6-RgDAAO bio-activity in solution determined by amperometry, (b) the adsorption mechanism of His6-RgDAAO on bare gold and carboxylated modified substrates in the absence (substrate/COO-) and presence of Ni(II) (substrate/COO- + Ni(II)) determined by reflectometry, and (c) the bio-activity of the His6-RgDAAO bio-functionalized platforms determined by amperometry. Comparing the adsorption behavior and bio-activity of His6-RgDAAO on these different solid substrates allows understanding the contribution of the diverse interactions responsible for the platform performance. His6-RgDAAO enzymatic performance in solution is highly improved when compared to the previously used pig kidney (pk) DAAO. His6-RgDAAO exhibits an amperometrically detectable bio-activity at concentrations as low as those expected on a bio-functional platform; hence, it is a viable bio-recognition element of D-amino acids to be coupled to electrochemical platforms. Moreover, His6-RgDAAO bio-functionalized platforms exhibit a higher surface activity than pkDAAO physically adsorbed on gold. The platform built on Ni(II) modified substrates present enhanced bio-activity because the surface complexes histidine-Ni(II) provide with site-oriented, native-like enzymes. The adsorption mechanism responsible of the excellent performance of the bio-functionalized platform takes place in two steps involving electrostatic and bio-affinity interactions whose prevalence depends on the degree of surface coverage.

Ginsenoside Rg3 Inhibits Melanoma Cell Proliferation through Down-Regulation of Histone Deacetylase 3 (HDAC3) and Increase of p53 Acetylation

PubMed Central

Shan, Xiu; Fu, Yuan-Shan; Aziz, Faisal; Wang, Xiao-Qi; Yan, Qiu; Liu, Ji-Wei

2014-01-01

Malignant melanoma is an aggressive and deadly form of skin cancer, and despite recent advances in available therapies, is still lacking in completely effective treatments. Rg3, a monomer extracted from ginseng roots, has been attempted for the treatment of many cancers. It is reported that the expressions of histone deacetylase 3 (HDAC3) and p53 acetylation correlate with tumor cell growth. However, the antitumor effect of Rg3 on melanoma and the mechanism by which it regulates HDAC3 expression and p53 acetylation remain unknown. We found high expression of HDAC3 in human melanoma tissues to be significantly correlated to lymph node metastasis and clinical stage of disease (p<0.05). In melanoma cells, Rg3 inhibited cell proliferation and induced G0/G1 cell cycle arrest. Rg3 also decreased the expression of HDAC3 and increased the acetylation of p53 on lysine (k373/k382). Moreover, suppression of HDAC3 by either siRNA or a potent HDAC3 inhibitor (MS-275) inhibited cell proliferation, increased p53 acetylation and transcription activity. In A375 melanoma xenograft studies, we demonstrated that Rg3 and HDAC3 short hairpin RNA (shHDAC3) inhibited the growth of xenograft tumors with down-regulation of HDAC3 expression and up-regulation of p53 acetylation. In conclusion, Rg3 has antiproliferative activity against melanoma by decreasing HDAC3 and increasing acetylation of p53 both in vitro and in vivo. Thus, Rg3 serves as a potential therapeutic agent for the treatment of melanoma. PMID:25521755

Binding interaction between rice glutelin and amylose: Hydrophobic interaction and conformational changes.

PubMed

Xu, Xingfeng; Liu, Wei; Zhong, Junzhen; Luo, Liping; Liu, Chengmei; Luo, Shunjing; Chen, Lin

2015-11-01

The interaction of rice glutelin (RG) with amylose was characterized by spectroscopic and molecular docking studies. The intrinsic fluorescence of RG increased upon the addition of amylose. The binding sites, binding constant and thermodynamic features indicated that binding process was spontaneous and the main driving force of the interaction was hydrophobic interaction. The surface hydrophobicity of RG decreased with increasing amount of amylose. Furthermore, synchronous fluorescence and circular dichroism (CD) spectra provided data concerning conformational and micro-environmental changes of RG. With the concentration of amylose increasing, the polarity around the tyrosine residues increased while the hydrophobicity decreased. Alteration of protein conformation was observed with increasing of α-helix and reducing of β-sheet. Finally, a visual representation of two binding sites located in the amorphous area of RG was presented by molecular modeling studies. Copyright © 2015 Elsevier B.V. All rights reserved.

Bouncing and emergent cosmologies from Arnowitt–Deser–Misner RG flows

NASA Astrophysics Data System (ADS)

Bonanno, Alfio; Gionti, S. J. Gabriele; Platania, Alessia

2018-03-01

Asymptotically safe gravity provides a framework for the description of gravity from the trans-Planckian regime to cosmological scales. According to this scenario, the cosmological constant and Newton’s coupling are functions of the energy scale whose evolution is dictated by the renormalization group (RG) equations. The formulation of the RG equations on foliated spacetimes, based on the Arnowitt–Deser–Misner (ADM) formalism, furnishes a natural way to construct the RG energy scale from the spectrum of the Laplacian operator on the spatial slices. Combining this idea with an RG improvement procedure, in this work we study quantum gravitational corrections to the Einstein–Hilbert action on Friedmann–Lemaître–Robertson–Walker backgrounds. The resulting quantum-corrected Friedmann equations can give rise to both bouncing cosmologies and emergent Universe solutions. Our bouncing models do not require the presence of exotic matter and emergent Universe solutions can be constructed for any allowed topology of the spatial slices.

Ab initio correlated calculations of rare-gas dimer quadrupoles

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

Donchev, Alexander G.

2007-10-15

This paper reports ab initio calculations of rare gas (RG=Kr, Ar, Ne, and He) dimer quadrupoles at the second order of Moeller-Plesset perturbation theory (MP2). The study reveals the crucial role of the dispersion contribution to the RG{sub 2} quadrupole in the neighborhood of the equilibrium dimer separation. The magnitude of the dispersion quadrupole is found to be much larger than that predicted by the approximate model of Hunt. As a result, the total MP2 quadrupole moment is significantly smaller than was assumed in virtually all previous related studies. An analytical model for the distance dependence of the RG{sub 2}more » quadrupole is proposed. The model is based on the effective-electron approach of Jansen, but replaces the original Gaussian approximation to the electron density in an RG atom by an exponential one. The role of the nonadditive contribution in RG{sub 3} quadrupoles is discussed.« less

The role of conduct disorder in the relationship between alcohol, nicotine and cannabis use disorders.

PubMed

Grant, J D; Lynskey, M T; Madden, P A F; Nelson, E C; Few, L R; Bucholz, K K; Statham, D J; Martin, N G; Heath, A C; Agrawal, A

2015-12-01

Genetic influences contribute significantly to co-morbidity between conduct disorder and substance use disorders. Estimating the extent of overlap can assist in the development of phenotypes for genomic analyses. Multivariate quantitative genetic analyses were conducted using data from 9577 individuals, including 3982 complete twin pairs and 1613 individuals whose co-twin was not interviewed (aged 24-37 years) from two Australian twin samples. Analyses examined the genetic correlation between alcohol dependence, nicotine dependence and cannabis abuse/dependence and the extent to which the correlations were attributable to genetic influences shared with conduct disorder. Additive genetic (a(2) = 0.48-0.65) and non-shared environmental factors explained variance in substance use disorders. Familial effects on conduct disorder were due to additive genetic (a(2) = 0.39) and shared environmental (c(2) = 0.15) factors. All substance use disorders were influenced by shared genetic factors (rg = 0.38-0.56), with all genetic overlap between substances attributable to genetic influences shared with conduct disorder. Genes influencing individual substance use disorders were also significant, explaining 40-73% of the genetic variance per substance. Among substance users in this sample, the well-documented clinical co-morbidity between conduct disorder and substance use disorders is primarily attributable to shared genetic liability. Interventions targeted at generally reducing deviant behaviors may address the risk posed by this shared genetic liability. However, there is also evidence for genetic and environmental influences specific to each substance. The identification of these substance-specific risk factors (as well as potential protective factors) is critical to the future development of targeted treatment protocols.

78 FR 30935 - Notice of Lodging of Proposed Settlement Under the Clean Air Act, the Clean Water Act, and the...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-23

... Steel Sparrows Point, LLC; RG Steel Warren, LLC; and RG Steel Wheeling, LLC. Specifically, the... in the amount of $8,431 in connection with EPA's claim that RG Steel Sparrows Point is liable for... its former facility located in Sparrows Point, Maryland. The publication of this notice opens a period...

Predicted NMR properties of noble gas hydride cations RgH +

NASA Astrophysics Data System (ADS)

Cukras, Janusz; Sadlej, Joanna

2008-12-01

The NMR shielding constants and, for the first time, the spin-spin coupling constants of Rg and H in RgH + compounds for Rg = Ne, Ar, Kr, Xe have been investigated by non-relativistic Hartree-Fock (HF) and relativistic Dirac-Hartree-Fock (DHF) methods. Electron-correlation effects have been furthermore calculated using SOPPA and CCSD at the non-relativistic level. The correlation effects are large on both parameters and opposite to the relativistic effects. The results indicate that both the relativistic and correlation effects need to be taken into account in a quantitative computations, especially in the case of the spin-spin coupling constants.

Enhanced adsorptive removal of p-nitrophenol from water by aluminum metal-organic framework/reduced graphene oxide composite

NASA Astrophysics Data System (ADS)

Wu, Zhibin; Yuan, Xingzhong; Zhong, Hua; Wang, Hou; Zeng, Guangming; Chen, Xiaohong; Wang, Hui; Zhang, Lei; Shao, Jianguang

2016-05-01

In this study, the composite of aluminum metal-organic framework MIL-68(Al) and reduced graphene oxide (MA/RG) was synthesized via a one-step solvothermal method, and their performances for p-nitrophenol (PNP) adsorption from aqueous solution were systematically investigated. The introduction of reduced graphene oxide (RG) into MIL-68(Al) (MA) significantly changes the morphologies of the MA and increases the surface area. The MA/RG-15% prepared at RG-to-MA mass ratio of 15% shows a PNP uptake rate 64% and 123% higher than MIL-68(Al) and reduced graphene oxide (RG), respectively. The hydrogen bond and π - π dispersion were considered to be the major driving force for the spontaneous and endothermic adsorption process for PNP removal. The adsorption kinetics, which was controlled by film-diffusion and intra-particle diffusion, was greatly influenced by solution pH, ionic strength, temperature and initial PNP concentration. The adsorption kinetics and isotherms can be well delineated using pseudo-second-order and Langmuir equations, respectively. The presence of phenol or isomeric nitrophenols in the solution had minimal influence on PNP adsorption by reusable MA/RG composite.

Biotransformation of ginsenoside Rb1 to ginsenoside Rg3 by endophytic bacterium Burkholderia sp. GE 17-7 isolated from Panax ginseng.

PubMed

Fu, Y; Yin, Z-H; Yin, C-Y

2017-06-01

To isolate a novel endophytic bacterium from Panax ginseng that could have excellent properties in converting ginsenoside Rb1 to ginsenoside Rg3. Based on a 16S rDNA gene sequence, the strain named GE 17-7 was identified as Burkholderia sp. This strain has shown the highest activity in converting ginsenoside Rb1 to 20(S)-ginsenoside Rg3. During the biotransformation of ginsenoside Rb1, the final metabolite was identified by nuclear magnetic resonance analysis and the transformation pathway of ginsenoside Rb1 was also identified by thin-layer chromatography and high performance liquid chromatography analysis in this study. We have successfully isolated a β-glucosidase-producing endophytic bacterium GE 17-7 from P. ginseng. Ginsenoside Rg3 was produced by strain GE 17-7 from ginsenoside Rb1 via ginsenoside Rd. This is the first report of the conversion of major ginsenoside Rb1 into minor ginsenoside Rg3 by fermentation with Burkholderia sp. endophytic bacteria in P. ginseng. These results suggest a new preparation method for ginsenoside Rg3 using strain GE 17-7 in the pharmaceutical industry. © 2017 The Society for Applied Microbiology.

Enhanced adsorptive removal of p-nitrophenol from water by aluminum metal–organic framework/reduced graphene oxide composite

PubMed Central

Wu, Zhibin; Yuan, Xingzhong; Zhong, Hua; Wang, Hou; Zeng, Guangming; Chen, Xiaohong; Wang, Hui; zhang, Lei; Shao, Jianguang

2016-01-01

In this study, the composite of aluminum metal–organic framework MIL-68(Al) and reduced graphene oxide (MA/RG) was synthesized via a one–step solvothermal method, and their performances for p–nitrophenol (PNP) adsorption from aqueous solution were systematically investigated. The introduction of reduced graphene oxide (RG) into MIL-68(Al) (MA) significantly changes the morphologies of the MA and increases the surface area. The MA/RG-15% prepared at RG-to-MA mass ratio of 15% shows a PNP uptake rate 64% and 123% higher than MIL-68(Al) and reduced graphene oxide (RG), respectively. The hydrogen bond and π – π dispersion were considered to be the major driving force for the spontaneous and endothermic adsorption process for PNP removal. The adsorption kinetics, which was controlled by film–diffusion and intra–particle diffusion, was greatly influenced by solution pH, ionic strength, temperature and initial PNP concentration. The adsorption kinetics and isotherms can be well delineated using pseudo–second–order and Langmuir equations, respectively. The presence of phenol or isomeric nitrophenols in the solution had minimal influence on PNP adsorption by reusable MA/RG composite. PMID:27181188

Simultaneous determination of 30 ginsenosides in Panax ginseng preparations using ultra performance liquid chromatography

PubMed Central

Park, Hee-Won; In, Gyo; Han, Sung-Tai; Lee, Myoung-Woo; Kim, So-Young; Kim, Kyung-Tack; Cho, Byung-Goo; Han, Gyeong-Ho; Chang, Il-Moo

2013-01-01

A quick and simple method for simultaneous determination of the 30 ginsenosides (ginsenoside Ro, Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, 20(S)-Rg2, 20(R)-Rg2, 20(S)-Rg3, 20(R)-Rg3, 20(S)-Rh1, 20(S)-Rh2, 20(R)-Rh2, F1, F2, F4, Ra1, Rg6, Rh4, Rk3, Rg5, Rk1, Rb3, Rk2, Rh3, compound Y, compound K, and notoginsenoside R1) in Panax ginseng preparations was developed and validated by an ultra performance liquid chromatography photo diode array detector. The separation of the 30 ginsenosides was efficiently undertaken on the Acquity BEH C-18 column with gradient elution with phosphoric acids. Especially the chromatogram of the ginsenoside Ro was dramatically enhanced by adding phosphoric acid. Under optimized conditions, the detection limits were 0.4 to 1.7 mg/L and the calibration curves of the peak areas for the 30 ginsenosides were linear over three orders of magnitude with a correlation coefficients greater than 0.999. The accuracy of the method was tested by a recovery measurement of the spiked samples which yielded good results of 89% to 118%. From these overall results, the proposed method may be helpful in the development and quality of P. ginseng preparations because of its wide range of applications due to the simultaneous analysis of many kinds of ginsenosides. PMID:24235860

Chemical dampening of Ly6C(hi) monocytes in the periphery produces anti-depressant effects in mice.

PubMed

Zheng, Xiao; Ma, Sijing; Kang, An; Wu, Mengqiu; Wang, Lin; Wang, Qiong; Wang, Guangji; Hao, Haiping

2016-01-19

The involvement of systemic immunity in depression pathogenesis promises a periphery-targeting paradigm in novel anti-depressant discovery. However, relatively little is known about druggable targets in the periphery for mental and behavioral control. Here we report that targeting Ly6C(hi) monocytes in blood can serve as a strategy for anti-depressant purpose. A natural compound, ginsenoside Rg1 (Rg1), was firstly validated as a periphery-restricted chemical probe. Rg1 selectively suppressed Ly6C(hi) monocytes recruitment to the inflamed mice brain. The proinflammatory potential of Ly6C(hi) monocytes to activate astrocytes was abrogated by Rg1, which led to a blunted feedback release of CCL2 to recruit the peripheral monocytes. In vitro study demonstrated that Rg1 pretreatment on activated THP-1 monocytes retarded their ability to trigger CCL2 secretion from co-cultured U251 MG astrocytes. CCL2-triggered p38/MAPK and PI3K/Akt activation were involved in the action of Rg1. Importantly, in mice models, we found that dampening Ly6C(hi) monocytes at the periphery ameliorated depression-like behavior induced by neuroinflammation or chronic social defeat stress. Together, our work unravels that blood Ly6C(hi) monocytes may serve as the target to enable remote intervention on the depressed brain, and identifies Rg1 as a lead compound for designing drugs targeting peripheral CCL2 signals.

Shear wave velocity models retrieved using Rg wave dispersion data in shallow crust in some regions of southern Ontario, Canada

NASA Astrophysics Data System (ADS)

Ma, Shutian; Motazedian, Dariush; Corchete, Victor

2013-04-01

Many crucial tasks in seismology, such as locating seismic events and estimating focal mechanisms, need crustal velocity models. The velocity models of shallow structures are particularly important in the simulation of ground motions. In southern Ontario, Canada, many small shallow earthquakes occur, generating high-frequency Rayleigh ( Rg) waves that are sensitive to shallow structures. In this research, the dispersion of Rg waves was used to obtain shear-wave velocities in the top few kilometers of the crust in the Georgian Bay, Sudbury, and Thunder Bay areas of southern Ontario. Several shallow velocity models were obtained based on the dispersion of recorded Rg waves. The Rg waves generated by an m N 3.0 natural earthquake on the northern shore of Georgian Bay were used to obtain velocity models for the area of an earthquake swarm in 2007. The Rg waves generated by a mining induced event in the Sudbury area in 2005 were used to retrieve velocity models between Georgian Bay and the Ottawa River. The Rg waves generated by the largest event in a natural earthquake swarm near Thunder Bay in 2008 were used to obtain a velocity model in that swarm area. The basic feature of all the investigated models is that there is a top low-velocity layer with a thickness of about 0.5 km. The seismic velocities changed mainly within the top 2 km, where small earthquakes often occur.

Methane production and methanogen levels in steers that differ in residual gain.

PubMed

Freetly, H C; Lindholm-Perry, A K; Hales, K E; Brown-Brandl, T M; Kim, M; Myer, P R; Wells, J E

2015-05-01

Methane (CH4) gas released by cattle isa product of fermentation in the digestive tract. The 2 primary sites of CH4 production in ruminants are the reticulum-rumen complex and the cecum. Methane release from cattle represents a 2% to 12% loss of the energy intake. Reducing the proportion of feed energy lost as CH4 has the potential of improving feed efficiency as well as decreasing the contribution of cattle to greenhouse gas production. Feed intake and growth were measured on 132 fall-born steers for 70 d. Seven steers with extreme positive residual gain (RG) and 7 steers with extreme negative RG whose DMI was within 0.32 SD of the mean intake were selected for subsequent measurements. Enteric CH4 production was measured via indirect calorimetry. Rumen, cecum, and rectal contents were obtained from steers at slaughter for measurement of in vitro CH4 production and methanogen 16S rRNA levels. Enteric CH4 production did not differ (P = 0.11) between the positive RG (112 ± 13 L/d)and the negative RG (74 ± 13 L/d) steers. In vitro rumen methane production did not differ between positive RG(64.26 × 10(-5) ± 10.85 × 10(-5) mmol∙g(-1) DM∙min(-1)) and negative RG (61.49 × 10(-5) ± 10.85 × 10(-5) mmol∙g(-1)DM∙min(-1); P = 0.86). In vitro cecum methane production did not differ between positive RG (4.24 ×10(-5) ± 1.90 × 10(-5) mmol∙g(-1) DM∙min(-1)) and negative RG (4.35 × 10(-5) ± 1.90 × 10(-5) mmol∙g(-1) DM∙min(-1); P = 0.97). Methanogen 16S rRNA as a percentage of the total bacteria16S rRNA did not differ between RG groups (P = 0.18). The methanogen 16S rRNA as a percentage of rumen fluid total bacteria 16S rRNA (5.3% ±3.1%) did not differ from the methanogen 16S rRNA asa percentage of cecum content total bacteria 16S rRNA(11.8% ± 3.1%; P = 0.14). The methanogen 16S rRNA as a percentage of the rectum content total bacteria 16SrRNA (0.7% ± 3.1%) was not different from the rumen content (P = 0.29) but was less than the cecum content(P = 0.01). Methanomicrobiales 16S rRNA as a percentage of total methanogen 16S rRNA did not differ across sample sites (P = 0.81); however, steers with positive RG (10.5% ± 1.6%) were more numerous than steers with negative RG (5.1% ± 1.6%; P = 0.02). Cattle that differ in RG at the same DMI do not differ in characteristics associated with CH4 production.

Interplay of Coulomb interactions and disorder in three-dimensional quadratic band crossings without time-reversal symmetry and with unequal masses for conduction and valence bands

NASA Astrophysics Data System (ADS)

Mandal, Ipsita; Nandkishore, Rahul M.

2018-03-01

Coulomb interactions famously drive three-dimensional quadratic band crossing semimetals into a non-Fermi liquid phase of matter. In a previous work [Nandkishore and Parameswaran, Phys. Rev. B 95, 205106 (2017), 10.1103/PhysRevB.95.205106], the effect of disorder on this non-Fermi liquid phase was investigated, assuming that the band structure was isotropic, assuming that the conduction and valence bands had the same band mass, and assuming that the disorder preserved exact time-reversal symmetry and statistical isotropy. It was shown that the non-Fermi liquid fixed point is unstable to disorder and that a runaway flow to strong disorder occurs. In this paper, we extend that analysis by relaxing the assumption of time-reversal symmetry and allowing the electron and hole masses to differ (but continuing to assume isotropy of the low energy band structure). We first incorporate time-reversal symmetry breaking disorder and demonstrate that there do not appear any new fixed points. Moreover, while the system continues to flow to strong disorder, time-reversal-symmetry-breaking disorder grows asymptotically more slowly than time-reversal-symmetry-preserving disorder, which we therefore expect should dominate the strong-coupling phase. We then allow for unequal electron and hole masses. We show that whereas asymmetry in the two masses is irrelevant in the clean system, it is relevant in the presence of disorder, such that the `effective masses' of the conduction and valence bands should become sharply distinct in the low-energy limit. We calculate the RG flow equations for the disordered interacting system with unequal band masses and demonstrate that the problem exhibits a runaway flow to strong disorder. Along the runaway flow, time-reversal-symmetry-preserving disorder grows asymptotically more rapidly than both time-reversal-symmetry-breaking disorder and the Coulomb interaction.

Rg1 protects rat bone marrow stem cells against hydrogen peroxide-induced cell apoptosis through the PI3K/Akt pathway.

PubMed

Hu, Junzheng; Gu, Yanqing; Fan, Weimin

2016-07-01

The aim of the present study was to investigate the protective mechanism of ginsenoside Rg1 against the apoptosis of rat bone marrow stem cells (rBMSCs) under oxidative stress, and to determine the association with the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. H2O2 was used to induce oxidative injury in rBMSCs. The cells in the H2O2 model group were treated with 800 µM H2O2 for 6 h to induce oxidative injury. The cells in the ginsenoside Rg1 group were treated with 10 µM ginsenoside Rg1 for 24 h, followed by H2O2 treatment. The cells in the Akt pathway blockage group were treated with 25 µM LY294002 for 1 h, followed by ginsenoside Rg1 + H2O2 treatment. The cell counting kit-8 assay was performed to determine cell viability. Cell apoptosis was detected by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The results of flow cytometry and TUNEL staining indicated that the apoptotic rate of the H2O2 model group was significantly higher compared with that of the control group. Following the ginsenoside Rg1 pretreatment, the apoptotic rate was significantly reduced. In the Akt pathway blockage group, no significant alterations in the levels of cell apoptosis were observed compared with the H2O2 model group. Western blot analysis demonstrated that the ginsenoside Rg1 group had a significant downregulation of Bax and cleaved caspase‑3 and an upregulation of Bcl‑2 and phosphorylated Akt protein expression levels compared with the H2O2 model group and the Akt pathway blockage group. In conclusion, ginsenoside Rg1 had a protective effect against the H2O2‑induced oxidative stress of rBMSCs, and the specific mechanism may be associated with the activation of the PI3K/Akt pathway by ginsenoside Rg1.

High-resolution genetic mapping at the Bph15 locus for brown planthopper resistance in rice (Oryza sativa L.).

PubMed

Yang, Haiyuan; You, Aiqing; Yang, Zhifan; Zhang, Futie; He, Ruifeng; Zhu, Lili; He, Guangcun

2004-12-01

Resistance to the brown planthopper (BPH), Nilaparvata lugens Stal, a devastating sucking insect pest of rice, is an important breeding objective in rice improvement programs. Bph15, one of the 17 major BPH resistance genes so far identified in both cultivated and wild rice, has been identified in an introgression line, B5, and mapped on chromosome 4 flanked by restriction fragment length polymorphism markers C820 and S11182. In order to pave the way for positional cloning of this gene, we have developed a high-resolution genetic map of Bph15 by positioning 21 DNA markers in the target chromosomal region. Mapping was based on a PCR-based screening of 9,472 F(2) individuals derived from a cross between RI93, a selected recombinant inbred line of B5 bearing the resistance gene Bph15, and a susceptible variety, Taichung Native 1, in order to identify recombinant plants within the Bph15 region. Recombinant F(2) individuals with the Bph15 genotype were determined by phenotype evaluation. Analysis of recombination events in the Bph15 region delimited the gene locus to an interval between markers RG1 and RG2 that co-segregated with the M1 marker. A genomic library of B5 was screened using these markers, and bacterial artificial chromosome clones spanning the Bph15 chromosome region were obtained. An assay of the recombinants using the sub-clones of these clones in combination with sequence analysis delimited the Bph15 gene to a genomic segment of approximately 47 kb. This result should serve as the basis for eventual isolation of the Bph15 resistance gene.

Selecting broiler chickens for ultimate pH of breast muscle: analysis of divergent selection experiment and phenotypic consequences on meat quality, growth, and body composition traits.

PubMed

Alnahhas, N; Berri, C; Boulay, M; Baéza, E; Jégo, Y; Baumard, Y; Chabault, M; Le Bihan-Duval, E

2014-09-01

Genetic parameters for ultimate pH of pectoralis major muscle (PM-pHu) and sartorius muscle (SART-pHu); color parameters L*, a*, b*; logarithm of drip loss (LogDL) of pectoralis major (PM) muscle; breast meat yield (BMY); thigh and drumstick yield (TY); abdominal fat percentage (AFP); and BW at 6 wk (BW6) were estimated in 2 lines of broiler chickens divergently selected for PM-pHu. Effects of selection on all the previous traits and on glycolytic potential, pectoralis major muscle pH at 15 min postmortem, curing-cooking yield (CCY), cooking loss (CL), and Warner-Bratzler shear force (WBSF) of the PM muscle were also analyzed after 5 generations. Strong genetic determinism of PM-pHu was observed, with estimated h(2) of 0.57 ± 0.02. There was a significant positive genetic correlation (rg) between PM-pHu and SART-pHu (0.54 ± 0.04), indicating that selection had a general rather than a specific effect on energy storage in skeletal muscles. The h(2) estimates of L*, a*, and b* parameters were 0.58 ± 0.02, 0.39 ± 0.02, and 0.48 ± 0.02, respectively. Heritability estimates for TY, BMY, and AFP were 0.39 ± 0.04, 0.52 ± 0.01, and 0.71 ± 0.02, respectively. Our results indicated different genetic control of LogDL and L* of the meat between the 2 lines; these traits had a strong rg with PM-pHu in the line selected for low ultimate pH (pHu) value (pHu-; -0.80 and -0.71, respectively), which was not observed in the line selected for high pHu value (pHu+; -0.04 and -0.29, respectively). A significant positive rg (0.21 ± 0.04) was observed between PM-pHu and BMY but not between PM-pHu and BW6, AFP, or TY. Significant phenotypic differences were observed after 5 generations of selection between the 2 lines. The mean differences (P < 0.001) in pHu between the 2 lines were 0.42 and 0.21 pH units in the breast and thigh muscle, respectively. Breast meat in the pHu+ line exhibited lower L* (-5 units; P < 0.001), a* (-0.22 units; P < 0.001), b* (-1.53 units; P < 0.001), and drip loss (-1.6 units; P < 0.001) than in the pHu- line. Breast meat of the pHu+ line was also characterized by greater CCY (+6.1 units; P < 0.001), lower CL (-1.66 units; P < 0.01), and lower WBSF after cooking (-5.1 units; P < 0.001) compared to the pHu- line. This study highlighted that selection based on pHu can be effective in improving the processing ability of breast meat and reducing the incidence of meat quality defects without affecting chicken growth performance.

Genetics of human body size and shape: pleiotropic and independent genetic determinants of adiposity.

PubMed

Livshits, G; Yakovenko, K; Ginsburg, E; Kobyliansky, E

1998-01-01

The present study utilized pedigree data from three ethnically different populations of Kirghizstan, Turkmenia and Chuvasha. Principal component analysis was performed on a matrix of genetic correlations between 22 measures of adiposity, including skinfolds, circumferences and indices. Findings are summarized as follows: (1) All three genetic matrices were not positive definite and the first four factors retained even after exclusion RG > or = 1.0, explained from 88% to 97% of the total additive genetic variation in the 22 trials studied. This clearly emphasizes the massive involvement of pleiotropic gene effects in the variability of adiposity traits. (2) Despite the quite natural differences in pairwise correlations between the adiposity traits in the three ethnically different samples under study, factor analysis revealed a common basic pattern of covariability for the adiposity traits. In each of the three samples, four genetic factors were retained, namely, the amount of subcutaneous fat, the total body obesity, the pattern of distribution of subcutaneous fat and the central adiposity distribution. (3) Genetic correlations between the retained four factors were virtually non-existent, suggesting that several independent genetic sources may be governing the variation of adiposity traits. (4) Variance decomposition analysis on the obtained genetic factors leaves no doubt regarding the substantial familial and (most probably genetic) effects on variation of each factor in each studied population. The similarity of results in the three different samples indicates that the findings may be deemed valid and reliable descriptions of the genetic variation and covariation pattern of adiposity traits in the human species.

Stellar encounters involving neutron stars in globular cluster cores

NASA Technical Reports Server (NTRS)

Davies, M. B.; Benz, W.; Hills, J. G.

1992-01-01

Encounters between a 1.4 solar mass neutron star and a 0.8 solar mass red giant (RG) and between a 1.4 solar mass neutron star (NS) and an 0.8 solar mass main-sequence (MS) star have been successfully simulated. In the case of encounters involving an RG, bound systems are produced when the separation at periastron passage R(MIN) is less than about 2.5 R(RG). At least 70 percent of these bound systems are composed of the RG core and NS forming a binary engulfed in a common envelope of what remains of the former RG envelope. Once the envelope is ejected, a tight white dwarf-NS binary remains. For MS stars, encounters with NSs will produce bound systems when R(MIN) is less than about 3.5 R(MS). Some 50 percent of these systems will be single objects with the NS engulfed in a thick disk of gas almost as massive as the original MS star. The ultimate fate of such systems is unclear.

Solar photocatalytic degradation of mono azo methyl orange and diazo reactive green 19 in single and binary dye solutions: adsorbability vs photodegradation rate.

PubMed

Ong, Soon-An; Min, Ohm-Mar; Ho, Li-Ngee; Wong, Yee-Shian

2013-05-01

The objective of this study was to examine the effects of adsorbability and number of sulfonate group on solar photocatalytic degradation of mono azo methyl orange (MO) and diazo Reactive Green 19 (RG19) in single and binary dye solutions. The adsorption capacity of MO and RG19 onto the TiO₂ was 16.9 and 26.8 mg/g, respectively, in single dye solution, and reduced to 5.0 and 23.1 mg/g, respectively, in the binary dye solution. The data obtained for photocatalytic degradation of MO and RG19 in single and binary dye solution were well fitted with the Langmuir-Hinshelwood kinetic model. The pseudo-first-order rate constants of diazo RG19 were significant higher than the mono azo MO either in single or binary dye solutions. The higher number of sulfonate group in RG19 contributed to better adsorption capacity onto the surface of TiO₂ than MO indicating greater photocatalytic degradation rate.

A new subtype of progenitor cell in the mouse embryonic neocortex

PubMed Central

Wang, Xiaoqun; Tsai, Jin-Wu; LaMonica, Bridget; Kriegstein, Arnold R.

2011-01-01

A hallmark of mammalian brain evolution is cortical expansion, which reflects an increase in the number of cortical neurons established by the progenitor cell subtypes present and the number of their neurogenic divisions. Recent studies have revealed a new class of radial glia-like (oRG) progenitor cells in the human brain, which reside in the outer subventricular zone. Expansion of the subventricular zone and appearance of oRG cells may have been essential evolutionary steps leading from lissencephalic to gyrencephalic neocortex. Here we show that oRG-like progenitor cells are present in the mouse embryonic neocortex. They arise from asymmetric divisions of radial glia and undergo self-renewing asymmetric divisions to generate neurons. Moreover, mouse oRG cells undergo mitotic somal translocation whereby centrosome movement into the basal process during interphase preceeds nuclear translocation. Our finding of oRG cells in the developing rodent brain fills a gap in our understanding of neocortical expansion. PMID:21478886

Effects of ginsenosides Rg1 and Rb1 of Panax ginseng on mitosis in root tip cells of Allium cepa.

PubMed

Ng, W Y; Chao, C Y

1981-01-01

The effects of ginsenosides Rg1 and Rb1 of Panax ginseng on mitosis in the onion root tip cells as well as on the rate of DNA synthesis in onion seedlings were studied. Results obtained from the concentration and time course study in bulb and seeding root tip cells indicate that Rg1 promotes and Rb1 inhibits mitosis, both being dose-dependent. The promoting effect of Rg1 on the rate of DNA synthesis was observed at the peak hour which occurs at the same time as that of the control. Rb1 was found to shift the peak hour of DNA synthesis to a later period of the experiment. These results are in agreement with the results obtained from the study of the cell cycle by pulse labeling and autoradiography, which show that Rg1 shortens the mitotic cell cycle and S period while Rb1 lengthens them. They in turn increase and decrease the mitotic indices respectively.

Prototype Technology for Monitoring Volatile Organics. Volume 1.

DTIC Science & Technology

1988-03-01

117, pp. 285-294. Grote, J.O. and Westendorf , R.G., "An Automatic Purge and Trap Concentrator," American Laboratory, December 1979. Khromchenko, Y.L...Environmental Monitoring and Support Laboratory, Office of Research and Development, Cincinnati, OH. Westendorf , R.G., "Closed-loop Stripping Analysis...Technique and Applications," American Laboratory, December 1982. Westendorf , R.G., "Development Application of A Semi-Automatic Purge and Trap Concentrator

Structure of a Unimolecular Dendritic Reverse Micelle in Dense CO2 Via Small Angle Scattering

NASA Astrophysics Data System (ADS)

Lin, J. S.

1997-03-01

Dilute solutions in dense CO2 (5Kpsi and 25 degC) of a unimolecular reverse micelle were studied via small angle x ray scattering (SAXS). The unimolecular micelle was based on a fourth generation poly(propylene imine) dendrimer, functionalized with perfluoropolyether acid fluoride chains. A value of 26 added chains per dendrimer was obtained from other characterization techniques, and this number of chains was fixed in the fitting of the SAXS data to an f-arm star model. The molecular weight ( 33.5K g mol-1) agreed well with estimates from other techniques. The observed negative second virial coefficient, A2 = -1.2 x 10-4 cm^3 g-2 mol, correlates with prior observations, as does the observed radius of gyration, Rg = 32ÅSponsors: Div. of Mat. Sci., Basic Energy Sc., USDOE, contract DE-AC05-96OR22464, Oak Ridge Nat. Lab., managed by Lockheed Martin Energy Research Corp.; The Royal Commission for the Exhibition of 1851; National Science Foundation; Consortium for the Sythesis and Processing of Polymeric Materials in Carbon Dioxide.

Protective Effect of Dietary Xylitol on Influenza A Virus Infection

PubMed Central

Yin, Sun Young; Kim, Hyoung Jin; Kim, Hong-Jin

2014-01-01

Xylitol has been used as a substitute for sugar to prevent cavity-causing bacteria, and most studies have focused on its benefits in dental care. Meanwhile, the constituents of red ginseng (RG) are known to be effective in ameliorating the symptoms of influenza virus infection when they are administered orally for 14 days. In this study, we investigated the effect of dietary xylitol on influenza A virus infection (H1N1). We designed regimens containing various fractions of RG (RGs: whole extract, water soluble fraction, saponin and polysaccharide) and xylitol, and combination of xylitol with the RG fractions. Mice received the various combinations orally for 5 days prior to lethal influenza A virus infection. Almost all the mice died post challenge when xylitol or RGs were administered separately. Survival was markedly enhanced when xylitol was administered along with RGs, pointing to a synergistic effect. The effect of xylitol plus RG fractions increased with increasing dose of xylitol. Moreover, dietary xylitol along with the RG water soluble fraction significantly reduced lung virus titers after infection. Therefore, we suggest that dietary xylitol is effective in ameliorating influenza-induced symptoms when it is administered with RG fractions, and this protective effect of xylitol should be considered in relation to other diseases. PMID:24392148

Differential Expression of NADPH Oxidases Depends on Skeletal Muscle Fiber Type in Rats.

PubMed

Loureiro, Adriano César Carneiro; do Rêgo-Monteiro, Igor Coutinho; Louzada, Ruy A; Ortenzi, Victor Hugo; de Aguiar, Angélica Ponte; de Abreu, Ewerton Sousa; Cavalcanti-de-Albuquerque, João Paulo Albuquerque; Hecht, Fabio; de Oliveira, Ariclécio Cunha; Ceccatto, Vânia Marilande; Fortunato, Rodrigo S; Carvalho, Denise P

2016-01-01

NADPH oxidases (NOX) are important sources of reactive oxygen species (ROS) in skeletal muscle, being involved in excitation-contraction coupling. Thus, we aimed to investigate if NOX activity and expression in skeletal muscle are fiber type specific and the possible contribution of this difference to cellular oxidative stress. Oxygen consumption rate, NOX activity and mRNA levels, and the activity of catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD), as well as the reactive protein thiol levels, were measured in the soleus (SOL), red gastrocnemius (RG), and white gastrocnemius (WG) muscles of rats. RG showed higher oxygen consumption flow than SOL and WG, while SOL had higher oxygen consumption than WG. SOL showed higher NOX activity, as well as NOX2 and NOX4 mRNA levels, antioxidant enzymatic activities, and reactive protein thiol contents when compared to WG and RG. NOX activity and NOX4 mRNA levels as well as antioxidant enzymatic activities were higher in RG than in WG. Physical exercise increased NOX activity in SOL and RG, specifically NOX2 mRNA levels in RG and NOX4 mRNA levels in SOL. In conclusion, we demonstrated that NOX activity and expression differ according to the skeletal muscle fiber type, as well as antioxidant defense.

Autotoxic Ginsenosides in the Rhizosphere Contribute to the Replant Failure of Panax notoginseng

PubMed Central

Yang, Min; Zhang, Xiaodan; Xu, Yanguo; Mei, Xinyue; Jiang, Bingbing; Liao, Jingjing; Yin, Zhaobo; Zheng, Jianfen; Zhao, Zhi; Fan, Liming; He, Xiahong; Zhu, Youyong; Zhu, Shusheng

2015-01-01

Background and Aims Sanqi ginseng (Panax notoginseng) growth is often hampered by replant failure. In this study, we aimed to examine the role of autotoxicity in Sanqi replant failures and assess the role of ginsenosides in autotoxicity. Methods The autotoxicities were measured using seedling emergence bioassays and root cell vigor staining. The ginsenosides in the roots, soils, and root exudates were identified with HPLC-MS. Results The seedling emergence and survival rate decreased significantly with the continuous number of planting years from one to three years. The root exudates, root extracts, and extracts from consecutively cultivated soils also showed significant autotoxicity against seedling emergence and growth. Ginsenosides, including R1, Rg1, Re, Rb1, Rb3, Rg2, and Rd, were identified in the roots and consecutively cultivated soil. The ginsenosides, Rg1, Re, Rg2, and Rd, were identified in the root exudates. Furthermore, the ginsenosides, R1, Rg1, Re, Rg2, and Rd, caused autotoxicity against seedling emergence and growth and root cell vigor at a concentration of 1.0 µg/mL. Conclusion Our results demonstrated that autotoxicity results in replant failure of Sanqi ginseng. While Sanqi ginseng consecutively cultivated, some ginsenosides can accumulate in rhizosphere soils through root exudates or root decomposition, which impedes seedling emergence and growth. PMID:25695831

Alveolar bone dynamics in osteoporotic rats treated with raloxifene or alendronate: confocal microscopy analysis

NASA Astrophysics Data System (ADS)

Ramalho-Ferreira, Gabriel; Faverani, Leonardo Perez; Grossi-Oliveira, Gustavo Augusto; Okamoto, Tetuo; Okamoto, Roberta

2015-03-01

In this study, the characteristics of the alveolar bone of rats with induced osteoporosis were examined. Thirty-two rats were divided into four groups according to the induction of osteoporosis and drugs administered: OG, osteoporotic rats without treatment (negative control); SG, rats which underwent sham surgery ovariectomy (SHAM); alendronate (AG), osteoporotic rats treated with alendronate; and RG, osteoporotic rats treated with raloxifene (RG). On the 8th day after ovariectomy and SHAM surgeries, drug therapy was started with AG or RG. On the 52nd day, 20 mg/kg calcein was administered to all of the rats, and on the 80th day, 20 mg/kg alizarin red was administered. Euthanasia was performed on the 98th day. The bone area marked by fluorochromes was calculated and data were subjected to two-way ANOVA test and Tukey's post-hoc test (p<0.05). The comparison of the induced osteoporosis groups showed no statistically significant differences in bone turnover only between RG and SG (p=0.074) and AG and OG (p=0.138). All other comparisons showed significant differences (p<0.001). The largest bone turnover was observed in RG and SG groups. RG was the medication that improved the dynamics of the alveolar bone of rats with induced osteoporosis, resembling that of healthy rats.

Thermodynamic and structural insights into nanocomposites engineering by comparing two materials assembly techniques for graphene.

PubMed

Zhu, Jian; Zhang, Huanan; Kotov, Nicholas A

2013-06-25

Materials assembled by layer-by-layer (LBL) assembly and vacuum-assisted flocculation (VAF) have similarities, but a systematic study of their comparative advantages and disadvantages is missing. Such a study is needed from both practical and fundamental perspectives aiming at a better understanding of structure-property relationships of nanocomposites and purposeful engineering of materials with unique properties. Layered composites from polyvinyl alcohol (PVA) and reduced graphene (RG) are made by both techniques. We comparatively evaluate their structure, mechanical, and electrical properties. LBL and VAF composites demonstrate clear differences at atomic and nanoscale structural levels but reveal similarities in micrometer and submicrometer organization. Epitaxial crystallization and suppression of phase transition temperatures are more pronounced for PVA in LBL than for VAF composites. Mechanical properties are virtually identical for both assemblies at high RG contents. We conclude that mechanical properties in layered RG assemblies are largely determined by the thermodynamic state of PVA at the polymer/nanosheet interface rather than the nanometer scale differences in RG packing. High and nearly identical values of toughness for LBL and VAF composites reaching 6.1 MJ/m(3) observed for thermodynamically optimal composition confirm this conclusion. Their toughness is the highest among all other layered assemblies from RG, cellulose, clay, etc. Electrical conductivity, however, is more than 10× higher for LBL than for VAF composites for the same RG contents. Electrical properties are largely determined by the tunneling barrier between RG sheets and therefore strongly dependent on atomic/nanoscale organization. These findings open the door for application-oriented methods of materials engineering using both types of layered assemblies.

Identification and characterization of glycosyltransferases involved in the synthesis of the side chains of the cell wall pectic polysaccharide rhamnogalacturonan II

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

O'Neill, Malcolm

Our goal was to gain insight into the genes and proteins involved in the biosynthesis of rhamnogalacturonan II (RG-II), a borate cross-linked and structurally conserved pectic polysaccharide present in the primary cell walls of all vascular plants. The research conducted during the funding period established that (i) Avascular plants have the ability to synthesize UDP-apiose but lack the glycosyltransferase machinery required to synthesize RG-II or other apiose-containing cell wall glycans. (ii) RG-II structure is highly conserved in the Lemnaceae (duckweeds and relatives). However, the structures of other wall pectins and hemicellulose have changed substantial during the diversification of the Lemnaceae.more » This supports the notion that a precise structure of RG-II must be maintained to allow borate cross-linking to occur in a controlled manner. (iii) Enzymes involved in the conversion of UDP-GlcA to UDP-Api, UDP-Xyl, and UDP-Ara may have an important role in controlling the composition of duckweed cell walls. (iv) RG-II exists as the borate ester cross-linked dimer in the cell walls of soybean root hairs and roots. Thus, RG-II is present in the walls of plants cells that grow by tip or by expansive growth. (v) A reduction in RG-II cross-linking in the maize tls1 mutant, which lacks a borate channel protein, suggests that the growth defects observed in the mutant are, at least in part, due to defects in the cell wall.« less

α -decay chains of the superheavy nuclei Rg-350255

NASA Astrophysics Data System (ADS)

Santhosh, K. P.; Nithya, C.

2017-05-01

The decay modes and half-lives of 96 isotopes of the superheavy element roentgenium (Rg) within the range of 255 ≤A ≤350 come under investigation in the present paper. The isotopes which lie beyond the proton drip line are identified by calculating the one-proton and two-proton separation energies. The α -decay half-lives are calculated using the Coulomb and proximity potential model for deformed nuclei (CPPMDN). For a theoretical comparison the α half-lives are also evaluated using the Viola-Seaborg semiempirical relation, the universal curve of Poenaru et al., the analytical formula of Royer, and the universal decay law of Qi et al. Spontaneous fission half-lives are computed with the shell-effect-dependent formula of Santhosh and Nithya and the semiempirical formula of Xu et al. The decay modes are predicted by comparing the α -decay half-lives within the CPPMDN with the corresponding spontaneous fission half-lives computed by the shell-effect-dependent formula of Santhosh and Nithya. In our paper it is seen that the isotopes 255-271,273Rg lie beyond the proton drip line and hence decay through proton emission. The isotopes 272,274-277Rg exhibit long α chains. Three α chains are predicted from the isotopes Rg-282278. The isotopes Rg-345283 decay through spontaneous fission. The isotopes Rg-350346 are found to be stable against α decay. The theoretical results are compared with the available experimental results and are seen to be matching well. We hope that our predictions will be useful in future experimental investigations.

Holography as a highly efficient renormalization group flow. I. Rephrasing gravity

NASA Astrophysics Data System (ADS)

Behr, Nicolas; Kuperstein, Stanislav; Mukhopadhyay, Ayan

2016-07-01

We investigate how the holographic correspondence can be reformulated as a generalization of Wilsonian renormalization group (RG) flow in a strongly interacting large-N quantum field theory. We first define a highly efficient RG flow as one in which the Ward identities related to local conservation of energy, momentum and charges preserve the same form at each scale. To achieve this, it is necessary to redefine the background metric and external sources at each scale as functionals of the effective single-trace operators. These redefinitions also absorb the contributions of the multitrace operators to these effective Ward identities. Thus, the background metric and external sources become effectively dynamical, reproducing the dual classical gravity equations in one higher dimension. Here, we focus on reconstructing the pure gravity sector as a highly efficient RG flow of the energy-momentum tensor operator, leaving the explicit constructive field theory approach for generating such RG flows to the second part of the work. We show that special symmetries of the highly efficient RG flows carry information through which we can decode the gauge fixing of bulk diffeomorphisms in the corresponding gravity equations. We also show that the highly efficient RG flow which reproduces a given classical gravity theory in a given gauge is unique provided the endpoint can be transformed to a nonrelativistic fixed point with a finite number of parameters under a universal rescaling. The results obtained here are used in the second part of this work, where we do an explicit field-theoretic construction of the RG flow and obtain the dual classical gravity theory.

Comparison of the removal of ethanethiol in twin-biotrickling filters inoculated with strain RG-1 and B350 mixed microorganisms.

PubMed

An, Taicheng; Wan, Shungang; Li, Guiying; Sun, Lei; Guo, Bin

2010-11-15

This study aims to compare the biological degradation performance of ethanethiol using strain RG-1 and B350 commercial mixed microorganisms, which were inoculated and immobilized on ceramic particles in twin-biotrickling filter columns. The parameters affecting the removal efficiency, such as empty bed residence time (EBRT) and inlet concentration, were investigated in detail. When EBRT ranged from 332 to 66 s at a fixed inlet concentration of 1.05 mg L(-1), the total removal efficiencies for RG-1 and B350 both decreased from 100% to 70.90% and 47.20%, respectively. The maximum elimination capacities for RG-1 and B350 were 38.36 (removal efficiency=89.20%) and 25.82 g m(-3) h(-1) (removal efficiency=57.10%), respectively, at an EBRT of 83 s. The variation of the inlet concentration at a fixed EBRT of 110 s did not change the removal efficiencies which remained at 100% for RG-1 and B350 at concentrations of less than 1.05 and 0.64 mg L(-1), respectively. The maximum elimination capacities were 39.93 (removal efficiency=60.30%) and 30.34 g m(-3) h(-1) (removal efficiency=46.20%) for RG-1 and B350, respectively, at an inlet concentration of 2.03 mg L(-1). Sulfate was the main metabolic product of sulfur in ethanethiol. Based the results, strain RG-1 would be a better choice than strain B350 for the biodegradation of ethanethiol. Copyright © 2010 Elsevier B.V. All rights reserved.

Depth Discrimination Using Rg-to-Sg Spectral Amplitude Ratios for Seismic Events in Utah Recorded at Local Distances

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

Tibi, Rigobert; Koper, Keith D.; Pankow, Kristine L.

Short-period fundamental-mode Rayleigh waves (Rg) are commonly observed on seismograms of anthropogenic seismic events and shallow, naturally occurring tectonic earthquakes (TEs) recorded at local distances. In the Utah region, strong Rg waves traveling with an average group velocity of about 1.8 km/s are observed at ~1 Hz on waveforms from shallow events ( depth<10 km ) recorded at distances up to about 150 km. At these distances, Sg waves, which are direct shear waves traveling in the upper crust, are generally the dominant signals for TEs. Here in this study, we leverage the well-known notion that Rg amplitude decreases dramaticallymore » with increasing event depth to propose a new depth discriminant based on Rg-to-Sg spectral amplitude ratios. The approach is successfully used to discriminate shallow events (both earthquakes and anthropogenic events) from deeper TEs in the Utah region recorded at local distances ( <150 km ) by the University of Utah Seismographic Stations (UUSS) regional seismic network. Using Mood’s median test, we obtained probabilities of nearly zero that the median Rg-to-Sg spectral amplitude ratios are the same between shallow events on the one hand (including both shallow TEs and anthropogenic events), and deeper earthquakes on the other, suggesting that there is a statistically significant difference in the estimated Rg-to-Sg ratios between the two populations. We also observed consistent disparities between the different types of shallow events (e.g., mining blasts vs. mining-induced earthquakes), implying that it may be possible to separate the subpopulations that make up this group. Lastly, this suggests that using local distance Rg-to-Sg spectral amplitude ratios one can not only discriminate shallow events from deeper events but may also be able to discriminate among different populations of shallow events.« less

RgIA4 Potently Blocks Mouse α9α10 nAChRs and Provides Long Lasting Protection against Oxaliplatin-Induced Cold Allodynia.

PubMed

Christensen, Sean B; Hone, Arik J; Roux, Isabelle; Kniazeff, Julie; Pin, Jean-Philippe; Upert, Grégory; Servent, Denis; Glowatzki, Elisabeth; McIntosh, J Michael

2017-01-01

Transcripts for α9 and α10 nicotinic acetylcholine receptor (nAChR) subunits are found in diverse tissues. The function of α9α10 nAChRs is best known in mechanosensory cochlear hair cells, but elsewhere their roles are less well-understood. α9α10 nAChRs have been implicated as analgesic targets and α-conotoxins that block α9α10 nAChRs produce analgesia. However, some of these peptides show large potency differences between species. Additionally several studies have indicated that these conotoxins may also activate GABA B receptors (GABA B Rs). To further address these issues, we cloned the cDNAs of mouse α9 and α10 nAChR subunits. When heterologously expressed in Xenopus oocytes, the resulting α9α10 nAChRs had the expected pharmacology of being activated by acetylcholine and choline but not by nicotine. A conotoxin analog, RgIA4, potently, and selectively blocked mouse α9α10 nAChRs with low nanomolar affinity indicating that RgIA4 may be effectively used to study murine α9α10 nAChR function. Previous reports indicated that RgIA4 attenuates chemotherapy-induced cold allodynia. Here we demonstrate that RgIA4 analgesic effects following oxaliplatin treatment are sustained for 21 days after last RgIA4 administration indicating that RgIA4 may provide enduring protection against nerve damage. RgIA4 lacks activity at GABA B receptors; a bioluminescence resonance energy transfer assay was used to demonstrate that two other analgesic α-conotoxins, Vc1.1 and AuIB, also do not activate GABA B Rs expressed in HEK cells. Together these findings further support the targeting of α9α10 nAChRs in the treatment of pain.

Endophytic Bacterium Pseudomonas fluorescens RG11 May Transform Tryptophan to Melatonin and Promote Endogenous Melatonin Levels in the Roots of Four Grape Cultivars

PubMed Central

Ma, Yaner; Jiao, Jian; Fan, Xiucai; Sun, Haisheng; Zhang, Ying; Jiang, Jianfu; Liu, Chonghuai

2017-01-01

Endophytes have been verified to synthesize melatonin in vitro and promote abiotic stress-induced production of endogenous melatonin in grape (Vitis vinifera L.) roots. This study aimed to further characterize the biotransformation of tryptophan to melatonin in the endophytic bacterium Pseudomonas fluorescens RG11 and to investigate its capacity for enhancing endogenous melatonin levels in the roots of different grape cultivars. Using ultra performance liquid chromatography-tandem mass spectrometry combined with 15N double-labeled L-tryptophan as the precursor for melatonin, we detected isotope-labeled 5-hydroxytryptophan, serotonin, N-acetylserotonin, and melatonin, but tryptamine was not detected during the in vitro incubation of P. fluorescens RG11. Furthermore, the production capacity of these four compounds peaked during the exponential growth phase. RG11 colonization increased the endogenous levels of 5-hydroxytryptophan, N-acetylserotonin, and melatonin, but reduced those of tryptamine and serotonin, in the roots of the Red Globe grape cultivar under salt stress conditions. Quantitative real-time PCR revealed that RG11 reduced the transcription of grapevine tryptophan decarboxylase and serotonin N-acetyltransferase genes when compared to the un-inoculated control. These results correlated with decreased reactive oxygen species bursts and cell damage, which were alleviated by RG11 colonization under salt stress conditions. Additionally, RG11 promoted plant growth and enhanced the levels of endogenous melatonin in different grape cultivars. Intraspecific variation in the levels of melatonin precursors was found among four grape cultivars, and the associated root crude extracts appeared to significantly induce RG11 melatonin biosynthesis in vitro. Overall, this study provides useful information that enhances the existing knowledge of a potential melatonin synthesis pathway in rhizobacteria, and it reveals plant–rhizobacterium interactions that affect melatonin biosynthesis in plants subjected to abiotic stress conditions. PMID:28119731

Endophytic Bacterium Pseudomonas fluorescens RG11 May Transform Tryptophan to Melatonin and Promote Endogenous Melatonin Levels in the Roots of Four Grape Cultivars.

PubMed

Ma, Yaner; Jiao, Jian; Fan, Xiucai; Sun, Haisheng; Zhang, Ying; Jiang, Jianfu; Liu, Chonghuai

2016-01-01

Endophytes have been verified to synthesize melatonin in vitro and promote abiotic stress-induced production of endogenous melatonin in grape ( Vitis vinifera L.) roots. This study aimed to further characterize the biotransformation of tryptophan to melatonin in the endophytic bacterium Pseudomonas fluorescens RG11 and to investigate its capacity for enhancing endogenous melatonin levels in the roots of different grape cultivars. Using ultra performance liquid chromatography-tandem mass spectrometry combined with 15N double-labeled L -tryptophan as the precursor for melatonin, we detected isotope-labeled 5-hydroxytryptophan, serotonin, N -acetylserotonin, and melatonin, but tryptamine was not detected during the in vitro incubation of P. fluorescens RG11. Furthermore, the production capacity of these four compounds peaked during the exponential growth phase. RG11 colonization increased the endogenous levels of 5-hydroxytryptophan, N -acetylserotonin, and melatonin, but reduced those of tryptamine and serotonin, in the roots of the Red Globe grape cultivar under salt stress conditions. Quantitative real-time PCR revealed that RG11 reduced the transcription of grapevine tryptophan decarboxylase and serotonin N -acetyltransferase genes when compared to the un-inoculated control. These results correlated with decreased reactive oxygen species bursts and cell damage, which were alleviated by RG11 colonization under salt stress conditions. Additionally, RG11 promoted plant growth and enhanced the levels of endogenous melatonin in different grape cultivars. Intraspecific variation in the levels of melatonin precursors was found among four grape cultivars, and the associated root crude extracts appeared to significantly induce RG11 melatonin biosynthesis in vitro . Overall, this study provides useful information that enhances the existing knowledge of a potential melatonin synthesis pathway in rhizobacteria, and it reveals plant-rhizobacterium interactions that affect melatonin biosynthesis in plants subjected to abiotic stress conditions.

Advantageous use of HepaRG cells for the screening and mechanistic study of drug-induced steatosis

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

Tolosa, Laia

Only a few in vitro assays have been proposed to evaluate the steatotic potential of new drugs. The present study examines the utility of HepaRG cells as a cell-based assay system for screening drug-induced liver steatosis. A high-content screening assay was run to evaluate multiple toxicity-related cell parameters in HepaRG cells exposed to 28 compounds, including drugs reported to cause steatosis through different mechanisms and non-steatotic compounds. Lipid content was the most sensitive parameter for all the steatotic drugs, whereas no effects on lipid levels were produced by non-steatotic compounds. Apart from fat accumulation, increased ROS production and altered mitochondrialmore » membrane potential were also found in the cells exposed to steatotic drugs, which indicates that all these cellular events contributed to drug-induced hepatotoxicity. These findings are of clinical relevance as most effects were observed at drug concentrations under 100-fold of the therapeutic peak plasmatic concentration. HepaRG cells showed increased lipid overaccumulation vs. HepG2 cells, which suggests greater sensitivity to drug-induced steatosis. An altered expression profile of transcription factors and the genes that code key proteins in lipid metabolism was also found in the cells exposed to drugs capable of inducing liver steatosis. Our results generally indicate the value of HepaRG cells for assessing the risk of liver damage associated with steatogenic compounds and for investigating the molecular mechanisms involved in drug-induced steatosis. - Highlights: • HepaRG cells were explored as an in vitro model to detect steatogenic potential. • Multiple toxicity-related endpoints were analysed by HCS. • HepaRG showed a greater sensitivity to drug-induced steatosis than HepG2 cells. • Changes in the expression of genes related to lipid metabolism were revealed. • HepaRG allow mechanistic understanding of liver damage induced by steatogenic drugs.« less

Measuring Responsible Gambling amongst Players: Development of the Positive Play Scale

PubMed Central

Wood, Richard T. A.; Wohl, Michael J. A.; Tabri, Nassim; Philander, Kahlil

2017-01-01

The modern gambling industry has, by-in-large, assumed a duty of care to minimize the risks associated with gambling, which has manifested in responsible gambling (RG) programming (e.g., educating players about the odds of success). The current study fills a void in gambling operators, regulators, and researchers ability to measure RG beliefs and behavior in their player-base, with the development and validation of the Positive Play Scale (PPS). In Study 1, we reviewed the literature and consulted 30 players as well as 10 RG experts to help generate a definition of RG beliefs and behavior that helped guide item generation. In Study 2, regular players (N = 1,551) of a Canadian provincial gambling operator completed a positive play survey. Four components from a principal components analysis (PCA) were extracted: Honesty and Control, Pre-commitment, Personal Responsibility, and Gambling Literacy. The PPS subscales were either not associated with gambling frequency or had small-to-moderate negative relationships with frequency of play for games most often associated with disordered gambling (e.g., electronic games). In Study 3 (N = 413), the factor structure of the PPS was confirmed and refined in a new sample of players. Moreover, a 1-month follow-up session demonstrated that the PPS has high test-retest reliability. The PPS is the first validated scale that reliably assesses the extent to which a consumer base has positive beliefs about gambling and gambles in a positive manner. The PPS can be used by the gambling industry to objectively assess the efficacy of their RG strategy, pinpoint specific areas for future focus, as well as examine the utility of new RG initiatives that aim to promote healthy patterns of gambling consumption. Furthermore, by examining the PPS scores for different player segments (e.g., sex, age, games played) it becomes possible to tailor RG strategy to the needs of specific players. In this way, RG strategy can be optimized by focusing resources where they will be most effective. PMID:28280472

Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of RG7667, a Combination Monoclonal Antibody, for Prevention of Cytomegalovirus Infection in High-Risk Kidney Transplant Recipients

PubMed Central

Ishida, Julie H.; Patel, Anita; Mehta, Aneesh K.; Gatault, Philippe; McBride, Jacqueline M.; Burgess, Tracy; Derby, Michael A.; Snydman, David R.; Emu, Brinda; Feierbach, Becket; Fouts, Ashley E.; Maia, Mauricio; Deng, Rong; Rosenberger, Carrie M.; Gennaro, Lynn A.; Striano, Natalee S.; Liao, X. Charlene

2016-01-01

ABSTRACT Cytomegalovirus (CMV) infection is a significant complication after kidney transplantation. We examined the ability of RG7667, a combination of two monoclonal antibodies, to prevent CMV infection in high-risk kidney transplant recipients in a randomized, double-blind, placebo-controlled trial. CMV-seronegative recipients of a kidney transplant from a CMV-seropositive donor (D+R−) were randomized to receive RG7667 (n = 60) or placebo (n = 60) at the time of transplant and 1, 4, and 8 weeks posttransplant. Patients were monitored for CMV viremia every 1 to 2 weeks posttransplant for 24 weeks. Patients who had seroconverted (D+R+) or withdrawn before dosing were excluded from the analysis (n = 4). CMV viremia occurred in 27 of 59 (45.8%) patients receiving RG7667 and 35 of 57 (61.4%) patients receiving placebo (stratum-adjusted difference, 15.3%; P = 0.100) within 12 weeks posttransplant and in 30 of 59 (50.8%) patients receiving RG7667 and 40 of 57 (70.2%) patients receiving placebo (stratum-adjusted difference, 19.3%; P = 0.040) within 24 weeks posttransplant. Median time to CMV viremia was 139 days in patients receiving RG7667 compared to 46 days in patients receiving placebo (hazard ratio, 0.53; P = 0.009). CMV disease was less common in the RG7667 than placebo group (3.4% versus 15.8%; P = 0.030). Adverse events were generally balanced between treatment groups. In high-risk kidney transplant recipients, RG7667 was well tolerated, numerically reduced the incidence of CMV infection within 12 and 24 weeks posttransplant, delayed time to CMV viremia, and was associated with less CMV disease than the placebo. (This study has been registered at ClinicalTrials.gov under registration no. NCT01753167.) PMID:27872061

Selenium-Rich Ricegrass Juice Improves Antioxidant Properties and Nitric Oxide Inhibition in Macrophage Cells

PubMed Central

Puttarak, Panupong; Brantner, Adelheid; Siripongvutikorn, Sunisa

2018-01-01

Ricegrass juice (Oryza sativa L.) was introduced as a functional food as the consumption of sprouts or seedlings has been claimed to provide high nutritive value. Selenium (Se) is a trace mineral that plays a key role in the human antioxidation scheme. Supplementation of Se into plants is one strategy to enhance plant bioactivities, and the consumption of Se plant foods may confer superior health benefits. In this study, ricegrass juice extract was analyzed for its major phenolic components. The effect of ricegrass juice extracts bio-fortified with 0, 10 and 40 mg Se/L named as RG0, RG10, and RG40, respectively, were investigated for a percentage of cell viability, changes of endogenous antioxidant enzymes, lipid peroxidation, and nitric oxide inhibition in RAW264.7 macrophage cells. Flavone glycosides, namely chrysoeriol arabinosyl arabinoside derivatives, were found to be the foremost bioactive components in ricegrass juice extract indicated by UHPLC-MS. The results of cell culture assessment revealed that RG40 showed an ability to promote macrophage cell proliferation at low concentration. Ricegrass juice extract in all treatments possessed the ability to reduce malondialdehyde content, which may be regarded as the bioactivity of phenolic compounds. Moreover, Se also played a role in this effect since RG40 showed the greatest ability via increasing the level of GPx enzyme. It was also discovered that phenolic compounds in the extracts played a role in inhibiting nitric oxide in LPS-induced RAW264.7 cells. Furthermore, RG40 expressed significantly higher NO inhibition properties at IC50 118.76 µg/mL compared to RG0 and RG10, at 147.02 and 147.73 µg/mL, respectively. Se bio-fortified ricegrass juice could be considered as a new potent functional food that can lower the risk of oxidative stress and chronic inflammation diseases. PMID:29652839

Smart Ultrasound Remote Guidance Experiment (SURGE)- Concept of Operations Evaluation for Using Remote Guidance Ultrasound for Planetary Space Flight

NASA Technical Reports Server (NTRS)

Hurst, Victor, IV; Peterson, Sean; Garcia, Kathleen; Sargsyan, Ashot; Ebert, Douglas; Ham, David; Amponsah, David; Dulchavsky, Scott

2010-01-01

Introduction Use of remote guidance (RG) techniques aboard the International Space Station (ISS) has enabled astronauts to collect diagnostic-level ultrasound images. Exploration class missions will require this cohort of (typically) non-formally trained sonographers to operate with greater autonomy given the longer communication delays (2 seconds for ISS vs. >6 seconds for missions beyond the Moon) and communication blackouts. To determine the feasibility and training requirements for autonomous ultrasound image collection by non-expert ultrasound operators, ultrasound images were collected from a similar cohort using three different image collection protocols: RG only, RG with a computer-based learning tool (LT), and autonomous image collection with LT. The groups were assessed for both image quality and time to collect the images. Methods Subjects were randomized into three groups: RG only, RG with LT, and autonomous with LT. Each subject received 10 minutes of standardized training before the experiment. The subjects were tasked with making the following ultrasound assessments: 1) bone fracture and 2) focused assessment with sonography in trauma (FAST) to assess a patient s abdomen. Human factors-related questionnaire data were collected immediately after the assessments. Results The autonomous group did not out-perform the two groups that received RG. The mean time for the autonomous group to collect images was less than the RG groups, however the mean image quality for the autonomous group was less compared to both RG groups. Discussion Remote guidance continues to produce higher quality ultrasound images than autonomous ultrasound operation. This is likely due to near-instant feedback on image quality from the remote guider. Expansion in communication time delays, however, diminishes the capability to provide this feedback, thus requiring more autonomous ultrasound operation. The LT has the potential to be an excellent training and coaching component for autonomous ultrasound image collection during exploration missions.

Capsicum chinensis L. growth and nutraceutical properties are enhanced by biostimulants in a long-term period: chemical and metabolomic approaches

PubMed Central

Ertani, Andrea; Pizzeghello, Diego; Francioso, Ornella; Sambo, Paolo; Sanchez-Cortes, Santiago; Nardi, Serenella

2014-01-01

Two biostimulants, one derived from alfalfa plants (AH) and the other obtained from red grape (RG), were chemically characterized using enzyme linked immuno-sorbent assays, Fourier transform infrared (FT-IR) and Raman spectroscopies. Two doses (50 and 100 mL L−1 for RG, and 25 and 50 mL L−1 for AH) of biostimulants were applied to Capsicum chinensis L. plants cultivated in pots inside a tunnel. The experimental design consisted of the factorial combination of treatment (no biostimulant, plus AH, plus RG) at three doses (zero, low, and high) and two time-course applications (at the second and fourth week after transplantation) and the effects were recorded at flowering and maturity. Both biostimulants contained different amounts of indoleacetic acid and isopentenyladenosine; the AH spectra exhibited amino acid functional groups in the peptidic structure, while the RG spectra showed the presence of polyphenols, such as resveratrol. These results revealed that at flowering, RG and AH increased the weights of fresh leaves and fruits and the number of green fruits, whereas at maturity, the biostimulants most affected the fresh weight and number of red fruits. At flowering, the leaves of the treated plants contained high amounts of epicatechin, ascorbic acid, quercetin, and dihydrocapsaicin. At maturity, the leaves of the treated plants exhibited elevated amounts of fructose, glucose, chlorogenic, and ferulic acids. Moreover, green fruits exhibited a high content of chlorogenic acid, p-hydroxybenzoic acid, p-coumaric acid and antioxidant activity, while both AH- and RG-treated red fruits were highly endowed in capsaicin. The 1H high-resolution magic-angle spinning (HRMAS)-nuclear magnetic resonance (NMR) spectra of red fruits revealed that both products induced a high amount of NADP+, whereas RG also increased glucose, fumarate, ascorbate, thymidine and high molecular weight species. Our results suggested that AH and RG promoted plant growth and the production of secondary metabolites, such as phenols. PMID:25136346

FLP-18 Functions through the G-Protein-Coupled Receptors NPR-1 and NPR-4 to Modulate Reversal Length in Caenorhabditis elegans

PubMed Central

Dahiya, Yogesh; Babu, Kavita

2018-01-01

Animal behavior is critically dependent on the activity of neuropeptides. Reversals, one of the most conspicuous behaviors in Caenorhabditis elegans, plays an important role in determining the navigation strategy of the animal. Our experiments on hermaphrodite C. elegans show the involvement of a neuropeptide FLP-18 in modulating reversal length in these hermaphrodites. We show that FLP-18 controls the reversal length by regulating the activity of AVA interneurons through the G-protein-coupled neuropeptide receptors, NPR-4 and NPR-1. We go on to show that the site of action of these receptors is the AVA interneuron for NPR-4 and the ASE sensory neurons for NPR-1. We further show that mutants in the neuropeptide, flp-18, and its receptors show increased reversal lengths. Consistent with the behavioral data, calcium levels in the AVA neuron of freely reversing C. elegans were significantly higher and persisted for longer durations in flp-18, npr-1, npr-4, and npr-1 npr-4 genetic backgrounds compared with wild-type control animals. Finally, we show that increasing FLP-18 levels through genetic and physiological manipulations causes shorter reversal lengths. Together, our analysis suggests that the FLP-18/NPR-1/NPR-4 signaling is a pivotal point in the regulation of reversal length under varied genetic and environmental conditions. PMID:29712787

2012 ENFORCE. Project Manager Force Projection Briefing to ENFORCE

DTIC Science & Technology

2012-04-16

M-ATV Logistics MRAP Vehicle Systems (Joint Program) •Navistar MaxxPro •GDLS RG-31 •BAE-TVS Caiman •BAE RG-33 SOCOM •BAE RG-33 SOCOM AUV...Handling Equipment • Container Handling Equipment •Loaders • Cranes •Dozers •Excavators Force Sustainment Systems •Cargo Airdrop Systems...Boruff DPM: Mr. Dennis Mazurek Mine Resistant Ambush Protected Vehicles PM: Mr. Carl Owens DPM: COL Jeffrey Carr Tactical

Successful rotational atherectomy over RG3 guidewire after failure of various techniques to deliver RotaWire.

PubMed

Kaneko, Umihiko; Kashima, Yoshifumi; Kanno, Daitaro; Sugie, Takuro; Kobayashi, Ken; Fujita, Tsutomu

2017-10-01

Although performing rotational atherectomy (RA) requires guidewire exchange for the dedicated guidewire, RotaWire guidewire (Boston Scientific) exhibits much lower performance than conventional guidewire. Consequently, there are times when RotaWire cannot be advanced past the lesion independently or using a microcatheter exchange technique, rendering RA impossible. We present a case of a heavily calcified, device-uncrossable, and non-expansible chronic total occlusion lesion successfully revascularized with RA over RG3 guidewire (Asahi Intecc), which has a length of 330 cm, hydrophilic coating, and a 0.010-inch-long shaft. RG3 provided excellent cross-ability and RA could also be performed over RG3 without guidewire exchange for the RotaWire.

RG-inspired machine learning for lattice field theory

NASA Astrophysics Data System (ADS)

Foreman, Sam; Giedt, Joel; Meurice, Yannick; Unmuth-Yockey, Judah

2018-03-01

Machine learning has been a fast growing field of research in several areas dealing with large datasets. We report recent attempts to use renormalization group (RG) ideas in the context of machine learning. We examine coarse graining procedures for perceptron models designed to identify the digits of the MNIST data. We discuss the correspondence between principal components analysis (PCA) and RG flows across the transition for worm configurations of the 2D Ising model. Preliminary results regarding the logarithmic divergence of the leading PCA eigenvalue were presented at the conference. More generally, we discuss the relationship between PCA and observables in Monte Carlo simulations and the possibility of reducing the number of learning parameters in supervised learning based on RG inspired hierarchical ansatzes.

Reverse Genetics Approaches for the Development of Influenza Vaccines

PubMed Central

Nogales, Aitor; Martínez-Sobrido, Luis

2016-01-01

Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines. With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells. These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis. In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines. In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines. PMID:28025504

The genetic basis for cognitive ability, memory, and depression symptomatology in middle-aged and elderly chinese twins.

PubMed

Xu, Chunsheng; Sun, Jianping; Ji, Fuling; Tian, Xiaocao; Duan, Haiping; Zhai, Yaoming; Wang, Shaojie; Pang, Zengchang; Zhang, Dongfeng; Zhao, Zhongtang; Li, Shuxia; Hjelmborg, Jacob V B; Christensen, Kaare; Tan, Qihua

2015-02-01

The genetic influences on aging-related phenotypes, including cognition and depression, have been well confirmed in the Western populations. We performed the first twin-based analysis on cognitive performance, memory and depression status in middle-aged and elderly Chinese twins, representing the world's largest and most rapidly aging population. The sample consisted of 384 twin pairs with a median age of 50 years. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) scale; memory was assessed using the revised Wechsler Adult Intelligence scale; depression symptomatology was evaluated by the self-reported 30-item Geriatric Depression (GDS-30)scale. Both univariate and multivariate twin models were fitted to the three phenotypes with full and nested models and compared to select the best fitting models. Univariate analysis showed moderate-to-high genetic influences with heritability 0.44 for cognition and 0.56 for memory. Multivariate analysis by the reduced Cholesky model estimated significant genetic (rG = 0.69) and unique environmental (rE = 0.25) correlation between cognitive ability and memory. The model also estimated weak but significant inverse genetic correlation for depression with cognition (-0.31) and memory (-0.28). No significant unique environmental correlation was found for depression with other two phenotypes. In conclusion, there can be a common genetic architecture for cognitive ability and memory that weakly correlates with depression symptomatology, but in the opposite direction.

Accuracy of Igenity genomically estimated breeding values for predicting Australian Angus BREEDPLAN traits.

PubMed

Boerner, V; Johnston, D; Wu, X-L; Bauck, S

2015-02-01

Genomically estimated breeding values (GEBV) for Angus beef cattle are available from at least 2 commercial suppliers (Igenity [http://www.igenity.com] and Zoetis [http://www.zoetis.com]). The utility of these GEBV for improving genetic evaluation depends on their accuracies, which can be estimated by the genetic correlation with phenotypic target traits. Genomically estimated breeding values of 1,032 Angus bulls calculated from prediction equations (PE) derived by 2 different procedures in the U.S. Angus population were supplied by Igenity. Both procedures were based on Illuminia BovineSNP50 BeadChip genotypes. In procedure sg, GEBV were calculated from PE that used subsets of only 392 SNP, where these subsets were individually selected for each trait by BayesCπ. In procedure rg GEBV were calculated from PE derived in a ridge regression approach using all available SNP. Because the total set of 1,032 bulls with GEBV contained 732 individuals used in the Igenity training population, GEBV subsets were formed characterized by a decreasing average relationship between individuals in the subsets and individuals in the training population. Accuracies of GEBV were estimated as genetic correlations between GEBV and their phenotypic target traits modeling GEBV as trait observations in a bivariate REML approach, in which phenotypic observations were those recorded in the commercial Australian Angus seed stock sector. Using results from the GEBV subset excluding all training individuals as a reference, estimated accuracies were generally in agreement with those already published, with both types of GEBV (sg and rg) yielding similar results. Accuracies for growth traits ranged from 0.29 to 0.45, for reproductive traits from 0.11 to 0.53, and for carcass traits from 0.3 to 0.75. Accuracies generally decreased with an increasing genetic distance between the training and the validation population. However, for some carcass traits characterized by a low number of phenotypic records (weight, intramuscular fat, and eye muscle area), accuracies were observed to increase but had large SE. Therefore, Igenity GEBV can be useful to Australian Angus breeders, either for blending EBV or as the sole basis for selection decisions if no other information is available. However, for carcass traits, additional phenotypic data are required.

[Effect of ginsenoside Rg3 on Pim-3 and Bad proteins in human pancreatic cancer cell line PANC-1].

PubMed

Jian, Jie; Hu, Zhi-Fang; Huang, Yuan

2009-05-01

Ginsenoside Rg3 is a traditional Chinese medicine monomer which possesses anticancer effects. This study was to investigate the effects of ginsenoside Rg3 on Pim-3 and phosphorylated Bad (pBad) proteins, pBad (Ser112) and pBad (Ser136) in human pancreatic cancer cell line PANC-1. PANC-1 cells were exposed to 10, 20, 40 and 80 micromol/L ginsenoside Rg3 for 24 h. A short hairpin RNA (shRNA) of Pim-3 was cloned and inserted into a eukaryotic expression vector pSilencer 3.1-H1 Neo to construct pSilencer 3.1-H1 Neo-Pim-3. pSilencer 3.1-H1 Neo-Pim-3 was then transfected into PANC-1 cells. Cell proliferation was measured by MTT assay; cell apoptosis was observed under an invert microscope and measured by flow cytometry with Annexin V/PI staining; protein expressions of Pim-3, Bad, pBad (Ser112) and pBad (Ser136) were measured by Western blot. The inhibitory rates of 10, 20, 40 and 80 micromol/L ginsenoside Rg3 on PANC-1 cells were 20.2%, 33.4%, 52.8% and 65.3%, respectively. Typical morphological changes in apoptosis were induced by ginsenoside Rg3. The apoptotic rate of PANC-1 cells was significantly higher in the ginsenoside Rg3 treatment group (80 micromol/L) than in the control group (12.2% vs. 3.3%, P<0.05). Ginsenoside Rg3 had no influence on the total Bad protein expression, but decreased both Pim-3 and pBad (Ser112) expressions in a dose-dependent manner. pBad (Ser136) was not expressed in PANC-1 cells. Compared with the control group, the percentages of early and total apoptotic cells were significantly increased in PANC-1 cells transfected with pim-3-shRNA [(11.5+/-3.7)% vs. (5.8+/-2.2)%,P<0.01;(20.8+/-2.6)% vs.(13.0+/-4.1)%,P<0.05], while the expressions of pim-3 and pBad (Ser112) were both decreased. The anti-tumor effect of ginsenoside Rg3 may be associated with the decrease of Pim-3 and pBad (Ser112).

Tick infestations in extensively grazed cattle and efficacy trial of high-cis cypermethrin pour-on preparation for control of ticks in Mvomero district in Tanzania.

PubMed

Hezron E, Nonga; Adrian, Muwonge; Robinson H, Mdegela

2012-11-19

This study aimed at determining the extent of tick infestations in extensively grazed cattle and assess the efficacy of Ecotix® acaricide (2.5% high cis cypermethrin) in Mvomero district in Tanzania. A total of 1200 Tanzanian short horn Zebu (TSHZ) from two farms in two villages were qualitatively assessed for tick infestations and 40 animals (grouped in 10s from each farm) were separated in their herds and quantitatively examined to establish the tick load. The animals were grouped in treatment regime groups (TxRG 1, 2, 3, and 4), TxRG 1 being the control group was treated with water. Ecotix® was applied on day 0 for TxRG 2, days 0 and 7 for TxRG 3 and days 0, 7 and 14 for TxRG 4 and tick load was monitored for 28 days. All the animals examined were infested with ticks. The identified ticks were Rhipicephalus appendiculatus (55%), Amblyomma variegatum (18%), R. (Boophilus) microplus (12.9%), R. (B) decoloratus (7.1%), R. evertsi evertsi (4.4%) and R. composites (2.6%). The overall mean (mean±SEM) tick density on day zero was 63±30 ticks per animal (ranging from 20-160). The mean tick density on day zero was 44.6±25.4, 74.6±30.3, 55.0±26.2 and 77±33.5 for groups one, two, three and four respectively. Post-treatment quantitative assessment of tick burden revealed that the TxRG 1 animals maintained a tick load throughout the study period. A significant decrease in tick load in animals in groups TxRG 2, 3 and 4 (P=0.0001) with increasing frequency of Ecotix® application was recorded. There was however no significant difference in tick reduction between TxRG 3 and 4 (P=0.0986). Thus TxRG 3 would be sufficient for the monthly tick treatment and with this regime, the farmer would save up to 2.5 USD per animal during six months of dry season. The study revealed a high tick infestation among the TSHZ kept in extensive grazing systems in Mvomero district and that when treated with Ecotix® as pour-on preparation using a two application regime per month, the tick control strategy was effective.

Renewability and sustainability aspects of nuclear energy

NASA Astrophysics Data System (ADS)

Şahin, Sümer

2014-09-01

Renewability and sustainability aspects of nuclear energy have been presented on the basis of two different technologies: (1) Conventional nuclear technology; CANDU reactors. (2) Emerging nuclear technology; fusion/fission (hybrid) reactors. Reactor grade (RG) plutonium, 233U fuels and heavy water moderator have given a good combination with respect to neutron economy so that mixed fuel made of (ThO2/RG-PuO2) or (ThC/RG-PuC) has lead to very high burn up grades. Five different mixed fuel have been selected for CANDU reactors composed of 4 % RG-PuO2 + 96 % ThO2; 6 % RG-PuO2 + 94 % ThO2; 10 % RG-PuO2 + 90 % ThO2; 20 % RG-PuO2 + 80 % ThO2; 30 % RG-PuO2 + 70 % ThO2, uniformly taken in each fuel rod in a fuel channel. Corresponding operation lifetimes have been found as ˜ 0.65, 1.1, 1.9, 3.5, and 4.8 years and with burn ups of ˜ 30 000, 60 000, 100 000, 200 000 and 290 000 MW.d/ton, respectively. Increase of RG-PuO2 fraction in radial direction for the purpose of power flattening in the CANDU fuel bundle has driven the burn up grade to 580 000 MW.d/ton level. A laser fusion driver power of 500 MWth has been investigated to burn the minor actinides (MA) out of the nuclear waste of LWRs. MA have been homogenously dispersed as carbide fuel in form of TRISO particles with volume fractions of 0, 2, 3, 4 and 5 % in the Flibe coolant zone in the blanket surrounding the fusion chamber. Tritium breeding for a continuous operation of the fusion reactor is calculated as TBR = 1.134, 1.286, 1.387, 1.52 and 1.67, respectively. Fission reactions in the MA fuel under high energetic fusion neutrons have lead to the multiplication of the fusion energy by a factor of M = 3.3, 4.6, 6.15 and 8.1 with 2, 3, 4 and 5 % TRISO volume fraction at start up, respectively. Alternatively with thorium, the same fusion driver would produce ˜160 kg 233U per year in addition to fission energy production in situ, multiplying the fusion energy by a factor of ˜1.3.

Reinventing the ames test as a quantitative lab that connects classical and molecular genetics.

PubMed

Goodson-Gregg, Nathan; De Stasio, Elizabeth A

2009-01-01

While many institutions use a version of the Ames test in the undergraduate genetics laboratory, students typically are not exposed to techniques or procedures beyond qualitative analysis of phenotypic reversion, thereby seriously limiting the scope of learning. We have extended the Ames test to include both quantitative analysis of reversion frequency and molecular analysis of revertant gene sequences. By giving students a role in designing their quantitative methods and analyses, students practice and apply quantitative skills. To help students connect classical and molecular genetic concepts and techniques, we report here procedures for characterizing the molecular lesions that confer a revertant phenotype. We suggest undertaking reversion of both missense and frameshift mutants to allow a more sophisticated molecular genetic analysis. These modifications and additions broaden the educational content of the traditional Ames test teaching laboratory, while simultaneously enhancing students' skills in experimental design, quantitative analysis, and data interpretation.

Low resolution brain electromagnetic tomography in a realistic geometry head model: a simulation study

NASA Astrophysics Data System (ADS)

Ding, Lei; Lai, Yuan; He, Bin

2005-01-01

It is of importance to localize neural sources from scalp recorded EEG. Low resolution brain electromagnetic tomography (LORETA) has received considerable attention for localizing brain electrical sources. However, most such efforts have used spherical head models in representing the head volume conductor. Investigation of the performance of LORETA in a realistic geometry head model, as compared with the spherical model, will provide useful information guiding interpretation of data obtained by using the spherical head model. The performance of LORETA was evaluated by means of computer simulations. The boundary element method was used to solve the forward problem. A three-shell realistic geometry (RG) head model was constructed from MRI scans of a human subject. Dipole source configurations of a single dipole located at different regions of the brain with varying depth were used to assess the performance of LORETA in different regions of the brain. A three-sphere head model was also used to approximate the RG head model, and similar simulations performed, and results compared with the RG-LORETA with reference to the locations of the simulated sources. Multi-source localizations were discussed and examples given in the RG head model. Localization errors employing the spherical LORETA, with reference to the source locations within the realistic geometry head, were about 20-30 mm, for four brain regions evaluated: frontal, parietal, temporal and occipital regions. Localization errors employing the RG head model were about 10 mm over the same four brain regions. The present simulation results suggest that the use of the RG head model reduces the localization error of LORETA, and that the RG head model based LORETA is desirable if high localization accuracy is needed.

Changes in ginsenoside compositions and antioxidant activities of hydroponic-cultured ginseng roots and leaves with heating temperature

PubMed Central

Hwang, Cho Rong; Lee, Sang Hoon; Jang, Gwi Yeong; Hwang, In Guk; Kim, Hyun Young; Woo, Koan Sik; Lee, Junsoo; Jeong, Heon Sang

2014-01-01

Background This study evaluated changes in ginsenoside compositions and antioxidant activities in hydroponic-cultured ginseng roots (HGR) and leaves (HGL) with heating temperature. Methods Heat treatment was performed at temperatures of 90°C, 110°C, 130°C, and 150°C for 2 hours. Results The ginsenoside content varied significantly with heating temperature. The levels of ginsenosides Rg1 and Re in HGR decreased with increasing heating temperature. Ginsenosides F2, F4, Rk3, Rh4, Rg3 (S form), Rg3 (R form), Rk1, and Rg5, which were absent in the raw ginseng, were formed after heat treatment. The levels of ginsenosides Rg1, Re, Rf, and Rb1 in HGL decreased with increasing heating temperature. Conversely, ginsenosides Rk3, Rh4, Rg3 (R form), Rk1, and Rg5 increased with increasing heating temperature. In addition, ginsenoside contents of heated HGL were slightly higher than those of HGR. The highest extraction yield was 14.39% at 130°C, whereas the lowest value was 10.30% at 150°C. After heating, polyphenol contents of HGR and HGL increased from 0.43 mg gallic acid equivalent/g (mg GAE eq/g) and 0.74 mg GAE eq/g to 6.16 mg GAE eq/g and 2.86 mg GAE eq/g, respectively. Conclusion Antioxidant activities of HGR and HGL, measured by 1,1-diphenyl-2-picrylhydrazyl and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical scavenging ability, increased with increasing heating temperature. These results may aid in improving the biological activity and quality of ginseng subjected to heat treatments. PMID:25378992

Glycosylinositol phosphorylceramides from Rosa cell cultures are boron-bridged in the plasma membrane and form complexes with rhamnogalacturonan II.

PubMed

Voxeur, Aline; Fry, Stephen C

2014-07-01

Boron (B) is essential for plant cell-wall structure and membrane functions. Compared with its role in cross-linking the pectic domain rhamnogalacturonan II (RG-II), little information is known about the biological role of B in membranes. Here, we investigated the involvement of glycosylinositol phosphorylceramides (GIPCs), major components of lipid rafts, in the membrane requirement for B. Using thin-layer chromatography and mass spectrometry, we first characterized GIPCs from Rosa cell culture. The major GIPC has one hexose residue, one hexuronic acid residue, inositol phosphate, and a ceramide moiety with a C18 trihydroxylated mono-unsaturated long-chain base and a C24 monohydroxylated saturated fatty acid. Disrupting B bridging (by B starvation in vivo or by treatment with cold dilute HCl or with excess borate in vitro) enhanced the GIPCs' extractability. As RG-II is the main B-binding site in plants, we investigated whether it could form a B-centred complex with GIPCs. Using high-voltage paper electrophoresis, we showed that addition of GIPCs decreased the electrophoretic mobility of radiolabelled RG-II, suggesting formation of a GIPC-B-RG-II complex. Last, using polyacrylamide gel electrophoresis, we showed that added GIPCs facilitate RG-II dimerization in vitro. We conclude that B plays a structural role in the plasma membrane. The disruption of membrane components by high borate may account for the phytotoxicity of excess B. Moreover, the in-vitro formation of a GIPC-B-RG-II complex gives the first molecular explanation of the wall-membrane attachment sites observed in vivo. Finally, our results suggest a role for GIPCs in the RG-II dimerization process. © 2014 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.

Stable Overexpression of the Constitutive Androstane Receptor Reduces the Requirement for Culture with Dimethyl Sulfoxide for High Drug Metabolism in HepaRG Cells.

PubMed

van der Mark, Vincent A; Rudi de Waart, D; Shevchenko, Valery; Elferink, Ronald P J Oude; Chamuleau, Robert A F M; Hoekstra, Ruurdtje

2017-01-01

Dimethylsulfoxide (DMSO) induces cellular differentiation and expression of drug metabolic enzymes in the human liver cell line HepaRG; however, DMSO also induces cell death and interferes with cellular activities. The aim of this study was to examine whether overexpression of the constitutive androstane receptor (CAR, NR1I3), the nuclear receptor controlling various drug metabolism genes, would sufficiently promote differentiation and drug metabolism in HepaRG cells, optionally without using DMSO. By stable lentiviral overexpression of CAR, HepaRG cultures were less affected by DMSO in total protein content and obtained increased resistance to acetaminophen- and amiodarone-induced cell death. Transcript levels of CAR target genes were significantly increased in HepaRG-CAR cultures without DMSO, resulting in increased activities of cytochrome P450 (P450) enzymes and bilirubin conjugation to levels equal or surpassing those of HepaRG cells cultured with DMSO. Unexpectedly, CAR overexpression also increased the activities of non-CAR target P450s, as well as albumin production. In combination with DMSO treatment, CAR overexpression further increased transcript levels and activities of CAR targets. Induction of CYP1A2 and CYP2B6 remained unchanged, whereas CYP3A4 was reduced. Moreover, the metabolism of low-clearance compounds warfarin and prednisolone was increased. In conclusion, CAR overexpression creates a more physiologically relevant environment for studies on hepatic (drug) metabolism and differentiation in HepaRG cells without the utilization of DMSO. DMSO still may be applied to accomplish higher drug metabolism, required for sensitive assays, such as low-clearance studies and identification of (rare) metabolites, whereas reduced total protein content after DMSO culture is diminished by CAR overexpression. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

The effects of reduced gluten barley diet on humoral and cell-mediated systemic immune responses of gluten-sensitive rhesus macaques.

PubMed

Sestak, Karol; Thwin, Hazel; Dufour, Jason; Aye, Pyone P; Liu, David X; Moehs, Charles P

2015-03-06

Celiac disease (CD) affects approximately 1% of the general population while an estimated additional 6% suffers from a recently characterized, rapidly emerging, similar disease, referred to as non-celiac gluten sensitivity (NCGS). The only effective treatment of CD and NCGS requires removal of gluten sources from the diet. Since required adherence to a gluten-free diet (GFD) is difficult to accomplish, efforts to develop alternative treatments have been intensifying in recent years. In this study, the non-human primate model of CD/NCGS, e.g., gluten-sensitive rhesus macaque, was utilized with the objective to evaluate the treatment potential of reduced gluten cereals using a reduced gluten (RG; 1% of normal gluten) barley mutant as a model. Conventional and RG barleys were used for the formulation of experimental chows and fed to gluten-sensitive (GS) and control macaques to determine if RG barley causes a remission of dietary gluten-induced clinical and immune responses in GS macaques. The impacts of the RG barley diet were compared with the impacts of the conventional barley-containing chow and the GFD. Although remission of the anti-gliadin antibody (AGA) serum responses and an improvement of clinical diarrhea were noted after switching the conventional to the RG barley diet, production of inflammatory cytokines, e.g., interferon-gamma (IFN-γ), tumor necrosis factor (TNF) and interleukin-8 (IL-8) by peripheral CD4+ T helper lymphocytes, persisted during the RG chow treatment and were partially abolished only upon re-administration of the GFD. It was concluded that the RG barley diet might be used for the partial improvement of gluten-induced disease but its therapeutic value still requires upgrading-by co-administration of additional treatments.

The Effects of Reduced Gluten Barley Diet on Humoral and Cell-Mediated Systemic Immune Responses of Gluten-Sensitive Rhesus Macaques

PubMed Central

Sestak, Karol; Thwin, Hazel; Dufour, Jason; Aye, Pyone P.; Liu, David X.; Moehs, Charles P.

2015-01-01

Celiac disease (CD) affects approximately 1% of the general population while an estimated additional 6% suffers from a recently characterized, rapidly emerging, similar disease, referred to as non-celiac gluten sensitivity (NCGS). The only effective treatment of CD and NCGS requires removal of gluten sources from the diet. Since required adherence to a gluten-free diet (GFD) is difficult to accomplish, efforts to develop alternative treatments have been intensifying in recent years. In this study, the non-human primate model of CD/NCGS, e.g., gluten-sensitive rhesus macaque, was utilized with the objective to evaluate the treatment potential of reduced gluten cereals using a reduced gluten (RG; 1% of normal gluten) barley mutant as a model. Conventional and RG barleys were used for the formulation of experimental chows and fed to gluten-sensitive (GS) and control macaques to determine if RG barley causes a remission of dietary gluten-induced clinical and immune responses in GS macaques. The impacts of the RG barley diet were compared with the impacts of the conventional barley-containing chow and the GFD. Although remission of the anti-gliadin antibody (AGA) serum responses and an improvement of clinical diarrhea were noted after switching the conventional to the RG barley diet, production of inflammatory cytokines, e.g., interferon-gamma (IFN-γ), tumor necrosis factor (TNF) and interleukin-8 (IL-8) by peripheral CD4+ T helper lymphocytes, persisted during the RG chow treatment and were partially abolished only upon re-administration of the GFD. It was concluded that the RG barley diet might be used for the partial improvement of gluten-induced disease but its therapeutic value still requires upgrading—by co-administration of additional treatments. PMID:25756783

Glycosylinositol phosphorylceramides from Rosa cell cultures are boron-bridged in the plasma membrane and form complexes with rhamnogalacturonan II

PubMed Central

Voxeur, Aline; Fry, Stephen C

2014-01-01

Boron (B) is essential for plant cell-wall structure and membrane functions. Compared with its role in cross-linking the pectic domain rhamnogalacturonan II (RG-II), little information is known about the biological role of B in membranes. Here, we investigated the involvement of glycosylinositol phosphorylceramides (GIPCs), major components of lipid rafts, in the membrane requirement for B. Using thin-layer chromatography and mass spectrometry, we first characterized GIPCs from Rosa cell culture. The major GIPC has one hexose residue, one hexuronic acid residue, inositol phosphate, and a ceramide moiety with a C18 trihydroxylated mono-unsaturated long-chain base and a C24 monohydroxylated saturated fatty acid. Disrupting B bridging (by B starvation in vivo or by treatment with cold dilute HCl or with excess borate in vitro) enhanced the GIPCs’ extractability. As RG-II is the main B-binding site in plants, we investigated whether it could form a B-centred complex with GIPCs. Using high-voltage paper electrophoresis, we showed that addition of GIPCs decreased the electrophoretic mobility of radiolabelled RG-II, suggesting formation of a GIPC–B–RG-II complex. Last, using polyacrylamide gel electrophoresis, we showed that added GIPCs facilitate RG-II dimerization in vitro. We conclude that B plays a structural role in the plasma membrane. The disruption of membrane components by high borate may account for the phytotoxicity of excess B. Moreover, the in-vitro formation of a GIPC–B–RG-II complex gives the first molecular explanation of the wall–membrane attachment sites observed in vivo. Finally, our results suggest a role for GIPCs in the RG-II dimerization process. PMID:24804932

Effects of a Chinese medical herbs complex on cellular immunity and toxicity-related conditions of breast cancer patients.

PubMed

Zhuang, S R; Chiu, H F; Chen, S L; Tsai, J H; Lee, M Y; Lee, H S; Shen, Y C; Yan, Y Y; Shane, G T; Wang, C-K

2012-03-01

Rose geranium (Pelargonium graveolens, Geraniaceae) has anti-cancer and anti-inflammatory properties, and promotes wound healing. Similarly, Ganoderma tsugae (Ganodermataceae), Codonopsis pilosula (Campanulaceae) and Angelica sinensis (Apiaceae) are traditional Chinese herbs associated with immunomodulatory functions. In the present study, a randomised, double-blind, placebo-controlled study was conducted to examine whether the Chinese medicinal herb complex, RG-CMH, which represents a mixture of rose geranium and extracts of G. tsugae, C. pilosula and A. sinensis, can improve the immune cell count of cancer patients receiving chemotherapy and/or radiotherapy to prevent leucopenia and immune impairment that usually occurs during cancer therapy. A total of fifty-eight breast cancer patients who received chemotherapy or radiotherapy were enrolled. Immune cell levels in patient serum were determined before, and following, 6 weeks of cancer treatment for patients receiving either an RG-CMH or a placebo. Administration of RG-CMH was associated with a significant reduction in levels of leucocytes from 31·5 % for the placebo group to 13·4 % for the RG-CMH group. Similarly, levels of neutrophils significantly decreased from 35·6 % for the placebo group to 11·0 % for the RG-CMH group. RG-CMH intervention was also associated with a decrease in levels of T cells, helper T cells, cytotoxic T cells and natural killer cells compared with the placebo group. However, these differences between the two groups were not statistically significant. In conclusion, administration of RG-CMH to patients receiving chemotherapy/radiotherapy may have the capacity to delay, or ease, the reduction in levels of leucocytes and neutrophils that are experienced by patients during cancer treatment.

The gene responsible for borate cross-linking of pectin Rhamnogalacturonan-II is required for plant reproductive tissue development and fertilization

PubMed Central

Iwai, Hiroaki; Hokura, Akiko; Oishi, Masahiro; Chida, Hiroshi; Ishii, Tadashi; Sakai, Shingo; Satoh, Shinobu

2006-01-01

Deficiencies in boron, a microelement that is essential for the growth and development of higher plants, often cause problems in reproductive growth. Rhamnogalacturonan-II (RG-II) in cell wall pectin acts as the sole receptor for boron in plant cells, forming a borate cross-linked RG-II dimer (dRG-II-B), but the physiological functions of dRG-II-B remain unknown. We have previously shown that the pectin glucuronyltransferase 1 gene NpGUT1, which is involved in the biosynthesis of RG-II sugar chains, is essential for the formation of the RG-II-B complex, resulting in tight intercellular attachment in meristematic tissues. Because NpGUT1 expression was found to be abundant in reproductive organs in addition to meristematic tissues, we analyzed the expression and functions of NpGUT1 in more detail in tobacco reproductive tissues. Specific NpGUT1 expression was detected in the tapetum of flower buds and in the pollen, pollen tube tips, and transmitting tissue of the pistils of flowers. Dexamethasone-induced expression of the NpGUT1 antisense gene in flower buds resulted in the formation of sterile flowers with aberrant development of pollen and transmitting tissue. Pollen tubes could not pass through pistils with aborted transmitting tissue, and expression of an NpGUT1 antisense gene in germinating pollen inhibited pollen tube elongation, accompanied by the absence of pectin RG-II and boron in the pollen tube tip. These results indicate that expression of NpGUT1 is required for the development and functions of male and female tissues. PMID:17053077

Comparative Proteomics Reveals Novel Components at the Plasma Membrane of Differentiated HepaRG Cells and Different Distribution in Hepatocyte- and Biliary-Like Cells

PubMed Central

Woods, Alisa G.; Lazar, Catalin; Radu, Gabriel L.; Darie, Costel C.; Branza-Nichita, Norica

2013-01-01

Hepatitis B virus (HBV) is a human pathogen causing severe liver disease and eventually death. Despite important progress in deciphering HBV internalization, the early virus-cell interactions leading to infection are not known. HepaRG is a human bipotent liver cell line bearing the unique ability to differentiate towards a mixture of hepatocyte- and biliary-like cells. In addition to expressing metabolic functions normally found in liver, differentiated HepaRG cells support HBV infection in vitro, thus resembling cultured primary hepatocytes more than other hepatoma cells. Therefore, extensive characterization of the plasma membrane proteome from HepaRG cells would allow the identification of new cellular factors potentially involved in infection. Here we analyzed the plasma membranes of non-differentiated and differentiated HepaRG cells using nanoliquid chromatography-tandem mass spectrometry to identify the differences between the proteomes and the changes that lead to differentiation of these cells. We followed up on differentially-regulated proteins in hepatocytes- and biliary-like cells, focusing on Cathepsins D and K, Cyclophilin A, Annexin 1/A1, PDI and PDI A4/ERp72. Major differences between the two proteomes were found, including differentially regulated proteins, protein-protein interactions and intracellular localizations following differentiation. The results advance our current understanding of HepaRG differentiation and the unique properties of these cells. PMID:23977166

Novel nitrogen-fixing Acetobacter nitrogenifigens sp. nov., isolated from Kombucha tea.

PubMed

Dutta, Debasree; Gachhui, Ratan

2006-08-01

The four nitrogen-fixing bacteria so far described in the family Acetobacteraceae belong to the genera Gluconacetobacter and Acetobacter. Nitrogen-fixing bacterial strain RG1(T) was isolated from Kombucha tea and, based on the phylogenetic analysis of 16S rRNA gene sequence which is supported by a high bootstrap value, was found to belong to the genus Acetobacter. Strain RG1(T) differed from Acetobacter aceti, the nearest member with a 16S rRNA gene sequence similarity of 98.2 %, and type strains of other Acetobacter species with regard to several characteristics of growth features in culture media, growth in nitrogen-free medium, production of gamma-pyrone from glucose and dihydroxyacetone from glycerol. Strain RG1(T) utilized maltose, glycerol, sorbitol, fructose, galactose, arabinose and ethanol, but not methanol as a carbon source. These results, along with electrophoretic mobility patterns of nine metabolic enzymes, suggest that strain RG1(T) represents a novel nitrogen-fixing species. The ubiquinone present was Q-9 and DNA G+C content was 64.1 mol%. Strain RG1(T) exhibited a low value of 2-24 % DNA-DNA relatedness to the type strains of related acetobacters, which placed it as a separate taxon. On the basis of this data, the name Acetobacter nitrogenifigens sp. nov. is proposed, with the type strain RG1(T) (=MTCC 6912(T)=LMG 23498(T)).

Comparative proteomics reveals novel components at the plasma membrane of differentiated HepaRG cells and different distribution in hepatocyte- and biliary-like cells.

PubMed

Petrareanu, Catalina; Macovei, Alina; Sokolowska, Izabela; Woods, Alisa G; Lazar, Catalin; Radu, Gabriel L; Darie, Costel C; Branza-Nichita, Norica

2013-01-01

Hepatitis B virus (HBV) is a human pathogen causing severe liver disease and eventually death. Despite important progress in deciphering HBV internalization, the early virus-cell interactions leading to infection are not known. HepaRG is a human bipotent liver cell line bearing the unique ability to differentiate towards a mixture of hepatocyte- and biliary-like cells. In addition to expressing metabolic functions normally found in liver, differentiated HepaRG cells support HBV infection in vitro, thus resembling cultured primary hepatocytes more than other hepatoma cells. Therefore, extensive characterization of the plasma membrane proteome from HepaRG cells would allow the identification of new cellular factors potentially involved in infection. Here we analyzed the plasma membranes of non-differentiated and differentiated HepaRG cells using nanoliquid chromatography-tandem mass spectrometry to identify the differences between the proteomes and the changes that lead to differentiation of these cells. We followed up on differentially-regulated proteins in hepatocytes- and biliary-like cells, focusing on Cathepsins D and K, Cyclophilin A, Annexin 1/A1, PDI and PDI A4/ERp72. Major differences between the two proteomes were found, including differentially regulated proteins, protein-protein interactions and intracellular localizations following differentiation. The results advance our current understanding of HepaRG differentiation and the unique properties of these cells.

In vitro anti-mycobacterial activity of (E)-N'-(monosubstituted-benzylidene) isonicotinohydrazide derivatives against isoniazid-resistant strains

PubMed Central

Coelho, Tatiane S.; Cantos, Jessica B.; Bispo, Marcelle L.F.; Gonçalves, Raoni S.B.; Lima, Camilo H.S.; da Silva, Pedro E.A.; Souza, Marcus V. N.

2012-01-01

A series of twenty-three N-acylhydrazones derived from isoniazid (INH 1-23) have been evaluated for their in vitro antibacterial activity against INH- susceptible strain of M. tuberculosis (RG500) and three INH-resistant clinical isolates (RG102, RG103 and RG113). In general, derivatives 4, 14, 15 and 16 (MIC=1.92, 1.96, 1.96 and 1.86 µM, respectively) showed relevant activities against RG500 strain, while the derivative 13 (MIC=0.98 µM) was more active than INH (MIC=1.14 µM). However, these derivatives were inactive against RGH102, which displays a mutation in the coding region of inhA. These results suggest that the activities of these compounds depend on the inhibition of this enzyme. However, the possibility of other mechanisms of action cannot be excluded, since compounds 2, 4, 6, 7, 12–17, 19, 21 and 23 showed good activities against katG-resistant strain RGH103, being more than 10-fold more active than INH. PMID:24470920

Centennial variations in sunspot number, open solar flux, and streamer belt width: 2. Comparison with the geomagnetic data

NASA Astrophysics Data System (ADS)

Lockwood, M.; Owens, M. J.; Barnard, L.

2014-07-01

We investigate the relationship between interdiurnal variation geomagnetic activity indices, IDV and IDV(1d), corrected sunspot number, RC , and the group sunspot number RG . RC uses corrections for both the "Waldmeier discontinuity," as derived in Paper 1, and the "Wolf discontinuity" revealed by Leussu et al. (2013). We show that the simple correlation of the geomagnetic indices with RCn or RGn masks a considerable solar cycle variation. Using IDV(1d) or IDV to predict or evaluate the sunspot numbers, the errors are almost halved by allowing for the fact that the relationship varies over the solar cycle. The results indicate that differences between RC and RG have a variety of causes and are highly unlikely to be attributable to errors in either RG alone, as has recently been assumed. Because it is not known if RC or RG is a better predictor of open flux emergence before 1874, a simple sunspot number composite is suggested which, like RG , enables modeling of the open solar flux for 1610 onward in Paper 3 but maintains the characteristics of RC .

Effects of fragility and reduced glass transition temperature on the glass formation ability of amorphous alloys

NASA Astrophysics Data System (ADS)

Xu, Xiao-Jin; Long, Zhi-Lin; Liu, Wei; Liao, Guang-Kai

2017-11-01

In this paper, based on the reduced glass transition temperature ({{T}rg} ) proposed by Turnbull and the relation between the glass-forming ability (GFA) and the short-range bond ordering of liquids demonstrated by Tanaka, a detailed analysis on the specific roles of {{T}rg} and fragility of the glass forming liquid (m) in characterizing the GFA has been conducted, and then a novel GFA parameter α [=2/3× (100{{T}rg}{)}-(16/100)× m=67{{T}rg}-0.16m] was put forward. This new GFA parameter α , which increases with a decrease in the critical cooling rate (R c) for glass formation, is a complex function of {{T}rg} and m. The relationship between R c and the parameter α was identified and verified using available literature data for broad range of amorphous alloys with widely varying GFA. The correlation coefficient (R 2) of 0.9 clearly shows an excellent correlation between GFA and the parameter α and that α is a more superior indicator compared to currently reported similar GFA parameters.

Investigation of structural heterogeneity at the SPE site using combined P–wave travel times and Rg phase velocities

DOE PAGES

Rowe, Charlotte A.; Patton, Howard J.

2015-10-01

Here, we present analyses of the 2D seismic structure beneath Source Physics Experiments (SPE) geophone lines that extended radially at 100 m spacing from 100 to 2000 m from the source borehole. With seismic sources at only one end of the geophone lines, standard refraction profiling methods cannot resolve seismic velocity structures unambiguously. In previous work, we demonstrated overall agreement between body-wave refraction modeling and Rg dispersion curves for the least complex of the five lines. A more detailed inspection supports a 2D reinterpretation of the structure. We obtained Rg phase velocity measurements in both the time and frequency domains,more » then used iterative adjustment of the initial 1D body-wave model to predict Rg dispersion curves to fit the observed values. Our method applied to the most topographically severe of the geophone lines is supplemented with a 2D ray-tracing approach, whose application to P-wave arrivals supports the Rg analysis. In addition, midline sources will allow us to refine our characterization in future work.« less

Gene expression of the p16(INK4a)-Rb and p19(Arf)-p53-p21(Cip/Waf1) signaling pathways in the regulation of hematopoietic stem cell aging by ginsenoside Rg1.

PubMed

Yue, Z; Rong, J; Ping, W; Bing, Y; Xin, Y; Feng, L D; Yaping, W

2014-12-04

The elucidation of the molecular mechanisms underlying the effects of traditional Chinese medicines in clinical practice is a key step toward their worldwide application, and this topic is currently a subject of intense research interest. Rg1, a component of ginsenoside, has recently been shown to perform several pharmacological functions; however, the underlying mechanisms of these effects remain unclear. In the present study, we investigated whether Rg1 has an anti-senescence effect on hematopoietic stem cells (HSCs) and the possible molecular mechanisms driving any effects. The results showed that Rg1 could effectively delay tert-butyl hydroperoxide (t-BHP)-induced senescence and inhibit gene expression in the p16(INK4a)-Rb and p19(Arf)-p53-p21(Cip/Waf1) signaling pathways in HSCs. Our study suggested that these two signaling pathways might be potential targets for elucidating the molecular mechanisms of the Rg1 anti-senescence effect.

Thermodynamic properties for bunsenite, NiO, magnetite, Fe3O4, and hematite, Fe2O3, with comments on selected oxygen buffer reactions

USGS Publications Warehouse

Hemingway, B.S.

1990-01-01

Smoothed values of the heat capacities and derived thermodynamic functions are given for bunsenite, magnetite, and hematite for the temperature interval 298.15 to 1800 K. The Gibbs free energy for the reaction Ni + 0.5O2 = NiO is given by the equation ??rG0T = -238.39 + 0.1146T - 3.72 ?? 10-3T ln T and is valid from 298.15 K to 1700 K. The Gibbs free energy (in kJ) of the reaction 2 magnetite + 3 quartz = 3 fayalite + O2 may be calculated from the equation ??rG0T = 474.155 - 0.16120 T in kJ and between 800 and 1400 K. The Gibbs free energy (in kJ) of the reaction 6 hematite = 4 magnetite + O2 may be calculated from the following equations: ??rG0T = 496.215 - 0.27114T, ??rG0T = 514.690 - 0.29753T, ??rG0T = 501.348 - 0.2854T. -from Author

Study on Quality Indicator System of Rhythmic Gymnasts in Analytic Hierarchy Process

NASA Astrophysics Data System (ADS)

Luo, Lin

2017-08-01

The rhythmic gymnastics (RG) is a sport item with the direct aim of winning as well as a good ornamental value. The scientific selection by the rhythmic gymnasts is necessary for the success, and also the beginning for the scientific training of the gymnasts in their special training stage. According to RG characteristics and the physical characteristics of the gymnasts, also in combination with the investigations & interviews to the coaches who have years of training experience in RG, the experts & scholars on RG study & teaching in universities, and by referring to relevant documents, this paper established the quality indicator system in analytic hierarchy process (AHP). We summarized and selected several indicators obviously influencing the RG training and divided them into the three types of factors: physical factors, flexibility & strength factors, and speed & dexterity factors, according to which 12 specific indicators, their weights and comprehensive evaluation coefficients. Based on these indicators, we established the quality indicator system of the gymnasts, and developed corresponding software system, providing scientific theoretical basis & practical application basis for the selection & evaluation of the gymnasts.

Effects of a long-acting mutant bacterial cocaine esterase on acute cocaine toxicity in rats

PubMed Central

Collins, Gregory T.; Zaks, Matthew E.; Cunningham, Alyssa R.; St. Clair, Carley; Nichols, Joseph; Narasimhan, Diwahar; Ko, Mei-Chuan; Sunahara, Roger K.; Woods, James H.

2011-01-01

Background A longer acting, double mutant bacterial cocaine esterase (CocE T172R/G173Q; DM CocE) has been shown to protect mice from cocaine-induced lethality, inhibit the reinforcing effects of cocaine in rats, and reverse cocaine’s cardiovascular effects in rhesus monkeys. The current studies evaluated the effectiveness of DM CocE to protect against, and reverse cocaine’s cardiovascular, convulsant, and lethal effects in male and female rats. Methods Pretreatment studies were used to determine the effectiveness and in vivo duration of action for DM CocE to protect rats against the occurrence of cardiovascular changes, convulsion and lethality associated with acute cocaine toxicity. Posttreatment studies were used to evaluate the capacity of DM CocE to rescue rats from the cardiovascular and lethal effects of large doses of cocaine. In addition, male and female rats were studied to determine if there were any potential effects of sex on the capacity of DM CocE to protect against, or reverse acute cocaine toxicity in rats. Results Pretreatment with DM CocE dose-dependently protected rats against cocaine-induced cardiovascular changes, convulsion and lethality, with higher doses active for up to 4 hrs, and shifting cocaine-induced lethality at least 10-fold to the right. In addition to dose-dependently recovering rats from an otherwise lethal dose of cocaine, post-treatment with DM CocE also reversed the cardiovascular effects of cocaine. There were no sex-related differences in the effectiveness of DM CocE to protect against, or reverse acute cocaine toxicity. Conclusions Together, these results support the development of DM CocE for the treatment of acute cocaine toxicity. PMID:21481548

High-performance supercapacitors based on poly(ionic liquid)-modified graphene electrodes.

PubMed

Kim, Tae Young; Lee, Hyun Wook; Stoller, Meryl; Dreyer, Daniel R; Bielawski, Christopher W; Ruoff, Rodney S; Suh, Kwang S

2011-01-25

We report a high-performance supercapacitor incorporating a poly(ionic liquid)-modified reduced graphene oxide (PIL:RG-O) electrode and an ionic liquid (IL) electrolyte (specifically, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide or EMIM-NTf(2)). PIL:RG-O provides enhanced compatibility with the IL electrolyte, thereby increasing the effective electrode surface area accessible to electrolyte ions. The supercapacitor assembled with PIL:RG-O electrode and EMIM-NTf(2) electrolyte showed a stable electrochemical response up to 3.5 V operating voltage and was capable of yielding a maximum energy density of 6.5 W·h/kg with a power density of 2.4 kW/kg. These results demonstrate the potential of the PIL:RG-O material as an electrode in high-performance supercapacitors.

Whole-Genome Sequence of Pseudomonas fluorescens EK007-RG4, a Promising Biocontrol Agent against a Broad Range of Bacteria, Including the Fire Blight Bacterium Erwinia amylovora.

PubMed

Habibi, Roghayeh; Tarighi, Saeed; Behravan, Javad; Taheri, Parissa; Kjøller, Annelise Helene; Brejnrod, Asker; Madsen, Jonas Stenløkke; Sørensen, Søren Johannes

2017-03-30

Here, we report the first draft whole-genome sequence of Pseudomonas fluorescens strain EK007-RG4, which was isolated from the phylloplane of a pear tree. P. fluorescens EK007-RG4 displays strong antagonism against Erwinia amylovora , the causal agent for fire blight disease, in addition to several other pathogenic and non-pathogenic bacteria. Copyright © 2017 Habibi et al.

Renovascular hypertension

MedlinePlus

... and Rector's The Kidney . 10th ed. Philadelphia, PA: Elsevier Saunders; 2015:chap 48. Victor RG. Arterial hypertension. ... eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 67. Victor RG. Systemic hypertension: ...

[The bonding characteristic of titanium and RG experiment porcelain].

PubMed

Ren, Wei-hong; Guo, Tian-wen; Tian, Jie-mo; Zhang, Yun-long

2003-07-01

To study the bonding characteristic of Titanium and RG experiment porcelain. 5 specimens with a size of 10 mm x 5 mm x 1.4 mm were cast from pure titanium. Then 1 mm of RG experiment opaque and body porcelain were fused on the surface of the titanium specimens. The interface of titanium and porcelain was analyzed with a scanning electron microscope with energy-despersive spectrometry; 6 metal specimens with the size of 25 mm x 3 mm x 0.5 mm were cast from Ni-Cr alloy and a uniform thickness of 1 mm of VMK 99 porcelain was veneered on the central area of 8 mm x 3 mm 18 metal specimens as the same size were cast from pure titanium. The uniform thickness of 1 mm of VITA TITANKERAMIK porcelain, of Noritake super porcelain Ti-22 and of RG experiment porcelain were veneered on every 6 specimens respectively in the central area of 8 mm x 3 mm. The specimens were subjected to a three-point bending test on a load-test machine with a span of 20 mm, then the failure loads were recorded and statistically analysised. The RG porcelain/titanium crown was fabricated by fusing RG opaque porcelain and body porcelain to cast titanium substrate crown. The SEM results show no porosity and crackle were found in the interface. The energy-dispersive spectrometry show that there are Si, Ti and O in the 1 micro m layer between porcelain and titanium, which suggesting titanium and experiment porcelain bonding well. The three point test showed the fracture force for the combinations of titanium/VITA TITANKERAMIK porcelain, titanium/Noritake super porcelain Ti-22 and titanium/RG experiment porcelain were (7.233 +/- 2.539) N, (5.533 +/- 1.199) N and (6.316 +/- 1.433) N respectively. There were not statistically significant differences among them (t test, P < 0.01). The fracture force for the Ni-Cr alloy/VMK99 porcelain combination (12.733 +/- 3.297) N was significantly greater than those of the cast titanium/porcelain (t test, P > 0.05). The crown was translucent with no crack. RG porcelain is well compatible with titanium.

Chimeric L2-Based Virus-Like Particle (VLP) Vaccines Targeting Cutaneous Human Papillomaviruses (HPV).

PubMed

Huber, Bettina; Schellenbacher, Christina; Shafti-Keramat, Saeed; Jindra, Christoph; Christensen, Neil; Kirnbauer, Reinhard

2017-01-01

Common cutaneous human papillomavirus (HPV) types induce skin warts, whereas species beta HPV are implicated, together with UV-radiation, in the development of non-melanoma skin cancer (NMSC) in immunosuppressed patients. Licensed HPV vaccines contain virus-like particles (VLP) self-assembled from L1 major capsid proteins that provide type-restricted protection against mucosal HPV infections causing cervical and other ano-genital and oro-pharyngeal carcinomas and warts (condylomas), but do not target heterologous HPV. Experimental papillomavirus vaccines have been designed based on L2 minor capsid proteins that contain type-common neutralization epitopes, to broaden protection to heterologous mucosal and cutaneous HPV types. Repetitive display of the HPV16 L2 cross-neutralization epitope RG1 (amino acids (aa) 17-36) on the surface of HPV16 L1 VLP has greatly enhanced immunogenicity of the L2 peptide. To more directly target cutaneous HPV, L1 fusion proteins were designed that incorporate the RG1 homolog of beta HPV17, the beta HPV5 L2 peptide aa53-72, or the common cutaneous HPV4 RG1 homolog, inserted into DE surface loops of HPV1, 5, 16 or 18 L1 VLP scaffolds. Baculovirus expressed chimeric proteins self-assembled into VLP and VLP-raised NZW rabbit immune sera were evaluated by ELISA and L1- and L2-based pseudovirion (PsV) neutralizing assays, including 12 novel beta PsV types. Chimeric VLP displaying the HPV17 RG1 epitope, but not the HPV5L2 aa53-72 epitope, induced cross-neutralizing humoral immune responses to beta HPV. In vivo cross-protection was evaluated by passive serum transfer in a murine PsV challenge model. Immune sera to HPV16L1-17RG1 VLP (cross-) protected against beta HPV5/20/24/38/96/16 (but not type 76), while antisera to HPV5L1-17RG1 VLP cross-protected against HPV20/24/96 only, and sera to HPV1L1-4RG1 VLP cross-protected against HPV4 challenge. In conclusion, RG1-based VLP are promising next generation vaccine candidates to target cutaneous HPV infections.

HepaRG human hepatic cell line utility as a surrogate for primary human hepatocytes in drug metabolism assessment in vitro.

PubMed

Lübberstedt, Marc; Müller-Vieira, Ursula; Mayer, Manuela; Biemel, Klaus M; Knöspel, Fanny; Knobeloch, Daniel; Nüssler, Andreas K; Gerlach, Jörg C; Zeilinger, Katrin

2011-01-01

Primary human hepatocytes are considered as a highly predictive in vitro model for preclinical drug metabolism studies. Due to the limited availability of human liver tissue for cell isolation, there is a need of alternative cell sources for pharmaceutical research. In this study, the metabolic activity and long-term stability of the human hepatoma cell line HepaRG were investigated in comparison to primary human hepatocytes (pHH). Hepatocyte-specific parameters (albumin and urea synthesis, galactose and sorbitol elimination) and the activity of human-relevant cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) were assayed in both groups over a period of 14 days subsequently to a two week culture period in differentiated state in case of the HepaRG cells, and compared with those of cryopreserved hepatocytes in suspension. In addition, the inducibility of CYP enzymes and the intrinsic clearances of eleven reference drugs were determined. The results show overall stable metabolic activity of HepaRG cells over the monitored time period. Higher albumin production and galactose/sorbitol elimination rates were observed compared with pHH, while urea production was not detected. CYP enzyme-dependent drug metabolic capacities were shown to be stable over the cultivation time in HepaRG cells and were comparable or even higher (CYP2C9, CYP2D6, CYP3A4) than in pHH, whereas commercially available hepatocytes showed a different pattern The intrinsic clearance rates of reference drugs and enzyme induction of most CYP enzymes were similar in HepaRG cells and pHH. CYP1A2 activity was highly inducible in HepaRG by β-naphthoflavone. In conclusion, the results from this study indicate that HepaRG cells could provide a suitable alternative to pHH in pharmaceutical research and development for metabolism studies such as CYP induction or sub-chronic to chronic hepatotoxicity studies. Copyright © 2010 Elsevier Inc. All rights reserved.

Thymidylate Synthase Gene Polymorphism Affects the Response to Preoperative 5-Fluorouracil Chemoradiation Therapy in Patients With Rectal Cancer

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

Hur, Hyuk; Kang, Jeonghyun; Kim, Nam Kyu, E-mail: namkyuk@yuhs.ac

2011-11-01

Purpose: This study aims to correlate thymidylate synthase (TS) gene polymorphisms with the tumor response to preoperative 5-fluorouracil (5-FU)-based chemoradiation therapy (CRT) in patients with rectal cancer. Methods and Materials: Forty-four patients with rectal cancer treated with 5-FU-based preoperative CRT were prospectively enrolled in this study. Thymidylate synthase expression and TS gene polymorphisms were evaluated in tumor obtained before preoperative CRT and were correlated with the pathologic response, as assessed by histopathologic staging (pTNM) and tumor regression grade. Results: Patients exhibited 2R/3R and 3R/3R tandem repeat polymorphisms in the TS gene. With regard to TS expression in these genotypes, 2R/3RCmore » and 3RC/3RC were defined as the low-expression group and 2R/3RG, 3RC/3RG, and 3RG/3RG as the high-expression group. There was no significant correlation between TS expression and tumor response. There was no significant difference in the tumor response between patients homozygous for 3R/3R and patients heterozygous for 2R/3R. However, 13 of 14 patients in the low-expression group with a G>C single-nucleotide polymorphism (SNP) (2R/3RC [n = 5] or 3RC/3RC [n = 9]) exhibited a significantly greater tumor downstaging rate, as compared with only 12 of 30 patients in the high-expression group without the SNP (2R/3RG [n = 10], 3RC/3RG [n = 9], or 3RG/3RG [n = 11]) (p = 0.001). The nodal downstaging rate was also significantly greater in this low-expression group, as compared with the high-expression group (12 of 14 vs. 14 of 30, p = 0.014). However, there was no significant difference in the tumor regression grade between these groups. Conclusions: This study suggests that SNPs within the TS enhancer region affect the tumor response to preoperative 5-FU-based CRT in rectal cancer.« less

Reconstitution of the R compound allele in maize.

PubMed

Dooner, H K; Kermicle, J L

1974-10-01

The R(r):standard allele in maize, which conditions anthocyanin pigmentation in plant and seed tissues in the presence of appropriate complementary factors, is associated with a tandem duplication. The proximal member of the duplication carries P, the plant pigmenting determiner and the distal member member carries S, the seed pigmenting determiner. Derivatives from R(r) that have lost S function are designated r(r). They represent either losses of the distal member of the duplication (P derivatives) or mutations of S to s (P s). Derivatives that have lost P function are designated R(g), and represent either losses of the proximal member of the duplication (S derivatives) or mutations of P to p (p S).-All four possible types of r(r)/R(g) heterozygotes were tested for their capacity to yield R(r) reconstitution by crossing over. No R(r) derivatives were obtained from P/S heterozygotes, a result consistent with the view that P and S occupy corresponding positions in homologous chromosome segments. R(r) reconstitution was detected in both tandem duplication heterozygotes P s/S and P/p S, and was found to be about ten times more frequent in the latter. The ratio of R(r) reconstitution in the two heterozygotes is a function of position of the anthocyanin marker within the duplicated segment. The data from these heterozygotes allow one to measure the distance between P and S, that is to say, the genetic length of the duplicated segment. This distance was found to be 0.16 map units. The highest frequency of R(r) reconstitution was obtained from P s/p S heterozygotes, since direct pairing (see PDF) as well as the p//s type of displaced pairing have the potential to produce R(r) derivatives. One of the R(g) derivatives used in this study, R(g) (6), was found to back-mutate in some sublines to R(r). The basis for this instability remains unknown.

230Th-U dating of surficial deposits using the ion microprobe (SHRIMP-RG): A microstratigraphic perspective

USGS Publications Warehouse

Maher, K.; Wooden, J.L.; Paces, J.B.; Miller, D.M.

2007-01-01

We used the sensitive high-resolution ion microprobe reverse-geometry (SHRIMP-RG) to date pedogenic opal using the 230Th-U system. Due to the high-spatial resolution of an ion microprobe (typically 30 ??m), regions of pure opal within a sample can be targeted and detrital material can be avoided. In addition, because the technique is non-destructive, the sample can be preserved for other types of analyses including electron microprobe or other stable isotope or trace element ion microprobe measurements. The technique is limited to material with U concentrations greater than ???50 ppm. However, the high spatial resolution, small sample requirements, and the ability to avoid detrital material make this technique a suitable technique for dating many Pleistocene deposits formed in semi-arid environments. To determine the versatility of the method, samples from several different deposits were analyzed, including silica-rich pebble coatings from pedogenic carbonate horizons, a siliceous sinter deposit, and opaline silica deposited as a spring mound. U concentrations for 30-??m-diameter spots ranged from 50 to 1000 ppm in these types of materials. The 230Th/232Th activity ratios also ranged from ???100 to 106, eliminating the need for detrital Th corrections that reduce the precision of traditional U-Th ages for many milligram- and larger-sized samples. In pedogenic material, layers of high-U opal (ca. 500 ppm) are commonly juxtaposed next to layers of calcite with much lower U concentrations (1-2 ppm). If these types of samples are not analyzed using a technique with the appropriate spatial resolution, the ages may be strongly biased towards the age of the opal. Comparison with standard TIMS (Thermal Ionization Mass Spectrometry) measurements from separate microdrilled samples suggests that although the analytical precision of the ion microprobe (SHRIMP-RG) measurements is less than TIMS, the high spatial resolution results in better accuracy in the age determination for finely layered or complex deposits. The ion microprobe approach also may be useful for pre-screening samples to determine the age and degree of post-depositional alteration, analyzing finely layered samples or samples with complex growth histories, and obtaining simultaneous measurements of trace elements.

Sex reversal triggers the rapid transition from genetic to temperature-dependent sex.

PubMed

Holleley, Clare E; O'Meally, Denis; Sarre, Stephen D; Marshall Graves, Jennifer A; Ezaz, Tariq; Matsubara, Kazumi; Azad, Bhumika; Zhang, Xiuwen; Georges, Arthur

2015-07-02

Sex determination in animals is amazingly plastic. Vertebrates display contrasting strategies ranging from complete genetic control of sex (genotypic sex determination) to environmentally determined sex (for example, temperature-dependent sex determination). Phylogenetic analyses suggest frequent evolutionary transitions between genotypic and temperature-dependent sex determination in environmentally sensitive lineages, including reptiles. These transitions are thought to involve a genotypic system becoming sensitive to temperature, with sex determined by gene-environment interactions. Most mechanistic models of transitions invoke a role for sex reversal. Sex reversal has not yet been demonstrated in nature for any amniote, although it occurs in fish and rarely in amphibians. Here we make the first report of reptile sex reversal in the wild, in the Australian bearded dragon (Pogona vitticeps), and use sex-reversed animals to experimentally induce a rapid transition from genotypic to temperature-dependent sex determination. Controlled mating of normal males to sex-reversed females produces viable and fertile offspring whose phenotypic sex is determined solely by temperature (temperature-dependent sex determination). The W sex chromosome is eliminated from this lineage in the first generation. The instantaneous creation of a lineage of ZZ temperature-sensitive animals reveals a novel, climate-induced pathway for the rapid transition between genetic and temperature-dependent sex determination, and adds to concern about adaptation to rapid global climate change.

Sorbitol-based osmotic diarrhea: Possible causes and mechanism of prevention investigated in rats

PubMed Central

Islam, Md Shahidul; Sakaguchi, Ei

2006-01-01

AIM: To study the possible causes of sorbitol (S)-based diarrhea and its mechanism of reduction by rice gruel (RG) in cecectomized rats. METHODS: S was dissolved either in distilled water or in RG (50 g/L) and ingested as a single oral dose (1.2 g/kg body mass, containing 0.5 g/L phenol red as a recovery marker) by S (control) and S + RG groups (n = 7), respectively. This dose is over the laxative dose for humans. Animals were sacrificed exactly 1 h after dose ingestion, without any access to drinking water. The whole gastro-intestinal tract was divided into seven segments and sampled to analyze the S and marker remaining in its contents. RESULTS: Gastric-emptying and intestinal transit were comparatively slower in the S + RG group. Also, the S absorption index in the 3rd and last quarter of the small intestine (24.85 ± 18.88% vs 0.0 ± 0.0% and 39.09 ± 32.75% vs 0.0 ± 0.0%, respectively, P < 0.05) was significantly higher in the S + RG group than in the control group. The S absorption index and the intestinal fluid volume are inversely related to each other. CONCLUSION: The intestinal mal-absorption of S is the main reason for S-based osmotic diarrhea. Where RG enhanced the absorption of S through passive diffusion, the degree of diarrhea was reduced in cecectomized rats. PMID:17171792

Nuclease-free Adeno-Associated Virus-Mediated Il2rg Gene Editing in X-SCID Mice.

PubMed

Hiramoto, Takafumi; Li, Li B; Funk, Sarah E; Hirata, Roli K; Russell, David W

2018-05-02

X-linked severe combined immunodeficiency (X-SCID) has been successfully treated by hematopoietic stem cell (HSC) transduction with retroviral vectors expressing the interleukin-2 receptor subunit gamma gene (IL2RG), but several patients developed malignancies due to vector integration near cellular oncogenes. This adverse side effect could in principle be avoided by accurate IL2RG gene editing with a vector that does not contain a functional promoter or IL2RG gene. Here, we show that adeno-associated virus (AAV) gene editing vectors can insert a partial Il2rg cDNA at the endogenous Il2rg locus in X-SCID murine bone marrow cells and that these ex vivo-edited cells repopulate transplant recipients and produce CD4 + and CD8 + T cells. Circulating, edited lymphocytes increased over time and appeared in secondary transplant recipients, demonstrating successful editing in long-term repopulating cells. Random vector integration events were nearly undetectable, and malignant transformation of the transplanted cells was not observed. Similar editing frequencies were observed in human hematopoietic cells. Our results demonstrate that therapeutically relevant HSC gene editing can be achieved by AAV vectors in the absence of site-specific nucleases and suggest that this may be a safe and effective therapy for hematopoietic diseases where in vivo selection can increase edited cell numbers. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Investigations of the Rg-BrCl (Rg = He, Ne, Ar, Kr, Xe) binary van der Waals complexes: ab initio intermolecular potential energy surfaces, vibrational states and predicted pure rotational transition frequencies

NASA Astrophysics Data System (ADS)

Li, Song; Zheng, Rui; Chen, Shan-Jun; Chen, Yan; Chen, Peng

2017-03-01

The intermolecular potential energy surfaces (PESs) of the ground electronic state for the Rg-BrCl (Rg = He, Ne, Ar, Kr, Xe) van der Waals complexes have been constructed by using the coupled-cluster method in combination with the augmented quadruple-zeta correlation-consistent basis sets supplemented with an additional set of bond functions. The features of the anisotropic PESs for these complexes are remarkably similar, which are characterized by three minima and two saddle points between them. The global minimum corresponds to a collinear Rg-Br-Cl configuration. Two local minima, correlate with an anti-linear Rg-Cl-Br geometry and a nearly T-shaped structure, can also be located on each PES. The quantum bound state calculations enable us to investigate intermolecular vibrational states and rotational energy levels of the complexes. The transition frequencies are predicted and are fitted to obtain their corresponding spectroscopic constants. In general, the periodic trends are observed for this complex family. Comparisons with available experimental data for the collinear isomer of Ar-BrCl demonstrate reliability of our theoretical predictions, and our results for the other two isomers of Ar-BrCl as well as for other members of the complex family are also anticipated to be trustable. Except for the collinear isomer of Ar-BrCl, the data presented in this paper would be beneficial to improve our knowledge for these experimentally unknown species.

Rg excitation by underground explosions: insights from source modelling the 1997 Kazakhstan depth-of-burial experiment

NASA Astrophysics Data System (ADS)

Patton, Howard J.; Bonner, Jessie L.; Gupta, Indra N.

2005-12-01

Near-field seismograms of chemical explosions detonated as part of the 1997 depth-of-burial (DOB) experiment at the former Semipalatinsk nuclear test site provide an excellent opportunity to study the excitation of Rg waves for source effects. Rg waves were identified with particle-motion analysis and isolated from other arrivals using group velocity filtering. Amplitude and phase spectra of Rg waves were corrected for path effects based on observed attenuation in the near-field and path-specific phase velocity models. The path-corrected spectra were inputs to a grid-search method for finding source parameters of an axisymmetric source consisting of a monopole plus a compensated linear vector dipole (CLVD) or a horizontal tensile crack. The suite of observations, including ground-zero accelerograms and geophysical data from borehole logs, are best satisfied by models involving a CLVD with static (zero-frequency) seismic moment Mo. The CLVD source is related to tensile failure occurring at depths above the shotpoint. A static Mo distinguishes this source from classical models of spall, which are usually characterized by horizontal cracks that dynamically open and close with no permanent displacement (i.e. no static Mo). The CLVD source in this study appears to be more closely related to a driven block motion model envisaged by Masse. Rg source amplitudes are consistent with mb(Lg) measurements at station MAK, as would be expected if near-field Rg-to-S scattering plays a role in generating S waves observed at regional distances.

A wide and collimated radio jet in 3C84 on the scale of a few hundred gravitational radii

NASA Astrophysics Data System (ADS)

Giovannini, G.; Savolainen, T.; Orienti, M.; Nakamura, M.; Nagai, H.; Kino, M.; Giroletti, M.; Hada, K.; Bruni, G.; Kovalev, Y. Y.; Anderson, J. M.; D'Ammando, F.; Hodgson, J.; Honma, M.; Krichbaum, T. P.; Lee, S.-S.; Lico, R.; Lisakov, M. M.; Lobanov, A. P.; Petrov, L.; Sohn, B. W.; Sokolovsky, K. V.; Voitsik, P. A.; Zensus, J. A.; Tingay, S.

2018-06-01

Understanding the formation of relativistic jets in active galactic nuclei remains an elusive problem1. This is partly because observational tests of jet formation models suffer from the limited angular resolution of ground-based very-long-baseline interferometry that has thus far been able to probe the structure of the jet acceleration and collimation region in only two sources2,3. Here, we report observations of 3C84 (NGC 1275)—the central galaxy of the Perseus cluster—made with an interferometric array including the orbiting radio telescope of the RadioAstron4 mission. The data transversely resolve the edge-brightened jet in 3C84 only 30 μas from the core, which is ten times closer to the central engine than was possible in previous ground-based observations5 and allows us to measure the jet collimation profile from 102 to 104 gravitational radii (rg) from the black hole. The previously found5, almost cylindrical jet profile on scales larger than a few thousand rg is seen to continue at least down to a few hundred rg from the black hole, and we find a broad jet with a transverse radius of ≳250 rg at only 350 rg from the core. This implies that either the bright outer jet layer goes through a very rapid lateral expansion on scales ≲102 rg or it is launched from the accretion disk.

From repulsive to attractive glass: A rheological investigation.

PubMed

Zhou, Zhi; Jia, Di; Hollingsworth, Javoris V; Cheng, He; Han, Charles C

2015-12-21

Linear rheological properties and yielding behavior of polystyrene core and poly (N-isopropylacrylamide) (PNIPAM) shell microgels were investigated to understand the transition from repulsive glass (RG) to attractive glass (AG) and the A3 singularity. Due to the volume phase transition of PNIPAM in aqueous solution, the microgel-microgel interaction potential gradually changes from repulsive to attractive. In temperature and frequency sweep experiments, the storage modulus (G') and loss modulus (G″) increased discontinuously when crossing the RG-to-AG transition line, while G' at low frequency exhibited a different volume fraction (Φ) dependence. By fitting the data of RG and AG, and then extrapolating to high volume fraction, the difference between RG and AG decreased and the existence of A3 singularity was verified. Dynamic strain sweep experiments were conducted to confirm these findings. RG at 25 °C exhibited one-step yielding, whereas AG at 40 °C showed a typical two-step yielding behavior; the first yielding strain remained constant and the second one gradually decreased as the volume fraction increased. By extrapolating the second yield strain to that of the first one, the predicted A3 singularity was at 0.61 ± 0.02. At 37 °C, when Φeff = 0.59, AG showed one step yielding as the length of the attractive bond increased. The consistency and agreement of the experimental results reaffirmed the existence of A3 singularity, where the yielding behavior of RG and AG became identical.

Beneficial effects of fermented black ginseng and its ginsenoside 20(S)-Rg3 against cisplatin-induced nephrotoxicity in LLC-PK1 cells

PubMed Central

Han, Myoung-Sik; Han, Im-Ho; Lee, Dahae; An, Jun Min; Kim, Su-Nam; Shin, Myoung-Sook; Yamabe, Noriko; Hwang, Gwi Seo; Yoo, Hye Hyun; Choi, Suk-Jung; Kang, Ki Sung; Jang, Hyuk-Jai

2015-01-01

Background Nephrotoxicity is a common side effect of medications. Panax ginseng is one of the best-known herbal medicines, and its individual constituents enhance renal function. Identification of its efficacy and mechanisms of action against drug-induced nephrotoxicity, as well as the specific constituents mediating this effect, have recently emerged as an interesting research area focusing on the kidney protective efficacy of P. ginseng. Methods The present study investigated the kidney protective effect of fermented black ginseng (FBG) and its active component ginsenoside 20(S)-Rg3 against cisplatin (chemotherapy drug)-induced damage in pig kidney (LLC-PK1) cells. It focused on assessing the role of mitogen-activated protein kinases as important mechanistic elements in kidney protection. Results The reduced cell viability induced by cisplatin was significantly recovered with FBG extract and ginsenoside 20(S)-Rg3 dose-dependently. The cisplatin-induced elevated protein levels of phosphorylated c-Jun N-terminal kinase (JNK), p53, and cleaved caspase-3 were decreased after cotreatment with FBG extract or ginsenoside 20(S)-Rg3. The elevated percentage of apoptotic LLC-PK1 cells induced by cisplatin treatment was significantly abrogated by cotreatment with FBG and the ginsenoside 20(S)-Rg3. Conclusion FBG and its major ginsenoside 20(S)-Rg3, ameliorated cisplatin-induced nephrotoxicity in LLC-PK1 cells by blocking the JNK–p53–caspase-3 signaling cascade. PMID:27158234

Beneficial effects of fermented black ginseng and its ginsenoside 20(S)-Rg3 against cisplatin-induced nephrotoxicity in LLC-PK1 cells.

PubMed

Han, Myoung-Sik; Han, Im-Ho; Lee, Dahae; An, Jun Min; Kim, Su-Nam; Shin, Myoung-Sook; Yamabe, Noriko; Hwang, Gwi Seo; Yoo, Hye Hyun; Choi, Suk-Jung; Kang, Ki Sung; Jang, Hyuk-Jai

2016-04-01

Nephrotoxicity is a common side effect of medications. Panax ginseng is one of the best-known herbal medicines, and its individual constituents enhance renal function. Identification of its efficacy and mechanisms of action against drug-induced nephrotoxicity, as well as the specific constituents mediating this effect, have recently emerged as an interesting research area focusing on the kidney protective efficacy of P. ginseng. The present study investigated the kidney protective effect of fermented black ginseng (FBG) and its active component ginsenoside 20(S)-Rg3 against cisplatin (chemotherapy drug)-induced damage in pig kidney (LLC-PK1) cells. It focused on assessing the role of mitogen-activated protein kinases as important mechanistic elements in kidney protection. The reduced cell viability induced by cisplatin was significantly recovered with FBG extract and ginsenoside 20(S)-Rg3 dose-dependently. The cisplatin-induced elevated protein levels of phosphorylated c-Jun N-terminal kinase (JNK), p53, and cleaved caspase-3 were decreased after cotreatment with FBG extract or ginsenoside 20(S)-Rg3. The elevated percentage of apoptotic LLC-PK1 cells induced by cisplatin treatment was significantly abrogated by cotreatment with FBG and the ginsenoside 20(S)-Rg3. FBG and its major ginsenoside 20(S)-Rg3, ameliorated cisplatin-induced nephrotoxicity in LLC-PK1 cells by blocking the JNK-p53-caspase-3 signaling cascade.

A wide and collimated radio jet in 3C84 on the scale of a few hundred gravitational radii

NASA Astrophysics Data System (ADS)

Giovannini, G.; Savolainen, T.; Orienti, M.; Nakamura, M.; Nagai, H.; Kino, M.; Giroletti, M.; Hada, K.; Bruni, G.; Kovalev, Y. Y.; Anderson, J. M.; D'Ammando, F.; Hodgson, J.; Honma, M.; Krichbaum, T. P.; Lee, S.-S.; Lico, R.; Lisakov, M. M.; Lobanov, A. P.; Petrov, L.; Sohn, B. W.; Sokolovsky, K. V.; Voitsik, P. A.; Zensus, J. A.; Tingay, S.

2018-04-01

Understanding the formation of relativistic jets in active galactic nuclei remains an elusive problem1. This is partly because observational tests of jet formation models suffer from the limited angular resolution of ground-based very-long-baseline interferometry that has thus far been able to probe the structure of the jet acceleration and collimation region in only two sources2,3. Here, we report observations of 3C84 (NGC 1275)—the central galaxy of the Perseus cluster—made with an interferometric array including the orbiting radio telescope of the RadioAstron4 mission. The data transversely resolve the edge-brightened jet in 3C84 only 30 μas from the core, which is ten times closer to the central engine than was possible in previous ground-based observations5 and allows us to measure the jet collimation profile from 102 to 104 gravitational radii (rg) from the black hole. The previously found5, almost cylindrical jet profile on scales larger than a few thousand rg is seen to continue at least down to a few hundred rg from the black hole, and we find a broad jet with a transverse radius of ≳250 rg at only 350 rg from the core. This implies that either the bright outer jet layer goes through a very rapid lateral expansion on scales ≲102 rg or it is launched from the accretion disk.

Stimulation of Innate Immune Function by Panax ginseng after Heat Processing.

PubMed

Shin, Myoung-Sook; Song, Ji Hoon; Choi, Pilju; Lee, Jong Hun; Kim, Song-Yi; Shin, Kwang-Soon; Ham, Jungyeob; Kang, Ki Sung

2018-05-09

Panax ginseng Meyer has been used for the treatment of immune diseases and for strengthening the immune function. In this study, we evaluated the innate immune-stimulating functions and action mechanisms of white ginseng (WG) and heat-processed ginseng (HPG) in RAW264.7 cells. According to LC-MS analysis results, WG contained typical ginsenosides, such as Rb1, Rc, Rb2, Rd, and Rg1, whereas HPG contained Rg3, Rk1, and Rg5 as well as typical ginsenosides. HPG, not WG, enhanced NF-κB transcriptional activity, cytokine production (IL-6 and TNF-α), and MHC class I and II expression in RAW264.7 cells. In addition, HPG phosphorylated MAPKs and NF-kB pathways. In experiments with inhibitors, the ERK inhibitor completely suppressed the effect of HPG on IL-6 and TNF-α production. HPG-induced c-Jun activation was suppressed by an ERK inhibitor and partially suppressed by JNK, p38, and IκBα inhibitors. Collectively, these results suggested that HPG containing Rg3, Rg5, and Rk1 increased macrophage activation which was regulated by the ERK/c-Jun pathway in RAW264.7 cells.

Neonatal, placental, and umbilical cord blood parameters in pregnant women residing in areas with intensive pesticide application.

PubMed

Quintana, María Martha; Vera, Berta; Magnarelli, Gladis; Guiñazú, Natalia; Rovedatti, María Gabriela

2017-09-01

In rural populations, the proximity to areas with intensive pesticide application represents a risk factor of xenobiotic exposure. Here, we investigated whether newborns born to mothers residing in an area with intensive pesticide application show alterations in placental and neonatal morphometric standards, umbilical cord blood (UCB) biochemical parameters, and/or biomarkers related to oxidative stress and oxidative damage. Samples were collected from 151 healthy pregnant women residing in a rural area (rural group; RG) during the pesticide spraying (SS) and nonspraying (NSS) seasons, as well as from women from an urban population (control group; CG), and grouped according to the delivery type (vaginal or cesarean). In the vaginal delivery group, the placental weight and placental index were higher in the RG groups than in the CG (p = 0.01), whereas in the cesarean delivery group, newborn weight was lower in the RG-SS group than in the CG. In the RG-SS group, UCB erythrocyte osmotic fragility and the DNA damage index (DI) were higher, and superoxide dismutase (SOD) activity was lower than in the RG-NSS group. Acetylcholinesterase and SOD activities were found to be inversely correlated with the DI.

ORF73 LANA homologs of RRV and MneRV2 contain an extended RGG/RG-rich nuclear and nucleolar localization signal that interacts directly with importin β1 for non-classical nuclear import.

PubMed

Howard, Kellie; Cherezova, Lidia; DeMaster, Laura K; Rose, Timothy M

2017-11-01

The latency-associated nuclear antigens (LANA) of KSHV and macaque RFHVMn, members of the RV1 rhadinovirus lineage, are closely related with conservation of complex nuclear localization signals (NLS) containing bipartite KR-rich motifs and RG-rich domains, which interact distinctly with importins α and ß1 for nuclear import via classical and non-classical pathways, respectively. RV1 LANAs are expressed in the nucleus of latently-infected cells where they inhibit replication and establish a dominant RV1 latency. Here we show that LANA homologs of macaque RRV and MneRV2 from the more distantly-related RV2 lineage, lack the KR-rich NLS, and instead have a large RG-rich NLS with multiple RG dipeptides and a conserved RGG motif. The RG-NLS interacts uniquely with importin β1, which mediates nuclear import and accumulation of RV2 LANA in the nucleolus. The alternative nuclear import and localization of RV2 LANA homologs may contribute to the dominant RV2 lytic replication phenotype. Copyright © 2017. Published by Elsevier Inc.

The Role of Retinal Determination Gene Network (RDGN) in Hormone Signaling Transduction and Prostate Tumorigenes

DTIC Science & Technology

2015-12-01

S, Zhang W, Zhou J, Wang J, Ertel A, Li Z, Rui H, Quong A, Lisanti MP, Tozeren A, Tanes C, Addya S, Gormley M, Wang C, McMahon SB, Pestell RG...MP, Wang C, Pestell RG. Acetylation of the cell-fate factor dachshund determines p53 binding and signaling modules in breast cancer. Oncotarget...MP, Quong A, Ertel A, Pestell RG. Cell fate factor DACH1 represses YB-1-mediated oncogenic transcription and translation. Cancer Res. 2014;74(3):829

The Role of Retinal Determination Gene Network (RDGN) in Hormone Signaling Transduction and Prostate Tumorigenesis

DTIC Science & Technology

2013-10-01

Wu K, Wang L, Jiao X, Ju X, Li Z, Ertel A, Addya S, McCue P, Lisanti MP, Wang C, Davis RJ, Mardon G, Pestell RG. Androgen therapy resistant...Li Z, Hu J, Chen K, Wu J, Pestell RG. DACH1 inhibited prostate cancer cellular proliferation and Interleukon-6 signaling. AACR 103rd Annual Meeting...March 31 – April 4, 2012, Chicago, IL.  Wang J, Cai S, Chen K, Sun Y, Li S, Pestell RG, Wu K. Regulation of AR transcriptional activity and

[Active constituents reducing side-effects of prednisone acetate in leaves of Panax ginseng C.A.Mey].

PubMed

Dou, D; Wen, Y; Pei, Y; Chen, Y; Ma, Z

1997-03-01

The rise of total lipid, triglyceride and total cholesterol, and the drop of cortisol in serum induced by PA can be significantly inhibited by total ginsenosides in the leaves of Panax ginseng [GSL, 60 mg/(kg.d)]. From GSL ten compounds have been isolated and identified as ginsenoside-Rb2, -Rc, -Rd, -Re, -Rg1 -F3, F2, -Rg2, 20(R)-Rg2 and -Rh1, respectively. Pharmacological study has proved ginsenoside-Re to be the chief active constituent of GSL.

Sex Reversal in Birds.

PubMed

Major, Andrew T; Smith, Craig A

2016-01-01

Sexual differentiation in birds is controlled genetically as in mammals, although the sex chromosomes are different. Males have a ZZ sex chromosome constitution, while females are ZW. Gene(s) on the sex chromosomes must initiate gonadal sex differentiation during embryonic life, inducing paired testes in ZZ individuals and unilateral ovaries in ZW individuals. The traditional view of avian sexual differentiation aligns with that expounded for other vertebrates; upon sexual differentiation, the gonads secrete sex steroid hormones that masculinise or feminise the rest of the body. However, recent studies on naturally occurring or experimentally induced avian sex reversal suggest a significant role for direct genetic factors, in addition to sex hormones, in regulating sexual differentiation of the soma in birds. This review will provide an overview of sex determination in birds and both naturally and experimentally induced sex reversal, with emphasis on the key role of oestrogen. We then consider how recent studies on sex reversal and gynandromorphic birds (half male:half female) are shaping our understanding of sexual differentiation in avians and in vertebrates more broadly. Current evidence shows that sexual differentiation in birds is a mix of direct genetic and hormonal mechanisms. Perturbation of either of these components may lead to sex reversal. © 2016 S. Karger AG, Basel.

Efficient and Robust Paramyxoviridae Reverse Genetics Systems

PubMed Central

Beaty, Shannon M.; Won, Sohui T.; Hong, Patrick; Lyons, Michael; Vigant, Frederic; Freiberg, Alexander N.; tenOever, Benjamin R.; Duprex, W. Paul

2017-01-01

ABSTRACT The notoriously low efficiency of Paramyxoviridae reverse genetics systems has posed a limiting barrier to the study of viruses in this family. Previous approaches to reverse genetics have utilized a wide variety of techniques to overcome the technical hurdles. Although robustness (i.e., the number of attempts that result in successful rescue) has been improved in some systems with the use of stable cell lines, the efficiency of rescue (i.e., the proportion of transfected cells that yield at least one successful rescue event) has remained low. We have substantially increased rescue efficiency for representative viruses from all five major Paramyxoviridae genera (from ~1 in 106-107 to ~1 in 102-103 transfected cells) by the addition of a self-cleaving hammerhead ribozyme (Hh-Rbz) sequence immediately preceding the start of the recombinant viral antigenome and the use of a codon-optimized T7 polymerase (T7opt) gene to drive paramyxovirus rescue. Here, we report a strategy for robust, reliable, and high-efficiency rescue of paramyxovirus reverse genetics systems, featuring several major improvements: (i) a vaccinia virus-free method, (ii) freedom to use any transfectable cell type for viral rescue, (iii) a single-step transfection protocol, and (iv) use of the optimal T7 promoter sequence for high transcription levels from the antigenomic plasmid without incorporation of nontemplated G residues. The robustness of our T7opt-HhRbz system also allows for greater latitude in the ratios of transfected accessory plasmids used that result in successful rescue. Thus, our system may facilitate the rescue and interrogation of the increasing number of emerging paramyxoviruses. IMPORTANCE The ability to manipulate the genome of paramyxoviruses and evaluate the effects of these changes at the phenotypic level is a powerful tool for the investigation of specific aspects of the viral life cycle and viral pathogenesis. However, reverse genetics systems for paramyxoviruses are notoriously inefficient, when successful. The ability to efficiently and robustly rescue paramyxovirus reverse genetics systems can be used to answer basic questions about the biology of paramyxoviruses, as well as to facilitate the considerable translational efforts being devoted to developing live attenuated paramyxovirus vaccine vectors. PMID:28405630

Genetic characterization of Bombyx mori (Lepidoptera: Bombycidae) breeding and hybrid lines with different geographic origins.

PubMed

Furdui, Emilia M; Mărghitaş, Liviu A; Dezmirean, Daniel S; Paşca, Ioan; Pop, Iulia F; Erler, Silvio; Schlüns, Ellen A

2014-01-01

The domesticated silkworm Bombyx mori L. comprises a large number of geographical breeds and hybrid lines. Knowing the genetic structure of those may provide information to improve the conservation of commercial lines by estimating inbreeding over generations and the consequences of excessive use of those lineages. Here, we analyzed the genetic diversity of seven breeds and eight hybrid lines from Eastern Europe and Asia using highly polymorphic microsatellites markers to determine its genetical impact on their use in global breeding programs. No consistent pattern of deviation from Hardy-Weinberg equilibrium was found for most breed and hybrids; and the absence of a linkage disequilibrium also suggests that the strains are in equilibrium. A principal coordinate analysis revealed a clear separation of two silkworm breeds from the rest: one (IBV) originated from India and the other one (RG90) from Romania/Japan. The tendency of the other breeds from different geographic origins to cluster together in a general mix might be due to similar selection pressures (climate and anthropogenic factors) in different geographic locations. Phylogenetic analyses grouped the different silkworm breeds but not the hybrids according to their geographic origin and confirmed the pattern found in the principal coordinate analysis. © The Author 2014. Published by Oxford University Press on behalf of the Entomological Society of America.

Genetic Characterization of Bombyx mori (Lepidoptera: Bombycidae) Breeding and Hybrid Lines With Different Geographic Origins

PubMed Central

Furdui, Emilia M.; Mărghitaş, Liviu A.; Dezmirean, Daniel S.; Paşca, Ioan; Pop, Iulia F.; Erler, Silvio; Schlüns, Ellen A.

2014-01-01

Abstract The domesticated silkworm Bombyx mori L. comprises a large number of geographical breeds and hybrid lines. Knowing the genetic structure of those may provide information to improve the conservation of commercial lines by estimating inbreeding over generations and the consequences of excessive use of those lineages. Here, we analyzed the genetic diversity of seven breeds and eight hybrid lines from Eastern Europe and Asia using highly polymorphic microsatellites markers to determine its genetical impact on their use in global breeding programs. No consistent pattern of deviation from Hardy–Weinberg equilibrium was found for most breed and hybrids; and the absence of a linkage disequilibrium also suggests that the strains are in equilibrium. A principal coordinate analysis revealed a clear separation of two silkworm breeds from the rest: one (IBV) originated from India and the other one (RG 90 ) from Romania/Japan. The tendency of the other breeds from different geographic origins to cluster together in a general mix might be due to similar selection pressures (climate and anthropogenic factors) in different geographic locations. Phylogenetic analyses grouped the different silkworm breeds but not the hybrids according to their geographic origin and confirmed the pattern found in the principal coordinate analysis. PMID:25502023

The Effects of 52 Weeks of Soccer or Resistance Training on Body Composition and Muscle Function in +65-Year-Old Healthy Males – A Randomized Controlled Trial

PubMed Central

Andersen, Thomas Rostgaard; Schmidt, Jakob Friis; Pedersen, Mogens Theisen; Krustrup, Peter; Bangsbo, Jens

2016-01-01

The effects of 52 weeks of soccer or resistance training were investigated in untrained elderly men. The subjects aged 68.1±2.1 yrs were randomised into a soccer (SG; n = 9), a resistance (RG; n = 9) and a control group (CG; n = 8). The subjects in SG and RG, respectively, trained 1.7±0.3 and 1.8±0.3 times weekly on average during the intervention period. Muscle function and body composition were determined before and after 16 and 52 weeks of the intervention period. In SG, BMI was reduced by 1.5% and 3.0% (p<0.05) after 16 and 52 weeks, respectively, unchanged in RG and 2% higher (p<0.05) in CG after 52 weeks of the intervention period. In SG, the response to a glucose tolerance test was 16% lower (p<0.05) after 16 wks, but not after 52 wks, compared to before the intervention period, and unchanged in RG and CG. In SG, superoxide dismutase-2 expression was 59% higher (p<0.05) after 52 wks compared to before the intervention period, and unchanged in RG and CG. In RG, upper body lean mass was 3 and 2% higher (p<0.05) after 16 and 52 wks, respectively, compared to before the intervention period, and unchanged in SG and CG. In RG, Akt-2 expression increased by 28% (p<0.01) and follistatin expression decreased by 38% (p<0.05) during the 52-wk intervention period, and was unchanged in SG and CG. Thus, long-term soccer training reduces BMI and improves anti-oxidative capacity, while long-term resistance training impacts muscle protein enzyme expression and increases lean body mass in elderly men. Trial Registration ClinicalTrials.gov: NCT01530035 PMID:26886262

The Effects of 52 Weeks of Soccer or Resistance Training on Body Composition and Muscle Function in +65-Year-Old Healthy Males--A Randomized Controlled Trial.

PubMed

Andersen, Thomas Rostgaard; Schmidt, Jakob Friis; Pedersen, Mogens Theisen; Krustrup, Peter; Bangsbo, Jens

2016-01-01

The effects of 52 weeks of soccer or resistance training were investigated in untrained elderly men. The subjects aged 68.1±2.1 yrs were randomised into a soccer (SG; n = 9), a resistance (RG; n = 9) and a control group (CG; n = 8). The subjects in SG and RG, respectively, trained 1.7±0.3 and 1.8±0.3 times weekly on average during the intervention period. Muscle function and body composition were determined before and after 16 and 52 weeks of the intervention period. In SG, BMI was reduced by 1.5% and 3.0% (p<0.05) after 16 and 52 weeks, respectively, unchanged in RG and 2% higher (p<0.05) in CG after 52 weeks of the intervention period. In SG, the response to a glucose tolerance test was 16% lower (p<0.05) after 16 wks, but not after 52 wks, compared to before the intervention period, and unchanged in RG and CG. In SG, superoxide dismutase-2 expression was 59% higher (p<0.05) after 52 wks compared to before the intervention period, and unchanged in RG and CG. In RG, upper body lean mass was 3 and 2% higher (p<0.05) after 16 and 52 wks, respectively, compared to before the intervention period, and unchanged in SG and CG. In RG, Akt-2 expression increased by 28% (p<0.01) and follistatin expression decreased by 38% (p<0.05) during the 52-wk intervention period, and was unchanged in SG and CG. Thus, long-term soccer training reduces BMI and improves anti-oxidative capacity, while long-term resistance training impacts muscle protein enzyme expression and increases lean body mass in elderly men. Trial Registration: ClinicalTrials.gov: NCT01530035.

Near-Source Scattering of Explosion-Generated Rg: Insight From Difference Spectrograms of NTS Explosions

NASA Astrophysics Data System (ADS)

Gupta, I.; Chan, W.; Wagner, R.

2005-12-01

Several recent studies of the generation of low-frequency Lg from explosions indicate that the Lg wavetrain from explosions contains significant contributions from (1) the scattering of explosion-generated Rg into S and (2) direct S waves from the non-spherical spall source associated with a buried explosion. The pronounced spectral nulls observed in Lg spectra of Yucca Flats (NTS) and Semipalatinsk explosions (Patton and Taylor, 1995; Gupta et al., 1997) are related to Rg excitation caused by spall-related block motions in a conical volume over the shot point, which may be approximately represented by a compensated linear vector dipole (CLVD) source (Patton et al., 2005). Frequency-dependent excitation of Rg waves should be imprinted on all scattered P, S and Lg waves. A spectrogram may be considered as a three-dimensional matrix of numbers providing amplitude and frequency information for each point in the time series. We found difference spectrograms, derived from a normal explosion and a closely located over-buried shot recorded at the same common station, to be remarkably useful for an understanding of the origin and spectral contents of various regional phases. This technique allows isolation of source characteristics, essentially free from path and recording site effects, since the overburied shot acts as the empirical Green's function. Application of this methodology to several pairs of closely located explosions shows that the scattering of explosion-generated Rg makes significant contribution to not only Lg and its coda but also to the two other regional phases Pg (presumably by the scattering of Rg into P) and Sn. The scattered energy, identified by the presence of a spectral null at the appropriate frequency, generally appears to be more prominent in the somewhat later-arriving sections of Pg, Sn, and Lg than in the initial part. Difference spectrograms appear to provide a powerful new technique for understanding the mechanism of near-source scattering of explosion-generated Rg and its contribution to various regional phases.

Pharmacological inhibition of DNA methylation attenuates pressure overload-induced cardiac hypertrophy in rats.

PubMed

Stenzig, Justus; Schneeberger, Yvonne; Löser, Alexandra; Peters, Barbara S; Schaefer, Andreas; Zhao, Rong-Rong; Ng, Shi Ling; Höppner, Grit; Geertz, Birgit; Hirt, Marc N; Tan, Wilson; Wong, Eleanor; Reichenspurner, Hermann; Foo, Roger S-Y; Eschenhagen, Thomas

2018-07-01

Heart failure is associated with altered gene expression and DNA methylation. De novo DNA methylation is associated with gene silencing, but its role in cardiac pathology remains incompletely understood. We hypothesized that inhibition of DNA methyltransferases (DNMT) might prevent the deregulation of gene expression and the deterioration of cardiac function under pressure overload (PO). To test this hypothesis, we evaluated a DNMT inhibitor in PO in rats and analysed DNA methylation in cardiomyocytes. Young male Wistar rats were subjected to PO by transverse aortic constriction (TAC) or to sham surgery. Rats from both groups received solvent or 12.5 mg/kg body weight of the non-nucleosidic DNMT inhibitor RG108, initiated on the day of the intervention. After 4 weeks, we analysed cardiac function by MRI, fibrosis with Sirius Red staining, gene expression by RNA sequencing and qPCR, and DNA methylation by reduced representation bisulphite sequencing (RRBS). RG108 attenuated the ~70% increase in heart weight/body weight ratio of TAC over sham to 47% over sham, partially rescued reduced contractility, diminished the fibrotic response and the downregulation of a set of genes including Atp2a2 (SERCA2a) and Adrb1 (beta1-adrenoceptor). RG108 was associated with significantly lower global DNA methylation in cardiomyocytes by ~2%. The differentially methylated pathways were "cardiac hypertrophy", "cell death" and "xenobiotic metabolism signalling". Among these, "cardiac hypertrophy" was associated with significant methylation differences in the group comparison sham vs. TAC, but not significant between sham+RG108 and TAC+RG108 treatment, suggesting that RG108 partially prevented differential methylation. However, when comparing TAC and TAC+RG108, the pathway cardiac hypertrophy was not significantly differentially methylated. DNMT inhibitor treatment is associated with attenuation of cardiac hypertrophy and moderate changes in cardiomyocyte DNA methylation. The potential mechanistic link between these two effects and the role of non-myocytes need further clarification. Copyright © 2018 Elsevier Ltd. All rights reserved.

Transmammary transfer of toxicity to nursing kids from Isocoma pluriflora (rayless goldenrod) dosed to lactating goats.

PubMed

Pfister, James A; Stegelmeier, Bryan L; Lee, Stephen T; Davis, T Zane; Green, Ben T

2018-05-01

Rayless goldenrod (RG; Isocoma pluriflora) poisons livestock in the southwestern U.S., west Texas, and northern Mexico. The putative toxin(s) have historically been thought to be benzofuran ketones. Goats have been used successfully as a model of RG poisoning. The transmammary transfer of toxicity to offspring from lactating goats has not been studied, thus the objective of this study was to determine if nursing kids would become poisoned via mother's milk when the dams were dosed with RG. Twelve lactating goats (6 controls and 6 treated; all with twin kids) were dosed via oral gavage with alfalfa or rayless goldenrod at 2% of BW per day for 14 days. Two kids showed overt clinical signs near the end of the study; however, no dams showed clinical signs, and none developed exercise intolerance or muscle weakness. After day 11 of treatment, the RG kids showed increased (P < 0.05) serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine kinase (CK) activities until exposure to the plant via mothers' milk ended. Serum CK activity of kids declined rapidly over 7 days after transmammary exposure ended. Histopathology revealed that one kid had extensive myonecrosis that involved both myocardium and skeletal muscles. The other kids from RG-treated does had minimal myocyte degeneration and necrosis characterized by individual myofiber swelling, hypereosinophilia and loss of striation. Benzofuran ketones were not detected in the milk of lactating goats; further, dosing with RG did not alter milk composition. In summary, milk ingestion from does dosed with >300 mg/kg BW of benzofuran ketones from RG over 14 days increased mean CK concentrations in treated kids compared to controls; however kids rapidly recovered when exposure ended. Additional work is needed to better define benzofuran ketone metabolism, toxicity, and animal susceptibility. Copyright © 2018 Elsevier Ltd. All rights reserved.

The administration of a high refined carbohydrate diet promoted an increase in pulmonary inflammation and oxidative stress in mice exposed to cigarette smoke

PubMed Central

Pena, Karina Braga; Ramos, Camila de Oliveira; Soares, Nícia Pedreira; da Silva, Pamela Félix; Bandeira, Ana Carla Balthar; Costa, Guilherme de Paula; Cangussú, Sílvia Dantas; Talvani, André; Bezerra, Frank Silva

2016-01-01

This study aimed to evaluate the effects of a high refined carbohydrate diet and pulmonary inflammatory response in C57BL/6 mice exposed to cigarette smoke (CS). Twenty-four male mice were divided into four groups: control group (CG), which received a standard diet; cigarette smoke group (CSG), which was exposed to CS; a high refined carbohydrate diet group (RG), which received a high refined carbohydrate diet; and a high refined carbohydrates diet and cigarette smoke group (RCSG), which received a high refined carbohydrate diet and was exposed to CS. The animals were monitored for food intake and body weight gain for 12 weeks. After this period, the CSG and RCSG were exposed to CS for five consecutive days. At the end of the experimental protocol, all animals were euthanized for subsequent analyses. There was an increase of inflammatory cells in the bronchoalveolar lavage fluid (BALF) of CSG compared to CG and RCSG compared to CG, CSG, and RG. In addition, in the BALF, there was an increase of tumor necrosis factor alpha in RCSG compared to CG, CSG, and RG; interferon gamma increase in RCSG compared to the CSG; and increase in interleukin-10 in RCSG compared to CG and RG. Lipid peroxidation increased in RCSG compared to CG, CSG, and RG. Furthermore, the oxidation of proteins increased in CSG compared to CG. The analysis of oxidative stress showed an increase in superoxide dismutase in RCSG compared to CG, CSG, and RG and an increase in the catalase activity in RCSG compared with CG. In addition, there was a decrease in the glutathione reduced/glutathione total ratio of CSG, RG, and RCSG compared to CG. Therefore, the administration of a high refined carbohydrate diet promoted an increase in pulmonary inflammation and oxidative stress in mice exposed to CS. PMID:28008246

Analysis of a renormalization group method and normal form theory for perturbed ordinary differential equations

NASA Astrophysics Data System (ADS)

DeVille, R. E. Lee; Harkin, Anthony; Holzer, Matt; Josić, Krešimir; Kaper, Tasso J.

2008-06-01

For singular perturbation problems, the renormalization group (RG) method of Chen, Goldenfeld, and Oono [Phys. Rev. E. 49 (1994) 4502-4511] has been shown to be an effective general approach for deriving reduced or amplitude equations that govern the long time dynamics of the system. It has been applied to a variety of problems traditionally analyzed using disparate methods, including the method of multiple scales, boundary layer theory, the WKBJ method, the Poincaré-Lindstedt method, the method of averaging, and others. In this article, we show how the RG method may be used to generate normal forms for large classes of ordinary differential equations. First, we apply the RG method to systems with autonomous perturbations, and we show that the reduced or amplitude equations generated by the RG method are equivalent to the classical Poincaré-Birkhoff normal forms for these systems up to and including terms of O(ɛ2), where ɛ is the perturbation parameter. This analysis establishes our approach and generalizes to higher order. Second, we apply the RG method to systems with nonautonomous perturbations, and we show that the reduced or amplitude equations so generated constitute time-asymptotic normal forms, which are based on KBM averages. Moreover, for both classes of problems, we show that the main coordinate changes are equivalent, up to translations between the spaces in which they are defined. In this manner, our results show that the RG method offers a new approach for deriving normal forms for nonautonomous systems, and it offers advantages since one can typically more readily identify resonant terms from naive perturbation expansions than from the nonautonomous vector fields themselves. Finally, we establish how well the solution to the RG equations approximates the solution of the original equations on time scales of O(1/ɛ).

Radiation risk assessment in professionals working in dental radiology area using buccal micronucleus cytome assay.

PubMed

Sadatullah, Syed; Dawasaz, Ali Azhar; Luqman, Master; Assiry, Ali A; Almeshari, Ahmed A; Togoo, Rafi Ahmad

2013-11-01

The aim of this study was to assess the incidence of micronuclei (MN) in buccal mucosal cells of professionals working in radiology area to determine the risk of stochastic effects of radiation. All the professionals and students working in King Khalid University - College of Dentistry radiology area were included in the Risk Group (RG = 27). The Control Group (CG = 27) comprised of healthy individual matching the gender and age of the RG. Buccal mucosal scraping from all the 54 subjects of RG and CG were stained with Papanicolaou stain and observed under oil immersion lens (×100) for the presence of micronuclei (MN) in the exfoliated epithelial cells. There was no significant difference between the incidence of MN in RG and CG (p = >0.05) using t-test. Routine radiation protection protocol does minimize the risk of radiation induced cytotoxicity, however, screening of professionals should be carried out at regular intervals.

Plant rhamnogalacturonan II complexation of heavy metal cations

DOEpatents

O`Neill, M.A.; Pellerin, P.J.M.; Warrenfeltz, D.; Vidal, S.; Darvill, A.G.; Albersheim, P.

1999-03-02

The present invention provides rhamnogalacturonan-II (RG-II) and relates to its ability to complex specific multivalent heavy metal cations. In the presence of boric acid, RG-II monomers form dimers that are cross-linked by a borate ester. The yield of such borate ester cross-linked dimers of RG-II is enhanced in the presence of specific heavy metal cations. The present invention further relates to the utility of RG-II in assays for the detection of specific heavy metal contamination; as a reagent useful in the removal of specific heavy metal cations contaminating foods and liquids, for example, fish, wines, etc.; as a pharmaceutical composition useful as an antidote in specific heavy metal cation poisoning; as a treatment for the detoxification of specific heavy metal cations from blood and/or tissues; and in a method of remediation of waters and soils contaminated with specific heavy metal cations. 15 figs.

Plant rhamnogalacturonan II complexation of heavy metal cations

DOEpatents

O'Neill, Malcolm A.; Pellerin, Patrice J. M.; Warrenfeltz, Dennis; Vidal, Stephane; Darvill, Alan G.; Albersheim, Peter

1999-01-01

The present invention provides rhamnogalacturonan-II (RG-II) and relates to its ability to complex specific multivalent heavy metal cations. In the presence of boric acid, RG-II monomers form dimers that are cross-linked by a borate ester. The yield of such borate ester cross-linked dimers of RG-II is enhanced in the presence of specific heavy metal cations. The present invention further relates to the utility of RG-II in assays for the detection of specific heavy metal contamination; as a reagent useful in the removal of specific heavy metal cations contaminating foods and liquids, for example, fish, wines, etc.; as a pharmaceutical composition useful as an antidote in specific heavy metal cation poisoning; as a treatment for the detoxification of specific heavy metal cations from blood and/or tissues; and in a method of remediation of waters and soils contaminated with specific heavy metal cations.

Immunological markers of frequently recurrent genital herpes simplex virus and their response to hypnotherapy: a pilot study.

PubMed

Fox, P A; Henderson, D C; Barton, S E; Champion, A J; Rollin, M S; Catalan, J; McCormack, S M; Gruzelier, J

1999-11-01

Patients were recruited for hypnotherapy from a clinic for patients with frequently recurrent genital herpes simplex virus (rgHSV). Psychological and immunological parameters were measured 6 weeks prior to hypnotherapy and 6 weeks afterwards, during which time each patient kept a diary of symptoms of rgHSV. Following hypnotherapy there was a significant overall reduction in the number of reported episodes of rgHSV, accompanied by an increase in the numbers of CD3 and CD8 lymphocytes, which may represent a non specific effect of hypnosis. The improvers showed significant rises in natural killer (NK) cell counts, HSV specific lymphokine activated killer (LAK) activity, and reduced levels of anxiety when compared to non-improvers. NK cell numbers and HSV specific LAK activity may therefore be important in the reduction in rgHSV following hypnotherapy.

Mutual information, neural networks and the renormalization group

NASA Astrophysics Data System (ADS)

Koch-Janusz, Maciej; Ringel, Zohar

2018-06-01

Physical systems differing in their microscopic details often display strikingly similar behaviour when probed at macroscopic scales. Those universal properties, largely determining their physical characteristics, are revealed by the powerful renormalization group (RG) procedure, which systematically retains `slow' degrees of freedom and integrates out the rest. However, the important degrees of freedom may be difficult to identify. Here we demonstrate a machine-learning algorithm capable of identifying the relevant degrees of freedom and executing RG steps iteratively without any prior knowledge about the system. We introduce an artificial neural network based on a model-independent, information-theoretic characterization of a real-space RG procedure, which performs this task. We apply the algorithm to classical statistical physics problems in one and two dimensions. We demonstrate RG flow and extract the Ising critical exponent. Our results demonstrate that machine-learning techniques can extract abstract physical concepts and consequently become an integral part of theory- and model-building.

Genome-Wide Association Mapping Combined with Reverse Genetics Identifies New Effectors of Low Water Potential-Induced Proline Accumulation in Arabidopsis1[W][OPEN

PubMed Central

Verslues, Paul E.; Lasky, Jesse R.; Juenger, Thomas E.; Liu, Tzu-Wen; Kumar, M. Nagaraj

2014-01-01

Arabidopsis (Arabidopsis thaliana) exhibits natural genetic variation in drought response, including varying levels of proline (Pro) accumulation under low water potential. As Pro accumulation is potentially important for stress tolerance and cellular redox control, we conducted a genome-wide association (GWAS) study of low water potential-induced Pro accumulation using a panel of natural accessions and publicly available single-nucleotide polymorphism (SNP) data sets. Candidate genomic regions were prioritized for subsequent study using metrics considering both the strength and spatial clustering of the association signal. These analyses found many candidate regions likely containing gene(s) influencing Pro accumulation. Reverse genetic analysis of several candidates identified new Pro effector genes, including thioredoxins and several genes encoding Universal Stress Protein A domain proteins. These new Pro effector genes further link Pro accumulation to cellular redox and energy status. Additional new Pro effector genes found include the mitochondrial protease LON1, ribosomal protein RPL24A, protein phosphatase 2A subunit A3, a MADS box protein, and a nucleoside triphosphate hydrolase. Several of these new Pro effector genes were from regions with multiple SNPs, each having moderate association with Pro accumulation. This pattern supports the use of summary approaches that incorporate clusters of SNP associations in addition to consideration of individual SNP probability values. Further GWAS-guided reverse genetics promises to find additional effectors of Pro accumulation. The combination of GWAS and reverse genetics to efficiently identify new effector genes may be especially applicable for traits difficult to analyze by other genetic screening methods. PMID:24218491

Heritability of Neuropsychological Measures in Schizophrenia and Nonpsychiatric Populations: A Systematic Review and Meta-analysis.

PubMed

Blokland, Gabriëlla A M; Mesholam-Gately, Raquelle I; Toulopoulou, Timothea; Del Re, Elisabetta C; Lam, Max; DeLisi, Lynn E; Donohoe, Gary; Walters, James T R; Seidman, Larry J; Petryshen, Tracey L

2017-07-01

Schizophrenia is characterized by neuropsychological deficits across many cognitive domains. Cognitive phenotypes with high heritability and genetic overlap with schizophrenia liability can help elucidate the mechanisms leading from genes to psychopathology. We performed a meta-analysis of 170 published twin and family heritability studies of >800 000 nonpsychiatric and schizophrenia subjects to accurately estimate heritability across many neuropsychological tests and cognitive domains. The proportion of total variance of each phenotype due to additive genetic effects (A), shared environment (C), and unshared environment and error (E), was calculated by averaging A, C, and E estimates across studies and weighting by sample size. Heritability ranged across phenotypes, likely due to differences in genetic and environmental effects, with the highest heritability for General Cognitive Ability (32%-67%), Verbal Ability (43%-72%), Visuospatial Ability (20%-80%), and Attention/Processing Speed (28%-74%), while the lowest heritability was observed for Executive Function (20%-40%). These results confirm that many cognitive phenotypes are under strong genetic influences. Heritability estimates were comparable in nonpsychiatric and schizophrenia samples, suggesting that environmental factors and illness-related moderators (eg, medication) do not substantially decrease heritability in schizophrenia samples, and that genetic studies in schizophrenia samples are informative for elucidating the genetic basis of cognitive deficits. Substantial genetic overlap between cognitive phenotypes and schizophrenia liability (average rg = -.58) in twin studies supports partially shared genetic etiology. It will be important to conduct comparative studies in well-powered samples to determine whether the same or different genes and genetic variants influence cognition in schizophrenia patients and the general population. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Use of the RenalGuard system to prevent contrast-induced AKI: A meta-analysis.

PubMed

Mattathil, Stephanie; Ghumman, Saad; Weinerman, Jonathan; Prasad, Anand

2017-10-01

Contrast-induced kidney injury (CI-AKI) following cardiovascular interventions results in increased morbidity and mortality. RenalGuard (RG) is a novel, closed loop system which balances volume administration with forced diuresis to maintain a high urine output. We performed a meta-analysis of the existing data comparing use of RG to conventional volume expansion. Ten studies were found eligible, of which four were randomized controlled trials. Of an aggregate sample size (N) of 1585 patients, 698 were enrolled in the four RCTs and 887 belonged to the remaining registries included in this meta-analysis. Primary outcomes included CI-AKI incidence and relative risk. Mortality, dialysis, and major adverse cardiovascular events (MACCE) were secondary outcomes. A random effects model was used and data were evaluated for publication bias. RG was associated with significant risk reduction in CI-AKI compared to control (RR: 0.30, 95%CI: 0.18-0.50, P < 0.01). CI-AKI in RG was found to be 7.7% versus 23.6% in the control group (P < 0.01). Use of RG was associated with decreased mortality (RR: 0.43, 95%CI: 0.18-0.99, P = 0.05), dialysis (RR: 0.20, 95%CI: 0.06-0.61, P = 0.01), and MACCE (RR: 0.42, 95%CI: 0.27-0.65, P < 0.01) compared to control. RG significantly reduces rates of CI-AKI compared to standard volume expansion and is also associated with decreased rates of death, dialysis, and MACCE. © 2017, Wiley Periodicals, Inc.

Optimisation techniques in vaginal cuff brachytherapy.

PubMed

Tuncel, N; Garipagaoglu, M; Kizildag, A U; Andic, F; Toy, A

2009-11-01

The aim of this study was to explore whether an in-house dosimetry protocol and optimisation method are able to produce a homogeneous dose distribution in the target volume, and how often optimisation is required in vaginal cuff brachytherapy. Treatment planning was carried out for 109 fractions in 33 patients who underwent high dose rate iridium-192 (Ir(192)) brachytherapy using Fletcher ovoids. Dose prescription and normalisation were performed to catheter-oriented lateral dose points (dps) within a range of 90-110% of the prescribed dose. The in-house vaginal apex point (Vk), alternative vaginal apex point (Vk'), International Commission on Radiation Units and Measurements (ICRU) rectal point (Rg) and bladder point (Bl) doses were calculated. Time-position optimisations were made considering dps, Vk and Rg doses. Keeping the Vk dose higher than 95% and the Rg dose less than 85% of the prescribed dose was intended. Target dose homogeneity, optimisation frequency and the relationship between prescribed dose, Vk, Vk', Rg and ovoid diameter were investigated. The mean target dose was 99+/-7.4% of the prescription dose. Optimisation was required in 92 out of 109 (83%) fractions. Ovoid diameter had a significant effect on Rg (p = 0.002), Vk (p = 0.018), Vk' (p = 0.034), minimum dps (p = 0.021) and maximum dps (p<0.001). Rg, Vk and Vk' doses with 2.5 cm diameter ovoids were significantly higher than with 2 cm and 1.5 cm ovoids. Catheter-oriented dose point normalisation provided a homogeneous dose distribution with a 99+/-7.4% mean dose within the target volume, requiring time-position optimisation.

Evaluation of a New Motion-correction Algorithm Using On-rigid Registration in Respiratory-gated PET/CT Images of Liver Tumors.

PubMed

Wagatsuma, Kei; Osawa, Tatsufumi; Yokokawa, Naoki; Miwa, Kenta; Oda, Keiichi; Kudo, Yoshiro; Unno, Yasushi; Ito, Kimiteru; Ishii, Kenji

2016-01-01

The present study aimed to determine the qualitative and quantitative accuracy of the Q.Freeze algorithm in PET/CT images of liver tumors. A body phantom and hot spheres representing liver tumors contained 5.3 and 21.2 kBq/mL of a solution containing 18 F radioactivity, respectively. The phantoms were moved in the superior-inferior direction at a motion displacement of 20 mm. Conventional respiratory-gated (RG) and Q.Freeze images were sorted into 6, 10, and 13 phase-groups. The SUV ave was calculated from the background of the body phantom, and the SUV max was determined from the hot spheres of the liver tumors. Three patients with four liver tumors were also clinically assessed by whole-body and RG PET. The RG and Q.Freeze images derived from the clinical study were also sorted into 6, 10 and 13 phase-groups. Liver signal-to-noise ratio (SNR) and SUV max were determined from the RG and Q.Freeze clinical images. The SUV ave of Q.Freeze images was the same as those derived from the body phantom using RG. The liver SNR improved with Q.Freeze, and the SUVs max was not overestimated when Q.Freeze was applied in both the phantom and clinical studies. Q.Freeze did not degrade the liver SNR and SUV max even though the phase number was larger. Q.Freeze delivered qualitative and quantitative motion correction than conventional RG imaging even in 10-phase groups.

Investigations of the Rg-BrCl (Rg=He, Ne, Ar, Kr, Xe) binary van der Waals complexes: ab initio intermolecular potential energy surfaces, vibrational states and predicted pure rotational transition frequencies.

PubMed

Li, Song; Zheng, Rui; Chen, Shan-Jun; Chen, Yan; Chen, Peng

2017-03-05

The intermolecular potential energy surfaces (PESs) of the ground electronic state for the Rg-BrCl (Rg=He, Ne, Ar, Kr, Xe) van der Waals complexes have been constructed by using the coupled-cluster method in combination with the augmented quadruple-zeta correlation-consistent basis sets supplemented with an additional set of bond functions. The features of the anisotropic PESs for these complexes are remarkably similar, which are characterized by three minima and two saddle points between them. The global minimum corresponds to a collinear Rg-Br-Cl configuration. Two local minima, correlate with an anti-linear Rg-Cl-Br geometry and a nearly T-shaped structure, can also be located on each PES. The quantum bound state calculations enable us to investigate intermolecular vibrational states and rotational energy levels of the complexes. The transition frequencies are predicted and are fitted to obtain their corresponding spectroscopic constants. In general, the periodic trends are observed for this complex family. Comparisons with available experimental data for the collinear isomer of Ar-BrCl demonstrate reliability of our theoretical predictions, and our results for the other two isomers of Ar-BrCl as well as for other members of the complex family are also anticipated to be trustable. Except for the collinear isomer of Ar-BrCl, the data presented in this paper would be beneficial to improve our knowledge for these experimentally unknown species. Copyright © 2016 Elsevier B.V. All rights reserved.

Inherited XX sex reversal originating from wild medaka populations.

PubMed

Shinomiya, A; Otake, H; Hamaguchi, S; Sakaizumi, M

2010-11-01

The teleost fish, medaka (Oryzias latipes), has an XX/XY sex-determining mechanism. A Y-linked DM domain gene, DMY, has been isolated by positional cloning as the sex-determining gene in this species. Previously, we conducted a field survey of genotypic sex and found that approximately 1% of wild medaka are sex-reversed (XX males and XY females). Here, we performed genetic analyses of nine spontaneous XX sex-reversed males to elucidate its genetic basis. In all cases, the F(1) progeny were all females, whereas XX males reappeared in the backcross (BC) progeny, suggesting that XX sex reversal is a recessive trait. Although the incidences of sex reversal in the BC progeny were mostly low, 40% were males derived from one XX male. We performed linkage analysis using 55 BC males and located a single major factor, sda-1 (sex-determining autosomal factor-1), controlling sex reversal in an autosomal linkage group. Thus, genes involved in the sex-determining pathway can be isolated from spontaneous mutants in wild populations.

77 FR 44677 - RG Steel Sparrows Point LLC, Formerly Known as Severstal Sparrows Point LLC, a Subsidiary of RG...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-30

... Leased Workers From Echelon Service Company, Sun Associated Industries, Inc., MPI Consultants LLC...-site leased workers from Echelon Service Company, Sun Associated Industries, Inc., MPI Consultants LLC...

Chimeric L2-Based Virus-Like Particle (VLP) Vaccines Targeting Cutaneous Human Papillomaviruses (HPV)

PubMed Central

Huber, Bettina; Schellenbacher, Christina; Shafti-Keramat, Saeed; Jindra, Christoph; Christensen, Neil

2017-01-01

Common cutaneous human papillomavirus (HPV) types induce skin warts, whereas species beta HPV are implicated, together with UV-radiation, in the development of non-melanoma skin cancer (NMSC) in immunosuppressed patients. Licensed HPV vaccines contain virus-like particles (VLP) self-assembled from L1 major capsid proteins that provide type-restricted protection against mucosal HPV infections causing cervical and other ano-genital and oro-pharyngeal carcinomas and warts (condylomas), but do not target heterologous HPV. Experimental papillomavirus vaccines have been designed based on L2 minor capsid proteins that contain type-common neutralization epitopes, to broaden protection to heterologous mucosal and cutaneous HPV types. Repetitive display of the HPV16 L2 cross-neutralization epitope RG1 (amino acids (aa) 17–36) on the surface of HPV16 L1 VLP has greatly enhanced immunogenicity of the L2 peptide. To more directly target cutaneous HPV, L1 fusion proteins were designed that incorporate the RG1 homolog of beta HPV17, the beta HPV5 L2 peptide aa53-72, or the common cutaneous HPV4 RG1 homolog, inserted into DE surface loops of HPV1, 5, 16 or 18 L1 VLP scaffolds. Baculovirus expressed chimeric proteins self-assembled into VLP and VLP-raised NZW rabbit immune sera were evaluated by ELISA and L1- and L2-based pseudovirion (PsV) neutralizing assays, including 12 novel beta PsV types. Chimeric VLP displaying the HPV17 RG1 epitope, but not the HPV5L2 aa53-72 epitope, induced cross-neutralizing humoral immune responses to beta HPV. In vivo cross-protection was evaluated by passive serum transfer in a murine PsV challenge model. Immune sera to HPV16L1-17RG1 VLP (cross-) protected against beta HPV5/20/24/38/96/16 (but not type 76), while antisera to HPV5L1-17RG1 VLP cross-protected against HPV20/24/96 only, and sera to HPV1L1-4RG1 VLP cross-protected against HPV4 challenge. In conclusion, RG1-based VLP are promising next generation vaccine candidates to target cutaneous HPV infections. PMID:28056100

Lassa Virus Reverse Genetics.

PubMed

Martínez-Sobrido, Luis; Paessler, Slobodan; de la Torre, Juan Carlos

2017-01-01

The Old World (OW) arenavirus Lassa (LASV ) is estimated to infect several hundred thousand people yearly in West Africa, resulting in high numbers of Lassa fever (LF), a viral hemorrhagic fever (HF) disease associated with high morbidity and mortality. To date, no licensed vaccines are available to LASV infections, and anti-LASV drug therapy is limited to an off-label use of ribavirin (Rib) that is only partially effective. The development of reverse genetics has provided investigators with a novel and powerful approach for the investigation of the molecular, cell biology, and pathogenesis of LASV. The use of cell-based LASV minigenome (MG) systems has allowed examining the cis- and trans-acting factors involved in genome replication and gene transcription and the identification of novel drugable LASV targets. Likewise, it is now feasible to rescue infectious recombinant (r)LASV entirely from cloned cDNAs containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis, as well as to facilitate screens to identify antiviral drugs against LASV and the implementation of novel strategies to develop live-attenuated vaccines (LAV). In this chapter we will summarize the state-of-the-art experimental procedures for implementation of LASV reverse genetics. In addition, we will briefly discuss some significant translational research developments that have been made possible upon the development of LASV reverse genetics.

Reverse genetics in high throughput: rapid generation of complete negative strand RNA virus cDNA clones and recombinant viruses thereof.

PubMed

Nolden, T; Pfaff, F; Nemitz, S; Freuling, C M; Höper, D; Müller, T; Finke, Stefan

2016-04-05

Reverse genetics approaches are indispensable tools for proof of concepts in virus replication and pathogenesis. For negative strand RNA viruses (NSVs) the limited number of infectious cDNA clones represents a bottleneck as clones are often generated from cell culture adapted or attenuated viruses, with limited potential for pathogenesis research. We developed a system in which cDNA copies of complete NSV genomes were directly cloned into reverse genetics vectors by linear-to-linear RedE/T recombination. Rapid cloning of multiple rabies virus (RABV) full length genomes and identification of clones identical to field virus consensus sequence confirmed the approache's reliability. Recombinant viruses were recovered from field virus cDNA clones. Similar growth kinetics of parental and recombinant viruses, preservation of field virus characters in cell type specific replication and virulence in the mouse model were confirmed. Reduced titers after reporter gene insertion indicated that the low level of field virus replication is affected by gene insertions. The flexibility of the strategy was demonstrated by cloning multiple copies of an orthobunyavirus L genome segment. This important step in reverse genetics technology development opens novel avenues for the analysis of virus variability combined with phenotypical characterization of recombinant viruses at a clonal level.

Development of a PCR-Based Reverse Genetics System for an Attenuated Duck Tembusu Virus Strain

PubMed Central

Wu, Xiaogang; Shi, Ying; Yan, Dawei; Li, Xuesong; Yan, Pixi; Gao, Xuyuan; Zhang, Yuee; Yu, Lei; Ren, Chaochao; Li, Guoxin; Yan, Liping; Teng, Qiaoyang; Li, Zejun

2016-01-01

The infectious disease caused by the duck Tembusu virus (DTMUV) has resulted in massive economic losses to the Chinese duck industry in China since 2010. Research on the molecular basis of DTMUV pathogenicity has been hampered by the lack of a reliable reverse genetics system for this virus. Here we developed a PCR-based reverse genetics system with high fidelity for the attenuated DTMUV strain FX2010-180P. The rescued virus was characterized by using both indirect immunofluorescence assays (IFA) and whole genome sequencing. The rescued virus (rFX2010-180P) grew to similar titers as compared with the wild-type virus in DF-1 cells, and had similar replication and immunogenicity properties in ducks. To determine whether exogenous proteins could be expressed from DTMUV, both an internal ribosomal entry site (IRES) and the enhanced green fluorescent protein (eGFP) gene were introduced between the NS5 gene and the 3' non-coding sequence of FX2010-180P. A recombinant DTMUV expressing eGFP was rescued, but eGFP expression was unstable after 4 passages in DF-1 cells due to a deletion of 1,294 nucleotides. The establishment of a reliable reverse genetics system for FX2010-180P provides a foundation for future studies of DTMUV. PMID:27248497

Development of a PCR-Based Reverse Genetics System for an Attenuated Duck Tembusu Virus Strain.

PubMed

Wu, Xiaogang; Shi, Ying; Yan, Dawei; Li, Xuesong; Yan, Pixi; Gao, Xuyuan; Zhang, Yuee; Yu, Lei; Ren, Chaochao; Li, Guoxin; Yan, Liping; Teng, Qiaoyang; Li, Zejun

2016-01-01

The infectious disease caused by the duck Tembusu virus (DTMUV) has resulted in massive economic losses to the Chinese duck industry in China since 2010. Research on the molecular basis of DTMUV pathogenicity has been hampered by the lack of a reliable reverse genetics system for this virus. Here we developed a PCR-based reverse genetics system with high fidelity for the attenuated DTMUV strain FX2010-180P. The rescued virus was characterized by using both indirect immunofluorescence assays (IFA) and whole genome sequencing. The rescued virus (rFX2010-180P) grew to similar titers as compared with the wild-type virus in DF-1 cells, and had similar replication and immunogenicity properties in ducks. To determine whether exogenous proteins could be expressed from DTMUV, both an internal ribosomal entry site (IRES) and the enhanced green fluorescent protein (eGFP) gene were introduced between the NS5 gene and the 3' non-coding sequence of FX2010-180P. A recombinant DTMUV expressing eGFP was rescued, but eGFP expression was unstable after 4 passages in DF-1 cells due to a deletion of 1,294 nucleotides. The establishment of a reliable reverse genetics system for FX2010-180P provides a foundation for future studies of DTMUV.

Genetic screens for mutations affecting development of Xenopus tropicalis.

PubMed

Goda, Tadahiro; Abu-Daya, Anita; Carruthers, Samantha; Clark, Matthew D; Stemple, Derek L; Zimmerman, Lyle B

2006-06-01

We present here the results of forward and reverse genetic screens for chemically-induced mutations in Xenopus tropicalis. In our forward genetic screen, we have uncovered 77 candidate phenotypes in diverse organogenesis and differentiation processes. Using a gynogenetic screen design, which minimizes time and husbandry space expenditures, we find that if a phenotype is detected in the gynogenetic F2 of a given F1 female twice, it is highly likely to be a heritable abnormality (29/29 cases). We have also demonstrated the feasibility of reverse genetic approaches for obtaining carriers of mutations in specific genes, and have directly determined an induced mutation rate by sequencing specific exons from a mutagenized population. The Xenopus system, with its well-understood embryology, fate map, and gain-of-function approaches, can now be coupled with efficient loss-of-function genetic strategies for vertebrate functional genomics and developmental genetics.

Reverse-engineering the genetic circuitry of a cancer cell with predicted intervention in chronic lymphocytic leukemia.

PubMed

Vallat, Laurent; Kemper, Corey A; Jung, Nicolas; Maumy-Bertrand, Myriam; Bertrand, Frédéric; Meyer, Nicolas; Pocheville, Arnaud; Fisher, John W; Gribben, John G; Bahram, Seiamak

2013-01-08

Cellular behavior is sustained by genetic programs that are progressively disrupted in pathological conditions--notably, cancer. High-throughput gene expression profiling has been used to infer statistical models describing these cellular programs, and development is now needed to guide orientated modulation of these systems. Here we develop a regression-based model to reverse-engineer a temporal genetic program, based on relevant patterns of gene expression after cell stimulation. This method integrates the temporal dimension of biological rewiring of genetic programs and enables the prediction of the effect of targeted gene disruption at the system level. We tested the performance accuracy of this model on synthetic data before reverse-engineering the response of primary cancer cells to a proliferative (protumorigenic) stimulation in a multistate leukemia biological model (i.e., chronic lymphocytic leukemia). To validate the ability of our method to predict the effects of gene modulation on the global program, we performed an intervention experiment on a targeted gene. Comparison of the predicted and observed gene expression changes demonstrates the possibility of predicting the effects of a perturbation in a gene regulatory network, a first step toward an orientated intervention in a cancer cell genetic program.

Laboratory and Sky Testing Results for the TIS H4RG-10 4k x 4k, 10 micron Visible CMOS-Hybrid Detector

DTIC Science & Technology

2007-01-01

extremely important. In this paper we discuss Teledyne Imaging Sensor’s (TIS)# H4RG-10 CMOS-Hybrid Focal Plane Assembly (FPA)@. The H4RG-10 is a...receipt of a loaned engineering grade unit ( EGU ) that was used initially for electronics set up and testing. We plan on irradiating the EGU at a later...persistence, since exposure to high energy proton flux that is typical of the space environment results in the generation of new traps in the detector

Absence of first-order unbinding transitions of fluid and polymerized membranes

NASA Technical Reports Server (NTRS)

Grotehans, Stefan; Lipowsky, Reinhard

1990-01-01

Unbinding transitions of fluid and polymerized membranes are studied by renormalization-group (RG) methods. Two different RG schemes are used and found to give rather consistent results. The fixed-point structure of both RG's exhibits a complex behavior as a function of the decay exponent tau for the fluctuation-induced interaction of the membranes. For tau greater than tau(S2) interacting membranes can undergo first-order transitions even in the strong-fluctuation regime. These estimates for tau(S2) imply, however, that both fluid and polymerized membranes unbind in a continuous way in the absence of lateral tension.

The Effects of Moderate Whole Grain Consumption on Fasting Glucose and Lipids, Gastrointestinal Symptoms, and Microbiota

PubMed Central

Cooper, Danielle N.; Kable, Mary E.; Marco, Maria L.; De Leon, Angela; Rust, Bret; Baker, Julita E.; Horn, William; Burnett, Dustin; Keim, Nancy L.

2017-01-01

This study was designed to determine if providing wheat, corn, and rice as whole (WG) or refined grains (RG) under free-living conditions will change parameters of health over a six-week intervention in healthy, habitual non-WG consumers. Measurements of body composition, fecal microbiota, fasting blood glucose, total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), and triglycerides were made at baseline and post intervention. Subjects were given adequate servings of either WG or RG products based on their caloric need and asked to keep records of grain consumption, bowel movements, and GI symptoms weekly. After six weeks, subjects repeated baseline testing. Significant decreases in total, LDL, and non-HDL cholesterol were seen after the WG treatments but were not observed in the RG treatment. During Week 6, bowel movement frequency increased with increased WG consumption. No significant differences in microbiota were seen between baseline and post intervention, although, abundance of order Erysipelotrichales increased in RG subjects who ate more than 50% of the RG market basket products. Increasing consumption of WGs can alter parameters of health, but more research is needed to better elucidate the relationship between the amount consumed and the health-related outcome. PMID:28230784

Patient-reported outcomes measured by BREAST-Q after implant-based breast reconstruction: A cross-sectional controlled study in Brazilian patients.

PubMed

Aguiar, Isabella de Carvalho; Veiga, Daniela Francescato; Marques, Thaline Figueiredo; Novo, Neil Ferreira; Sabino Neto, Miguel; Ferreira, Lydia Masako

2017-02-01

The purpose of this study was to assess patient-reported outcomes of breast reconstruction with implants, using the BREAST-Q, in the late postoperative period. A total of 114 women previously operated due to breast cancer, in the late postoperative period (range 6-24 months) were enrolled in this cross-sectional study, and were allocated to either the mastectomy group (MG, n = 57) or reconstruction group (RG, n = 57). Patients in MG and RG, respectively, completed the Brazilian versions of Mastectomy and Reconstruction Modules of the BREAST-Q. The mean age of patients was 46.6 and 44.3 years in MG and RG, respectively. All patients underwent chemotherapy and 6% and 11% of patients underwent radiotherapy in MG and RG, respectively. Patients in the RG reported higher satisfaction with surgical outcome (P < 0.0001). However, no significant between-group differences were found in physical and sexual well-being, or satisfaction with the plastic surgeon, medical team, and office staff. Breast reconstruction with implants increased patient satisfaction with the surgical outcome, but did not influence patients' physical and sexual well-being or their satisfaction with the treatment received. Copyright © 2016 Elsevier Ltd. All rights reserved.

RG-I regions from elderflower pectins substituted on GalA are strong immunomodulators.

PubMed

Ho, Giang Thanh Thi; Zou, Yuan-Feng; Wangensteen, Helle; Barsett, Hilde

2016-11-01

Sambuci flos, also known as elderflower, has traditionally been used and is still in use for treatment of various types of illnesses related to the immune system such as cold, flu, fever and inflammation. Pectic polysaccharides from 50% EtOH, 50°C water and 100°C water extracts from elderflowers were treated with endo-α-d-(1-4)-polygalacturonase after previous de-esterification with the intention of isolating hairy regions and relate variation in structure to immunomodulating activity. High molecular weight sub-fractions (25-29kDa) and medium molecular weight sub-fractions (6-17kDa) were isolated after enzymatic treatment in addition to oligogalacturonides. Structural elucidation indicated that RG-I regions with AG-I and AG-II sidechains were the predominant structures in the high molecular weight sub-fractions, and two of three 1,4-linked GalA units in the rhamnogalacturonan backbone were branched in either position 2 or 3. The medium molecular weight sub-fractions had monomers and linkages typical for both RG-I and RG-II. The results showed that the high molecular RG-I containing polymers exhibit the highest dose-dependent complement fixing and macrophage stimulating activities. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterization of anthocyanins in the hybrid progenies derived from Iris dichotoma and I. domestica by HPLC-DAD-ESI/MS analysis.

PubMed

Xu, Wenji; Luo, Gangjun; Yu, Fengyang; Jia, Qingxiang; Zheng, Yang; Bi, Xiaoying; Lei, Jiajun

2018-06-01

Iris dichotoma with different flower colors and I. domestica are beardless wild irises belonging to the family Iridaceae that bloom in the summer and have long flowering periods. In this study, we collected three accessions of I. dichotoma with violet, yellow, and white flowers, respectively, in China, and crossed them with I. domestica individuals. The flower color of the hybrids derived from these crosses was categorized into eight groups: violet, purple, brown, orange, red, pink, yellow, and white. From this population, 45 individuals were selected for analysis, and their fully expanded inner and outer perianths were harvested for extraction of anthocyanins. Using high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis, 29 anthocyanins were identified by comparing MS and UV-visible spectra and elution order based on published data and guidelines. The 29 anthocyanins were classified into six groups: non-acylated glycosides (3RG, 3RG5G), acetylglycosides (3acRG5G), p-coumaroylglycosides (3pCRG, 3pCRG5G), caffeoylglycosides (3CRG5G), feruloylglycosides (3feRG, 3feRG5G), and acetyl-(p-coumaroyl) glycosides (3ac-pCRG5G). Acylated anthocyanin contents were considerably higher than non-acylated anthocyanin contents in the individuals evaluated, regardless of flower color, except in the yellow-flowered I. dichotoma and its yellow-flowered progeny. We found ten anthocyanins derived from pelargonidin, including pelargonidin 3-O-(caffeoyl)rutinoside-5-O-glucoside (Pg3CRG5G), pelargonidin 3-O-(feruloyl)rutinoside-5-O-glucoside (Pg3feRG5G), and pelargonidin 3-O-(feruloyl)rutinoside (Pg3feRG), that have not yet been reported in other Iris species. Moreover, delphinidin 3-O-(feruloyl) rutinoside-5-O-glucoside (Dp3feRG5G), and delphinidin 3-O-(feruloyl)rutinoside (Dp3feRG) were also characterized for the first time in Iris. Two to five major anthocyanins were detected in the petals of the violet and purple groups, whereas those of the brown group contained three to six anthocyanins. Petals of the orange, red, and pink groups contained two to four major anthocyanins. The total variance explained by the first two principal components (PC) in a PC analysis of the intensities of the compound peaks detected in individuals representing the eight color groups was 44.7%. Individuals were classified into 10 types (A-I to A-X) according to their anthocyanidin composition in the flower petals. Knowledge of the types of anthocyanins determining flower petal color will aid comprehensive understanding of flower color characteristics in hybrid progeny and will contribute to the development of breeding Iris cultivars of diverse flower colors. Copyright © 2018 Elsevier Ltd. All rights reserved.

Reverse Genetics of Newcastle Disease Virus.

PubMed

Cardenas-Garcia, Stivalis; Afonso, Claudio L

2017-01-01

Reverse genetics allows for the generation of recombinant viruses or vectors used in functional studies, vaccine development, and gene therapy. This technique enables genetic manipulation and cloning of viral genomes, gene mutation through site-directed mutagenesis, along with gene insertion or deletion, among other studies. An in vitro infection-based system including the highly attenuated vaccinia virus Ankara strain expressing the T7 RNA polymerase from bacteriophage T7, with co-transfection of three helper plasmids and a full-length cDNA plasmid, was successfully developed to rescue genetically modified Newcastle disease viruses in 1999. In this chapter, the materials and the methods involved in rescuing Newcastle disease virus (NDV) from cDNA, utilizing site-directed mutagenesis and gene replacement techniques, are described in detail.

Sex differences in genetic and environmental influences on educational attainment and income.

PubMed

Orstavik, Ragnhild E; Czajkowski, Nikolai; Røysamb, Espen; Knudsen, Gun Peggy; Tambs, Kristian; Reichborn-Kjennerud, Ted

2014-12-01

In many Western countries, women now reach educational levels comparable to men, although their income remains considerably lower. For the past decades, it has become increasingly clear that these measures of socio-economic status are influenced by genetic as well as environmental factors. Less is known about the relationship between education and income, and sex differences. The aim of this study was to explore genetic and environmental factors influencing education and income in a large cohort of young Norwegian twins, with special emphasis on gender differences. National register data on educational level and income were obtained for 7,710 twins (aged 29-41 years). Bivariate Cholesky models were applied to estimate qualitative and quantitative gender differences in genetic and environmental influences, the relative contribution of genetic and environmental factors to the correlation between education and income, and genetic correlations within and between sexes and phenotypes. The phenotypic correlation between educational level and income was 0.34 (0.32-0.39) for men and 0.45 (0.43-0.48) for women. An ACE model with both qualitative and quantitative sex differences fitted the data best. The genetic correlation between men and women (rg) was 0.66 (0.22-1.00) for educational attainment and 0.38 (0.01-0.75) for income, and between the two phenotypes 0.31 (0.08-0.52) for men and 0.72 (0.64-0.85) for women. Our results imply that, in relatively egalitarian societies with state-supported access to higher education and political awareness of gender equality, genetic factors may play an important role in explaining sex differences in the relationship between education and income.

Sensitivity of Female Inbreds of Cucumis sativus to Sex Reversion by Gibberellin.

PubMed

Shifriss, O; George, W L

1964-03-27

Two female inbred cucumbers were developed by substituting gene Acr for acr in the genetic backgrounds of the monoecious races Marketer and Tokyo, which exhibit weak and strong male tendency respectively. Marketer females are resistant and Tokyo females are sensitive to sex reversion in response to treatments with gibberellin A(3). Resistance and sensitivity of this type appear to depend upon the genetic system which controls sex tendency.

Reverse Genetics for Newcastle Disease Virus as a Vaccine Vector.

PubMed

Kim, Shin-Hee; Samal, Siba K

2018-02-22

Newcastle disease virus (NDV) is an economically important pathogen in the poultry industry worldwide. Recovery of infectious NDV from cDNA using reverse genetics has made it possible to manipulate the genome of NDV. This has greatly contributed to our understanding of the molecular biology and pathogenesis of NDV. Furthermore, NDV has modular genome and accommodates insertion of a foreign gene as a transcriptional unit, thus enabling NDV as a vaccine vector against diseases of humans and animals. Avirulent NDV strains (e.g., LaSota and B1) have been commonly used as vaccine vectors. In this protocol, we have described reverse genetics of NDV to be used as a vaccine vector by exemplifying the recovery of NDV vectored avian influenza virus vaccine. Specifically, cloning and recovery of NDV expressing the hemagglutinin protein of highly pathogenic influenza virus were explained. © 2018 by John Wiley & Sons, Inc. Copyright © 2018 John Wiley & Sons, Inc.

Ossicles of lumbar articular facets: normal variant or spondylolytic variant?

PubMed

Kumar, Dalavaye S; Fotiadou, Anastasia; Lalam, Radhesh; Ginder, Laurence M; Eisenstein, Stephen M; Tins, Bernard J; Tyrrell, Prudencia N M; Delieu, John M; McCall, Iain W; Rees, Dai A; Cassar-Pullicino, Victor N

2012-12-01

The objective of this study was to establish the prevalence and significance of ossicles of lumbar articular facets (OLAF) in young athletes with backache diagnosed by multi-detector computed tomography (MDCT). The MDCT examinations of the lumbar spine carried out for suspected spondylolysis on 46 consecutive symptomatic young athletes presenting to a sports injury clinic over a 1-year period were retrospectively reviewed. OLAF study included detailed correlation with the structural and morphological stress features of the posterior neural arches. This was then compared with a control group composed of 39 patients. Twenty-three OLAF were identified in 15 patients. Eleven of the 15 patients with ossicles had posterior element stress changes (PEST)/pars defects. In the control group, two OLAF were identified in two patients, one demonstrating PEST changes. The high prevalence of OLAF in young symptomatic athletes compared with the asymptomatic control group is indicative of stress fractures. The non-united articular process fractures should be regarded as part of the spectrum of stress-induced changes in the posterior neural arch in the same way as spondylolysis. MDCT with volumetric acquisition and multi-planar reformation is the most reliable investigation in the diagnosis of OLAF. 1) This CT study supports a traumatic aetiology for lumbar articular facets ossicles. 2) OLAF represent part of a spectrum of stress-induced changes in the posterior neural arch. 3) OLAF are associated with typical spondylolysis. 4) OLAF can be overlooked on reverse gantry angle computed tomography (RG-CT). 5) OLAF may account for some of the discrepancy between radionuclide and RG-CT studies.

The ginsenoside PPD exerts anti-endometriosis effects by suppressing estrogen receptor-mediated inhibition of endometrial stromal cell autophagy and NK cell cytotoxicity.

PubMed

Zhang, Bing; Zhou, Wen-Jie; Gu, Chun-Jie; Wu, Ke; Yang, Hui-Li; Mei, Jie; Yu, Jia-Jun; Hou, Xiao-Fan; Sun, Jian-Song; Xu, Feng-Yuan; Li, Da-Jin; Jin, Li-Ping; Li, Ming-Qing

2018-05-14

Endometriosis (EMS) is an estrogen-dependent gynecological disease with a low autophagy level of ectopic endometrial stromal cells (eESCs). Impaired NK cell cytotoxic activity is involved in the clearance obstruction of the ectopic endometrial tissue in the abdominopelvic cavity. Protopanaxadiol (PPD) and protopanaxatriol (PPT) are two metabolites of ginsenosides, which have profound biological functions, such as anti-cancer activities. However, the role and mechanism of ginsenosides and metabolites in endometriosis are completely unknown. Here, we found that the compounds PPD, PPT, ginsenoside-Rg3 (G-Rg3), ginsenoside-Rh2 (G-Rh2), and esculentoside A (EsA) led to significant decreases in the viability of eESCs, particularly PPD (IC50 = 30.64 µM). In vitro and in vivo experiments showed that PPD promoted the expression of progesterone receptor (PR) and downregulated the expression of estrogen receptor α (ERα) in eESCs. Treatment with PPD obviously induced the autophagy of eESCs and reversed the inhibitory effect of estrogen on eESC autophagy. In addition, eESCs pretreated with PPD enhanced the cytotoxic activity of NK cells in response to eESCs. PPD decreased the numbers and suppressed the growth of ectopic lesions in a mouse EMS model. These results suggest that PPD plays a role in anti-EMS activation, possibly by restricting estrogen-mediated autophagy regulation and enhancing the cytotoxicity of NK cells. This result provides a scientific basis for potential therapeutic strategies to treat EMS by PPD or further structural modification.

Population genetic structure and direct observations reveal sex-reversed patterns of dispersal in a cooperative bird.

PubMed

Harrison, Xavier A; York, Jennifer E; Young, Andrew J

2014-12-01

Sex-biased dispersal is pervasive and has diverse evolutionary implications, but the fundamental drivers of dispersal sex biases remain unresolved. This is due in part to limited diversity within taxonomic groups in the direction of dispersal sex biases, which leaves hypothesis testing critically dependent upon identifying rare reversals of taxonomic norms. Here, we use a combination of observational and genetic data to demonstrate a rare reversal of the avian sex bias in dispersal in the cooperatively breeding white-browed sparrow weaver (Plocepasser mahali). Direct observations revealed that (i) natal philopatry was rare, with both sexes typically dispersing locally to breed, and (ii), unusually for birds, males bred at significantly greater distances from their natal group than females. Population genetic analyses confirmed these patterns, as (i) corrected Assignment index (AIc), FST tests and isolation-by-distance metrics were all indicative of longer dispersal distances among males than females, and (ii) spatial autocorrelation analysis indicated stronger within-group genetic structure among females than males. Examining the spatial scale of extra-group mating highlighted that the resulting 'sperm dispersal' could have acted in concert with individual dispersal to generate these genetic patterns, but gamete dispersal alone cannot account entirely for the sex differences in genetic structure observed. That leading hypotheses for the evolution of dispersal sex biases cannot readily account for these sex-reversed patterns of dispersal in white-browed sparrow weavers highlights the continued need for attention to alternative explanations for this enigmatic phenomenon. We highlight the potential importance of sex differences in the distances over which dispersal opportunities can be detected. © 2014 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

A DUF-246 family glycosyltransferase-like gene affects male fertility and the biosynthesis of pectic arabinogalactans

DOE PAGES

Stonebloom, Solomon; Ebert, Berit; Xiong, Guangyan; ...

2016-04-18

We report pectins are a group of structurally complex plant cell wall polysaccharides whose biosynthesis and function remain poorly understood. The pectic polysaccharide rhamnogalacturonan-I (RG-I) has two types of arabinogalactan side chains, type-I and type-II arabinogalactans. To date few enzymes involved in the biosynthesis of pectin have been described. Here we report the identification of a highly conserved putative glycosyltransferase encoding gene, Pectic ArabinoGalactan synthesis-Related (PAGR), affecting the biosynthesis of RG-I arabinogalactans and critical for pollen tube growth. T-DNA insertions in PAGR were identified in Arabidopsis thaliana and were found to segregate at a 1:1 ratio of heterozygotes to wildmore » type. We were unable to isolate homozygous pagr mutants as pagr mutant alleles were not transmitted via pollen. In vitro pollen germination assays revealed reduced rates of pollen tube formation in pollen from pagr heterozygotes. To characterize a loss-of-function phenotype for PAGR, the Nicotiana benthamiana orthologs, NbPAGR-A and B, were transiently silenced using Virus Induced Gene Silencing. NbPAGR-silenced plants exhibited reduced internode and petiole expansion. Cell wall materials from NbPAGR-silenced plants had reduced galactose content compared to the control. Immunological and linkage analyses support that RG-I has reduced type-I arabinogalactan content and reduced branching of the RG-I backbone in NbPAGR-silenced plants. Arabidopsis lines overexpressing PAGR exhibit pleiotropic developmental phenotypes and the loss of apical dominance as well as an increase in RG-I type-II arabinogalactan content. Together, results support a function for PAGR in the biosynthesis of RG-I arabinogalactans and illustrate the essential roles of these polysaccharides in vegetative and reproductive plant growth.« less

A DUF-246 family glycosyltransferase-like gene affects male fertility and the biosynthesis of pectic arabinogalactans

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

Stonebloom, Solomon; Ebert, Berit; Xiong, Guangyan

We report pectins are a group of structurally complex plant cell wall polysaccharides whose biosynthesis and function remain poorly understood. The pectic polysaccharide rhamnogalacturonan-I (RG-I) has two types of arabinogalactan side chains, type-I and type-II arabinogalactans. To date few enzymes involved in the biosynthesis of pectin have been described. Here we report the identification of a highly conserved putative glycosyltransferase encoding gene, Pectic ArabinoGalactan synthesis-Related (PAGR), affecting the biosynthesis of RG-I arabinogalactans and critical for pollen tube growth. T-DNA insertions in PAGR were identified in Arabidopsis thaliana and were found to segregate at a 1:1 ratio of heterozygotes to wildmore » type. We were unable to isolate homozygous pagr mutants as pagr mutant alleles were not transmitted via pollen. In vitro pollen germination assays revealed reduced rates of pollen tube formation in pollen from pagr heterozygotes. To characterize a loss-of-function phenotype for PAGR, the Nicotiana benthamiana orthologs, NbPAGR-A and B, were transiently silenced using Virus Induced Gene Silencing. NbPAGR-silenced plants exhibited reduced internode and petiole expansion. Cell wall materials from NbPAGR-silenced plants had reduced galactose content compared to the control. Immunological and linkage analyses support that RG-I has reduced type-I arabinogalactan content and reduced branching of the RG-I backbone in NbPAGR-silenced plants. Arabidopsis lines overexpressing PAGR exhibit pleiotropic developmental phenotypes and the loss of apical dominance as well as an increase in RG-I type-II arabinogalactan content. Together, results support a function for PAGR in the biosynthesis of RG-I arabinogalactans and illustrate the essential roles of these polysaccharides in vegetative and reproductive plant growth.« less

Triazine dyes are agonists of the NAADP receptor

PubMed Central

Billington, Richard A; Bak, Judit; Martinez-Coscolla, Ana; Debidda, Marcella; Genazzani, Armando A

2004-01-01

NAADP has been shown to be a potent calcium-releasing second messenger in a wide variety of cell types to date. However, research has been hampered by a lack of pharmacological agents, with which to investigate NAADP-induced calcium release, and by the molecular identity of its cellular target protein being unknown.In the present paper, the sea urchin egg model was used to investigate whether triazine dyes, which can act as nucleotide mimetics, can bind to the NAADP receptor, induce Ca2+ release and be used for affinity chromatography of the receptor.Indeed, all the triazine dyes tested (Reactive Red 120 (RR120), Reactive Green 19 (RG19), Reactive Green 5 (RG5), Cibacron Blue 3GA and Reactive Yellow 86) displayed micromolar affinities, except for Reactive Orange 14. Furthermore, unlike NAADP, RR120, RG19 and RG5 did not bind in an irreversible manner.The compound that displayed the highest affinity, RR120, was tested in a 45Ca2+ efflux assay. This compound released Ca2+ via the NAADP receptor, as shown by the ability of subthreshold NAADP concentrations to inhibit this release. Furthermore, heparin and ruthenium red were unable to block RR120-induced Ca2+ release.We have also shown that RG5 and RG19, immobilised on resins, retain the ability to bind to the receptor, and that this interaction can be disrupted by high salt concentrations. As a proof of principle, we have shown that this can be used to partially purify the NAADP receptor by at least 75-fold.In conclusion, triazine dyes interact with the NAADP receptor, and this could be exploited in future to create a new generation of pharmacological tools to investigate this messenger and, in combination with other techniques, to purify the receptor. PMID:15265807

Enhanced Absorption Study of Ginsenoside Compound K (20-O-β-(D-Glucopyranosyl)-20(S)-protopanaxadiol) after Oral Administration of Fermented Red Ginseng Extract (HYFRG™) in Healthy Korean Volunteers and Rats

PubMed Central

Choi, Il-Dong; Ryu, Ju-Hee; Lee, Dong-Eun; Lee, Myoung-Hee; Shim, Jae-Joong; Ahn, Young-Tae; Sim, Jae-Hun; Huh, Chul-Sung; Shim, Wang-Seob; Yim, Sung-Vin; Chung, Eun-Kyoung

2016-01-01

To evaluate the pharmacokinetics of compound K after oral administration of HYFRG and RG in humans, an open-label, randomized, single-dose, fasting, and one-period pharmacokinetic study was conducted. After oral administration of a single 3 g dose of HYFRG and RG to 24 healthy Korean males, the mean (±SD) of AUC0–t and C max of compound K from HYFRG were 1466.83 ± 295.89 ng·h/mL and 254.45 ± 51.20 ng/mL, being 115.2- and 80-fold higher than those for RG (12.73 ± 7.83 ng·h/mL and 3.18 ± 1.70 ng/mL), respectively; in case of Sprague Dawley rats the mean (±SD) of AUC0–t and C max of compound K from HYFRG was 58.03 ± 32.53 ng·h/mL and 15.19 ± 10.69 ng/mL, being 6.3- and 6.0-fold higher than those from RG (9.21 ± 7.52 ng·h/mL and 2.55 ± 0.99 ng/mL), respectively. T max of compound K in humans and rats was 2.54 ± 0.92 and 3.33 ± 0.50 h for HYFRG and 9.11 ± 1.45 and 6.75 ± 3.97 hours for RG, respectively. In conclusion, the administration of HYFRG resulted in a higher and faster absorption of compound K in both humans and rats compared to RG. PMID:27516803

Characterizing a Full Spectrum of Physico-Chemical Properties of Ginsenosides Rb1 and Rg1 to Be Proposed as Standard Reference Materials

PubMed Central

Kim, Il-Woung; Hong, Hee-Do; Choi, Sang Yoon; Hwang, Da-Hye; Her, Youl; Kim, Si-Kwan

2011-01-01

Good manufacturing practice (GMP)-based quality control is an integral component of the common technical document, a formal documentation process for applying a marketing authorization holder to those countries where ginseng is classified as a medicine. In addition, authentication of the physico-chemical properties of ginsenoside reference materials, and qualitative and quantitative batch analytical data based on validated analytical procedures are prerequisites for certifying GMP. Therefore, the aim of this study was to propose an authentication process for isolated ginsenosides Rb1 and Rg1 as reference materials (RM) and for these compounds to be designated as RMs for ginseng preparations throughout the world. Ginsenoside Rb1 and Rg1 were isolated by Diaion HP-20 adsorption chromatography, silica gel flash chromatography, recrystallization, and preparative HPLC. HPLC fractions corresponding to those two ginsenosides were recrystallized in appropriate solvents for the analysis of physico-chemical properties. Documentation of the isolated ginsenosides was made according to the method proposed by Gaedcke and Steinhoff. The ginsenosides were subjected to analyses of their general characteristics, identification, purity, content quantitation, and mass balance tests. The isolated ginsenosides were proven to be a single compound when analyzed by three different HPLC systems. Also, the water content was found to be 0.940% for Rb1 and 0.485% for Rg1, meaning that the net mass balance for ginsenoside Rb1 and Rg1 were 99.060% and 99.515%, respectively. From these results, we could assess and propose a full spectrum of physicochemical properties for the ginsenosides Rb1 and Rg1 as standard reference materials for GMP-based quality control. PMID:23717096

Tumor segmentation on FDG-PET: usefulness of locally connected conditional random fields

NASA Astrophysics Data System (ADS)

Nishio, Mizuho; Kono, Atsushi K.; Koyama, Hisanobu; Nishii, Tatsuya; Sugimura, Kazuro

2015-03-01

This study aimed to develop software for tumor segmentation on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). To segment the tumor from the background, we used graph cut, whose segmentation energy was generally divided into two terms: the unary and pairwise terms. Locally connected conditional random fields (LCRF) was proposed for the pairwise term. In LCRF, a three-dimensional cubic window with length L was set for each voxel, and voxels within the window were considered for the pairwise term. To evaluate our method, 64 clinically suspected metastatic bone tumors were tested, which were revealed by FDG-PET. To obtain ground truth, the tumors were manually delineated via consensus of two board-certified radiologists. To compare the LCRF accuracy, other types of segmentation were also applied such as region-growing based on 35%, 40%, and 45% of the tumor maximum standardized uptake value (RG35, RG40, and RG45, respectively), SLIC superpixels (SS), and region-based active contour models (AC). To validate the tumor segmentation accuracy, a dice similarity coefficient (DSC) was calculated between manual segmentation and result of each technique. The DSC difference was tested using the Wilcoxon signed rank test. The mean DSCs of LCRF at L = 3, 5, 7, and 9 were 0.784, 0.801, 0.809, and 0.812, respectively. The mean DSCs of other techniques were RG35, 0.633; RG40, 0.675; RG45, 0.689; SS, 0.709; and AC, 0.758. The DSC differences between LCRF and other techniques were statistically significant (p <0.05). In conclusion, tumor segmentation was more reliably performed with LCRF relative to other techniques.

Responsible gambling among older adults: a qualitative exploration.

PubMed

Subramaniam, Mythily; Satghare, Pratika; Vaingankar, Janhavi A; Picco, Louisa; Browning, Colette J; Chong, Siow Ann; Thomas, Shane A

2017-04-04

Responsible gambling (RG) is defined as gambling for pleasure and entertainment but with an awareness of the likelihood of losing, an understanding of the associated risks and the ability to exercise control over one's gambling activity. The current study describes a qualitative approach to explore RG among older adults (aged 60 years and above) in Singapore and reports on the cognitive and behavioural strategies employed by them to regulate their gambling. Inclusion criteria included Singapore residents aged 60 years and above, who could speak in English, Chinese, Malay or Tamil and were current or past regular gamblers. Participants were recruited using a combination of network and purposive sampling. Socio-demographic information on age, age of onset of gambling, gender, ethnicity, marital status, education and employment was collected. The South Oaks Gambling Screen (SOGS) was used to collect information on gambling activities and problems associated with gambling behaviour. Qualitative interviews were conducted with 25 older adults (60 years and above) who currently gambled. The data was analyzed using thematic network analysis. This global theme of RG comprised two organising themes: self -developed strategies to limit gambling related harm and family interventions to reduce gambling harm. The basic themes included delayed gratification, perception of futility of gambling, setting limits, maintaining balance, help-seeking and awareness of disordered gambling in self or in others. Family interventions included pleading and threatening, compelling help-seeking as well as family exclusion order. The study highlights the significant role that families play in Asian societies in imposing RG. Education of family members both in terms of the importance of RG, and communication of the ways in which older adults can incorporate RG behaviours including the use of exclusion in specific scenarios is important.

Saponin and non-saponin fractions of red ginseng ameliorate cisplatin-induced pica in rats.

PubMed

Sathyanath, Rekha; Hanumantha Rao, Balaji Raghavendran; Kim, Hyeong-Geug; Cho, Jung-Hyo; Son, Chang-Gue

2013-08-01

Nausea and vomiting are considered as the foremost unpleasant side effects of chemotherapy experienced by 20-90% of cancer patients. In the present study, the effects of Korean Panax ginseng C.A. Meyer (Araliaceae) (RG), ginseng saponin (GS) and non-saponin (GNS) on cisplatin (CP)-induced pica and gastric damage in rats were investigated. Rats were treated with RG (25, 50, 100 mg/kg b.wt.), GS (5 and 10 mg/kg 100 mg/kg b.wt.) and GNS (50 and 100 mg/kg b.wt.) before or after a single intraperitoneal injection of CP (6 mg/kg b.wt.). Kaolin together with normal food intake, normal food alone, body weight, histological examination of stomach and small intestine were used as indices of CP-induced pica in rats. Pre-treatment with RG (50 and 100 mg/kg b.wt.) attenuated CP-induced kaolin intake at 24 h. CP-induced kaolin intake decreased upon post-treatment of rats with RG (50 and 100 mg/kg b.wt.) at 48 h. The incidence of body weight reduction at 48 and 72 h diminished in rats post-treated with RG (50 mg/kg b.wt.). Pre-treatment with GS (5 and 10 mg/kg b.wt.) and GNS (50 and 100 mg/kg b.wt.) attenuated CP-induced kaolin intake while normal food intake was not improved in 24 and 48 h. The gastro-protective effects of RG, GS and GNS were further confirmed by histopathological (damage in glandular portion and villi with dilated appearance) findings. The study indicates that both the red GS and GNS improve feeding behavior against CP-induced pica in rats.

Ratiometric imaging of gastrodermal lipid bodies in coral-dinoflagellate endosymbiosis

NASA Astrophysics Data System (ADS)

Luo, Y.-J.; Wang, L.-H.; Chen, W.-N. U.; Peng, S.-E.; Tzen, J. T.-C.; Hsiao, Y.-Y.; Huang, H.-J.; Fang, L.-S.; Chen, C.-S.

2009-03-01

Cnidaria-dinoflagellate endosymbiosis is the phenomenon of autotrophic symbionts living inside the gastrodermal cells of their animal hosts. The molecular mechanism that regulates this association remains unclear. Using quantitative microscopy, we now provide evidence that the dynamic lipid changes in gastrodermal “lipid bodies” (LBs) reflect the symbiotic status of the host cell and its symbiont in the hermatypic coral Euphyllia glabrescens. By dual-emission ratiometric imaging with a solvatochromic fluorescent probe, Nile red (9-diethylamino-5H-benzo[α]phenoxazine-5-one), we showed that the in situ distribution of polar versus neutral lipids in LBs in living gastrodermal cells and symbionts can be analyzed. The ratio of Nile red fluorescence at red (R) versus green (G) wavelength region (i.e., R/G ratio) correlated with the relative molar ratio of polar (P) versus neutral (NP) lipids (i.e., P/NP ratio). The R/G ratio in host LBs increased after bleaching, indicating a decrease in neutral lipid accumulation in gastrodermal cells. On the other hand, neutral lipid accumulation inside the symbiont LBs resulted in gradual decreases of the R/G ratio as a result of bleaching. In comparison with the bleaching event, there was no relative lipid concentration change in host LBs under continual light or dark treatments as shown by insignificant R/G ratio shift. Patterns of R/G ratio shift in symbiont LBs were also different between corals undergoing bleaching and continual light/dark treatment. In the latter, there was little lipid accumulation in symbionts, with no resulting R/G ratio decrease. These results, demonstrating that the symbiotic status positively correlated with morphological and compositional changes of lipid bodies, not only highlight the pivotal role of LBs, but also implicate an involvement of lipid trafficking in regulating the endosymbiosis.

Resterilized mesh in repair of abdominal wall defects in rats.

PubMed

Sucullu, Ilker; Akin, Mehmet Levhi; Yitgin, Selahattin; Filiz, Ali Ilker; Kurt, Yavuz

2008-01-01

A variety of negative opinions about repeated usage of relatively expensive resterilized synthetic meshes have been considered. It had been stated that resterilized polypropylene meshes inhibits fibroblastic activity, decreases proliferative activity, and increases apoptosis in human fibroblast culture, in vitro. The purpose of this study is the in vivo evaluation of the resterilized mesh repairs of abdominal hernia defects in rat models of incisional hernia by comparing primer repair and original mesh repairs. The rats (n = 22) were separated into three groups. While the abdominal defect was repaired by primary suture in the control group (CG), the defects were repaired by original mesh (OG) or resterilized mesh (RG) in mesh-repaired groups. After 21 days, the rats were evaluated for tissue tensile strengths, tissue hydroxyproline levels, tissue inflammation, fibrosis, and apoptosis. Although the tensile strengths in OG and RG were significantly higher than those of CG (p < .05 and p < .05), there was no significant difference between two groups. The tissue hydroxyproline levels in OG and RG were also higher than those of CG. The difference was not significant between the two groups. The inflammation and fibrosis indexes in OG and RG were significantly higher than those of CG (p < .0001 for both), but there was no difference between groups. While the apoptosis index in OG and RG was also higher than that of CG (p < .0001 for both), there was no significant difference between OG and RG. The usage of resterilized mesh in abdominal wall repair did not reduce the tissue tensile strength, did not affect the tissue hydroxyproline levels, did not decrease the fibrosis, and did not increase the tissue inflammation and apoptosis. In conclusion, usage of resterilized meshes in abdominal wall defects was as safe as sterilized meshes.

78 FR 58575 - Review of Experiments for Research Reactors

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-24

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0219] Review of Experiments for Research Reactors AGENCY... Commission (NRC) is withdrawing Regulatory Guide (RG) 2.4, ``Review of Experiments for Research Reactors... withdrawing RG 2.4, ``Review of Experiments for Research Reactors,'' (ADAMS Accession No. ML003740131) because...

Eco-friendly graphene synthesis on Cu foil electroplated by reusing Cu etchants

PubMed Central

Kwon, Ki Chang; Ham, Juyoung; Kim, Sungjun; Lee, Jong-Lam; Kim, Soo Young

2014-01-01

Graphene film grown by chemical vapor deposition using Cu substrate is promising for industrial applications. After etching the Cu substrate, which is essential step in graphene transfer process, the etchant solution must be chemically treated to prevent water pollution. Here we investigated that a method of reusing Cu etchant used to synthesize graphene, the synthesis of graphene on the resulting reused Cu films (R-G), and the application of R-G to organic light-emitting diodes (OLEDs) and organic photovoltaic cells (OPVs). The turn-on voltage of OLEDs based on the R-G electrode was 4.2 V, and the efficiencies of OPVs based on the R-G electrode were 5.9–5.95%, that are similar to or better than those of the indium-tin-oxide-based devices. These results suggest that the reusing of Cu foil by the electroplating method could reduce the cost of graphene synthesis, thus opening a wide range of applications in graphene electronics. PMID:24777344

Functional renormalization-group approaches, one-particle (irreducible) reducible with respect to local Green’s functions, with dynamical mean-field theory as a starting point

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

Katanin, A. A., E-mail: katanin@mail.ru

We consider formulations of the functional renormalization-group (fRG) flow for correlated electronic systems with the dynamical mean-field theory as a starting point. We classify the corresponding renormalization-group schemes into those neglecting one-particle irreducible six-point vertices (with respect to the local Green’s functions) and neglecting one-particle reducible six-point vertices. The former class is represented by the recently introduced DMF{sup 2}RG approach [31], but also by the scale-dependent generalization of the one-particle irreducible representation (with respect to local Green’s functions, 1PI-LGF) of the generating functional [20]. The second class is represented by the fRG flow within the dual fermion approach [16, 32].more » We compare formulations of the fRG approach in each of these cases and suggest their further application to study 2D systems within the Hubbard model.« less

Ecological changes in oral microcosm biofilm during maturation

NASA Astrophysics Data System (ADS)

Kim, Young-Seok; Kang, Si-Mook; Lee, Eun-Song; Lee, Ji Hyun; Kim, Bo-Ra; Kim, Baek-Il

2016-10-01

The aim of this study was to evaluate the ecological changes in the biofilm at different stages of maturation using 16S rDNA gene amplicon sequencing and to identify correlations between red/green (R/G) fluorescence ratio and ecological changes. An oral microcosm biofilm was initiated from the saliva of a single donor and grown anaerobically for up to 10 days in basal medium mucin. Quantitative light-induced fluorescence analysis was shown that the R/G ratio of the biofilm increased consistently, but the slope rapidly decreased after six days. The bacterial compositions of 10 species also consistently changed over time. However, there was no significant correlation between each bacteria and red fluorescence. The monitoring of the maturation process of oral microcosm biofilm over 10 days revealed that the R/G ratio and the bacterial composition within biofilm consistently changed. Therefore, the R/G fluorescence ratio of biofilm may be related with its ecological change rather than specific bacteria.

Rhamnogalacturonan-I Based Microcapsules for Targeted Drug Release

PubMed Central

Kusic, Anja; De Gobba, Cristian; Larsen, Flemming H.; Sassene, Philip; Zhou, Qi; van de Weert, Marco; Mullertz, Anette; Jørgensen, Bodil; Ulvskov, Peter

2016-01-01

Drug targeting to the colon via the oral administration route for local treatment of e.g. inflammatory bowel disease and colonic cancer has several advantages such as needle-free administration and low infection risk. A new source for delivery is plant-polysaccharide based delivery platforms such as Rhamnogalacturonan-I (RG-I). In the gastro-intestinal tract the RG-I is only degraded by the action of the colonic microflora. For assessment of potential drug delivery properties, RG-I based microcapsules (~1 μm in diameter) were prepared by an interfacial poly-addition reaction. The cross-linked capsules were loaded with a fluorescent dye (model drug). The capsules showed negligible and very little in vitro release when subjected to media simulating gastric and intestinal fluids, respectively. However, upon exposure to a cocktail of commercial RG-I cleaving enzymes, ~ 9 times higher release was observed, demonstrating that the capsules can be opened by enzymatic degradation. The combined results suggest a potential platform for targeted drug delivery in the terminal gastro-intestinal tract. PMID:27992455

Radiation profiles measured through clouds using a return glider radiosonde

NASA Astrophysics Data System (ADS)

Kräuchi, Andreas; Philipona, Rolf; Kivi, Rigel

2016-04-01

With new and improved radiation sensors in a small glider aircraft vertical flights through clouds have been conducted. This new Return Glider Radiosonde (RG-R) is lifted up with double balloon technique to keep the radiation instruments as horizontal as possible during ascent. The RG-R is equipped with a routine radiosonde to transmit the data to a ground station and an autopilot to fly the glider radiosonde back to the launch site, where it lands autonomous with a parachute. The RG-R was successfully tested and deployed for tropospheric and stratospheric radiation measurements up to 30 hPa (24 km altitude) at the GRUAN sites Payerne (Switzerland) and Sodankylä (Finland). Radiation profiles and the radiation budget through the atmosphere during different daytimes and under cloud-free and cloudy situations will be shown in relation to temperature and humidity at the surface and in the atmosphere. The RG-R flight characteristics and new measurement possibilities will also be discussed.

Boomerang RG flows in M-theory with intermediate scaling

NASA Astrophysics Data System (ADS)

Donos, Aristomenis; Gauntlett, Jerome P.; Rosen, Christopher; Sosa-Rodriguez, Omar

2017-07-01

We construct novel RG flows of D=11 supergravity that asymptotically approach AdS 4 × S 7 in the UV with deformations that break spatial translations in the dual field theory. In the IR the solutions return to exactly the same AdS 4 × S 7 vacuum, with a renormalisation of relative length scales, and hence we refer to the flows as `boomerang RG flows'. For sufficiently large deformations, on the way to the IR the solutions also approach two distinct intermediate scaling regimes, each with hyperscaling violation. The first regime is Lorentz invariant with dynamical exponent z = 1 while the second has z = 5/2. Neither ofthe two intermediatescaling regimesare associatedwith exact hyperscaling violation solutions of D = 11 supergravity. The RG flow solutions are constructed using the four dimensional N = 2 STU gauged supergravity theory with vanishing gauge fields, but non-vanishing scalar and pseudoscalar fields. In the ABJM dual field theory the flows are driven by spatially modulated deformation parameters for scalar and fermion bilinear operators.

Sedimentation of knotted polymers

NASA Astrophysics Data System (ADS)

Piili, J.; Marenduzzo, D.; Kaski, K.; Linna, R. P.

2013-01-01

We investigate the sedimentation of knotted polymers by means of stochastic rotation dynamics, a molecular dynamics algorithm that takes hydrodynamics fully into account. We show that the sedimentation coefficient s, related to the terminal velocity of the knotted polymers, increases linearly with the average crossing number nc of the corresponding ideal knot. This provides direct computational confirmation of this relation, postulated on the basis of sedimentation experiments by Rybenkov [J. Mol. Biol.10.1006/jmbi.1996.0876 267, 299 (1997)]. Such a relation was previously shown to hold with simulations for knot electrophoresis. We also show that there is an accurate linear dependence of s on the inverse of the radius of gyration Rg-1, more specifically with the inverse of the Rg component that is perpendicular to the direction along which the polymer sediments. When the polymer sediments in a slab, the walls affect the results appreciably. However, Rg-1 remains to a good precision linearly dependent on nc. Therefore, Rg-1 is a good measure of a knot's complexity.

Renormalization-group theory for finite-size scaling in extreme statistics

NASA Astrophysics Data System (ADS)

Györgyi, G.; Moloney, N. R.; Ozogány, K.; Rácz, Z.; Droz, M.

2010-04-01

We present a renormalization-group (RG) approach to explain universal features of extreme statistics applied here to independent identically distributed variables. The outlines of the theory have been described in a previous paper, the main result being that finite-size shape corrections to the limit distribution can be obtained from a linearization of the RG transformation near a fixed point, leading to the computation of stable perturbations as eigenfunctions. Here we show details of the RG theory which exhibit remarkable similarities to the RG known in statistical physics. Besides the fixed points explaining universality, and the least stable eigendirections accounting for convergence rates and shape corrections, the similarities include marginally stable perturbations which turn out to be generic for the Fisher-Tippett-Gumbel class. Distribution functions containing unstable perturbations are also considered. We find that, after a transitory divergence, they return to the universal fixed line at the same or at a different point depending on the type of perturbation.

Selective Detection of NO2 Using Cr-Doped CuO Nanorods

PubMed Central

Kim, Kang-Min; Jeong, Hyun-Mook; Kim, Hae-Ryong; Choi, Kwon-Il; Kim, Hyo-Joong; Lee, Jong-Heun

2012-01-01

CuO nanosheets, Cr-doped CuO nanosheets, and Cr-doped CuO nanorods were prepared by heating a slurry containing Cu-hydroxide/Cr-hydroxide. Their responses to 100 ppm NO2, C2H5OH, NH3, trimethylamine, C3H8, and CO were measured. For 2.2 at% Cr-doped CuO nanorods, the response (Ra/Rg, Ra: resistance in air, Rg: resistance in gas) to 100 ppm NO2 was 134.2 at 250 °C, which was significantly higher than that of pure CuO nano-sheets (Ra/Rg = 7.5) and 0.76 at% Cr-doped CuO nanosheets (Ra/Rg = 19.9). In addition, the sensitivity for NO2 was also markedly enhanced by Cr doping. Highly sensitive and selective detection of NO2 in 2.2 at% Cr-doped CuO nanorods is explained in relation to Cr-doping induced changes in donor density, morphology, and catalytic effects. PMID:22969384

Renormalization group scale-setting from the action—a road to modified gravity theories

NASA Astrophysics Data System (ADS)

Domazet, Silvije; Štefančić, Hrvoje

2012-12-01

The renormalization group (RG) corrected gravitational action in Einstein-Hilbert and other truncations is considered. The running scale of the RG is treated as a scalar field at the level of the action and determined in a scale-setting procedure recently introduced by Koch and Ramirez for the Einstein-Hilbert truncation. The scale-setting procedure is elaborated for other truncations of the gravitational action and applied to several phenomenologically interesting cases. It is shown how the logarithmic dependence of the Newton's coupling on the RG scale leads to exponentially suppressed effective cosmological constant and how the scale-setting in particular RG-corrected gravitational theories yields the effective f(R) modified gravity theories with negative powers of the Ricci scalar R. The scale-setting at the level of the action at the non-Gaussian fixed point in Einstein-Hilbert and more general truncations is shown to lead to universal effective action quadratic in the Ricci tensor.

Non-canonical features of the Golgi apparatus in bipolar epithelial neural stem cells

PubMed Central

Taverna, Elena; Mora-Bermúdez, Felipe; Strzyz, Paulina J.; Florio, Marta; Icha, Jaroslav; Haffner, Christiane; Norden, Caren; Wilsch-Bräuninger, Michaela; Huttner, Wieland B.

2016-01-01

Apical radial glia (aRG), the stem cells in developing neocortex, are unique bipolar epithelial cells, extending an apical process to the ventricle and a basal process to the basal lamina. Here, we report novel features of the Golgi apparatus, a central organelle for cell polarity, in mouse aRGs. The Golgi was confined to the apical process but not associated with apical centrosome(s). In contrast, in aRG-derived, delaminating basal progenitors that lose apical polarity, the Golgi became pericentrosomal. The aRG Golgi underwent evolutionarily conserved, accordion-like compression and extension concomitant with cell cycle-dependent nuclear migration. Importantly, in line with endoplasmic reticulum but not Golgi being present in the aRG basal process, its plasma membrane contained glycans lacking Golgi processing, consistent with direct ER-to-cell surface membrane traffic. Our study reveals hitherto unknown complexity of neural stem cell polarity, differential Golgi contribution to their specific architecture, and fundamental Golgi re-organization upon cell fate change. PMID:26879757

Bowel obstruction rates in antecolic/antegastric versus retrocolic/retrogastric Roux limb gastric bypass: a meta-analysis.

PubMed

Al Harakeh, Ayman B; Kallies, Kara J; Borgert, Andrew J; Kothari, Shanu N

2016-01-01

Previous literature is varied with regard to rates of bowel obstruction after laparoscopic Roux-en-Y gastric bypass (LRYGB). Internal herniation through mesenteric defects is a common cause of bowel obstructions. There are advantages and disadvantages to routing the Roux limb via a retrocolic/retrogastric (RC/RG) versus an antecolic/antegastric (AC/AG) position. To review the literature comparing obstruction rates in RYGB using the antecolic versus retrocolic approach. Community-based integrated multispecialty health system with a teaching hospital serving 19 counties over a 3-state region. A literature search for articles published from 1994-2013 was completed. Articles were included if they reported an n>25, Roux limb route, obstruction rate by route, and follow-up duration. Statistical analysis included χ(2) test by patient number. The initial search identified 241 articles; 8 met inclusion criteria. There were 4805 patients in the AC/AG group, and 2238 in the RC/RG group. Follow-up ranged from 0 to 68 months. A linear stapled technique was reported in 4231 (88%) patients in the AC/AG group and 1541 (69%) of RC/RG group. Handsewn closure of mesenteric defects was reported in 2152 (45%) patients in the AC/AG group and 1012 (45%) patients in the RC/RG group. Bowel obstructions occurred in 68 (1.4%) patients in the AC/AG group and 117 (5.2%) patients in the RC/RG group (P<.001). Internal hernias were reported in 65 (1.3%) patients in the AC/AG group and 52 (2.3%) patients in the RC/RG group (P<.001). Two mortalities were reported in the AC/AG group. Increased rates of bowel obstruction and internal hernia were observed in the RC/RG group compared with the AC/AG group. A prospective, randomized trial would be necessary to definitively determine the impact of Roux limb position and routine closure of mesenteric defects on bowel obstruction rates after gastric bypass. Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

History of the Office of the Secretary of Defense. Volume 1. The Formative Years, 1947-1950

DTIC Science & Technology

1984-01-01

of greatest- danger should occur at some other time than anticipated." Even though he now had Ken nan’s- views, Forrestal continued to seek spe- cific...RG 330, CD 18-1-36; terms of reference for Cie ° " " on Civilian Components, (n d). eric A to memo Folrestal for Royaill, 20 Nov 47. RG 330,.,CD 1-1...384-95; Truman, M*soki, 11-164-65, memo Ohly for Forressal, 14 May 48. RG 330, CD 6-2-47. 30 On the course of the war, see Netanel Loach , 1,rAtl

78 FR 40511 - RG Steel Sparrows Point LLC, Formerly Known as Severstal Sparrows Point LLC, a Subsidiary of RG...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-05

..., Alliance Engineering, Inc., Washington Group International, Javan & Walter, Inc., Kinetic Technical... Consulting, Crown Security, Eastern Automation, Eds(Hp), Teksystems, URS Corporation, B More Industrial..., Alliance Engineering, Inc., Washington Group International, Javan & Walter, Inc., Kinetic Technical...

Can ginsenosides protect human erythrocytes against free-radical-induced hemolysis?

PubMed

Liu, Zai-Qun; Luo, Xu-Yang; Sun, Yun-Xiu; Chen, Yan-Ping; Wang, Zhi-Cai

2002-08-15

Many studies have focused on the free-radical-initiated peroxidation of membrane lipid, which is associated with a variety of pathological events. Panax ginseng is used in traditional Chinese medicine to enhance stamina and capacity to deal with fatigue and physical stress. Many reports have been devoted to the effects of ginsenosides, the major active components in P. ginseng, on the lipid metabolism, immune function and cardiovascular system. The results, however, are usually contradictory since the usage of mixture of ginsenosides cannot identify the function of every individual ginsenosides on the experimental system. On the other hand, every individual ginsenosides is not compared under the same experimental condition. These facts motivate us to evaluate the antioxidant effect of various individual ginsenosides on the experimental system of free-radical-initiated peroxidation: the hemolysis of human erythrocyte induced thermally by water-soluble initiator, 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH). The inhibitory concentration of 50% inhibition (IC(50)) of AAPH-induced hemolysis of the erythrocyte has been studied firstly and found that the order of IC(50) is Rb3 - Rb1Rc>Re>Rh1>R1>Rg2>Rb3. Rg3, Rd and Rh2, however, act as synergistic prooxidants in the above experimental system. Rg1 does not show any synergistic antioxidative property. Although the antioxidative and prooxidative mechanism of various ginsenosides with or without TOH in AAPH-induced hemolysis of human erythrocytes will be further studied in detail, this information may be useful in the clinical usage of ginsenosides.

Prediction of metastable metal-rare gas fluorides: FMRgF (M=Be and Mg; Rg=Ar, Kr and Xe).

PubMed

Jayasekharan, T; Ghanty, T K

2008-04-14

The structure, stability, charge redistribution, bonding, and harmonic vibrational frequencies of rare gas containing group II-A fluorides with the general formula FMRgF (where M=Be and Mg; Rg=Ar, Kr, and Xe) have been investigated using second order Møller-Plesset perturbation theory, density functional theory, and coupled cluster theory [CCSD(T)] methods. The species, FMRgF show a quasilinear structure at the minima and a bent structure at the transition state. The predicted species are unstable with respect to the two-body dissociation channel, leading to the global minima (MF2+Rg) on the singlet potential energy surface. However, with respect to other two-body dissociation channel (FM+RgF), they are found to be stable and have high positive energies on the same surface. The computed binding energy for the two-body dissociation channels are 94.0, 164.7, and 199.7 kJ mol(-1) for FBeArF, FBeKrF, FBeXeF, respectively, at CCSD(T) method. The corresponding energy values are 83.4, 130.7, and 180.1 kJ mol(-1) for FMgArF, FMgKrF, and FMgXeF, respectively, at the same level of theory. With respect to the three-body dissociation (FM+Rg+F) channel as well as dissociation into atomic constituent, they are also found to be stable and have high positive energies. The dissociation of the predicted species typically proceeds via MRgF bending mode at the transition state. The computed barrier heights for the transition states are 11.4, 32.2, and 57.6 kJ mol(-1) for FBeArF, FBeKrF, and FBeXeF, respectively, at the CCSD(T) method. The corresponding barrier heights for the Mg containing species are 2.1, 9.2, and 32.1 kJ mol(-1) along the series Ar--Kr--Xe, respectively. The M--Rg bond energies of the FMRgF species is significantly higher than the corresponding bond energies of the M+--Rg species ( approximately 53 and approximately 15 kJ mol(-1) for Be+--Ar and Mg+--Ar, respectively). The computed energy diagram as well as the geometrical parameters along with the AIM results suggest that the species are metastable with partial covalent character in the M--Rg bonding. Thus, it may be possible to prepare and to characterize these species using low temperature matrix isolation technique.

Prediction of metastable metal-rare gas fluorides: FMRgF (M =Be and Mg; Rg =Ar, Kr and Xe)

NASA Astrophysics Data System (ADS)

Jayasekharan, T.; Ghanty, T. K.

2008-04-01

The structure, stability, charge redistribution, bonding, and harmonic vibrational frequencies of rare gas containing group II-A fluorides with the general formula FMRgF (where M =Be and Mg; Rg =Ar, Kr, and Xe) have been investigated using second order Møller-Plesset perturbation theory, density functional theory, and coupled cluster theory [CCSD(T)] methods. The species, FMRgF show a quasilinear structure at the minima and a bent structure at the transition state. The predicted species are unstable with respect to the two-body dissociation channel, leading to the global minima (MF2+Rg) on the singlet potential energy surface. However, with respect to other two-body dissociation channel (FM+RgF), they are found to be stable and have high positive energies on the same surface. The computed binding energy for the two-body dissociation channels are 94.0, 164.7, and 199.7kJmol-1 for FBeArF, FBeKrF, FBeXeF, respectively, at CCSD(T) method. The corresponding energy values are 83.4, 130.7, and 180.1kJmol-1 for FMgArF, FMgKrF, and FMgXeF, respectively, at the same level of theory. With respect to the three-body dissociation (FM+Rg+F) channel as well as dissociation into atomic constituent, they are also found to be stable and have high positive energies. The dissociation of the predicted species typically proceeds via MRgF bending mode at the transition state. The computed barrier heights for the transition states are 11.4, 32.2, and 57.6kJmol-1 for FBeArF, FBeKrF, and FBeXeF, respectively, at the CCSD(T) method. The corresponding barrier heights for the Mg containing species are 2.1, 9.2, and 32.1kJmol-1 along the series Ar KrXe, respectively. The M Rg bond energies of the FMRgF species is significantly higher than the corresponding bond energies of the M+Rg species (˜53 and ˜15kJmol-1 for Be+Ar and Mg+Ar, respectively). The computed energy diagram as well as the geometrical parameters along with the AIM results suggest that the species are metastable with partial covalent character in the M Rg bonding. Thus, it may be possible to prepare and to characterize these species using low temperature matrix isolation technique.

Forward and reverse mutagenesis in C. elegans

PubMed Central

Kutscher, Lena M.; Shaham, Shai

2014-01-01

Mutagenesis drives natural selection. In the lab, mutations allow gene function to be deciphered. C. elegans is highly amendable to functional genetics because of its short generation time, ease of use, and wealth of available gene-alteration techniques. Here we provide an overview of historical and contemporary methods for mutagenesis in C. elegans, and discuss principles and strategies for forward (genome-wide mutagenesis) and reverse (target-selected and gene-specific mutagenesis) genetic studies in this animal. PMID:24449699

An assessment of heavy ion irradiation mutagenesis for reverse genetics in wheat (Triticum aestivum L.).

PubMed

Fitzgerald, Timothy L; Powell, Jonathan J; Stiller, Jiri; Weese, Terri L; Abe, Tomoko; Zhao, Guangyao; Jia, Jizeng; McIntyre, C Lynne; Li, Zhongyi; Manners, John M; Kazan, Kemal

2015-01-01

Reverse genetic techniques harnessing mutational approaches are powerful tools that can provide substantial insight into gene function in plants. However, as compared to diploid species, reverse genetic analyses in polyploid plants such as bread wheat can present substantial challenges associated with high levels of sequence and functional similarity amongst homoeologous loci. We previously developed a high-throughput method to identify deletions of genes within a physically mutagenized wheat population. Here we describe our efforts to combine multiple homoeologous deletions of three candidate disease susceptibility genes (TaWRKY11, TaPFT1 and TaPLDß1). We were able to produce lines featuring homozygous deletions at two of the three homoeoloci for all genes, but this was dependent on the individual mutants used in crossing. Intriguingly, despite extensive efforts, viable lines possessing homozygous deletions at all three homoeoloci could not be produced for any of the candidate genes. To investigate deletion size as a possible reason for this phenomenon, we developed an amplicon sequencing approach based on synteny to Brachypodium distachyon to assess the size of the deletions removing one candidate gene (TaPFT1) in our mutants. These analyses revealed that genomic deletions removing the locus are relatively large, resulting in the loss of multiple additional genes. The implications of this work for the use of heavy ion mutagenesis for reverse genetic analyses in wheat are discussed.

An Assessment of Heavy Ion Irradiation Mutagenesis for Reverse Genetics in Wheat (Triticum aestivum L.)

PubMed Central

Fitzgerald, Timothy L.; Powell, Jonathan J.; Stiller, Jiri; Weese, Terri L.; Abe, Tomoko; Zhao, Guangyao; Jia, Jizeng; McIntyre, C. Lynne; Li, Zhongyi; Manners, John M.; Kazan, Kemal

2015-01-01

Reverse genetic techniques harnessing mutational approaches are powerful tools that can provide substantial insight into gene function in plants. However, as compared to diploid species, reverse genetic analyses in polyploid plants such as bread wheat can present substantial challenges associated with high levels of sequence and functional similarity amongst homoeologous loci. We previously developed a high-throughput method to identify deletions of genes within a physically mutagenized wheat population. Here we describe our efforts to combine multiple homoeologous deletions of three candidate disease susceptibility genes (TaWRKY11, TaPFT1 and TaPLDß1). We were able to produce lines featuring homozygous deletions at two of the three homoeoloci for all genes, but this was dependent on the individual mutants used in crossing. Intriguingly, despite extensive efforts, viable lines possessing homozygous deletions at all three homoeoloci could not be produced for any of the candidate genes. To investigate deletion size as a possible reason for this phenomenon, we developed an amplicon sequencing approach based on synteny to Brachypodium distachyon to assess the size of the deletions removing one candidate gene (TaPFT1) in our mutants. These analyses revealed that genomic deletions removing the locus are relatively large, resulting in the loss of multiple additional genes. The implications of this work for the use of heavy ion mutagenesis for reverse genetic analyses in wheat are discussed. PMID:25719507

Recovery of infectious classical swine fever virus (CSFV) from full-length genomic cDNA clones by a swine kidney cell line expressing bacteriophage T7 RNA polymerase.

PubMed

van Gennip, H G; van Rijn, P A; Widjojoatmodjo, M N; Moormann, R J

1999-03-01

A new method for the recovery of infectious classical swine fever virus (CSFV) from full-length genomic cDNA clones of the C-strain was developed. Classical reverse genetics is based on transfection of in vitro transcribed RNA to target cells to recover RNA viruses. However, the specific infectivity of such in vitro transcribed RNA in swine kidney cells is usually low. To improve reverse genetics for CSFV, a stable swine kidney cell line was established that expresses cytoplasmic bacteriophage T7 RNA polymerase (SK6.T7). A 200-fold increased virus titre was obtained from SK6.T7 cells transfected with linearized full-length cDNA compared to in vitro transcribed RNA, whereas transfection of circular full-length cDNA resulted in 20-fold increased virus titres. Viruses generated on the SK6.T7 cells are indistinguishable from the viruses generated by the classical reverse genetic procedures. These results show the improved recovery of infectious CSFV directly from full-length cDNAs. Furthermore, the reverse genetic procedures are simplified to a faster, one step protocol. We conclude that the SK6.T7 cell line will be a valuable tool for recovering mutant CSFV and will contribute to future pestivirus research.

Studies on a novel doughnut-shaped minitablet for intraocular drug delivery.

PubMed

Choonara, Yahya E; Pillay, Viness; Carmichael, Trevor; Danckwerts, Michael P

2007-12-28

The objective of this study was to evaluate the effect of 2 independent formulation variables on the drug release from a novel doughnut-shaped minitablet (DSMT) in order to optimize formulations for intraocular drug delivery. Formulations were based on a 3(2) full-factorial design. The 2 independent variables were the concentration of Resomer (% wt/wt) and the type of Resomer grade (RG502, RG503, and RG504), respectively. The evaluated response was the drug release rate constant computed from a referenced marketed product and in vitro drug release data obtained at pH 7.4 in simulated vitreous humor. DSMT devices were prepared containing either of 2 model drugs, ganciclovir or foscarnet, using a Manesty F3 tableting press fitted with a novel central-rod, punch, and die setup. Dissolution data revealed biphasic drug release behavior with 55% to 60% drug released over 120 days. The inherent viscosity of the various Resomer grades and the concentration were significant to achieve optimum release rate constants. Using the resultant statistical relationships with the release rate constant as a response, the optimum formulation predicted for devices formulated with foscarnet was 70% wt/wt of Resomer RG504, while 92% wt/wt of Resomer RG503 was ideal for devices formulated with ganciclovir. The results of this study revealed that the full-factorial design was a suitable tool to predict an optimized formulation for prolonged intraocular drug delivery.

Higher efficiency soluble prokaryotic expression, purification, and structural analysis of antimicrobial peptide G13.

PubMed

Che, Yuanyuan; Lu, Yinghu; Zha, Xiangdong; Huang, Huoqing; Yang, Peilong; Ma, Lijuan; Xu, Xuejiao

2016-03-01

G13 is a 19-residue cationic antimicrobial peptide derived from granulysin. In order to achieve high-level expression of G13 in Escherichia coli cells, and to reduce downstream processing costs, we introduced an Asp-Pro acid labile bond between the His-Patch thioredoxin and G13 and constructed the recombinant plasmid pThiohisA-DP-G13. The plasmid was transformed into E. coli BL21 (DE3). After induction with isopropyl-β-d-thiogalactopyranoside for 5 h, the fusion protein accumulated up to 200 mg/L in soluble form. The fusion protein was released by a high pressure homogenizer, cleaved using 13% acetic acid at 50 °C hydrolysis for 72 h. The recombinant G13 (r-G13) was then successively purified by fractional precipitation with ammonium sulfate and trichloroacetic acid, followed by one-step cation exchange chromatography. The purified r-G13 displayed a single band (about 2.2 kDa) as analyzed by Tris-Tricine buffered SDS-PAGE, and its precise molecular weight was confirmed using tandem mass spectrometry. Analysis of r-G13 by circular dichroism (CD) indicated that r-G13 contained predominantly β-sheet and random coil. Agar plate diffusion assay revealed that the r-G13 exhibited antibacterial activity against both Bacillus subtilis and E. coli. Copyright © 2015 Elsevier Inc. All rights reserved.

Modulation of Epstein–Barr Virus Nuclear Antigen 2-dependent transcription by protein arginine methyltransferase 5

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

Liu, Cheng-Der; Cheng, Chi-Ping; Fang, Jia-Shih

Highlights: ► Catalytic active PRMT5 substantially binds to the EBNA2 RG domain. ► PRMT5 augments the EBNA2-dependent transcription. ► PRMT5 triggers the symmetric dimethylation of the EBNA2 RG domain. ► PRMT5 enhances the promoter occupancy of EBNA2 on its target promoters. -- Abstract: Epstein–Barr Virus Nuclear Antigen (EBNA) 2 features an Arginine–Glycine repeat (RG) domain at amino acid positions 335–360, which is a known target for protein arginine methyltransferaser 5 (PRMT5). In this study, we performed protein affinity pull-down assays to demonstrate that endogenous PRMT5 derived from lymphoblastoid cells specifically associated with the protein bait GST-E2 RG. Transfection of amore » plasmid expressing PRMT5 induced a 2.5- to 3-fold increase in EBNA2-dependent transcription of both the LMP1 promoter in AKATA cells, which contain the EBV genome endogenously, and a Cp-Luc reporter plasmid in BJAB cells, which are EBV negative. Furthermore, we showed that there was a 2-fold enrichment of EBNA2 occupancy in target promoters in the presence of exogenous PRMT5. Taken together, we show that PRMT5 triggers the symmetric dimethylation of EBNA2 RG domain to coordinate with EBNA2-mediated transcription. This modulation suggests that PRMT5 may play a role in latent EBV infection.« less

Generalizations of holographic renormalization group flows

NASA Astrophysics Data System (ADS)

Suh, Minwoo

The AdS/CFT correspondence conjectures the duality between type IIB supergravity on AdS5 × S5 and N = 4 super Yang-Mills theory. Mass deformations of N = 4 super Yang-Mills theory drive renormalization group (RG) flows. Holographic RG flows are described by domain wall solutions interpolating between AdS5 geometries at critical points of N = 8 gauged supergravity in five dimensions. In this thesis we study two directions of generalizations of holographic RG flows. First, motivated by the Janus solutions, we study holographic RG flows with dilaton and axion fields. To be specific, we consider the SU (3)-invariant flow with dilaton and axion fields, and discover the known supersymmetric Janus solution in five dimensions. Then, by employing the lift ansatz, we uplift the supersymmetric Janus solution of the SU(3)-invariant truncation with dilaton and axion fields to a solution of type IIB supergravity. We identify the uplifted solution to be one of the known supersymmetric Janus solution in type IIB supergravity. Furthermore, we consider the SU(2) × U(1)-invariant N = 2 and N = 1 supersymmetric flows with dilaton and axion fields. Second, motivated by the development in AdS/CMT, we study holographic RG flows with gauge fields. We consider the SU(3)-invariant flow with electric potentials or magnetic fields, and find first-order systems of flow equations for each case.

Discovery of New Retrograde Substructures: The Shards of ω Centauri?

NASA Astrophysics Data System (ADS)

Myeong, G. C.; Evans, N. W.; Belokurov, V.; Sanders, J. L.; Koposov, S. E.

2018-06-01

We use the SDSS-Gaia catalogue to search for substructure in the stellar halo. The sample comprises 62 133 halo stars with full phase space coordinates and extends out to heliocentric distances of ˜10 kpc. As actions are conserved under slow changes of the potential, they permit identification of groups of stars with a common accretion history. We devise a method to identify halo substructures based on their clustering in action space, using metallicity as a secondary check. This is validated against smooth models and numerical constructed stellar halos from the Aquarius simulations. We identify 21 substructures in the SDSS-Gaia catalogue, including 7 high significance, high energy and retrograde ones. We investigate whether the retrograde substructures may be material stripped off the atypical globular cluster ω Centauri. Using a simple model of the accretion of the progenitor of the ω Centauri, we tentatively argue for the possible association of up to 5 of our new substructures (labelled Rg1, Rg3, Rg4, Rg6 and Rg7) with this event. This sets a minimum mass of 5× 108M⊙ for the progenitor, so as to bring ω Centauri to its current location in action - energy space. Our proposal can be tested by high resolution spectroscopy of the candidates to look for the unusual abundance patterns possessed by ω Centauri stars.

Relationships among rotational and conventional grazing systems, stream channels, and macroinvertebrates

USGS Publications Warehouse

Raymond, K.L.; Vondracek, B.

2011-01-01

Cattle grazing in riparian areas can reduce water quality, alter stream channel characteristics, and alter fish and macroinvertebrate assemblage structure. The U.S. Department of Agriculture, Natural Resources Conservation Services has recommended Rotational Grazing (RG) as an alternative management method on livestock and dairy operations to protect riparian areas and water quality. We evaluated 13 stream channel characteristics, benthic macroinvertebrate larvae (BML), and chironomid pupal exuviae (CPE) from 18 sites in the Upper Midwest of the United States in relation to RG and conventional grazing (CG). A Biotic Composite Score comprised of several macroinvertebrate metrics was developed for both the BML assemblage and the CPE assemblage. Multi-Response Permutation Procedures (MRPP) indicated a significant difference in stream channel characteristics between RG and CG. Nonmetric Multidimensional Scaling indicated that RG sites were associated with more stable stream banks, higher quality aquatic habitat, lower soil compaction, and larger particles in the streambed. However, neither MRPP nor Mann-Whitney U tests demonstrated a difference in Biotic Composite Scores for BML or CPE along RG and CG sites. The BML and CPE metrics were significantly correlated, indicating that they were likely responding to similar variables among the study sites. Although stream channel characteristics appeared to respond to grazing management, BML and CPE may have responded to land use throughout the watershed, as well as local land use. ?? 2011 Springer Science+Business Media B.V. (outside the USA).

Development of superparamagnetic iron oxide nanoparticles via direct conjugation with ginsenosides and its in-vitro study.

PubMed

Singh, Hina; Du, Juan; Singh, Priyanka; Mavlonov, Gafurjon Tom; Yi, Tae Hoo

2018-06-01

The current study focused on direct conjugation of superparamagnetic iron oxide nanoparticles (SPIONs) with ginsenosides CK and Rg3. The direct conjugation approach was low-cost, eco-friendly, simple, fast and high yield. The synthesized conjugates (SPION-CK and SPION-Rg3) were characterized by field emission transmission electron microscopy, dynamic light scattering, zeta potential, X-ray diffractometer, and magnetometer. The characterization results confirmed the formation of SPIONs conjugates. The maximum attaching percentage for ginsenosides to SPIONs was found to be 5%. In vitro cytotoxicity assay in HaCaT keratinocyte cells revealed that the conjugates were non-cytotoxic to normal cells. Moreover, the anti-inflammatory activity of SPION-CK and SPION-Rg3 were investigated. The expression of reactive oxygen species (ROS) in lipopolysaccharide-activated RAW 264.7 (murine macrophage cells) were inhibited by SPIONs conjugates in a dose-dependent manner. In addition, SPION-CK and SPION-Rg3 significantly reduced the production of nitric oxide and inducible nitric oxide synthase (iNOS) in a dose-dependent manner in the lipopolysaccharide-induced RAW 264.7 cells. Overall the results suggested that the SPIONs were conjugated with ginsenosides CK and Rg3 by using direct conjugation approach were non-cytotoxic and can be used as a carrier for intracellular release of ginsenosides in inflammatory diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

Melanoma Inhibition by Anthocyanins Is Associated with the Reduction of Oxidative Stress Biomarkers and Changes in Mitochondrial Membrane Potential.

PubMed

Diaconeasa, Zoriţa; Ayvaz, Huseyin; Ruginǎ, Dumitriţa; Leopold, Loredana; Stǎnilǎ, Andreea; Socaciu, Carmen; Tăbăran, Flaviu; Luput, Lavinia; Mada, Diana Carla; Pintea, Adela; Jefferson, Andrew

2017-12-01

Anthocyanins are water soluble pigments which have been proved to exhibit health benefits. Several studies have investigated their effects on several types of cancer, but little attention has been given to melanoma. The phytochemical content of nine different berry samples was assessed by liquid chromatography followed by electrospray ionization mass spectrometry (LC-ESI + -MS). Twenty-six anthocyanins were identified, after a previous C 18 Sep-pak clean-up procedure. Chokeberry and red grape anthocyanins rich extracts (C-ARE and RG-ARE) were selected to be tested on normal and melanoma cell lines, due to their different chemical pattern. C-ARE composition consists of cyanidin aglycone glycosylated with different sugars; while RG-ARE contains glucosylated derivatives of five different aglycones. Both C-ARE and RG-ARE anthocyanins reduced proliferation, increased oxidative stress biomarkers and diminished mitochondrial membrane potential in melanoma cells, having no negative influence on normal cells. A synergistic response may be attributed to the five different aglycones present in RG-ARE, which proved to exert greater effects on melanoma cells than the mixture of cyanidin derivatives with different sugars (C-ARE). In conclusion, C-ARE and RG-ARE anthocyanins may inhibit melanoma cell proliferation and increase the level of oxidative stress, with opposite effect on normal cells. Therefore, anthocyanins might be recommended as active ingredients for cosmetic and nutraceutical industry. Graphical Abstract ᅟ.

A reverse engineering algorithm for neural networks, applied to the subthalamopallidal network of basal ganglia.

PubMed

Floares, Alexandru George

2008-01-01

Modeling neural networks with ordinary differential equations systems is a sensible approach, but also very difficult. This paper describes a new algorithm based on linear genetic programming which can be used to reverse engineer neural networks. The RODES algorithm automatically discovers the structure of the network, including neural connections, their signs and strengths, estimates its parameters, and can even be used to identify the biophysical mechanisms involved. The algorithm is tested on simulated time series data, generated using a realistic model of the subthalamopallidal network of basal ganglia. The resulting ODE system is highly accurate, and results are obtained in a matter of minutes. This is because the problem of reverse engineering a system of coupled differential equations is reduced to one of reverse engineering individual algebraic equations. The algorithm allows the incorporation of common domain knowledge to restrict the solution space. To our knowledge, this is the first time a realistic reverse engineering algorithm based on linear genetic programming has been applied to neural networks.

Genomic DNA-based absolute quantification of gene expression in Vitis

USDA-ARS?s Scientific Manuscript database

Many studies in which gene expression is quantified by polymerase chain reaction represent the expression of a gene of interest (GOI) relative to that of a reference gene (RG). Relative expression is founded on the assumptions that RG expression is stable across samples, treatments, organs, etc., an...

75 FR 28074 - Advisory Committee on Reactor Safeguards

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-19

..., 2009, (74 FR 52829-52830). Wednesday, June 9, 2010, Conference Room T2-B1, Two White Flint North... Regulatory Guide (RG) 1.216, ``Containment Structural Integrity Evaluation for Internal Pressure Loadings... representatives of the NRC staff regarding draft final RG 1.216, ``Containment Structural Integrity Evaluation for...

75 FR 2894 - Withdrawal of Regulatory Guide 1.148

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-19

... Valve Assemblies in Systems Important to Safety in Nuclear Power Plants.'' FOR FURTHER INFORMATION... for Active Valve Assemblies in Systems Important to Safety in Nuclear Power Plants.'' RG 1.148 was... qualifying active mechanical equipment used in nuclear power plants. The NRC is withdrawing RG 1.148 because...

Reliability Generalization (RG) Analysis: The Test Is Not Reliable

ERIC Educational Resources Information Center

Warne, Russell

2008-01-01

Literature shows that most researchers are unaware of some of the characteristics of reliability. This paper clarifies some misconceptions by describing the procedures, benefits, and limitations of reliability generalization while using it to illustrate the nature of score reliability. Reliability generalization (RG) is a meta-analytic method…

78 FR 47015 - Software Requirement Specifications for Digital Computer Software Used in Safety Systems of...

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... NUCLEAR REGULATORY COMMISSION [NRC-2012-0195] Software Requirement Specifications for Digital Computer Software Used in Safety Systems of Nuclear Power Plants AGENCY: Nuclear Regulatory Commission... issuing a revised regulatory guide (RG), revision 1 of RG 1.172, ``Software Requirement Specifications for...

78 FR 19530 - RG Steel Sparrows Point LLC, Formerly Known as Severstal Sparrows Point LLC, a Subsidiary of RG...

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..., Alliance Engineering, Inc., Washington Group International, Javan & Walter, Inc., Kinetic Technical... Consulting, Crown Security, Eastern Automation, EDS (HP), TekSystems, URS Corporation, B More Industrial... Service Company, Sun Associated Industries, Inc., MPI Consultants LLC, Alliance Engineering, Inc...

77 FR 41806 - RG Steel Sparrows Point LLC, Formerly Known as Severstal Sparrows Point LLC, a Subsidiary of RG...

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... Leased Workers From Echelon Service Company, Sun Associated Industries, INC., MPI Consultants LLC... International, including on-site leased workers from Echelon Service Company, Sun Associated Industries, Inc... Company, Sun Associated Industries, Inc., MPI Consultants LLC, Alliance Engineering, Inc., Washington...

Effects of diet and arginine treatment during the luteal phase on ovarian NO/PGC-1α signaling in ewes.

PubMed

Guo, Yi-Xuan; Nie, Hai-Tao; Sun, Ling-Wei; Zhang, Guo-Min; Deng, Kai-Ping; Fan, Yi-Xuan; Wang, Feng

2017-07-01

The aim of this study was to determine whether arginine (Arg) supplementation of malnourished ewes affects the expression of key NO/PGC-1α signaling pathway genes in the ovary. On Day 6-15 of the estrous cycle, 24 multiparous Hu sheep (BW = 43.56 ± 1.53 kg) were randomly assigned to three groups: control group (CG; n = 6), restriction group (RG; n = 9) and l-arginine group (AG; n = 9), and administered Arg treatment (or vehicle) three times per day. The ewes were slaughtered at the end of treatment, and blood samples and ovaries were collected for analysis. The results of our analyses showed that both short-term feed-restriction and/or supplementation with L-Arg-HCl affected the number of different size follicles observed in the ovary, and the relative day of estrus behavior initiation of ewes. Specifically, the relative day of estrus behavior initiation was significantly advanced in AG compared with that in RG ewes (P < 0.05). Both the number of ≤2 mm-ovarian follicles (P < 0.05) and the total number of ovarian follicles (P < 0.05) were significantly increased in the RG and AG compared with that in the CG ewes. RG ewes exhibited a higher proportion of ≤2 mm (P < 0.05), but a lower proportion of >5 mm follicles than did CG ewes (P < 0.05). The mean number of corpus lutea ≥5 mm was significantly increased in AG as compared to that in either CG or RG ewes. Furthermore, the expression of eNOS, nNOS, iNOS, PDE5A, PDE9A, PRKG2, and PPARGC1A varied significantly among the treatment groups (P < 0.05). GUCY1A3 mRNA levels were significantly increased in RG and AG as compared to those in CG ewes (P < 0.05), whereas conversely, GUCY1B3 mRNA levels were significantly decreased in CG and RG as compared to those in AG ewes (P < 0.05). P53 mRNA levels were found to vary significantly among the three experimental treatment groups (P < 0.05), and similarly, the relative expression levels of P53 were greater in AG and RG than in CG ewes (P < 0.05). The levels of eNOS protein were significantly higher in RG than in either CG or AG ewes (P < 0.05). The relative expression levels of PGC-1α were significantly higher in RG (P < 0.05) and significantly lower in AG ewes (P < 0.05) than in CG ewes. In conclusion, the results of the present study indicate that feed-restriction negatively affects follicular development, and that Arg-supplementation may modulate the expression of key NO/PGC-1α signaling pathway genes in the ovary and thereby accelerate ovulatory processes and the estrous rate. Elucidation of mechanisms underlying these effects of Arg on gene expression in the ewe ovary requires further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

The art and design of genetic screens: maize

USDA-ARS?s Scientific Manuscript database

Maize (Zea mays) is an excellent model for basic research. Genetic screens have informed our understanding of developmental processes, meiosis, epigenetics and biochemical pathways--not only in maize but also in other cereal crops. We discuss the forward and reverse genetic screens that are possible...

Common Genetic Contributions to Depressive Symptoms and Inflammatory Markers in Middle-Aged Men: The Twins Heart Study

PubMed Central

Su, Shaoyong; Miller, Andrew H.; Snieder, Harold; Bremner, J. Douglas; Ritchie, James; Maisano, Carisa; Jones, Linda; Murrah, Nancy V.; Goldberg, Jack; Vaccarino, Viola

2010-01-01

Objective To examine the extent to which a common genetic pathway is also involved in the relationship between depressive symptoms, in the absence of major depressive disorder (MDD), and inflammation. Recent data suggested that MDD and inflammation share common genes. Methods We recruited 188 male twins from the Vietnam Era Twin Registry who were free of symptomatic coronary artery disease and MDD, with mean ± standard deviation (SD) age of 55 ± 2.75 years, including 54 monozygotic and 40 dizygotic twin pairs. These pairs were assessed for two inflammatory markers, interleukin (IL)-6 and C-reactive protein (CRP). Current depressive symptoms were measured with the Beck Depression Inventory-II. Generalized estimating equations were used to examine the phenotypic association between depression and inflammatory markers. Biometrical genetic modeling was performed to estimate the genetic and environmental contributions to this association. Results An association was observed between severity of current depressive symptoms and increased levels of inflammatory markers (p < .001 for IL-6 and p = .005 for CRP). After adjustment for other factors, the association was slightly attenuated but remained statistically significant for IL-6 (p = .002). The heritability of IL-6, CRP, and depressive symptoms were estimated as 0.37, 0.65, and 0.48, respectively. Genetic modeling found a significant genetic correlation between IL-6 and depressive symptoms (rG = 0.22, p = .046), indicating that about 66% of the covariance between them can be explained by shared genetic influences. Conclusions Current depressive symptoms are significantly correlated with inflammatory markers. This covariation is due, in large part, to genes that are common to depressive symptoms and inflammation. PMID:19073752

The Effects of Meiosis/Genetics Integration and Instructional Sequence on College Biology Student Achievement in Genetics.

ERIC Educational Resources Information Center

Browning, Mark

The purpose of the research was to manipulate two aspects of genetics instruction in order to measure their effects on college, introductory biology students' achievement in genetics. One instructional sequence that was used dealt first with monohybrid autosomal inheritance patterns, then sex-linkage. The alternate sequence was the reverse.…

A Strategy for Simultaneous Isolation of Less Polar Ginsenosides, Including a Pair of New 20-Methoxyl Isomers, from Flower Buds of Panax ginseng.

PubMed

Li, Sha-Sha; Li, Ke-Ke; Xu, Fei; Tao, Li; Yang, Li; Chen, Shu-Xiao; Gong, Xiao-Jie

2017-03-10

The present study was designed to simultaneously isolate the less polar ginsenosides from the flower buds of Panax ginseng (FBPG). Five ginsenosides, including a pair of new 20-methoxyl isomers, were extracted from FBPG and purified through a five-step integrated strategy, by combining ultrasonic extraction, Diaion Hp-20 macroporous resin column enrichment, solid phase extraction (SPE), reversed-phase high-performance liquid chromatography (RP-HPLC) analysis and preparation, and nuclear magnetic resonance (NMR) analysis. The quantification of the five ginsenosides was also discussed by a developed method with validations within acceptable limits. Ginsenoside Rg5 showed content of about 1% in FBPG. The results indicated that FBPG might have many different ginsenosides with diverse chemical structures, and the less polar ginsenosides were also important to the quality control and standardization of FBPG.

Neutron, gamma ray, and temperature effects on the electrical characteristics of thyristors

NASA Technical Reports Server (NTRS)

Frasca, A. J.; Schwarze, G. E.

1992-01-01

Experimental data showing the effects of neutrons, gamma rays, and temperature on the electrical and switching characteristics of phase-control and inverter-type SCR's are presented. The special test fixture built for mounting, heating, and instrumenting the test devices is described. Four SCR's were neutron irradiated at 300 K and four at 365 K for fluences up to 3.2 x 10 exp 13 n/sq. cm, and eight were gamma irradiated at 300 K only for gamma doses up to 5.1 Mrads. The electrical measurements were made during irradiation and the switching measurements were made only before and after irradiation. Radiation induced crystal defects, resulting primarily from fast neutrons, caused the reduction of minority carrier lifetime through the generation of R-G centers. The reduction in lifetime caused increases in the on-state voltage drop and in the reverse and forward leakage currents, and decreases in the turn-off time.

Neutron, gamma ray, and temperature effects on the electrical characteristics of thyristors

NASA Technical Reports Server (NTRS)

Frasca, A. J.; Schwarze, G. E.

1992-01-01

Experimental data showing the effects of neutrons, gamma rays, and temperature on the electrical and switching characteristics of phase-control and inverter-type SCR's are presented. The special test fixture built for mounting, heating, and instrumenting the test devices is described. Four SCR's were neutron irradiated at 300 K and four at 365 K for fluences up to 3.2 x 10 exp 13 pn/sq. cm, and eight were gamma irradiated at 300 K only for gamma doses up to 5.1 Mrads. The electrical measurements were made during irradiation and the switching measurements were made only before and after irradiation. Radiation induced crystal defects, resulting primarily from fast neutrons, caused the reduction of minority carrier lifetime through the generation of R-G centers. The reduction in lifetime caused increases in the on-state voltage drop and in the reverse and forward leakage currents, and decreases in the turn-off time.

Reverse genetics: Its origins and prospects

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

Berg, P.

1991-04-01

The nucleotide sequence of a gene and its flanking segments alone will not tell us how its expression is regulated during development and differentiation, or in response to environmental changes. To comprehend the physiological significance of the molecular details requires biological analysis. Recombinant DNA techniques provide a powerful experimental approach. A strategy termed reverse genetics' utilizes the analysis of the activities of mutant and normal genes and experimentally constructed mutants to explore the relationship between gene structure and function thereby helping elucidate the relationship between genotype and phenotype.

Development of renormalization group analysis of turbulence

NASA Technical Reports Server (NTRS)

Smith, L. M.

1990-01-01

The renormalization group (RG) procedure for nonlinear, dissipative systems is now quite standard, and its applications to the problem of hydrodynamic turbulence are becoming well known. In summary, the RG method isolates self similar behavior and provides a systematic procedure to describe scale invariant dynamics in terms of large scale variables only. The parameterization of the small scales in a self consistent manner has important implications for sub-grid modeling. This paper develops the homogeneous, isotropic turbulence and addresses the meaning and consequence of epsilon-expansion. The theory is then extended to include a weak mean flow and application of the RG method to a sequence of models is shown to converge to the Navier-Stokes equations.

Genetics Home Reference: nephronophthisis

MedlinePlus

... which can include liver fibrosis, heart abnormalities, or mirror image reversal of the position of one or ... Information from MedlinePlus (5 links) Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery and Rehabilitation Related ...

Kenneth Wilson and Renormalization

Science.gov Websites

of the Renormalization Group (RG) into a central tool in physics. ... He received a doctorate from one of the most amazing experiences of my life," says Peskin. "He was saying, 'I see the big actually the data you need to move from one scale to another. ... RG theory implies that, with enough

78 FR 47012 - Developing Software Life Cycle Processes Used in Safety Systems of Nuclear Power Plants

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2013-08-02

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0195] Developing Software Life Cycle Processes Used in... revised regulatory guide (RG), revision 1 of RG 1.173, ``Developing Software Life Cycle Processes for... Developing a Software Project Life Cycle Process,'' issued 2006, with the clarifications and exceptions as...

Transmammary transfer of toxicity to nursing kids from Isocoma pluriflora (rayless goldenrod) dosed to lactating goats

USDA-ARS?s Scientific Manuscript database

Rayless goldenrod (RG; Isocoma pluriflora) poisons livestock in the southwestern U.S., west Texas, and northern Mexico. The putative toxin(s) have historically been thought to be benzofuran ketones. Goats have been used successfully as a model of RG poisoning. The transmammary transfer of toxicity t...

Use of the HepaRG Cell Line to Assess Potential Human Hepatotoxicity of ToxCast™ Chemicals

EPA Science Inventory

The HepaRG cell line is a promising model system for predicting human hepatotoxicity in part because of the greater capacity to metabolize chemicals than other cell models. We hypothesized that this cell line would be a relevant model for toxicity testing of industrial chemicals....

78 FR 8588 - Rg Steel Sparrows Point LLC, Formerly Known as Severstal Sparrows Point LLC, a Subsidiary of RG...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-06

..., Alliance Engineering, Inc., Washington Group International, Javan & Walter, Inc., Kinetic Technical... Consulting, Crown Security, Eastern Automation, EDS(HP), Teksystems, URS Corporation, and B More Industrial... from B More Industrial Services LLC were employed on-site at the Sparrows Point, Maryland location of...

77 FR 24228 - Condition Monitoring Techniques for Electric Cables Used in Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-23

... Used in Nuclear Power Plants AGENCY: Nuclear Regulatory Commission. ACTION: Regulatory guide; issuance... guide, (RG) 1.218, ``Condition Monitoring Techniques for Electric Cables Used in Nuclear Power Plants... of electric cables for nuclear power plants. RG 1.218 is not intended to be prescriptive, instead it...

76 FR 52715 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on Regulatory...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-23

... review Draft Final Regulatory Guide (RG) 1.93, ``Availability of Electric Power Sources,'' Revision 1 and new Draft Final RG 1.218, ``Condition Monitoring Techniques for Electric Cables Used in Nuclear Power... NUCLEAR REGULATORY COMMISSION Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS...

78 FR 64027 - Preoperational Testing of Emergency Core Cooling Systems for Pressurized-Water Reactors

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-25

...The U.S. Nuclear Regulatory Commission (NRC) is issuing a revision to regulatory guide (RG), 1.79, ``Preoperational Testing of Emergency Core Cooling Systems for Pressurized-Water Reactors.'' This RG is being revised to incorporate guidance for preoperational testing of new pressurized water reactor (PWR) designs.

Characterization of the human analogue of a Scrapie-responsive gene.

PubMed

Dron, M; Dandoy-Dron, F; Guillo, F; Benboudjema, L; Hauw, J J; Lebon, P; Dormont, D; Tovey, M G

1998-07-17

We have recently described a novel mRNA denominated ScRG-1, the level of which is increased in the brains of Scrapie-infected mice (Dandoy-Dron, F., Guillo, F., Benboudjema, L., Deslys, J.-P., Lasmézas, C., Dormont, D., Tovey, M. G., and Dron, M. (1998) J. Biol. Chem. 273, 7691-7697). The increase in ScRG-1 mRNA in the brain follows the accumulation of PrPSc, the proteinase K-resistant form of the prion protein (PrP), and precedes the widespread neuronal death that occurs in late stage disease. In the present study, we have isolated a cDNA encoding the human counterpart of ScRG-1. Comparison of the human and mouse transcripts firmly established that both sequences encode a highly conserved protein of 98 amino acids that contains a signal peptide, suggesting that the protein may be secreted. Examination of the distribution of human ScRG-1 mRNA in adult and fetal tissues revealed that the gene was expressed primarily in the central nervous system as a 0.7-kilobase message and was under strict developmental control.

Renormalization-group flow of the effective action of cosmological large-scale structures

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

Floerchinger, Stefan; Garny, Mathias; Tetradis, Nikolaos

Following an approach of Matarrese and Pietroni, we derive the functional renormalization group (RG) flow of the effective action of cosmological large-scale structures. Perturbative solutions of this RG flow equation are shown to be consistent with standard cosmological perturbation theory. Non-perturbative approximate solutions can be obtained by truncating the a priori infinite set of possible effective actions to a finite subspace. Using for the truncated effective action a form dictated by dissipative fluid dynamics, we derive RG flow equations for the scale dependence of the effective viscosity and sound velocity of non-interacting dark matter, and we solve them numerically. Physically,more » the effective viscosity and sound velocity account for the interactions of long-wavelength fluctuations with the spectrum of smaller-scale perturbations. We find that the RG flow exhibits an attractor behaviour in the IR that significantly reduces the dependence of the effective viscosity and sound velocity on the input values at the UV scale. This allows for a self-contained computation of matter and velocity power spectra for which the sensitivity to UV modes is under control.« less

Development of an Indirect ELISA for Serological Diagnosis of Bovine herpesvirus 5

PubMed Central

Campos, Fabrício S.; da Rosa, Matheus C.; Finger, Paula F.; de Oliveira, Patricia D.; Conceição, Fabricio R.; Fischer, Geferson; Roehe, Paulo M.; Leite, Fábio P. L.

2016-01-01

Bovine herpesviruses 1 and 5 (BoHV-1 and BoHV-5) are economically important pathogens, associated with a variety of clinical syndromes, including respiratory and genital disease, reproductive failure and meningoencephalitis. The standard serological assay to diagnose BoHV-1 and BoHV-5 infections is the virus neutralization test (VNT), a time consuming procedure that requires manipulation of infectious virus. In the present study a highly sensitive and specific single dilution indirect ELISA was developed using recombinant glycoprotein D from BoHV-5 as antigen (rgD5ELISA). Bovine serum samples (n = 450) were screened by VNT against BoHV-5a and by rgD5ELISA. Compared with the VNT, the rgD5ELISA demonstrated accuracy of 99.8%, with 100% sensitivity, 96.7% specificity and coefficient of agreement between the tests of 0.954. The rgD5ELISA described here shows excellent agreement with the VNT and is shown to be a simple, convenient, specific and highly sensitive virus-free assay for detection of serum antibodies to BoHV-5. PMID:26866923

Silent IL2RG Gene Editing in Human Pluripotent Stem Cells.

PubMed

Li, Li B; Ma, Chao; Awong, Geneve; Kennedy, Marion; Gornalusse, German; Keller, Gordon; Kaufman, Dan S; Russell, David W

2016-03-01

Many applications of pluripotent stem cells (PSCs) require efficient editing of silent chromosomal genes. Here, we show that a major limitation in isolating edited clones is silencing of the selectable marker cassette after homologous recombination and that this can be overcome by using a ubiquitous chromatin opening element (UCOE) promoter-driven transgene. We use this strategy to edit the silent IL2RG locus in human PSCs with a recombinant adeno-associated virus (rAAV)-targeting vector in the absence of potentially genotoxic, site-specific nucleases and show that IL2RG is required for natural killer and T-cell differentiation of human PSCs. Insertion of an active UCOE promoter into a silent locus altered the histone modification and cytosine methylation pattern of surrounding chromatin, but these changes resolved when the UCOE promoter was removed. This same approach could be used to correct IL2RG mutations in X-linked severe combined immunodeficiency patient-derived induced PSCs (iPSCs), to prevent graft versus host disease in regenerative medicine applications, or to edit other silent genes.

Will-Nordtvedt PPN formalism applied to renormalization group extensions of general relativity

NASA Astrophysics Data System (ADS)

Toniato, Júnior D.; Rodrigues, Davi C.; de Almeida, Álefe O. F.; Bertini, Nicolas

2017-09-01

We apply the full Will-Nordtvedt version of the parametrized post-Newtonian (PPN) formalism to a class of general relativity extensions that are based on nontrivial renormalization group (RG) effects at large scales. We focus on a class of models in which the gravitational coupling constant G is correlated with the Newtonian potential. A previous PPN analysis considered a specific realization of the RG effects, and only within the Eddington-Robertson-Schiff version of the PPN formalism, which is a less complete and robust PPN formulation. Here we find stronger, more precise bounds, and with less assumptions. We also consider the external potential effect (EPE), which is an effect that is intrinsic to this framework and depends on the system environment (it has some qualitative similarities to the screening mechanisms of modified gravity theories). We find a single particular RG realization that is not affected by the EPE. Some physical systems have been pointed out as candidates for measuring the possible RG effects in gravity at large scales; for any of them the Solar System bounds need to be considered.

Differences in Vvufgt and VvmybA1 Gene Expression Levels and Phenolic Composition in Table Grape (Vitis vinifera L.) 'Red Globe' and Its Somaclonal Variant 'Pink Globe'.

PubMed

Bustamante, Luis; Sáez, Vania; Hinrichsen, Patricio; Castro, María H; Vergara, Carola; von Baer, Dietrich; Mardones, Claudia

2017-04-05

A novel 'Red Globe' (RG)-derived grape variety, 'Pink Globe' (PG), was described and registered as a new genotype, with earlier ripening and sweeter taste than those of RG. Microsatellite analysis revealed that PG and RG are undifferentiable; however, the PG VvmybA1c contains six single-nucleotide polymorphisms within the coding and noncoding region, possibly related to the reduced VvmybA1 expression levels. Conversely, HPLC-DAD-ESI-MS/MS analysis showed significantly lower anthocyanin content in PG skin than in RG skin, and PG had no detectable trihydroxylated anthocyanins. Total flavonols did not differ between the variants, although some quercetin derivate concentrations were lower in PG. HPLC-FLD analysis revealed slightly higher concentrations of epicatechin and a procyanidin dimer in PG seeds, although the antioxidant capacity of crude extracts from either variety did not differ significantly. These differences, particularly in monomeric anthocyanin content, can be attributed to altered activity of a MYB-type transcription factor, reducing Vvufgt expression.