Photo-antagonism of the GABAA receptor.

Science.gov (United States)

Mortensen, Martin; Iqbal, Favaad; Pandurangan, Arun P; Hannan, Saad; Huckvale, Rosemary; Topf, Maya; Baker, James R; Smart, Trevor G

2014-07-29

Neurotransmitter receptor trafficking is fundamentally important for synaptic transmission and neural network activity. GABAA receptors and inhibitory synapses are vital components of brain function, yet much of our knowledge regarding receptor mobility and function at inhibitory synapses is derived indirectly from using recombinant receptors, antibody-tagged native receptors and pharmacological treatments. Here we describe the use of a set of research tools that can irreversibly bind to and affect the function of recombinant and neuronal GABAA receptors following ultraviolet photoactivation. These compounds are based on the competitive antagonist gabazine and incorporate a variety of photoactive groups. By using site-directed mutagenesis and ligand-docking studies, they reveal new areas of the GABA binding site at the interface between receptor β and α subunits. These compounds enable the selected inactivation of native GABAA receptor populations providing new insight into the function of inhibitory synapses and extrasynaptic receptors in controlling neuronal excitation.

Exploitative and hierarchical antagonism in a cooperative bacterium.

Directory of Open Access Journals (Sweden)

Francesca Fiegna

2005-11-01

Full Text Available Social organisms that cooperate with some members of their own species, such as close relatives, may fail to cooperate with other genotypes of the same species. Such noncooperation may take the form of outright antagonism or social exploitation. Myxococcus xanthus is a highly social prokaryote that cooperatively develops into spore-bearing, multicellular fruiting bodies in response to starvation. Here we have characterized the nature of social interactions among nine developmentally proficient strains of M. xanthus isolated from spatially distant locations. Strains were competed against one another in all possible pairwise combinations during starvation-induced development. In most pairings, at least one competitor exhibited strong antagonism toward its partner and a majority of mixes showed bidirectional antagonism that decreased total spore production, even to the point of driving whole populations to extinction. Differential response to mixing was the primary determinant of competitive superiority rather than the sporulation efficiencies of unmixed populations. In some competitive pairings, the dominant partner sporulated more efficiently in mixed populations than in clonal isolation. This finding represents a novel form of exploitation in bacteria carried out by socially competent genotypes and is the first documentation of social exploitation among natural bacterial isolates. Patterns of antagonistic superiority among these strains form a highly linear dominance hierarchy. At least some competition pairs construct chimeric, rather than segregated, fruiting bodies. The cooperative prokaryote M. xanthus has diverged into a large number of distinct social types that cooperate with clone-mates but exhibit intense antagonism toward distinct social types of the same species. Most lengthy migration events in nature may thus result in strong antagonism between migratory and resident populations, and this antagonism may have large effects on local

Genome-wide prediction of cis-regulatory regions using supervised deep learning methods.

Science.gov (United States)

Li, Yifeng; Shi, Wenqiang; Wasserman, Wyeth W

2018-05-31

In the human genome, 98% of DNA sequences are non-protein-coding regions that were previously disregarded as junk DNA. In fact, non-coding regions host a variety of cis-regulatory regions which precisely control the expression of genes. Thus, Identifying active cis-regulatory regions in the human genome is critical for understanding gene regulation and assessing the impact of genetic variation on phenotype. The developments of high-throughput sequencing and machine learning technologies make it possible to predict cis-regulatory regions genome wide. Based on rich data resources such as the Encyclopedia of DNA Elements (ENCODE) and the Functional Annotation of the Mammalian Genome (FANTOM) projects, we introduce DECRES based on supervised deep learning approaches for the identification of enhancer and promoter regions in the human genome. Due to their ability to discover patterns in large and complex data, the introduction of deep learning methods enables a significant advance in our knowledge of the genomic locations of cis-regulatory regions. Using models for well-characterized cell lines, we identify key experimental features that contribute to the predictive performance. Applying DECRES, we delineate locations of 300,000 candidate enhancers genome wide (6.8% of the genome, of which 40,000 are supported by bidirectional transcription data), and 26,000 candidate promoters (0.6% of the genome). The predicted annotations of cis-regulatory regions will provide broad utility for genome interpretation from functional genomics to clinical applications. The DECRES model demonstrates potentials of deep learning technologies when combined with high-throughput sequencing data, and inspires the development of other advanced neural network models for further improvement of genome annotations.

UVA Causes Dual Inactivation of Cathepsin B and L Underlying Lysosomal Dysfunction in Human Dermal Fibroblasts

Science.gov (United States)

Lamore, Sarah D.; Wondrak, Georg T.

2013-01-01

Cutaneous exposure to chronic solar UVA-radiation is a causative factor in photocarcinogenesis and photoaging. Recently, we have identified the thiol-dependent cysteine-protease cathepsin B as a novel UVA-target undergoing photo-oxidative inactivation upstream of autophagic-lysosomal dysfunction in fibroblasts. In this study, we examined UVA effects on a wider range of cathepsins and explored the occurrence of UVA-induced cathepsin inactivation in other cultured skin cell types. In dermal fibroblasts, chronic exposure to non-cytotoxic doses of UVA caused pronounced inactivation of the lysosomal cysteine-proteases cathepsin B and L, effects not observed in primary keratinocytes and occurring only to a minor extent in primary melanocytes. In order to determine if UVA-induced lysosomal impairment requires single or dual inactivation of cathepsin B and/or L, we used a genetic approach (siRNA) to selectively downregulate enzymatic activity of these target cathepsins. Monitoring an established set of protein markers (including LAMP1, LC3-II, and p62) and cell ultrastructural changes detected by electron microscopy, we observed that only dual genetic antagonism (targeting both CTSB and CTSL expression) could mimic UVA-induced autophagic-lysosomal alterations, whereas single knockdown (targeting CTSB or CTSL only) did not display ‘UVA-mimetic’ effects failing to reproduce the UVA-induced phenotype. Taken together, our data demonstrate that chronic UVA inhibits both cathepsin B and L enzymatic activity and that dual inactivation of both enzymes is a causative factor underlying UVA-induced impairment of lysosomal function in dermal fibroblasts. PMID:23603447

Apoptosis in neural crest cells by functional loss of APC tumor suppressor gene

Science.gov (United States)

Hasegawa, Sumitaka; Sato, Tomoyuki; Akazawa, Hiroshi; Okada, Hitoshi; Maeno, Akiteru; Ito, Masaki; Sugitani, Yoshinobu; Shibata, Hiroyuki; Miyazaki, Jun-ichi; Katsuki, Motoya; Yamauchi, Yasutaka; Yamamura, Ken-ichi; Katamine, Shigeru; Noda, Tetsuo

2002-01-01

Apc is a gene associated with familial adenomatous polyposis coli (FAP) and its inactivation is a critical step in colorectal tumor formation. The protein product, adenomatous polyposis coli (APC), acts to down-regulate intracellular levels of β-catenin, a key signal transducer in the Wnt signaling. Conditional targeting of Apc in the neural crest of mice caused massive apoptosis of cephalic and cardiac neural crest cells at about 11.5 days post coitum, resulting in craniofacial and cardiac anomalies at birth. Notably, the apoptotic cells localized in the regions where β-catenin had accumulated. In contrast to its role in colorectal epithelial cells, inactivation of APC leads to dysregulation of β-catenin/Wnt signaling with resultant apoptosis in certain tissues including neural crest cells. PMID:11756652

Sequence conservation and combinatorial complexity of Drosophila neural precursor cell enhancers

Directory of Open Access Journals (Sweden)

Kuzin Alexander

2008-08-01

Full Text Available Abstract Background The presence of highly conserved sequences within cis-regulatory regions can serve as a valuable starting point for elucidating the basis of enhancer function. This study focuses on regulation of gene expression during the early events of Drosophila neural development. We describe the use of EvoPrinter and cis-Decoder, a suite of interrelated phylogenetic footprinting and alignment programs, to characterize highly conserved sequences that are shared among co-regulating enhancers. Results Analysis of in vivo characterized enhancers that drive neural precursor gene expression has revealed that they contain clusters of highly conserved sequence blocks (CSBs made up of shorter shared sequence elements which are present in different combinations and orientations within the different co-regulating enhancers; these elements contain either known consensus transcription factor binding sites or consist of novel sequences that have not been functionally characterized. The CSBs of co-regulated enhancers share a large number of sequence elements, suggesting that a diverse repertoire of transcription factors may interact in a highly combinatorial fashion to coordinately regulate gene expression. We have used information gained from our comparative analysis to discover an enhancer that directs expression of the nervy gene in neural precursor cells of the CNS and PNS. Conclusion The combined use EvoPrinter and cis-Decoder has yielded important insights into the combinatorial appearance of fundamental sequence elements required for neural enhancer function. Each of the 30 enhancers examined conformed to a pattern of highly conserved blocks of sequences containing shared constituent elements. These data establish a basis for further analysis and understanding of neural enhancer function.

Presenilins are required for maintenance of neural stem cells in the developing brain

Directory of Open Access Journals (Sweden)

Kim Woo-Young

2008-01-01

Full Text Available Abstract The early embryonic lethality of mutant mice bearing germ-line deletions of both presenilin genes precluded the study of their functions in neural development. We therefore employed the Cre-loxP technology to generate presenilin conditional double knockout (PS cDKO mice, in which expression of both presenilins is inactivated in neural progenitor cells (NPC or neural stem cells and their derivative neurons and glia beginning at embryonic day 11 (E11. In PS cDKO mice, dividing NPCs labeled by BrdU are decreased in number beginning at E13.5. By E15.5, fewer than 20% of NPCs remain in PS cDKO mice. The depletion of NPCs is accompanied by severe morphological defects and hemorrhages in the PS cDKO embryonic brain. Interkinetic nuclear migration of NPCs is also disrupted in PS cDKO embryos, as evidenced by displacement of S-phase and M-phase nuclei in the ventricular zone of the telencephalon. Furthermore, the depletion of neural progenitor cells in PS cDKO embryos is due to NPCs exiting cell cycle and differentiating into neurons rather than reentering cell cycle between E13.5 and E14.5 following PS inactivation in most NPCs. The length of cell cycle, however, is unchanged in PS cDKO embryos. Expression of Notch target genes, Hes1 and Hes5, is significantly decreased in PS cDKO brains, whereas Dll1 expression is up-regulated, indicating that Notch signaling is effectively blocked by PS inactivation. These findings demonstrate that presenilins are essential for neural progenitor cells to re-enter cell cycle and thus ensure proper expansion of neural progenitor pool during embryonic neural development.

MicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian cancer cell lines

Directory of Open Access Journals (Sweden)

Kumar Smriti

2011-09-01

Full Text Available Abstract Background Ovarian cancer is the leading cause of death from gynecologic cancer in women worldwide. According to the National Cancer Institute, ovarian cancer has the highest mortality rate among all the reproductive cancers in women. Advanced stage diagnosis and chemo/radio-resistance is a major obstacle in treating advanced ovarian cancer. The most commonly employed chemotherapeutic drug for ovarian cancer treatment is cis-platin. As with most chemotherapeutic drugs, many patients eventually become resistant to cis-platin and therefore, diminishing its effect. The efficacy of current treatments may be improved by increasing the sensitivity of cancer cells to chemo/radiation therapies. Methods The present study is focused on identifying the differential expression of regulatory microRNAs (miRNAs between cis-platin sensitive (A2780, and cis-platin resistant (A2780/CP70 cell lines. Cell proliferation assays were conducted to test the sensitivity of the two cell lines to cis-platin. Differential expression patterns of miRNA between cis-platin sensitive and cis-platin resistant cell lines were analyzed using novel LNA technology. Results Our results revealed changes in expression of 11 miRNAs out of 1,500 miRNAs analyzed. Out of the 11 miRNAs identified, 5 were up-regulated in the A2780/CP70 cell line and 6 were down regulated as compared to cis-platin sensitive A2780 cells. Our microRNA data was further validated by quantitative real-time PCR for these selected miRNAs. Ingenuity Pathway Analysis (IPA and Kyoto Encyclopedia of Genes and Genomes (KEGG analysis was performed for the selected miRNAs and their putative targets to identify the potential pathways and networks involved in cis-platin resistance. Conclusions Our data clearly showed the differential expression of 11 miRNAs in cis-platin resistant cells, which could potentially target many important pathways including MAPK, TGF-β signaling, actin cytoskeleton, ubiquitin mediated

Inactivation of Caliciviruses

Directory of Open Access Journals (Sweden)

Raymond Nims

2013-03-01

Full Text Available The Caliciviridae family of viruses contains clinically important human and animal pathogens, as well as vesivirus 2117, a known contaminant of biopharmaceutical manufacturing processes employing Chinese hamster cells. An extensive literature exists for inactivation of various animal caliciviruses, especially feline calicivirus and murine norovirus. The caliciviruses are susceptible to wet heat inactivation at temperatures in excess of 60 °C with contact times of 30 min or greater, to UV-C inactivation at fluence ≥30 mJ/cm2, to high pressure processing >200 MPa for >5 min at 4 °C, and to certain photodynamic inactivation approaches. The enteric caliciviruses (e.g.; noroviruses display resistance to inactivation by low pH, while the non-enteric species (e.g.; feline calicivirus are much more susceptible. The caliciviruses are inactivated by a variety of chemicals, including alcohols, oxidizing agents, aldehydes, and β-propiolactone. As with inactivation of viruses in general, inactivation of caliciviruses by the various approaches may be matrix-, temperature-, and/or contact time-dependent. The susceptibilities of the caliciviruses to the various physical and chemical inactivation approaches are generally similar to those displayed by other small, non-enveloped viruses, with the exception that the parvoviruses and circoviruses may require higher temperatures for inactivation, while these families appear to be more susceptible to UV-C inactivation than are the caliciviruses.

Triclosan antagonizes fluconazole activity against Candida albicans.

LENUS (Irish Health Repository)

Higgins, J

2012-01-01

Triclosan is a broad-spectrum antimicrobial compound commonly used in oral hygiene products. Investigation of its activity against Candida albicans showed that triclosan was fungicidal at concentrations of 16 mg\\/L. However, at subinhibitory concentrations (0.5-2 mg\\/L), triclosan antagonized the activity of fluconazole. Although triclosan induced CDR1 expression in C. albicans, antagonism was still observed in cdr1Δ and cdr2Δ strains. Triclosan did not affect fluconazole uptake or alter total membrane sterol content, but did induce the expression of FAS1 and FAS2, indicating that its mode of action may involve inhibition of fatty acid synthesis, as it does in prokaryotes. However, FAS2 mutants did not exhibit increased susceptibility to triclosan, and overexpression of both FAS1 and FAS2 alleles did not alter triclosan susceptibility. Unexpectedly, the antagonistic effect was specific for C. albicans under hypha-inducing conditions and was absent in the non-filamentous efg1Δ strain. This antagonism may be due to the membranotropic activity of triclosan and the unique composition of hyphal membranes.

cis sequence effects on gene expression

Directory of Open Access Journals (Sweden)

Jacobs Kevin

2007-08-01

Full Text Available Abstract Background Sequence and transcriptional variability within and between individuals are typically studied independently. The joint analysis of sequence and gene expression variation (genetical genomics provides insight into the role of linked sequence variation in the regulation of gene expression. We investigated the role of sequence variation in cis on gene expression (cis sequence effects in a group of genes commonly studied in cancer research in lymphoblastoid cell lines. We estimated the proportion of genes exhibiting cis sequence effects and the proportion of gene expression variation explained by cis sequence effects using three different analytical approaches, and compared our results to the literature. Results We generated gene expression profiling data at N = 697 candidate genes from N = 30 lymphoblastoid cell lines for this study and used available candidate gene resequencing data at N = 552 candidate genes to identify N = 30 candidate genes with sufficient variance in both datasets for the investigation of cis sequence effects. We used two additive models and the haplotype phylogeny scanning approach of Templeton (Tree Scanning to evaluate association between individual SNPs, all SNPs at a gene, and diplotypes, with log-transformed gene expression. SNPs and diplotypes at eight candidate genes exhibited statistically significant (p cis sequence effects in our study, respectively. Conclusion Based on analysis of our results and the extant literature, one in four genes exhibits significant cis sequence effects, and for these genes, about 30% of gene expression variation is accounted for by cis sequence variation. Despite diverse experimental approaches, the presence or absence of significant cis sequence effects is largely supported by previously published studies.

Cis-Lunar Base Camp

Science.gov (United States)

Merrill, Raymond G.; Goodliff, Kandyce E.; Mazanek, Daniel D.; Reeves, John D., Jr.

2012-01-01

Historically, when mounting expeditions into uncharted territories, explorers have established strategically positioned base camps to pre-position required equipment and consumables. These base camps are secure, safe positions from which expeditions can depart when conditions are favorable, at which technology and operations can be tested and validated, and facilitate timely access to more robust facilities in the event of an emergency. For human exploration missions into deep space, cis-lunar space is well suited to serve as such a base camp. The outer regions of cis-lunar space, such as the Earth-Moon Lagrange points, lie near the edge of Earth s gravity well, allowing equipment and consumables to be aggregated with easy access to deep space and to the lunar surface, as well as more distant destinations, such as near-Earth Asteroids (NEAs) and Mars and its moons. Several approaches to utilizing a cis-lunar base camp for sustainable human exploration, as well as some possible future applications are identified. The primary objective of the analysis presented in this paper is to identify options, show the macro trends, and provide information that can be used as a basis for more detailed mission development. Compared within are the high-level performance and cost of 15 preliminary cis-lunar exploration campaigns that establish the capability to conduct crewed missions of up to one year in duration, and then aggregate mass in cis-lunar space to facilitate an expedition from Cis-Lunar Base Camp. Launch vehicles, chemical propulsion stages, and electric propulsion stages are discussed and parametric sizing values are used to create architectures of in-space transportation elements that extend the existing in-space supply chain to cis-lunar space. The transportation options to cis-lunar space assessed vary in efficiency by almost 50%; from 0.16 to 0.68 kg of cargo in cis-lunar space for every kilogram of mass in Low Earth Orbit (LEO). For the 15 cases, 5-year campaign

23rd Workshop of the Italian Neural Networks Society (SIREN)

CERN Document Server

Esposito, Anna; Morabito, Francesco

2014-01-01

This volume collects a selection of contributions which has been presented at the 23rd Italian Workshop on Neural Networks, the yearly meeting of the Italian Society for Neural Networks (SIREN). The conference was held in Vietri sul Mare, Salerno, Italy during May 23-24, 2013. The annual meeting of SIREN is sponsored by International Neural Network Society (INNS), European Neural Network Society (ENNS) and IEEE Computational Intelligence Society (CIS). The book – as well as the workshop-  is organized in two main components, a special session and a group of regular sessions featuring different aspects and point of views of artificial neural networks, artificial and natural intelligence, as well as psychological and cognitive theories for modeling human behaviors and human machine interactions, including Information Communication applications of compelling interest.  .

Cis-trans photoisomerization of abscisic acid

International Nuclear Information System (INIS)

Brabham, D.E.; Biggs, R.H.

1981-01-01

An important regulator of numerous physiological processes in higher plants is abscisic acid (ABA), which is photoisomerized from the more biologically active cis isomer to the nearly inactive trans isomer by natural sunlight. It is possible that this photoisomerization is a UV control mechanism in functions regulated by ABA. The quantum yields of both the cis to trans and trans to cis photoisomerizations were measured under various conditions of pH and oxygen concentration at room temperature. The yield for photoisomerization of cis-ABA ranged from 0.25 at pH 3.0 to 0.11 at pH 7.0. Oxygen partially quenched the process. The quantum yield varied only slightly with wavelength. The quantum yield of photolysis of cis-ABA was reported for pH 3.0 as 0.06. This yield also varied slightly with wavelength and was relatively insensitive to oxygen. This relatively high yield explains the loss of potency of ABA during UV irradiation. Phosphorescence of cis- and trans-ABA was observed in methanol at 77 K. Onset of the emission was at 350 nm. The emission spectra were the same for both isomers. From these results a mechanism of UV action on plants based on the photoisomerization of the inactive trans-ABA to the biologically active cis isomer is proposed. (author)

Evaluating cis-2,6-Dimethylpiperidide (cis-DMP) as a Base Component in Lithium-Mediated Zincation Chemistry

Science.gov (United States)

Armstrong, David R; Garden, Jennifer A; Kennedy, Alan R; Leenhouts, Sarah M; Mulvey, Robert E; O'Keefe, Philip; O'Hara, Charles T; Steven, Alan

2013-01-01

Most recent advances in metallation chemistry have centred on the bulky secondary amide 2,2,6,6-tetramethylpiperidide (TMP) within mixed metal, often ate, compositions. However, the precursor amine TMP(H) is rather expensive so a cheaper substitute would be welcome. Thus this study was aimed towards developing cheaper non-TMP based mixed-metal bases and, as cis-2,6-dimethylpiperidide (cis-DMP) was chosen as the alternative amide, developing cis-DMP zincate chemistry which has received meagre attention compared to that of its methyl-rich counterpart TMP. A new lithium diethylzincate, [(TMEDA)LiZn(cis-DMP)Et2] (TMEDA=N,N,N′,N′-tetramethylethylenediamine) has been synthesised by co-complexation of Li(cis-DMP), Et2Zn and TMEDA, and characterised by NMR (including DOSY) spectroscopy and X-ray crystallography, which revealed a dinuclear contact ion pair arrangement. By using N,N-diisopropylbenzamide as a test aromatic substrate, the deprotonative reactivity of [(TMEDA)LiZn(cis-DMP)Et2] has been probed and contrasted with that of the known but previously uninvestigated di-tert-butylzincate, [(TMEDA)LiZn(cis-DMP)tBu2]. The former was found to be the superior base (for example, producing the ortho-deuteriated product in respective yields of 78 % and 48 % following D2O quenching of zincated benzamide intermediates). An 88 % yield of 2-iodo-N,N-diisopropylbenzamide was obtained on reaction of two equivalents of the diethylzincate with the benzamide followed by iodination. Comparisons are also drawn using 1,1,1,3,3,3-hexamethyldisilazide (HMDS), diisopropylamide and TMP as the amide component in the lithium amide, Et2Zn and TMEDA system. Under certain conditions, the cis-DMP base system was found to give improved results in comparison to HMDS and diisopropylamide (DA), and comparable results to a TMP system. Two novel complexes isolated from reactions of the di-tert-butylzincate and crystallographically characterised, namely the pre-metallation complex [{(iPr)2N(Ph)C=O}LiZn(cis

Comparative evaluation of capillary electrophoresis and high-performance liquid chromatography for the separation of cis-cis, cis-trans, and trans-trans isomers of atracurium besylate.

Science.gov (United States)

de Moraes, M de L; Polakiewicz, B; Mattua, M F; Tavares, M F

1998-01-01

Atracurium besylate is a highly selective nondepolarizing neuromuscular blocking agent routinely used during anesthetic procedures. The commercial presentation of this drug is a mixture of positional isomers, cis-cis, cis-trans, and trans-trans. Reversed-phase high-performance liquid chromatography has been the technique of choice for the analysis of atracurium besylate formulations at the quality control laboratory of Núcleo de Desenvolvimento Cristália (São Paulo, Brazil), a local pharmaceutical company. HPLC analysis is usually conducted under gradient elution using acetonitrile/0.1 M phosphate buffer eluent mixture as mobile phase and an octadecyl silica (ODS)-packed column. The complete elution of the three isomers takes about 1 hr. In this work, an alternative capillary electrophoresis methodology was developed. The complete resolution of all three isomers was accomplished in about 13 min (+20 kV/72 cm, 211 nm direct detection) using a 60-mM phosphate buffer solution (pH 4) containing 20 mM beta-cyclodextrin and 4 M urea. The isomer ratio was found to be 59.1% cis-cis, 35.9% cis-trans, and 5.02% trans-trans (expected ratio: 59:35:6). Laudanosine, a major metabolite of atracurium besylate, was identified in two commercially available formulations, Tracur (Núcleo de Desenvolvimento Cristália) and Tracrium (Glaxo Wellcome, S.A., Rio de Janeiro, Brazil). Its concentration increases considerably during storage of the product, even if the product is stored at low temperatures.

Antagonism of Innate Immunity by Paramyxovirus Accessory Proteins

Directory of Open Access Journals (Sweden)

Raychel Chambers

2009-10-01

Full Text Available Paramyxovirinae, a subfamily of Paramyxoviridae, are negative strand RNA viruses comprised of many important human and animal pathogens, which share a high degree of genetic and structural homology. The accessory proteins expressed from the P/V/C gene are major factors in the pathogenicity of the viruses, because of their ability to abrogate various facets of type I interferon (IFN induction and signaling. Most of the paramyxoviruses exhibit a commonality in their ability to antagonize innate immunity by blocking IFN induction and the Jak/STAT pathway. However, the manner in which the accessory proteins inhibit the pathway differs among viruses. Similarly, there are variations in the capability of the viruses to counteract intracellular detectors (RNA helicases, mda-5 and RIG-I. Furthermore, a functional specificity in the antagonism of the IFN response has been reported, suggesting that specificity in the circumvention of innate immunity restricts viral host range. Available evidence indicates that paramyxoviruses employ specific strategies to antagonize the IFN response of their specific hosts, which is one of the major factors that determine viral pathogenicity and host range.

10 points about buying C.I.S

International Nuclear Information System (INIS)

Anon.

1993-01-01

On October 16, 1992, the U.S. Department of Commerce (DOC) settled the antidumping case against the CIS republics by imposing price and volume quotas on CIS uranium imported into the United States. Bound by a suspension agreement, each of the six uranium-producing CIS republics is responsible for restricting the flow of imports to the US-either directly or indirectly. (As the NUKEM Market Report went to press, the Ukraine government notified the DOC of its intent not to terminate the suspension agreement.) This action is to prevent undercutting price levels in the US domestic uranium markets. What follows are ten points about everything you should know about importing uranium from the uranium-producing CIS republics- Kazakhstan, Kyrgyzstan, Russian Federation, Tajikistan, Ukraine and Uzbekistan. Newcomers to the CIS scene should follow this simple roadmap and be aware of the issues they face as importers in terms of Commerce/Customs requirements and documentation and where to get them, when to buy the material and how to transport it, how to deal effectively with CIS exporters, and how to avoid unnecessary complications when buying CIS

9-Cis retinoic acid protects against methamphetamine-induced neurotoxicity in nigrostriatal dopamine neurons.

Science.gov (United States)

Reiner, David J; Yu, Seong-Jin; Shen, Hui; He, Yi; Bae, Eunkyung; Wang, Yun

2014-04-01

Methamphetamine (MA) is a drug of abuse as well as a dopaminergic neurotoxin. 9-Cis retinoic acid (9cRA), a biologically active derivative of vitamin A, has protective effects against damage caused by H(2)O(2) and oxygen-glucose deprivation in vitro as well as infarction and terminal deoxynucleotidyl transferase-mediated dNTP nick-end labeling (TUNEL) labeling in ischemic brain. The purpose of this study was to examine if there was a protective role for 9cRA against MA toxicity in nigrostriatal dopaminergic neurons. Primary dopaminergic neurons, prepared from rat embryonic ventral mesencephalic tissue, were treated with MA. High doses of MA decreased tyrosine hydroxylase (TH) immunoreactivity while increasing TUNEL labeling. These toxicities were significantly reduced by 9cRA. 9cRA also inhibited the export of Nur77 from nucleus to cytosol, a response that activates apoptosis. The interaction of 9cRA and MA in vivo was next examined in adult rats. 9cRA was delivered intracerebroventricularly; MA was given (5 mg/kg, 4×) one day later. Locomotor behavior was measured 2 days after surgery for a period of 48 h. High doses of MA significantly reduced locomotor activity and TH immunoreactivity in striatum. Administration of 9cRA antagonized these changes. Previous studies have shown that 9cRA can induce bone morphogenetic protein-7 (BMP7) expression and that administration of BMP7 attenuates MA toxicity. We demonstrated that MA treatment significantly reduced BMP7 mRNA expression in nigra. Noggin (a BMP antagonist) antagonized 9cRA-induced behavioral recovery and 9cRA-induced normalization of striatal TH levels. Our data suggest that 9cRA has a protective effect against MA-mediated neurodegeneration in dopaminergic neurons via upregulation of BMP.

cis-Bifenthrin enantioselectively induces hepatic oxidative stress in mice.

Science.gov (United States)

Jin, Yuanxiang; Wang, Jiangcong; Pan, Xiuhong; Wang, Linggang; Fu, Zhengwei

2013-09-01

Bifenthrin (BF), as a chiral synthetic pyrethroid, is widely used to control field and household pests. In China, the commercial cis-BF contained two enantiomers including 1R-cis-BF and 1S-cis-BF. However, the difference in oxidative stress induced by the two enantiomers in mice still remains unclear. In the present study, 4 week-old adolescent male ICR mice were orally administered cis-BF, 1R-cis-BF or 1S-cis-BF daily for 2, 4 and 6 weeks at doses of 5 mg/kg/day, respectively. We found that the hepatic reactive oxygen species (ROS) levels, as well as the malondialdehyde (MDA) and glutathione (GSH) content both in the serum and liver increased significantly in the 4 or 6 weeks 1S-cis-BF treated groups. The activities of superoxide dismutase (SOD) and catalase (CAT) also changed significantly in the serum and liver of 1S-cis-BF treated mice. More importantly, the significant differences in MDA content and CAT activity both in the serum and liver, and the activities of total antioxidant capacity (T-AOC) and SOD in serum were also observed between the 1S-cis-BF and 1R-cis-BF treated groups. Moreover, the transcription of oxidative stress response related genes including Sod1, Cat and heme oxygenase-1(Ho-1) in the liver of 1S-cis-BF treated groups were also significant higher than those in 1R-cis-BF treated group. Thus, it was concluded that cis-BF induced hepatic oxidative stress in an enantiomer specific manner in mice when exposed during the puberty, and that 1S-cis-BF showed much more toxic in hepatic oxidative stress than 1R-cis-BF. Copyright © 2013 Elsevier Inc. All rights reserved.

CisLunar Habitat Internal Architecture Design Criteria

Science.gov (United States)

Jones, R.; Kennedy, K.; Howard, R.; Whitmore, M.; Martin, C.; Garate, J.

2017-01-01

BACKGROUND: In preparation for human exploration to Mars, there is a need to define the development and test program that will validate deep space operations and systems. In that context, a Proving Grounds CisLunar habitat spacecraft is being defined as the next step towards this goal. This spacecraft will operate differently from the ISS or other spacecraft in human history. The performance envelope of this spacecraft (mass, volume, power, specifications, etc.) is being defined by the Future Capabilities Study Team. This team has recognized the need for a human-centered approach for the internal architecture of this spacecraft and has commissioned a CisLunar Phase-1 Habitat Internal Architecture Study Team to develop a NASA reference configuration, providing the Agency with a "smart buyer" approach for future acquisition. THE CISLUNAR HABITAT INTERNAL ARCHITECTURE STUDY: Overall, the CisLunar Habitat Internal Architecture study will address the most significant questions and risks in the current CisLunar architecture, habitation, and operations concept development. This effort is achieved through definition of design criteria, evaluation criteria and process, design of the CisLunar Habitat Phase-1 internal architecture, and the development and fabrication of internal architecture concepts combined with rigorous and methodical Human-in-the-Loop (HITL) evaluations and testing of the conceptual innovations in a controlled test environment. The vision of the CisLunar Habitat Internal Architecture Study is to design, build, and test a CisLunar Phase-1 Habitat Internal Architecture that will be used for habitation (e.g. habitability and human factors) evaluations. The evaluations will mature CisLunar habitat evaluation tools, guidelines, and standards, and will interface with other projects such as the Advanced Exploration Systems (AES) Program integrated Power, Avionics, Software (iPAS), and Logistics for integrated human-in-the-loop testing. The mission of the Cis

Analysis of Determinants in Filovirus Glycoproteins Required for Tetherin Antagonism

Directory of Open Access Journals (Sweden)

Kerstin Gnirß

2014-04-01

Full Text Available The host cell protein tetherin can restrict the release of enveloped viruses from infected cells. The HIV-1 protein Vpu counteracts tetherin by removing it from the site of viral budding, the plasma membrane, and this process depends on specific interactions between the transmembrane domains of Vpu and tetherin. In contrast, the glycoproteins (GPs of two filoviruses, Ebola and Marburg virus, antagonize tetherin without reducing surface expression, and the domains in GP required for tetherin counteraction are unknown. Here, we show that filovirus GPs depend on the presence of their authentic transmembrane domains for virus-cell fusion and tetherin antagonism. However, conserved residues within the transmembrane domain were dispensable for membrane fusion and tetherin counteraction. Moreover, the insertion of the transmembrane domain into a heterologous viral GP, Lassa virus GPC, was not sufficient to confer tetherin antagonism to the recipient. Finally, mutation of conserved residues within the fusion peptide of Ebola virus GP inhibited virus-cell fusion but did not ablate tetherin counteraction, indicating that the fusion peptide and the ability of GP to drive host cell entry are not required for tetherin counteraction. These results suggest that the transmembrane domains of filoviral GPs contribute to tetherin antagonism but are not the sole determinants.

Dilemmas of compliance in the CIS

International Nuclear Information System (INIS)

Vorobyev, A.

1996-01-01

The objective of this paper is to examine some of the difficulties faced by Russia and other Common Independent States (CIS) in the field of compliance with disarmament treaties and non-proliferation regimes, as well as ways and means, particularly with regard to the legal framework, designed to overcome these difficulties. Naturally, the fate and pace of overcoming the existing problems will depend only partially on development of CIS States. A large variety of international factors and the general security will be essential for progress in resolving disarmament and arms control issues in the CIS

The Netrin-related domain of Sfrp1 interacts with Wnt ligands and antagonizes their activity in the anterior neural plate

Directory of Open Access Journals (Sweden)

Esteve Pilar

2008-08-01

Full Text Available Abstract Background Secreted frizzled related proteins (SFRPs are multifunctional modulators of Wnt and BMP (Bone Morphogenetic Protein signalling necessary for the development of most organs and the homeostasis of different adult tissues. SFRPs fold in two independent domains: the cysteine rich domain (SfrpCRD related to the extracellular portion of Frizzled (Fz, Wnt receptors and the Netrin module (SfrpNTR defined by homologies with molecules such as Netrin-1, inhibitors of metalloproteinases and complement proteins. Due to its structural relationship with Fz, it is believed that SfrpCRD interferes with Wnt signalling by binding and sequestering the ligand. In contrast, the functional relevance of the SfrpNTR has been barely addressed. Results Here, we combine biochemical studies, mutational analysis and functional assays in cell culture and medaka-fish embryos to show that the Sfrp1NTR mimics the function of the entire molecule, binds to Wnt8 and antagonizes Wnt canonical signalling. This activity requires intact tertiary structure and is shared by the distantly related Netrin-1NTR. In contrast, the Sfrp1CRD cannot mirror the function of the entire molecule in vivo but interacts with Fz receptors and antagonizes Wnt8-mediated β-catenin transcriptional activity. Conclusion On the basis of these results, we propose that SFRP modulation of Wnt signalling may involve multiple and differential interactions among Wnt, Fz and SFRPs.

Up front in the CIS

International Nuclear Information System (INIS)

Grey, C.A.

1994-01-01

A picture is drawn of the current supply side of the front-end fuel cycle production capacities in the CIS. Uranium production has been steadily declining, as in the West. Market realities have been reflected in local costs of production since the break-up of the former Soviet Union and some uneconomic mines have been closed. In terms of actual production, Kazakhstan, Russia and Uzbekistan, remain among the top five uranium producers in the world. Western government action has been taken to restrict the market access for natural uranium from the CIS. Reactors in the CIS continue to be supplied with fabricated fuel solely by Russian, though Western fuel fabricators have reduced Russian supplies to Eastern Europe. Russia's current dominance in conversion and enrichment services in both the CIS and Eastern Europe is likely to continue as long as the present surplus low enriched uranium stocks last and surplus production capacity exists. Market penetration in the West has been limited by government action but Russia in 1993 still held about 20% of the world's conversion market and nearly 19% of the enrichment market. (6 figures, 2 tables, 4 references) (UK)

cisMEP: an integrated repository of genomic epigenetic profiles and cis-regulatory modules in Drosophila.

Science.gov (United States)

Yang, Tzu-Hsien; Wang, Chung-Ching; Hung, Po-Cheng; Wu, Wei-Sheng

2014-01-01

Cis-regulatory modules (CRMs), or the DNA sequences required for regulating gene expression, play the central role in biological researches on transcriptional regulation in metazoan species. Nowadays, the systematic understanding of CRMs still mainly resorts to computational methods due to the time-consuming and small-scale nature of experimental methods. But the accuracy and reliability of different CRM prediction tools are still unclear. Without comparative cross-analysis of the results and combinatorial consideration with extra experimental information, there is no easy way to assess the confidence of the predicted CRMs. This limits the genome-wide understanding of CRMs. It is known that transcription factor binding and epigenetic profiles tend to determine functions of CRMs in gene transcriptional regulation. Thus integration of the genome-wide epigenetic profiles with systematically predicted CRMs can greatly help researchers evaluate and decipher the prediction confidence and possible transcriptional regulatory functions of these potential CRMs. However, these data are still fragmentary in the literatures. Here we performed the computational genome-wide screening for potential CRMs using different prediction tools and constructed the pioneer database, cisMEP (cis-regulatory module epigenetic profile database), to integrate these computationally identified CRMs with genomic epigenetic profile data. cisMEP collects the literature-curated TFBS location data and nine genres of epigenetic data for assessing the confidence of these potential CRMs and deciphering the possible CRM functionality. cisMEP aims to provide a user-friendly interface for researchers to assess the confidence of different potential CRMs and to understand the functions of CRMs through experimentally-identified epigenetic profiles. The deposited potential CRMs and experimental epigenetic profiles for confidence assessment provide experimentally testable hypotheses for the molecular mechanisms

Estrogen-mediated inactivation of FOXO3a by the G protein-coupled estrogen receptor GPER

International Nuclear Information System (INIS)

Zekas, Erin; Prossnitz, Eric R.

2015-01-01

, at least in part, to the survival of breast cancer cells, particularly in the presence of ER-targeted therapies involving SERMs and SERDs. Our results further suggest that GPER expression and FOXO3a localization could be utilized as prognostic markers in breast cancer therapy and that GPER antagonists could promote apoptosis in GPER-positive breast cancers, particularly in combination with chemotherapeutic and ER-targeted drugs, by antagonizing estrogen-mediated FOXO3a inactivation

Inactivation Data.xlsx

Data.gov (United States)

U.S. Environmental Protection Agency — The data set is a spreadsheet that contains results of inactivation experiments that were conducted to to determine the effectiveness of chlorine in inactivating B....

Ready access to functionally embellished cis-hydrindanes and cis-decalins: protecting group-free total syntheses of (±)-Nootkatone and (±)-Noreremophilane.

Science.gov (United States)

Handore, Kishor L; Seetharamsingh, B; Reddy, D Srinivasa

2013-08-16

A simple and efficient synthesis of functionalized cis-hydrindanes and cis-decalins was achieved using a sequential Diels-Alder/aldol approach in a highly diastereoselective manner. The scope of this method was tested with a variety of substrates and was successfully applied to the synthesis of two natural products in racemic form. The highlights of the present work provide ready access to 13 new cis-hydrindanes/cis-decalins, a protecting group-free total synthesis of an insect repellent Nootkatone, and the first synthesis of a Noreremophilane using the shortest sequence.

Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit

Directory of Open Access Journals (Sweden)

MIKI TSUJITA

2007-01-01

Full Text Available Morphine is often used in cancer pain and postoperative analgesic management but induces respiratory depression. Therefore, there is an ongoing search for drug candidates that can antagonize morphine-induced respiratory depression but have no effect on morphine-induced analgesia. Acetylcholine is an excitatory neurotransmitter in central respiratory control and physostigmine antagonizes morphine-induced respiratory depression. However, physostigmine has not been applied in clinical practice because it has a short action time, among other characteristics. We therefore asked whether donepezil (a long-acting acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease can antagonize morphine-induced respiratory depression. Using the anesthetized rabbit as our model, we measured phrenic nerve discharge as an index of respiratory rate and amplitude. We compared control indices with discharges after the injection of morphine and after the injection of donepezil. Morphine-induced depression of respiratory rate and respiratory amplitude was partly antagonized by donepezil without any effect on blood pressure and end-tidal C0(2. In the other experiment, apneic threshold PaC0(2 was also compared. Morphine increased the phrenic nerve apnea threshold but this was antagonized by donepezil. These findings indicate that systemically administered donepezil partially restores morphine-induced respiratory depression and morphine-deteriorated phrenic nerve apnea threshold in the anesthetized rabbit

Optimization of Pseudomonas putida KT2440 as host for the production of cis, cis-muconate from benzoate

NARCIS (Netherlands)

Duuren, van J.B.J.H.

2011-01-01

Optimization of Pseudomonas putida KT2440 as host for the production of cis, cis-muconate

from benzoate P. putida KT2440 was used as biocatalyst given its versatile and energetically robust metabolism.

Therefore, a mutant was generated and a process developed based on which a

Inactivation of pathogenic bacteria in food matrices: high pressure processing, photodynamic inactivation and pressure-assisted photodynamic inactivation

Science.gov (United States)

Cunha, A.; Couceiro, J.; Bonifácio, D.; Martins, C.; Almeida, A.; Neves, M. G. P. M. S.; Faustino, M. A. F.; Saraiva, J. A.

2017-09-01

Traditional food processing methods frequently depend on the application of high temperature. However, heat may cause undesirable changes in food properties and often has a negative impact on nutritional value and organoleptic characteristics. Therefore, reducing the microbial load without compromising the desirable properties of food products is still a technological challenge. High-pressure processing (HPP) can be classified as a cold pasteurization technique, since it is a non-thermal food preservation method that uses hydrostatic pressure to inactivate spoilage microorganisms. At the same time, it increases shelf life and retains the original features of food. Photodynamic inactivation (PDI) is also regarded as promising approach for the decontamination of food matrices. In this case, the inactivation of bacterial cells is achieved by the cytotoxic effects of reactive oxygens species (ROS) produced from the combined interaction of a photosensitizer molecule, light and oxygen. This short review examines some recent developments on the application of HPP and PDI with food-grade photosensitizers for the inactivation of listeriae, taken as a food pathogen model. The results of a proof-of-concept trial of the use of high-pressure as a coadjutant to increase the efficiency of photodynamic inactivation of bacterial endospores is also addressed.

Nominal Anchors in the CIS

OpenAIRE

Peter M Keller; Thomas J Richardson

2003-01-01

Monetary policy has become increasingly important in the countries of the Commonwealth of Independent States (CIS) as fiscal adjustment and structural reforms have taken root. Inflation has been brought down to relatively low levels in almost all of these countries, raising the question of what should be the appropriate nominal anchor at this stage. Formally, almost all CIS countries have floating exchange rate regimes, yet in practice they manage their exchange rates very heavily, perhaps be...

Natural Protection of Wood with Antagonism Fungi

Directory of Open Access Journals (Sweden)

Alba ZAREMSKI

2011-03-01

Full Text Available Biological environments contain a certain number of microbial populations which, within a givenecological niche, display various relations ranging from symbiosis to parasitism. Researchers have beeninterested in these types of relations for around fifty years, especially in one very particular type ofrelationship: the antagonism exerted between individuals of the same microbial population.Today, the role played by biological agents, bringing into play inhibitive or destructive antibioticsubstances, reveals a certain potential for their use in controlling microorganisms associated with suchdegradation processes.The work undertaken by HydroQuébec and CIRAD involved two types of experiment: 1 in Petri dishes toassess and characterize the antagonistic capacity of Trichoderma against white rot and brown rot fungi; 2on pieces taken from untreated poles in order to study confrontation between the basidiomycete and theantagonistic strain in wood.This study investigated the antagonism of three ascomycetes of the genus Trichoderma against two whiterot basidiomycetes, Pycnoporus sanguineus and Coriolus versicolor, and two brown rot basidiomycetes,Antrodia sp. and Coniophora puteana, through direct confrontation in Petri dishes and in the wood ofHydroQuébec poles.The results obtained seemed to complete each other coherently. They revealed that the Trichodermagroup of fungi was not aggressive to wood and the results obtained after direct confrontation in Petri disheswere confirmed in wood.By directly exposing the different basidiomycetes and antagonists to each other in Petri dishes, two bytwo, we effectively revealed an antagonism effect for a large majority of the pairs. However, there wassubstantial variability in reactions from one pair to the next.

Novel 9-cis/all-trans β-carotene isomerases from plastidic oil bodies in Dunaliella bardawil catalyze the conversion of all-trans to 9-cis β-carotene.

Science.gov (United States)

Davidi, Lital; Pick, Uri

2017-06-01

We identified and demonstrated the function of 9-cis/all-trans β-carotene isomerases in plastidic globules of Dunaliella bardawil, the species accumulating the highest levels of 9-cis β-carotene that is essential for humans. The halotolerant alga Dunaliella bardawil is unique in that it accumulates under light stress high levels of β-carotene in plastidic lipid globules. The pigment is composed of two major isomers: all-trans β-carotene, the common natural form of this pigment, and 9-cis β-carotene. The biosynthetic pathway of β-carotene is known, but it is not clear how the 9-cis isomer is formed. We identified in plastidic lipid globules that were isolated from D. bardawil two proteins with high sequence homology to the D27 protein-a 9-cis/all-trans β-carotene isomerase from rice (Alder et al. Science 335:1348-1351, 2012). The proteins are enriched in the oil globules by 6- to 17-fold compared to chloroplast proteins. The expression of the corresponding genes, 9-cis-βC-iso1 and 9-cis-βC-iso2, is enhanced under light stress. The synthetic proteins catalyze in vitro conversion of all-trans to 9-cis β-carotene. Expression of the 9-cis-βC-iso1 or of 9-cis-βC-iso2 genes in an E. coli mutant line that harbors β-carotene biosynthesis genes enhanced the conversion of all-trans into 9-cis β-carotene. These results suggest that 9-cis-βC-ISO1 and 9-cis-βC-ISO2 proteins are responsible for the formation of 9-cis β-carotene in D. bardawil under stress conditions.

Studies on radiosensitization of Escherichia coli cells by cis-platinum complexes

International Nuclear Information System (INIS)

Zimbrick, J.D.; Sukrochana, A.; Richmond, R.C.

1979-01-01

We recently reported that the antitumor drug cis-Pt(NH 3 ) 2 Cl 2 (cis-DDP) produces significant radiosensitization of anoxic E coli C cells. We have extended these studies to three other platinum drugs, all of which have been shown to be more effective antitumor drugs than cis-DDP. The drugs are: cis-dichloro bis(ethylene imine) Pt(II) (cis-DEP); cis-dichlorobicyclopentylamine Pt(II) (cis-PAD); and Pt-thymine blue (cis-PTB). Survival curve studies indicate that these drugs all produce greater anoxic radiosensitization of E coli C than cis-DDP at concentrations which are less toxic to the cells than similar concentrations of cis-DDP. If the cells are treated with any one of these drugs for two hours and then washed to remove the drug before irradiation, no detectable radiosensitization is found. We conclude that these drugs have the potential for being useful agents in combined modality therapy and that they warrant further study in mammalian systems

Identification and mechanism of ABA receptor antagonism

KAUST Repository

Melcher, Karsten; Xu, Yong; Ng, Ley-Moy; Zhou, X. Edward; Soon, Fen-Fen; Chinnusamy, Viswanathan; Suino-Powell, Kelly M.; Kovach, Amanda; Tham, Fook S.; Cutler, Sean R.; Li, Jun; Yong, Eu-Leong; Zhu, Jian-Kang; Xu, H. Eric

2010-01-01

The phytohormone abscisic acid (ABA) functions through a family of fourteen PYR/PYL receptors, which were identified by resistance to pyrabactin, a synthetic inhibitor of seed germination. ABA activates these receptors to inhibit type 2C protein phosphatases, such as ABI1, yet it remains unclear whether these receptors can be antagonized. Here we demonstrate that pyrabactin is an agonist of PYR1 and PYL1 but is unexpectedly an antagonist of PYL2. Crystal structures of the PYL2-pyrabactin and PYL1-pyrabactin-ABI1 complexes reveal the mechanism responsible for receptor-selective activation and inhibition, which enables us to design mutations that convert PYL1 to a pyrabactin-inhibited receptor and PYL2 to a pyrabactin-activated receptor and to identify new pyrabactin-based ABA receptor agonists. Together, our results establish a new concept of ABA receptor antagonism, illustrate its underlying mechanisms and provide a rational framework for discovering novel ABA receptor ligands. © 2010 Nature America, Inc. All rights reserved.

Identification and mechanism of ABA receptor antagonism

KAUST Repository

Melcher, Karsten

2010-08-22

The phytohormone abscisic acid (ABA) functions through a family of fourteen PYR/PYL receptors, which were identified by resistance to pyrabactin, a synthetic inhibitor of seed germination. ABA activates these receptors to inhibit type 2C protein phosphatases, such as ABI1, yet it remains unclear whether these receptors can be antagonized. Here we demonstrate that pyrabactin is an agonist of PYR1 and PYL1 but is unexpectedly an antagonist of PYL2. Crystal structures of the PYL2-pyrabactin and PYL1-pyrabactin-ABI1 complexes reveal the mechanism responsible for receptor-selective activation and inhibition, which enables us to design mutations that convert PYL1 to a pyrabactin-inhibited receptor and PYL2 to a pyrabactin-activated receptor and to identify new pyrabactin-based ABA receptor agonists. Together, our results establish a new concept of ABA receptor antagonism, illustrate its underlying mechanisms and provide a rational framework for discovering novel ABA receptor ligands. © 2010 Nature America, Inc. All rights reserved.

Paenibacillus polymyxa A26 sfp-type phosphopantetheinyl transferase inactivation limits bacterial antagonism against Fusarium graminearum but not of F. culmorum

Directory of Open Access Journals (Sweden)

Islam A eAbd El Daim

2015-05-01

Full Text Available Fusarium graminearum and F. culmorum are the causing agents of a destructive disease known as Fusarium head blight (FHB. FHB is a re-emerging disease in small grain cereals which impairs both the grain yield and the quality. Most serious consequence is the contamination of grain with Fusarium mycotoxins that are severe threat to humans and animals. Biological control has been suggested as one of the integrated management strategies to control FHB. Paenibacillus polymyxa is considered as a promising biocontrol agent due to its unique antibiotic spectrum. In order to optimize strain A26 production, formulation and application strategies traits important for its compatibility need to be revealed. Here we developed a toolbox comprising of dual culture plate assays and wheat kernel assays including simultaneous monitoring of FHB causing pathogens A26 and mycotoxins produced. Using this system we show that, besides generally known lipopeptide antibiotic production by P. polymyxa, biofilm formation ability may play a crucial role in the case of stain A26 F. culmorum antagonism.

Conformation regulation of the X chromosome inactivation center: a model.

Directory of Open Access Journals (Sweden)

Antonio Scialdone

2011-10-01

Full Text Available X-Chromosome Inactivation (XCI is the process whereby one, randomly chosen X becomes transcriptionally silenced in female cells. XCI is governed by the Xic, a locus on the X encompassing an array of genes which interact with each other and with key molecular factors. The mechanism, though, establishing the fate of the X's, and the corresponding alternative modifications of the Xic architecture, is still mysterious. In this study, by use of computer simulations, we explore the scenario where chromatin conformations emerge from its interaction with diffusing molecular factors. Our aim is to understand the physical mechanisms whereby stable, non-random conformations are established on the Xic's, how complex architectural changes are reliably regulated, and how they lead to opposite structures on the two alleles. In particular, comparison against current experimental data indicates that a few key cis-regulatory regions orchestrate the organization of the Xic, and that two major molecular regulators are involved.

Transformation of Migration Flows Between the Russian Far East and CIS and non-CIS States

Directory of Open Access Journals (Sweden)

Motrich E. L.

2010-06-01

Full Text Available Basic trends in the migration processes in the Russian Far East are shown. Special emphasis is placed on the transformation of migration interactions with CIS and non-CIS countries both at the level of the region as a whole, and at the level of the Far Eastern territories of the Russian Federation. An extent of using foreign labor in different periods of the Russian Far East socio-economic development and the regulatory support of this process are shown. Prospects for attracting and utilizing foreign labor are stated

Roles of bHLH genes in neural stem cell differentiation

International Nuclear Information System (INIS)

Kageyama, Ryoichiro; Ohtsuka, Toshiyuki; Hatakeyama, Jun; Ohsawa, Ryosuke

2005-01-01

Neural stem cells change their characteristics over time during development: they initially proliferate only and then give rise to neurons first and glial cells later. In the absence of the repressor-type basic helix-loop-helix (bHLH) genes Hes1, Hes3 and Hes5, neural stem cells do not proliferate sufficiently but prematurely differentiate into neurons and become depleted without making the later born cell types such as astrocytes and ependymal cells. Thus, Hes genes are essential for maintenance of neural stem cells to make cells not only in correct numbers but also in full diversity. Hes genes antagonize the activator-type bHLH genes, which include Mash1, Math and Neurogenin. The activator-type bHLH genes promote the neuronal fate determination and induce expression of Notch ligands such as Delta. These ligands activate Notch signaling and upregulate Hes1 and Hes5 expression in neighboring cells, thereby maintaining these cells undifferentiated. Thus, the activator-type and repressor-type bHLH genes regulate each other, allowing only subsets of cells to undergo differentiation while keeping others to stay neural stem cells. This regulation is essential for generation of complex brain structures of appropriate size, shape and cell arrangement

Platformed antagonism: Racist discourses on fake Muslim Facebook pages

DEFF Research Database (Denmark)

Farkas, Johan; Schou, Jannick; Neumayer, Christina

2018-01-01

This research examines how fake identities on social media create and sustain antagonistic and racist discourses. It does so by analysing 11 Danish Facebook pages, disguised as Muslim extremists living in Denmark, conspiring to kill and rape Danish citizens. It explores how anonymous content...... producers utilize Facebook's socio-technical characteristics to construct, what we propose to term as, platformed antagonism. This term refers to socio-technical and discursive practices that produce new modes of antagonistic relations on social media platforms. Through a discourse-theoretical analysis...... of posts, images, 'about' sections and user comments on the studied Facebook pages, the article highlights how antagonism between ethno-cultural identities is produced on social media through fictitious social media accounts, prompting thousands of user reactions. These findings enhance our current...

Stepwise encapsulation and controlled two-stage release system for cis-Diamminediiodoplatinum.

Science.gov (United States)

Chen, Yun; Li, Qian; Wu, Qingsheng

2014-01-01

cis-Diamminediiodoplatinum (cis-DIDP) is a cisplatin-like anticancer drug with higher anticancer activity, but lower stability and price than cisplatin. In this study, a cis-DIDP carrier system based on micro-sized stearic acid was prepared by an emulsion solvent evaporation method. The maximum drug loading capacity of cis-DIDP-loaded solid lipid nanoparticles was 22.03%, and their encapsulation efficiency was 97.24%. In vitro drug release in phosphate-buffered saline (pH =7.4) at 37.5°C exhibited a unique two-stage process, which could prove beneficial for patients with tumors and malignancies. MTT (3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay results showed that cis-DIDP released from cis-DIDP-loaded solid lipid nanoparticles had better inhibition activity than cis-DIDP that had not been loaded.

Reconceptualizing synergism and antagonism among multiple stressors.

Science.gov (United States)

Piggott, Jeremy J; Townsend, Colin R; Matthaei, Christoph D

2015-04-01

The potential for complex synergistic or antagonistic interactions between multiple stressors presents one of the largest uncertainties when predicting ecological change but, despite common use of the terms in the scientific literature, a consensus on their operational definition is still lacking. The identification of synergism or antagonism is generally straightforward when stressors operate in the same direction, but if individual stressor effects oppose each other, the definition of synergism is paradoxical because what is synergistic to one stressor's effect direction is antagonistic to the others. In their highly cited meta-analysis, Crain et al. (Ecology Letters, 11, 2008: 1304) assumed in situations with opposing individual effects that synergy only occurs when the cumulative effect is more negative than the additive sum of the opposing individual effects. We argue against this and propose a new systematic classification based on an additive effects model that combines the magnitude and response direction of the cumulative effect and the interaction effect. A new class of "mitigating synergism" is identified, where cumulative effects are reversed and enhanced. We applied our directional classification to the dataset compiled by Crain et al. (Ecology Letters, 11, 2008: 1304) to determine the prevalence of synergistic, antagonistic, and additive interactions. Compared to their original analysis, we report differences in the representation of interaction classes by interaction type and we document examples of mitigating synergism, highlighting the importance of incorporating individual stressor effect directions in the determination of synergisms and antagonisms. This is particularly pertinent given a general bias in ecology toward investigating and reporting adverse multiple stressor effects (double negative). We emphasize the need for reconsideration by the ecological community of the interpretation of synergism and antagonism in situations where

Orexin 1 and orexin 2 receptor antagonism in the basolateral amygdala modulate long-term potentiation of the population spike in the perforant path-dentate gyrus-evoked field potential in rats.

Science.gov (United States)

Ardeshiri, Motahareh Rouhi; Hosseinmardi, Narges; Akbari, Esmaeil

2018-03-01

Involvement of amygdalo-hippocampal substructures in patients with narcolepsy due to deficiencies in the orexinergic system, and the presence of hippocampus-dependent memory impairments in this disorder, have led us to investigate the effects of orexin 1 and 2 receptor antagonism in the basolateral amygdala (BLA) on long-term potentiation (LTP) of dentate gyrus (DG) granular cells. We used a 200-Hz high-frequency stimulation protocol in anesthetized rats. We studied the long-term synaptic plasticity of perforant path-dentate gyrus granule cells following the inactivation of orexin receptors before and after tetanic stimulation. LTP of the DG population spike was attenuated in the presence of orexin 1 and 2 receptor antagonism (treatment with SB-334867-A and TCS-OX2-29, respectively) in the BLA when compared to that observed following treatment with dimethyl sulfoxide (DMSO). However, the population excitatory post-synaptic potentials were not affected. Moreover, when orexin 1 and 2 receptors in the BLA were blocked after LTP induction, there were no differences between the DMSO and treatment groups. Our findings suggest that the orexinergic system of the BLA plays a modulatory role in the regulation of hippocampal plasticity in rats. Copyright © 2018 Elsevier Inc. All rights reserved.

Experimental testing of Mackay's model for functional antagonism in the isolated costo-uterus of the rat.

Science.gov (United States)

Henry, P. J.; Lulich, K. M.; Paterson, J. W.

1985-01-01

Several key predictions of a recently developed model for functional antagonism (Mackay, 1981) were experimentally tested using the rat isolated costo-uterine preparation. In the presence of the functional antagonist fenoterol (Fen), the functional constants (KAF) for carbachol and oxotremorine (Oxo) were respectively 9.9 and 3.4 fold greater than their corresponding affinity constants (KA). According to Mackay's model for functional antagonism, the higher KAF/KA ratio for carbachol indicates that this cholinoceptor agonist has a greater efficacy than Oxo. This was confirmed by using conventional pharmacological methods. As predicted from the model of functional antagonism, the plot of KAF/KA-1 against the fraction of cholinoceptors not irreversibly blocked by phenoxybenzamine (Pbz) was linear for both carbachol and Oxo and the lines of best fit crossed the axes at a point not significantly different from the origin. The value of 4.6 for the relative efficacy of carbachol to Oxo estimated from functional antagonism studies was comparable to the value of 5.6 calculated using the method of irreversible antagonism proposed by Furchgott (1966). PMID:3840396

Zebrafish msxB, msxC and msxE function together to refine the neural-nonneural border and regulate cranial placodes and neural crest development.

Science.gov (United States)

Phillips, Bryan T; Kwon, Hye-Joo; Melton, Colt; Houghtaling, Paul; Fritz, Andreas; Riley, Bruce B

2006-06-15

The zebrafish muscle segment homeobox genes msxB, msxC and msxE are expressed in partially overlapping domains in the neural crest and preplacodal ectoderm. We examined the roles of these msx genes in early development. Disrupting individual msx genes causes modest variable defects, whereas disrupting all three produces a reproducible severe phenotype, suggesting functional redundancy. Neural crest differentiation is blocked at an early stage. Preplacodal development begins normally, but placodes arising from the msx expression domain later show elevated apoptosis and are reduced in size. Cell proliferation is normal in these tissues. Unexpectedly, Msx-deficient embryos become ventralized by late gastrulation whereas misexpression of msxB dorsalizes the embryo. These effects appear to involve Distal-less (Dlx) protein activity, as loss of dlx3b and dlx4b suppresses ventralization in Msx-depleted embryos. At the same time, Msx-depletion restores normal preplacodal gene expression to dlx3b-dlx4b mutants. These data suggest that mutual antagonism between Msx and Dlx proteins achieves a balance of function required for normal preplacodal differentiation and placement of the neural-nonneural border.

Statistical significance of cis-regulatory modules

Directory of Open Access Journals (Sweden)

Smith Andrew D

2007-01-01

Full Text Available Abstract Background It is becoming increasingly important for researchers to be able to scan through large genomic regions for transcription factor binding sites or clusters of binding sites forming cis-regulatory modules. Correspondingly, there has been a push to develop algorithms for the rapid detection and assessment of cis-regulatory modules. While various algorithms for this purpose have been introduced, most are not well suited for rapid, genome scale scanning. Results We introduce methods designed for the detection and statistical evaluation of cis-regulatory modules, modeled as either clusters of individual binding sites or as combinations of sites with constrained organization. In order to determine the statistical significance of module sites, we first need a method to determine the statistical significance of single transcription factor binding site matches. We introduce a straightforward method of estimating the statistical significance of single site matches using a database of known promoters to produce data structures that can be used to estimate p-values for binding site matches. We next introduce a technique to calculate the statistical significance of the arrangement of binding sites within a module using a max-gap model. If the module scanned for has defined organizational parameters, the probability of the module is corrected to account for organizational constraints. The statistical significance of single site matches and the architecture of sites within the module can be combined to provide an overall estimation of statistical significance of cis-regulatory module sites. Conclusion The methods introduced in this paper allow for the detection and statistical evaluation of single transcription factor binding sites and cis-regulatory modules. The features described are implemented in the Search Tool for Occurrences of Regulatory Motifs (STORM and MODSTORM software.

Relative Stability of cis- and trans-Hydrindanones

Directory of Open Access Journals (Sweden)

Motoo Tori

2015-01-01

Full Text Available The relative stabilities of several cis- and trans-hydrindanones were compared using both isomerization experiments and MM2 calculations. The generally believed rule that cis-hydrindanones are more stable than trans-isomers is applicable, but is not always true. This review introduces examples, mainly from studies in our laboratory, to explain these facts.

In vitro antagonism of Trichoderma harzianum Rifai against Mycosphaerella fijiensis Morelet

Directory of Open Access Journals (Sweden)

Mayra Acosta-Suárez

2013-10-01

Full Text Available The in vitro antagonism of Trichoderma harzianum against Mycosphaerella fijiensis, foliar pathogen of banana and plantain, was evaluated. The assays were performed using the dual culture method. Competition for space and nutrients, the antagonistic capacity and forms and intensity of antagonism were determined considering the invasion of the surface of the colony, colonization and sporulation of T. harzianum on M. fijiensis after seven days of inoculation. Finally, the effect of volatile metabolites of T. harzianum was evaluated. The results showed in vitro antagonism of T. harzianum against M. fijiensis by competition for space and nutrients of the culture medium. Trichoderma grew over the pathogen colony with hyperparasitism and high intensity. Also, it completely covered the surface of the culture medium. T. harzianum not inhibited the growth of M. fijiensis by volatile metabolites. Damage was observed in the integrity of the cell wall of M. fijiensis hyphae and the cell content exit. The use of antagonistic fungi, could contribute to the design of strategies for integrated management of this disease. Key words: banana and plantain, biocontrol, mechanisms of action

The Community Intercomparison Suite (CIS)

Science.gov (United States)

Watson-Parris, Duncan; Schutgens, Nick; Cook, Nick; Kipling, Zak; Kershaw, Phil; Gryspeerdt, Ed; Lawrence, Bryan; Stier, Philip

2017-04-01

Earth observations (both remote and in-situ) create vast amounts of data providing invaluable constraints for the climate science community. Efficient exploitation of these complex and highly heterogeneous datasets has been limited however by the lack of suitable software tools, particularly for comparison of gridded and ungridded data, thus reducing scientific productivity. CIS (http://cistools.net) is an open-source, command line tool and Python library which allows the straight-forward quantitative analysis, intercomparison and visualisation of remote sensing, in-situ and model data. The CIS can read gridded and ungridded remote sensing, in-situ and model data - and many other data sources 'out-of-the-box', such as ESA Aerosol and Cloud CCI product, MODIS, Cloud CCI, Cloudsat, AERONET. Perhaps most importantly however CIS also employs a modular plugin architecture to allow for the reading of limitless different data types. Users are able to write their own plugins for reading the data sources which they are familiar with, and share them within the community, allowing all to benefit from their expertise. To enable the intercomparison of this data the CIS provides a number of operations including: the aggregation of ungridded and gridded datasets to coarser representations using a number of different built in averaging kernels; the subsetting of data to reduce its extent or dimensionality; the co-location of two distinct datasets onto a single set of co-ordinates; the visualisation of the input or output data through a number of different plots and graphs; the evaluation of arbitrary mathematical expressions against any number of datasets; and a number of other supporting functions such as a statistical comparison of two co-located datasets. These operations can be performed efficiently on local machines or large computing clusters - and is already available on the JASMIN computing facility. A case-study using the GASSP collection of in-situ aerosol observations

Optimization of Pseudomonas putida KT2440 as host for the production of cis, cis-muconate from benzoate

OpenAIRE

Duuren, van, J.B.J.H.

2011-01-01

Optimization of Pseudomonas putida KT2440 as host for the production of cis, cis-muconate from benzoate P. putida KT2440 was used as biocatalyst given its versatile and energetically robust metabolism. Therefore, a mutant was generated and a process developed based on which a life cycle assessment (LCA) was performed. Additionally, the growth related parameters were experimentally obtained to constrain the metabolic model iJP815 further. The mutant Pseudomonas putida KT2440-JD1 was deri...

Chiral synthesis of (Z)-3-cis-6,7-cis-9,10-diepoxyhenicosenes, sex pheromone components of the satin moth, Leucoma salicis.

Science.gov (United States)

Wimalaratne, Priyantha D C; Slessor, Keith N

2004-06-01

All four isomers of (Z)-3-cis-6,7-cis-9,10-diepoxyhenicosenes, 1-4, have been synthesized using D-xylose as the chirally pure starting material. D-Xylose was first converted to 2-deoxy-4,5-O-isopropylidene-3-t-butyldimethylsilyl-D-threopentose 11, via several steps of selective protection, dehydroxylation, and deprotection. Wittig coupling of 11 with nonyltriphenylphosphonium bromide followed by hydrogenation and acid catalyzed deprotection of hydroxyl groups yielded the chiral (2R,3R)-1,2,3-triol, 14, which was used as the precursor for the C-8 to C-21 unit of the (Z)-3-cis-6,7-cis-9,10-diepoxyhenicosenes. Selective tosylation of 14 followed by stereospecific cyclization yielded (2R,3R)-1,2-epoxytetradecan-3-ol, 16, which was then divergently converted to the t-butyldimethylsilyl ether 17 and tosylate 22, respectively. Establishment of the C-5 through C-7 unit of the target molecules was accomplished via regiospecific coupling of 17 with 1-t-butyldimethylsiloxy-2-propyne to form 18. Stepwise transformation of 18 via the formation of tosylate 19, desilylation, and stereospecific cyclization to form epoxy alcohol 20, followed by P2-Ni reduction yielded a key intermediate, allylic epoxy alcohol (Z)-2-(5S,6R)-cis-5,6-epoxyheptadecen-1-ol, 21. Similarly, the coupling of 22 with 1-t-butyldimethylsiloxy-2-propyne yielded 23, which was stereospecifically cyclized to form 24. Desilylation and P2-Ni reduction of 24 gave the antipodal intermediate, (Z)-2-(5R,6S)-cis-5,6-epoxyheptadecen-1-ol, 26. Asymmetric epoxidation of antipodes 21 and 26 with (L)- or (D)-diethyl tartrates resulted in the formation of diepoxy alcohols 27 and 29 from 21, and 33 and 31 from 26, respectively. Tosylation of these diepoxy alcohols followed by coupling with lithium dibutenyl cuprate yielded the four stereoisomers of (Z)-3-cis-6,7-cis-9,10-diepoxyhenicosenes, 1-4. Analysis of the retention characteristics of these materials revealed that one or both of the S*,R*,S*,R* stereoisomers comprise the

Multiple Functional Variants in cis Modulate PDYN Expression.

Science.gov (United States)

Babbitt, Courtney C; Silverman, Jesse S; Haygood, Ralph; Reininga, Jennifer M; Rockman, Matthew V; Wray, Gregory A

2010-02-01

Understanding genetic variation and its functional consequences within cis-regulatory regions remains an important challenge in human genetics and evolution. Here, we present a fine-scale functional analysis of segregating variation within the cis-regulatory region of prodynorphin, a gene that encodes an endogenous opioid precursor with roles in cognition and disease. In order to characterize the functional consequences of segregating variation in cis in a region under balancing selection in different human populations, we examined associations between specific polymorphisms and gene expression in vivo and in vitro. We identified five polymorphisms within the 5' flanking region that affect transcript abundance: a 68-bp repeat recognized in prior studies, as well as two microsatellites and two single nucleotide polymorphisms not previously implicated as functional variants. The impact of these variants on transcription differs by brain region, sex, and cell type, implying interactions between cis genotype and the differentiated state of cells. The effects of individual variants on expression level are not additive in some combinations, implying epistatic interactions between nearby variants. These data reveal an unexpectedly complex relationship between segregating genetic variation and its expression-trait consequences and highlights the importance of close functional scrutiny of natural genetic variation within even relatively well-studied cis-regulatory regions.

Skewed X-inactivation in cloned mice

International Nuclear Information System (INIS)

Senda, Sho; Wakayama, Teruhiko; Yamazaki, Yukiko; Ohgane, Jun; Hattori, Naka; Tanaka, Satoshi; Yanagimachi, Ryuzo; Shiota, Kunio

2004-01-01

In female mammals, dosage compensation for X-linked genes is accomplished by inactivation of one of two X chromosomes. The X-inactivation ratio (a percentage of the cells with inactivated maternal X chromosomes in the whole cells) is skewed as a consequence of various genetic mutations, and has been observed in a number of X-linked disorders. We previously reported that phenotypically normal full-term cloned mouse fetuses had loci with inappropriate DNA methylation. Thus, cloned mice are excellent models to study abnormal epigenetic events in mammalian development. In the present study, we analyzed X-inactivation ratios in adult female cloned mice (B6C3F1). Kidneys of eight naturally produced controls and 11 cloned mice were analyzed. Although variations in X-inactivation ratio among the mice were observed in both groups, the distributions were significantly different (Ansary-Bradley test, P < 0.01). In particular, 2 of 11 cloned mice showed skewed X-inactivation ratios (19.2% and 86.8%). Similarly, in intestine, 1 of 10 cloned mice had a skewed ratio (75.7%). Skewed X-inactivation was observed to various degrees in different tissues of different individuals, suggesting that skewed X-inactivation in cloned mice is the result of secondary cell selection in combination with stochastic distortion of primary choice. The present study is the first demonstration that skewed X-inactivation occurs in cloned animals. This finding is important for understanding both nuclear transfer technology and etiology of X-linked disorders

Free radical inactivation of trypsin

International Nuclear Information System (INIS)

Cudina, Ivana; Jovanovic, S.V.

1988-01-01

Reactivities of free radical oxidants, radical OH, Br2-anion radical and Cl 3 COO radical and a reductant, CO2-anion radical, with trypsin and reactive protein components were determined by pulse radiolysis of aqueous solutions at pH 7, 20 0 C. Highly reactive free radicals, radical OH, Br2-anion radical and CO2-anion radical, react with trypsin at diffusion controlled rates. Moderately reactive trichloroperoxy radical, k(Cl 3 COO radical + trypsin) preferentially oxidizes histidine residues. The efficiency of inactivation of trypsin by free radicals is inversely proportional to their reactivity. The yields of inactivation of trypsin by radical OH, Br2-anion radical and CO2-anion radical are low, G(inactivation) = 0.6-0.8, which corresponds to ∼ 10% of the initially produced radicals. In contrast, Cl 3 COO radical inactivates trypsin with ∼ 50% efficiency, i.e. G(inactivation) = 3.2. (author)

[Antagonism of Trichoderma spp. to fungi caused root rot of Sophora tonkinensis].

Science.gov (United States)

Qin, Liu-yan; Jiang, Ni; Tang, Mei-qiong; Miao, Jian-hua; Li, Lin-xuan

2011-04-01

To study the antagonism of Trichoderma spp. to fungi S9(Fusarium solani)which caused root rot of Sophora tonkinensis and discuss the further develop prospects of microbial biological control in soil-borne diseases on Chinese herbal medicines. Antagonism of H2 (Trichoderma harsianum), M6 (Trichoderma viride) and K1 (Trichoderma koningii) to Fusarium solani were researched by growth rate and confront culture. And their mechanisms were discussed. H2 and M6 had obvious competitive advantage, the growth rate of which were 1.43-2.72 times and 1.43-1.95 times as S9 respectively. The space competitive advantage of K1 was relatively weak; the growth rate was slower than S9. The antagonism of three species of Trichoderma spp. to S9 was in varying degrees. The antagonism to S9 of M6 and H2 was better,the inhibition rate were 100% and 82.35% respectively, even cultivated S9 for three days in advance. And their inhibition indexes were both reached class I. The inhibition index and inhibition rate of K1 was respectively 46.36% and class IV. The Trichoderma spp. could cause S9 mycelium to appear some phenomenon just like fracture, constriction reduced, digestion, etc. which were observed under the microscope. Trichoderma harsianum and Trichoderma viride showed the further develop prospects in the fight against soil-borne disease on Chinese herbal medicines.

Inactivation of human α-globin gene expression by a de novo deletion located upstream of the α-globin gene cluster

International Nuclear Information System (INIS)

Liebhaber, S.A.; Weiss, I.; Cash, F.E.; Griese, E.U.; Horst, J.; Ayyub, H.; Higgs, D.R.

1990-01-01

Synthesis of normal human hemoglobin A, α 2 β 2 , is based upon balanced expression of genes in the α-globin gene cluster on chromosome 15 and the β-globin gene cluster on chromosome 11. Full levels of erythroid-specific activation of the β-globin cluster depend on sequences located at a considerable distance 5' to the β-globin gene, referred to as the locus-activating or dominant control region. The existence of an analogous element(s) upstream of the α-globin cluster has been suggested from observations on naturally occurring deletions and experimental studies. The authors have identified an individual with α-thalassemia in whom structurally normal α-globin genes have been inactivated in cis by a discrete de novo 35-kilobase deletion located ∼30 kilobases 5' from the α-globin gene cluster. They conclude that this deletion inactivates expression of the α-globin genes by removing one or more of the previously identified upstream regulatory sequences that are critical to expression of the α-globin genes

Neurally mediated airway constriction in human and other species: a comparative study using precision-cut lung slices (PCLS.

Directory of Open Access Journals (Sweden)

Marco Schlepütz

Full Text Available The peripheral airway innervation of the lower respiratory tract of mammals is not completely functionally characterized. Recently, we have shown in rats that precision-cut lung slices (PCLS respond to electric field stimulation (EFS and provide a useful model to study neural airway responses in distal airways. Since airway responses are known to exhibit considerable species differences, here we examined the neural responses of PCLS prepared from mice, rats, guinea pigs, sheep, marmosets and humans. Peripheral neurons were activated either by EFS or by capsaicin. Bronchoconstriction in response to identical EFS conditions varied between species in magnitude. Frequency response curves did reveal further species-dependent differences of nerve activation in PCLS. Atropine antagonized the EFS-induced bronchoconstriction in human, guinea pig, sheep, rat and marmoset PCLS, showing cholinergic responses. Capsaicin (10 µM caused bronchoconstriction in human (4 from 7 and guinea pig lungs only, indicating excitatory non-adrenergic non-cholinergic responses (eNANC. However, this effect was notably smaller in human responder (30 ± 7.1% than in guinea pig (79 ± 5.1% PCLS. The transient receptor potential (TRP channel blockers SKF96365 and ruthenium red antagonized airway contractions after exposure to EFS or capsaicin in guinea pigs. In conclusion, the different species show distinct patterns of nerve-mediated bronchoconstriction. In the most common experimental animals, i.e. in mice and rats, these responses differ considerably from those in humans. On the other hand, guinea pig and marmoset monkey mimic human responses well and may thus serve as clinically relevant models to study neural airway responses.

CisSERS: Customizable In Silico Sequence Evaluation for Restriction Sites.

Science.gov (United States)

Sharpe, Richard M; Koepke, Tyson; Harper, Artemus; Grimes, John; Galli, Marco; Satoh-Cruz, Mio; Kalyanaraman, Ananth; Evans, Katherine; Kramer, David; Dhingra, Amit

2016-01-01

High-throughput sequencing continues to produce an immense volume of information that is processed and assembled into mature sequence data. Data analysis tools are urgently needed that leverage the embedded DNA sequence polymorphisms and consequent changes to restriction sites or sequence motifs in a high-throughput manner to enable biological experimentation. CisSERS was developed as a standalone open source tool to analyze sequence datasets and provide biologists with individual or comparative genome organization information in terms of presence and frequency of patterns or motifs such as restriction enzymes. Predicted agarose gel visualization of the custom analyses results was also integrated to enhance the usefulness of the software. CisSERS offers several novel functionalities, such as handling of large and multiple datasets in parallel, multiple restriction enzyme site detection and custom motif detection features, which are seamlessly integrated with real time agarose gel visualization. Using a simple fasta-formatted file as input, CisSERS utilizes the REBASE enzyme database. Results from CisSERS enable the user to make decisions for designing genotyping by sequencing experiments, reduced representation sequencing, 3'UTR sequencing, and cleaved amplified polymorphic sequence (CAPS) molecular markers for large sample sets. CisSERS is a java based graphical user interface built around a perl backbone. Several of the applications of CisSERS including CAPS molecular marker development were successfully validated using wet-lab experimentation. Here, we present the tool CisSERS and results from in-silico and corresponding wet-lab analyses demonstrating that CisSERS is a technology platform solution that facilitates efficient data utilization in genomics and genetics studies.

Monoclonal antibodies to DNA modified with cis- or trans-diamminedichloroplatinum(II)

International Nuclear Information System (INIS)

Sundquist, W.I.; Lippard, S.J.; Stollar, B.D.

1987-01-01

Murine monoclonal antibodies that bind selectively to adducts formed on DNA by the antitumor drug cis-diamminedichloroplatinum(II), cis-DDP, or to the chemothrapeutically inactive trans isomer trans-DDP were elicited by immunization with calf thymus DNA modified with either cis- or trans-DDP at ratios of bound platinum per nucleotide, (D/N)/sub b/, of 0.06-0.08. The binding of two monoclonal antibodies to cis-DDP-modified DNA was competitively inhibited in an enzyme-linked immunosorbent assay (ELISA) by 4-6 nM concentrations of cis-DDP bound to DNA. Adducts formed by cis-DDP on other synthetic DNA polymers did not inhibit antibody binding to cis-DDP-DNA. The biologically active compounds [Pt(en)Cl 2 ], [Pt(dach)Cl 2 ], and [Pt(NH 3 ) 2 (cbdca)] (carboplatin) all formed antibody-detectable adducts on DNA, whereas the inactive platinum complexes trans-DDP and [Pt(dien)Cl]Cl (dien, diethylenetriamine) did not. The monoclonal antibodies therefore recognize a bifunctional Pt-DNA adduct with cis stereochemistry in which platinum is coordinated by two adjacent guanines or, to a lesser degree, by adjacent adenine and guanine. A monoclonal antibody raised against trans-DDP-DNA was competitively inhibited in an ELISA by 40 nM trans-DDP bound to DNA. This antibody crossreacted with unmodified, denatured DNA. The recognition of cis- or trans-DDP-modified DNAs by monoclonal antibodies thus parallels the known modes of DNA binding of these compounds and may correlate with their biological activities

Stepwise encapsulation and controlled two-stage release system for cis-Diamminediiodoplatinum

Directory of Open Access Journals (Sweden)

Chen Y

2014-06-01

Full Text Available Yun Chen,1,* Qian Li,1,2,* Qingsheng Wu1 1Department of Chemistry, Key Laboratory of Yangtze River Water Environment, Ministry of Education, Tongji University, Shanghai; 2Shanghai Institute of Quality Inspection and Technical Research, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: cis-Diamminediiodoplatinum (cis-DIDP is a cisplatin-like anticancer drug with higher anticancer activity, but lower stability and price than cisplatin. In this study, a cis-DIDP carrier system based on micro-sized stearic acid was prepared by an emulsion solvent evaporation method. The maximum drug loading capacity of cis-DIDP-loaded solid lipid nanoparticles was 22.03%, and their encapsulation efficiency was 97.24%. In vitro drug release in phosphate-buffered saline (pH =7.4 at 37.5°C exhibited a unique two-stage process, which could prove beneficial for patients with tumors and malignancies. MTT (3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide assay results showed that cis-DIDP released from cis-DIDP-loaded solid lipid nanoparticles had better inhibition activity than cis-DIDP that had not been loaded. Keywords: stearic acid, emulsion solvent evaporation method, drug delivery, cis-DIDP, in vitro

Connections between Transcription Downstream of Genes and cis-SAGe Chimeric RNA.

Science.gov (United States)

Chwalenia, Katarzyna; Qin, Fujun; Singh, Sandeep; Tangtrongstittikul, Panjapon; Li, Hui

2017-11-22

cis-Splicing between adjacent genes (cis-SAGe) is being recognized as one way to produce chimeric fusion RNAs. However, its detail mechanism is not clear. Recent study revealed induction of transcriptions downstream of genes (DoGs) under osmotic stress. Here, we investigated the influence of osmotic stress on cis-SAGe chimeric RNAs and their connection to DoGs. We found,the absence of induction of at least some cis-SAGe fusions and/or their corresponding DoGs at early time point(s). In fact, these DoGs and their cis-SAGe fusions are inversely correlated. This negative correlation was changed to positive at a later time point. These results suggest a direct competition between the two categories of transcripts when total pool of readthrough transcripts is limited at an early time point. At a later time point, DoGs and corresponding cis-SAGe fusions are both induced, indicating that total readthrough transcripts become more abundant. Finally, we observed overall enhancement of cis-SAGe chimeric RNAs in KCl-treated samples by RNA-Seq analysis.

Enantioselective disruption of the endocrine system by Cis-Bifenthrin in the male mice.

Science.gov (United States)

Jin, Yuanxiang; Wang, Jiangcong; Pan, Xiuhong; Miao, Wenyu; Lin, Xiaojian; Wang, Linggang; Fu, Zhengwei

2015-07-01

Bifenthrin (BF), as a chiral pyrethroid, is widely used to control field and household pests in China. At present, the commercial BF is a mixed compound containing cis isomers (cis-BF) including two enantiomers of 1R-cis-BF and 1S-cis-BF. In the present study, the two individual cis-BF enantiomers were separated by a preparative supercritical fluid chromatography. Then, four week-old adolescent male ICR mice were orally administered 1R-cis-BF and 1S-cis-BF separately daily for 3 weeks at doses of 0, 7.5 and 15 mg/kg/day, respectively. Results showed that the transcription status of some genes involved in cholesterol synthesis and transport as well as testosterone (T) synthesis in the testes were influenced by cis-BF enantiomers. Especially, we observed that the transcription status of key genes on the pathway of T synthesis including cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc) and cytochrome P450 17α-hydroxysteroid dehydrogenase (P45017α)) were selectively altered in the testis of mice when treated with 1S-cis-BF, suggesting that it is the possible reason to explain why the lower serum T concentration in 1S-cis-BF treated group. Taken together, it concluded that both of the cis-BF enantiomers have the endocrine disruption activities, while 1S-cis-BF was higher than 1R-cis-BF in mice when exposed during the puberty. The data was helpful to understand the toxicity of cis-BF in mammals under enantiomeric level. © 2014 Wiley Periodicals, Inc.

CisSERS: Customizable In Silico Sequence Evaluation for Restriction Sites.

Directory of Open Access Journals (Sweden)

Richard M Sharpe

Full Text Available High-throughput sequencing continues to produce an immense volume of information that is processed and assembled into mature sequence data. Data analysis tools are urgently needed that leverage the embedded DNA sequence polymorphisms and consequent changes to restriction sites or sequence motifs in a high-throughput manner to enable biological experimentation. CisSERS was developed as a standalone open source tool to analyze sequence datasets and provide biologists with individual or comparative genome organization information in terms of presence and frequency of patterns or motifs such as restriction enzymes. Predicted agarose gel visualization of the custom analyses results was also integrated to enhance the usefulness of the software. CisSERS offers several novel functionalities, such as handling of large and multiple datasets in parallel, multiple restriction enzyme site detection and custom motif detection features, which are seamlessly integrated with real time agarose gel visualization. Using a simple fasta-formatted file as input, CisSERS utilizes the REBASE enzyme database. Results from CisSERS enable the user to make decisions for designing genotyping by sequencing experiments, reduced representation sequencing, 3'UTR sequencing, and cleaved amplified polymorphic sequence (CAPS molecular markers for large sample sets. CisSERS is a java based graphical user interface built around a perl backbone. Several of the applications of CisSERS including CAPS molecular marker development were successfully validated using wet-lab experimentation. Here, we present the tool CisSERS and results from in-silico and corresponding wet-lab analyses demonstrating that CisSERS is a technology platform solution that facilitates efficient data utilization in genomics and genetics studies.

Combinatorial Cis-regulation in Saccharomyces Species

Directory of Open Access Journals (Sweden)

Aaron T. Spivak

2016-03-01

Full Text Available Transcriptional control of gene expression requires interactions between the cis-regulatory elements (CREs controlling gene promoters. We developed a sensitive computational method to identify CRE combinations with conserved spacing that does not require genome alignments. When applied to seven sensu stricto and sensu lato Saccharomyces species, 80% of the predicted interactions displayed some evidence of combinatorial transcriptional behavior in several existing datasets including: (1 chromatin immunoprecipitation data for colocalization of transcription factors, (2 gene expression data for coexpression of predicted regulatory targets, and (3 gene ontology databases for common pathway membership of predicted regulatory targets. We tested several predicted CRE interactions with chromatin immunoprecipitation experiments in a wild-type strain and strains in which a predicted cofactor was deleted. Our experiments confirmed that transcription factor (TF occupancy at the promoters of the CRE combination target genes depends on the predicted cofactor while occupancy of other promoters is independent of the predicted cofactor. Our method has the additional advantage of identifying regulatory differences between species. By analyzing the S. cerevisiae and S. bayanus genomes, we identified differences in combinatorial cis-regulation between the species and showed that the predicted changes in gene regulation explain several of the species-specific differences seen in gene expression datasets. In some instances, the same CRE combinations appear to regulate genes involved in distinct biological processes in the two different species. The results of this research demonstrate that (1 combinatorial cis-regulation can be inferred by multi-genome analysis and (2 combinatorial cis-regulation can explain differences in gene expression between species.

Radiobiological inactivation of Epstein-Barr virus

International Nuclear Information System (INIS)

Henderson, E.; Heston, L.; Grogan, E.; Miller, G.

1978-01-01

Lymphocyte transforming properties of B95-8 strain Epstein-Barr virus (EBV) are very sensitive to inactivation by either uv or x irradiation. No dose of irradiation increases the transforming capacity of EBV. The x-ray dose needed for inactivation of EBV transformation (dose that results in 37% survival, 60,000 rads) is similar to the dose required for inactivation of plaque formation by herpes simplex virus type 1 (Fischer strain). Although herpes simplex virus is more sensitive than EBV to uv irradiation, this difference is most likely due to differences in the kinetics or mechanisms of repair of uv damage to the two viruses. The results lead to the hypothesis that a large part, or perhaps all, of the EBV genome is in some way needed to initiate transformation. The abilities of EBV to stimulate host cell DNA synthesis, to induce nuclear antigen, and to immortalize are inactivated in parallel. All clones of marmoset cells transformed by irradiated virus produce extracellular transforming virus. These findings suggest that the abilities of the virus to transform and to replicate complete progeny are inactivated together. The amounts of uv and x irradiation that inactivate transformation by B95-8 virus are less than the dose needed to inactivate early antigen induction by the nontransforming P 3 HR-1 strain of EBV. Based on radiobiological inactivation, 10 to 50% of the genome is needed for early antigen induction

Small RNAs and the regulation of cis-natural antisense transcripts in Arabidopsis

Directory of Open Access Journals (Sweden)

Lonardi Stefano

2008-01-01

Full Text Available Abstract Background In spite of large intergenic spaces in plant and animal genomes, 7% to 30% of genes in the genomes encode overlapping cis-natural antisense transcripts (cis-NATs. The widespread occurrence of cis-NATs suggests an evolutionary advantage for this type of genomic arrangement. Experimental evidence for the regulation of two cis-NAT gene pairs by natural antisense transcripts-generated small interfering RNAs (nat-siRNAs via the RNA interference (RNAi pathway has been reported in Arabidopsis. However, the extent of siRNA-mediated regulation of cis-NAT genes is still unclear in any genome. Results The hallmarks of RNAi regulation of NATs are 1 inverse regulation of two genes in a cis-NAT pair by environmental and developmental cues and 2 generation of siRNAs by cis-NAT genes. We examined Arabidopsis transcript profiling data from public microarray databases to identify cis-NAT pairs whose sense and antisense transcripts show opposite expression changes. A subset of the cis-NAT genes displayed negatively correlated expression profiles as well as inverse differential expression changes under at least one of the examined developmental stages or treatment conditions. By searching the Arabidopsis Small RNA Project (ASRP and Massively Parallel Signature Sequencing (MPSS small RNA databases as well as our stress-treated small RNA dataset, we found small RNAs that matched at least one gene in 646 pairs out of 1008 (64% protein-coding cis-NAT pairs, which suggests that siRNAs may regulate the expression of many cis-NAT genes. 209 putative siRNAs have the potential to target more than one gene and half of these small RNAs could target multiple members of a gene family. Furthermore, the majority of the putative siRNAs within the overlapping regions tend to target only one transcript of a given NAT pair, which is consistent with our previous finding on salt- and bacteria-induced nat-siRNAs. In addition, we found that genes encoding plastid- or

Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid (CLA) isomers on immune function in healthy men

NARCIS (Netherlands)

Albers, R.; Wielen, R.P.J. van der; Brink, E.J.; Hendriks, H.F.J.; Dorovska-Taran, V.N.; Mohede, I.C.M.

2003-01-01

Objectives: To study the effects of two different mixtures of the main conjugated linoleic acid (CLA) isomers cis-9, trans-11 CLA and trans-10, cis-12 CLA on human immune function. Design: Double-blind, randomized, parallel, reference-controlled intervention study. Subjects and intervention:

Reconceptualizing synergism and antagonism among multiple stressors

OpenAIRE

Piggott, Jeremy J; Townsend, Colin R; Matthaei, Christoph D

2015-01-01

The potential for complex synergistic or antagonistic interactions between multiple stressors presents one of the largest uncertainties when predicting ecological change but, despite common use of the terms in the scientific literature, a consensus on their operational definition is still lacking. The identification of synergism or antagonism is generally straightforward when stressors operate in the same direction, but if individual stressor effects oppose each other, the definition of syner...

Reversible brain inactivation induces discontinuous gas exchange in cockroaches.

Science.gov (United States)

Matthews, Philip G D; White, Craig R

2013-06-01

Many insects at rest breathe discontinuously, alternating between brief bouts of gas exchange and extended periods of breath-holding. The association between discontinuous gas exchange cycles (DGCs) and inactivity has long been recognised, leading to speculation that DGCs lie at one end of a continuum of gas exchange patterns, from continuous to discontinuous, linked to metabolic rate (MR). However, the neural hypothesis posits that it is the downregulation of brain activity and a change in the neural control of gas exchange, rather than low MR per se, which is responsible for the emergence of DGCs during inactivity. To test this, Nauphoeta cinerea cockroaches had their brains inactivated by applying a Peltier-chilled cold probe to the head. Once brain temperature fell to 8°C, cockroaches switched from a continuous to a discontinuous breathing pattern. Re-warming the brain abolished the DGC and re-established a continuous breathing pattern. Chilling the brain did not significantly reduce the cockroaches' MR and there was no association between the gas exchange pattern displayed by the insect and its MR. This demonstrates that DGCs can arise due to a decrease in brain activity and a change in the underlying regulation of gas exchange, and are not necessarily a simple consequence of low respiratory demand.

Effects of pyrethroid pesticide cis-bifenthrin on lipogenesis in hepatic cell line.

Science.gov (United States)

Xiang, Dandan; Chu, Tianyi; Li, Meng; Wang, Qiangwei; Zhu, Guonian

2018-06-01

Mounting evidence suggests there is a link between exposure to synthetic pyrethroids (SPs) and the development of obesity. The information presented in this study suggests that cis-bifenthrin (cis-BF) could activate pregnane X receptor (PXR) mediated pathway and lead to the lipid accumulation of human hepatoma (HepG2) cells. Cells were incubated in the control or different concentrations of cis-BF for 24 h. The 1 × 10 -7  M and 1 × 10 -6  M cis-BF exposure were found to induce cellular triglyceride (TG) accumulation significantly. This phenomenon was further supported by Oil Red O Staining assay. The cis-BF exposure caused upregulation of PXR gene and protein. Correspondingly, we also observed the increased expression of downstream genes involved in lipid formation and the inhibition of the expression of β-oxidation. As chiral pesticide，cis-BF was further conformed to behave enantioselectivity in the lipid metabolism. Rather than 1R-cis-BF, HepG2 cells incubated with 1S-cis-BF exhibited a significant TG accumulation. 1S-cis-BF also showed a higher binding level, of which the KD value was 9.184 × 10 -8  M in the SPR assay, compared with 1R-cis-BF (3.463 × 10 -6  M). In addition, the molecular docking simulation analyses correlated well with the KD values measured by the SPR, indicating that 1S-cis-BF showed a better binding affinity with PXR. The results in this study also elucidates the differences between the two enantiomers of pyrethroid-induced toxicity in lipid metabolism of non-target organism. Copyright © 2018 Elsevier Ltd. All rights reserved.

Antagonism in the carbon footprint between beef and dairy ...

African Journals Online (AJOL)

The higher increase in production (milk) of intensive dairy cows, compared to the increase in production (calf weight) of intensive beef cows, explains the antagonism in the carbon footprint between different beef and dairy production systems. Unfortunately, carbon sequestration estimates have been neglected and thus the ...

U.S./CIS eye joint nuclear rocket venture

Science.gov (United States)

Clark, John S.; Mcilwain, Melvin C.; Smetanikov, Vladimir; D'Yakov, Evgenij K.; Pavshuk, Vladimir A.

1993-01-01

An account is given of the significance for U.S. spacecraft development of a nuclear thermal rocket (NTR) reactor concept that has been developed in the (formerly Soviet) Commonwealth of Independent States (CIS). The CIS NTR reactor employs a hydrogen-cooled zirconium hydride moderator and ternary carbide fuels; the comparatively cool operating temperatures associated with this design promise overall robustness.

Chlorine inactivation of Tubifex tubifex in drinking water and the synergistic effect of sequential inactivation with UV irradiation and chlorine.

Science.gov (United States)

Nie, Xiao-Bao; Li, Zhi-Hong; Long, Yuan-Nan; He, Pan-Pan; Xu, Chao

2017-06-01

The inactivation of Tubifex tubifex is important to prevent contamination of drinking water. Chlorine is a widely-used disinfectant and the key factor in the inactivation of T. tubifex. This study investigated the inactivation kinetics of chlorine on T. tubifex and the synergistic effect of the sequential use of chlorine and UV irradiation. The experimental results indicated that the Ct (concentration × time reaction ) concept could be used to evaluate the inactivation kinetics of T. tubifex with chlorine, thus allowing for the use of a simpler Ct approach for the assessment of T. tubifex chlorine inactivation requirements. The inactivation kinetics of T. tubifex by chlorine was found to be well-fitted to a delayed pseudo first-order Chick-Watson expression. Sequential experiments revealed that UV irradiation and chlorine worked synergistically to effectively inactivate T. tubifex as a result of the decreased activation energy, E a , induced by primary UV irradiation. Furthermore, the inactivation effectiveness of T. tubifex by chlorine was found to be affected by several drinking water quality parameters including pH, turbidity, and chemical oxygen demand with potassium permanganate (COD Mn ) concentration. High pH exhibited pronounced inactivation effectiveness and the decrease in turbidity and COD Mn concentrations contributed to the inactivation of T. tubifex. Copyright © 2017 Elsevier Ltd. All rights reserved.

The H3K27 Demethylase JMJD3 Is Required for Maintenance of the Embryonic Respiratory Neuronal Network, Neonatal Breathing, and Survival

Directory of Open Access Journals (Sweden)

Thomas Burgold

2012-11-01

Full Text Available JMJD3 (KDM6B antagonizes Polycomb silencing by demethylating lysine 27 on histone H3. The interplay of methyltransferases and demethylases at this residue is thought to underlie critical cell fate transitions, and the dynamics of H3K27me3 during neurogenesis posited for JMJD3 a critical role in the acquisition of neural fate. Despite evidence of its involvement in early neural commitment, however, its role in the emergence and maturation of the mammalian CNS remains unknown. Here, we inactivated Jmjd3 in the mouse and found that its loss causes perinatal lethality with the complete and selective disruption of the pre-Bötzinger complex (PBC, the pacemaker of the respiratory rhythm generator. Through genetic and electrophysiological approaches, we show that the enzymatic activity of JMJD3 is selectively required for the maintenance of the PBC and controls critical regulators of PBC activity, uncovering an unanticipated role of this enzyme in the late structuring and function of neuronal networks.

Cis By Trans

OpenAIRE

Rodovalho,Amara Moira

2017-01-01

Cis, trans: above all, metaphors. Cisjordan, region skirting the Jordan River. Cisplatin, Uruguay’s ancient name, region occupying one of the banks of the Prata River. Trans- Amazonian, that which crosses the Amazon; transatlantic, that which crosses the Atlantic. Cisalpine, transalpine. The geometric isomerism of Organic Chemistry, where “cis” are atoms that, when molecules are divided in half, remain on the same side, and “trans” those remaining on opposite sides. Ev...

Arctigenin antagonizes mineralocorticoid receptor to inhibit the transcription of Na/K-ATPase.

Science.gov (United States)

Cheng, Ye; Zhou, Meili; Wang, Yan

2016-01-01

Hypertension is one of the most important risk factors in cardiovascular disease and is the most common chronic disease. Mineralocorticoid receptor (MR) antagonists have been successfully used in clinic for the treatment of hypertension. Our study aims to investigate whether Arctigenin can antagonize MR and inhibit the transcription of Na/K-ATPase. The yeast two-hybrid assay was used to screen natural products and Arctigenin was identified as an MR antagonist. The direct binding of Arctigenin to MR was determined using assays based on surface plasmon resonance, differential scanning calorimetry and fluorescence quenching. Furthermore, results from mammalian one-hybrid and transcriptional activation experiments also confirmed that Arctigenin can potently antagonize MR in cells. We demonstrated that Arctigenin can decrease the level of Na/K-ATPase mRNA by antagonizing MR in HK-2 cells. Our findings show that Arctigenin can effectively decrease Na/K-ATPase transcription; thus highlight its potential as an anti-hypertensive drug lead compound. Our current findings demonstrate that Arctigenin is an antagonist of MR and effectively decreases the Na/K-ATPase 1 gene expression. Our work provides a hint for the drug discovery against cardiovascular disease.

Communications and Information Sharing (CIS) Laboratory

Data.gov (United States)

Federal Laboratory Consortium — TheCommunications and Information Sharing (CIS) Laboratory is a Public Safety interoperable communications technology laboratory with analog and digital radios, and...

EIA for mining projects in the CIS

Energy Technology Data Exchange (ETDEWEB)

Coppin, N.J.; Wheeler, P. [Wardell Armstrong, Newcastle under Lyme (United Kingdom)

1996-12-31

This paper examines the Environmental Impact Assessment (EIA) requirements and procedures encountered during work on gold and coal mining projects in Kazakhstan, Uzbekistan and Mongolia. Observations on the implementation of former-Soviet inspired EIA in the Commonwealth of Independent States (CIS), and the differences with North American and European requirements and procedures are highlighted, particularly where these indicate lessons for the West. The main implications for mining companies considering or developing projects in the CIS are discussed, particularly the procedures that have to be followed for environmental permitting. 2 figs.

The meninges contribute to the conditioned taste avoidance induced by neural cooling in male rats.

Science.gov (United States)

Wang, Yuan; Chambers, Kathleen C

2002-08-21

After consumption of a novel sucrose solution, temporary cooling of neural areas that mediate conditioned taste avoidance can itself induce conditioned avoidance to the sucrose. It has been suggested that this effect is either a result of inactivation of neurons in these areas or of cooling the meninges. In a series of studies, we demonstrated that cooling the outer layer of the meninges, the dura mater, does not contribute to the conditioned taste avoidance induced by cooling any of these areas. The present experiments were designed to determine whether the inner layers of the meninges are involved. If they are involved, then one would expect that cooling locations in the brain that do not mediate conditioned taste avoidance, such as the caudate putamen (CP), would induce conditioned taste avoidance as long as the meninges were cooled as well. One also would expect that cooling neural tissue without cooling the meninges would reduce the strength of the conditioned taste avoidance. Experiment 1 established that the temperature of the neural tissue and meninges around the cold probes implanted in the CP were cooled to temperatures that have been shown to block synaptic transmission. Experiment 2 demonstrated that cooling the caudate putamen and overlying cortex and meninges induced conditioned taste avoidance. In experiment 3, a circle of meninges was cut away so that the caudate putamen and overlying cortex could be cooled without cooling the meninges. The strength of the conditioned taste avoidance was substantially reduced, but it was not entirely eliminated. These data support the hypothesis that cooling the meninges contributes to the conditioned taste avoidance induced by neural cooling. They also allow the possibility that neural inactivation produces physiological changes that can induce conditioned taste avoidance. Copyright 2002 Elsevier Science B.V.

Rhubarb Antagonizes Matrix Metalloproteinase-9-induced Vascular Endothelial Permeability

Directory of Open Access Journals (Sweden)

Yun-Liang Cui

2016-01-01

Conclusions: The rhubarb mixture of emodin, 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid, 1-O-caffeoyl-2-(4-hydroxyl-O-cinnamoyl-β-D-glucose, daucosterol linoleate, and rhein, at a low concentration, antagonized the MMP9-induced HUVEC monolayer permeability by promoting HUVEC proliferation and reducing extracellular VE-cadherin concentrations.

Differential effects of early-life NMDA receptor antagonism on aspartame-impaired insulin tolerance and behavior.

Science.gov (United States)

Collison, Kate S; Inglis, Angela; Shibin, Sherin; Andres, Bernard; Ubungen, Rosario; Thiam, Jennifer; Mata, Princess; Al-Mohanna, Futwan A

2016-12-01

We have previously showed that lifetime exposure to aspartame, commencing in utero via the mother's diet, may impair insulin tolerance and cause behavioral deficits in adulthood via mechanisms which are incompletely understood. The role of the CNS in regulating glucose homeostasis has been highlighted by recent delineation of the gut-brain axis, in which N-methyl-d-aspartic acid receptors (NMDARs) are important in maintaining glucose homeostasis, in addition to regulating certain aspects of behavior. Since the gut-brain axis can be modulated by fetal programming, we hypothesized that early-life NMDAR antagonism may affect aspartame-induced glucose deregulation in adulthood, and may alter the aspartame behavioral phenotype. Accordingly, C57Bl/6J mice were chronically exposed to aspartame commencing in utero, in the presence and absence of maternal administration of the competitive NMDAR antagonist CGP 39551, from conception until weaning. Drug/diet interactions in adulthood glucocentric and behavioral parameters were assessed. Aspartame exposure elevated blood glucose and impaired insulin-induced glucose disposal during an insulin tolerance test, which could be normalized by NMDAR antagonism. The same effects were not observed in control diet mice, suggesting an early-life drug/diet interaction. Behavioral analysis of adult offspring indicated that NMDAR antagonism of control diet mice caused hyperlocomotion and impaired spatial navigation. Conversely hypolocomotion, reduced exploratory activity and increased anxiety-related behavior were apparent in aspartame diet mice with early-life NMDAR antagonism. significant drug/diet interactions in glucocentric and behavioral parameters were identified in aspartame-exposed mice with early-life NMDAR antagonism. This suggests a possible involvement of early NMDAR interactions in aspartame-impaired glucose homeostasis and behavioral deficits. Copyright © 2016 Elsevier Inc. All rights reserved.

Mechanically induced cis to trans reisomerization of azobenzene

Science.gov (United States)

Turansky, Robert; Konopka, Martin; Stich, Ivan; Marx, Dominik

2007-03-01

Using density functional techniques we study mechanochemistry of the azobenzene molecule. Azobenzene is an optically switchable molecule. Laser light is normally used to achieve molecular switching between the cis and trans isomers. We use mechanochemistry to achieve the switching. Thiolate-gold bond can used to exert mechanical energy on the molecule bonded between two gold electrodes in static AFM apparatus. Our model consists of two realistic gold electrodes bridged by dithioazobenzene. We find that pulling the transisomer leads just to formation of gold nanowires and mechanical breakage of the electrodes. However, mechanochemistry with modest applied forces leads to cis trans reisomerization via rotation mechanism. Contrary, use of simple constraints instead of realistic gold electrodes, leads to cis trans reisomerization, albeit with significantly larger applied forces and via inversion mechanism. Important experimental and theoretical ramifications of these simulations will be discussed.

The effect of cis-diammine dichloro platinum(II) on radiation injury in the rat bowel

International Nuclear Information System (INIS)

Lee, Kyung Ja; Rhee, Chung Sik

1995-01-01

This experimental study was performed for evaluate the effects of cis-diamminedichloroplatinum(II) (cis-DDP) on the radiation injury of rat bowel by histopathologic changes. Rats were exposed to entire abdomen by a single doses of X-ray(6-10 Gy) without or with cis-DDP(2.5mg/kg). Rats were divided into 3 groups such as radiation alone, cis-DDP alone and combined group. In combined group, cis-DDP was given 30 minutes before or immediately after irradiation. Cis-DDP induced the inflammatory cell infiltrations with focal necrosis of the mucosa in the small bowel and no abnormal change in the large bowel. In radiation alone group, mucosal necrosis, submucosal fibrosis and muscular necrosis were prominent changes in small bowel and submucosal fibrosis in the large bowel. The submucosal fibrosis in the small bowel was appeared in 10 Gy of radiation alone group and 8 Gy of cis-DDP infusion after radiation and 6 Gy of cis-DDP infusion before radiation of combined group. In the large bowel, submucosal fibrosis was noted in 8 Gy of radiation alone group 8 Gy of cis-DDP infusion after radiation and 6 Gy of cis-DDP infusion before radiation of combined group. In the small bowel, the enhancement ratio was 1.67 in a group of cis-DDP infusion before radiation and 1.25 in group of cis-DDP infusion after radiation as the end point was the submucosal fibrosis. In the large bowel, the enhancement ratio was 1.33 in a group of cis-DDP infusion before radiation and 1.0 in a group of cis-DDP infusion after radiation as the end point was the submucosal fibrosis. This study suggested that cis-DDP enhance the radiation effect in the small and large bowel especially when cis-DDP was infused before radiation

Oxidation reactions of derivatives of cis-octalins promoted by thallium trinitrate (TTN); Reacoes de oxidacao de cis-octalinas promovidas por trinitrato de talio (TTN)

Energy Technology Data Exchange (ETDEWEB)

Ferraz, Helena M.C.; Carneiro, Vania M.T.; Vieira, Tiago O.; Silva Junior, Luiz F. [Universidade de Sao Paulo (USP), SP (Brazil). Inst. de Quimica]. E-mail: luizfsjr@iq.usp.br

2008-07-01

The reaction of ten cis-octalins and cis-octalones with thallium trinitrate (TTN) leads to different products, depending mainly on the substitution pattern of the substrate. Functionalized cis-hydrindanes were obtained from the reaction of 1,2,3,4,4a,5,8,8a-octahydro- 4a-methylnaphthalene and of 1,2,3,4,4a,5,8,8a-octahydro-4a,7-dimethylnaphthalene with TTN in acetonitrile, whereas a cyclic ether was formed treating 1,2,3,4,4a,5,8,8a-octahydro-6,8a-dimethylnaphthalene-1-ol with TTN in trimethylorthoformate (TMOF). (author)

Interleukin-1 Antagonism Decreases Cortisol Levels in Obese Individuals.

Science.gov (United States)

Urwyler, Sandrine Andrea; Schuetz, Philipp; Ebrahimi, Fahim; Donath, Marc Y; Christ-Crain, Mirjam

2017-05-01

Increased cortisol levels in obesity may contribute to the associated metabolic syndrome. In obesity, the activated innate immune system leads to increased interleukin (IL)-1β, which is known to stimulate the release of adrenocorticotropin hormone (ACTH). We hypothesized that in obesity IL-1 antagonism would result in downregulation of the hypothalamo-pituitary-adrenal axis, leading to decreased cortisol levels. In this prospective intervention study, we included 73 patients with obesity (body mass index [BMI] ≥30 kg/m2) and at least one additional feature of the metabolic syndrome. The primary end point was change in morning cortisol from baseline to after the administration of the IL-1 receptor antagonist (anakinra/Kineret®, total dose 3 × 100 mg). Secondary end points were effects on salivary cortisol and ACTH. Median age was 56 years, 50.7% of patients were female, and median BMI was 36.3 kg/m2. Median morning serum cortisol levels (nmol/L) decreased significantly after IL-1 antagonism [from baseline, 452 to 423; absolute difference, -38.7; 95% confidence interval (CI), -64 to -13.4; P = 0.0019]. Similar effects were found for salivary cortisol levels (-2.8; 95% CI, -4.4 to -1.3; P = 0.0007), ACTH levels (-2.2; 95% CI; -4.2 to -0.1; P = 0.038), systolic blood pressure (-5.2, 95% CI, -8.5 to -1.8; P = 0.0006), and heart rate (-2.9; 95% CI, -4.7 to -1.0; P = 0.0029). IL-1 antagonism in obese individuals with features of the metabolic syndrome leads to a decrease in serum cortisol, salivary cortisol, and ACTH levels along with a reduction in systolic blood pressure and heart rate. Copyright © 2017 Endocrine Society

Cis-bifenthrin induces immunotoxicity in adolescent male C57BL/6 mice.

Science.gov (United States)

Wang, Xia; Gao, Xingli; He, Bingnan; Zhu, Jiawei; Lou, Huihui; Hu, Qinglian; Jin, Yuanxiang; Fu, Zhengwei

2017-07-01

Bifenthrin (BF) is an important synthetic pyrethroid. Previous studies have demonstrated that cis-BF exhibits toxic effects on development, the neurological, reproductive and endocrine system. In this study, we evaluated the immunotoxicity caused by cis-BF in adolescent male C57BL/6 mice. Mice were exposed orally to 0, 5, 10, and 20 mg/kg/d for 3 weeks. The results showed that body weight, spleen weight, and splenic cellularity decreased in mice exposed to 20 mg/kg/d cis-BF. Additionally, we found that the mRNA levels of the pro-inflammatory factors IL-1β, IL-6, CXCL-1, and TNF-α, in peritoneal macrophages, the spleen, and the thymus were inhibited in the cis-BF-treated groups. Moreover, MTT assays demonstrated that cis-BF inhibited splenocyte proliferation stimulated by LPS or Con A, as well as the secretion of IFN-γ on Con A stimulation. Collectively, the results of this study suggest that exposure to cis-BF has the potential to induce immunotoxicity in adolescent male C57BL/6 mice. © 2017 Wiley Periodicals, Inc.

Biosynthesis of (+)-cis- and (+)-trans-sabinene hydrate from geranyl pyrophosphate by a soluble enzyme system from sweet marjoram (Majorana hortensis)

International Nuclear Information System (INIS)

Hallahan, T.W.

1988-01-01

A soluble enzyme preparation from the leaves of sweet marjoram (Majorana hortensis Moench) catalyzes the divalent cation-dependent cyclization of [1- 3 H]geranyl pyrophosphate to the bicyclic monoterpene alcohols (+)-cis- and (+)-trans-[6 3 H]sabinene hydrate, providing labeling patterns consistent with current mechanistic considerations. The two enzymatic activities were inseparable by several chromatographic procedures, and differential inactivation studies suggesting that the two activities reside with the same enzyme. The enzymatic cyclization is considered to proceed by the initial ionization and isomerization of geranyl pyrophosphate to (-)-(3R)-linalyl pyrophosphate and the subsequent cyclization of this enzyme bound tertiary allylic intermediate to the monocyclic (+)-(4R)-α-terpinyl cation. A 1,2-hydride shift and a second cyclization with water capture of the resulting cation completes the reaction sequence. No free intermediates were detectable in the conversion of geranyl pyrophosphate to the sabinene hydrates as determined by isotopic dilution experiments

Sexual antagonism and meiotic drive cause stable linkage disequilibrium and favour reduced recombination on the X chromosome.

Science.gov (United States)

Rydzewski, W T; Carioscia, S A; Liévano, G; Lynch, V D; Patten, M M

2016-06-01

Sexual antagonism and meiotic drive are sex-specific evolutionary forces with the potential to shape genomic architecture. Previous theory has found that pairing two sexually antagonistic loci or combining sexual antagonism with meiotic drive at linked autosomal loci augments genetic variation, produces stable linkage disequilibrium (LD) and favours reduced recombination. However, the influence of these two forces has not been examined on the X chromosome, which is thought to be enriched for sexual antagonism and meiotic drive. We investigate the evolution of the X chromosome under both sexual antagonism and meiotic drive with two models: in one, both loci experience sexual antagonism; in the other, we pair a meiotic drive locus with a sexually antagonistic locus. We find that LD arises between the two loci in both models, even when the two loci freely recombine in females and that driving haplotypes will be enriched for male-beneficial alleles, further skewing sex ratios in these populations. We introduce a new measure of LD, Dz', which accounts for population allele frequencies and is appropriate for instances where these are sex specific. Both models demonstrate that natural selection favours modifiers that reduce the recombination rate. These results inform observed patterns of congealment found on driving X chromosomes and have implications for patterns of natural variation and the evolution of recombination rates on the X chromosome. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

Directory of Open Access Journals (Sweden)

Liliana Costa

2012-06-01

Full Text Available Photodynamic inactivation (PDI has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.

Aggression, Sibling Antagonism, and Theory-of-Mind During the First Year of Siblinghood: A Developmental Cascade Model

Science.gov (United States)

Song, Ju-Hyun; Volling, Brenda L.; Lane, Jonathan D.; Wellman, Henry M.

2016-01-01

A developmental cascade model was tested to examine longitudinal associations among firstborn children’s aggression, Theory-of-Mind, and antagonism toward their younger sibling during the first year of siblinghood. Aggression and Theory-of-Mind were assessed before the birth of a sibling, and 4 and 12 months after the birth, and antagonism was examined at 4 and 12 months in a sample of 208 firstborn children (initial M age = 30 months, 56% girls) from primarily European American, middle- class families. Firstborns’ aggression consistently predicted high sibling antagonism both directly and through poorer Theory-of-Mind. Results highlight the importance of examining longitudinal influences across behavioral, social-cognitive, and relational factors that are closely intertwined even from the early years of life. PMID:27096923

Microbial Inactivation by Ultrasound Assisted Supercritical Fluids

Science.gov (United States)

Benedito, Jose; Ortuño, Carmen; Castillo-Zamudio, Rosa Isela; Mulet, Antonio

A method combining supercritical carbon dioxide (SC-CO2) and high power ultrasound (HPU) has been developed and tested for microbial/enzyme inactivation purposes, at different process conditions for both liquid and solid matrices. In culture media, using only SC-CO2, the inactivation rate of E. coli and S. cerevisiae increased with pressure and temperature; and the total inactivation (7-8 log-cycles) was attained after 25 and 140 min of SC-CO2 (350 bar, 36 °C) treatment, respectively. Using SC-CO2+HPU, the time for the total inactivation of both microorganisms was reduced to only 1-2 min, at any condition selected. The SC-CO2+HPU inactivation of both microorganisms was slower in juices (avg. 4.9 min) than in culture media (avg. 1.5 min). In solid samples (chicken, turkey ham and dry-cured pork cured ham) treated with SC-CO2 and SC-CO2+HPU, the inactivation rate of E. coli increased with temperature. The application of HPU to the SC-CO2 treatments accelerated the inactivation rate of E. coli and that effect was more pronounced in treatments with isotonic solution surrounding the solid food samples. The application of HPU enhanced the SC-CO2 inactivation mechanisms of microorganisms, generating a vigorous agitation that facilitated the CO2 solubilization and the mass transfer process. The cavitation generated by HPU could damage the cell walls accelerating the extraction of vital constituents and the microbial death. Thus, using the combined technique, reasonable industrial processing times and mild process conditions could be used which could result into a cost reduction and lead to the minimization in the food nutritional and organoleptic changes.

Cell inactivation by heavy charged particles

Energy Technology Data Exchange (ETDEWEB)

Blakely, E A [Lawrence Berkeley Lab., CA (United States). Cell and Molecular Biology Div.

1992-06-01

The inactivation of cells resulting in lethal or aberrant effects by charged particles is of growing interest. Charged particles at extremely high LET are capable of completely eliminating cell-type and cell-line differences in repair capacity. It is still not clear however whether the repair systems are inactivated, or merely that heavy-ion lesions are less repairable. Studies correlating the particle inactivation dose of radioresistant cells with intact DNA analyzed with pulse field gel electrophoresis and other techniques may be useful, but more experiments are also needed to assess the fidelity of repair. For particle irradiations between 40-100 keV/{mu}m there is however evidence for particle-induced activation of specific genes in mammalian cells, and certain repair processes in bacteria. New data are available on the inactivation of developmental processes in several systems including seeds, and cells of the nematode C. elegans. Future experimental and theoretical modeling research emphasis should focus on exploring particle-induced inactivation of endpoints assessing functionality and not just lethality, and on analyzing molecular damage and genetic effects arising in damage but non-inactivated survivors. The discrete nature of selective types of particle damage as a function of radiation quality indicates the value of accelerated ions as probes of normal and aberrant biological processes. Information obtained from molecular analyses of damage and repair must however be integrated into the context of cellular and tissue functions of the organism. (orig.).

C.I.S. natural gas-1

International Nuclear Information System (INIS)

Carson, M.; Stram, B.

1993-01-01

This paper reports that in the countries that make up the Commonwealth of Independent States (C.I.S.), with their vast resources and a considerable existing production base, prospects are good for further growth of the region's exportable gas surplus. Investment fundamentals are stronger for gas than for any other energy resources in the area. But the pipeline infrastructure to move large amounts of gas will need extensive refurbishment to ensure export reliability and growth. Given the potential in terms of production and markets, significant amounts of outside investment in oil, natural gas, and NGL infrastructure will likely increase dramatically in these countries in the near future. These are some of the major conclusions of Enron Corp.'s recent investigations in the C.I.S. and other former Soviet republics

Stat1-Vitamin D Receptor Interactions Antagonize 1,25-Dihydroxyvitamin D Transcriptional Activity and Enhance Stat1-Mediated Transcription

Science.gov (United States)

Vidal, Marcos; Ramana, Chilakamarti V.; Dusso, Adriana S.

2002-01-01

The cytokine gamma interferon (IFN-γ) and the calcitropic steroid hormone 1,25-dihydroxyvitamin D (1,25D) are activators of macrophage immune function. In sarcoidosis, tuberculosis, and several granulomatoses, IFN-γ induces 1,25D synthesis by macrophages and inhibits 1,25D induction of 24-hydroxylase, a key enzyme in 1,25D inactivation, causing high levels of 1,25D in serum and hypercalcemia. This study delineates IFN-γ-1,25D cross talk in human monocytes-macrophages. Nuclear accumulation of Stat1 and vitamin D receptor (VDR) by IFN-γ and 1,25D promotes protein-protein interactions between Stat1 and the DNA binding domain of the VDR. This prevents VDR-retinoid X receptor (RXR) binding to the vitamin D-responsive element, thus diverting the VDR from its normal genomic target on the 24-hydroxylase promoter and antagonizing 1,25D-VDR transactivation of this gene. In contrast, 1,25D enhances IFN-γ action. Stat1-VDR interactions, by preventing Stat1 deactivation by tyrosine dephosphorylation, cooperate with IFN-γ/Stat1-induced transcription. This novel 1,25D-IFN-γ cross talk explains the pathogenesis of abnormal 1,25D homeostasis in granulomatous processes and provides new insights into 1,25D immunomodulatory properties. PMID:11909970

Genomic DISC1 Disruption in hiPSCs Alters Wnt Signaling and Neural Cell Fate

Directory of Open Access Journals (Sweden)

Priya Srikanth

2015-09-01

Full Text Available Genetic and clinical association studies have identified disrupted in schizophrenia 1 (DISC1 as a candidate risk gene for major mental illness. DISC1 is interrupted by a balanced chr(1;11 translocation in a Scottish family in which the translocation predisposes to psychiatric disorders. We investigate the consequences of DISC1 interruption in human neural cells using TALENs or CRISPR-Cas9 to target the DISC1 locus. We show that disruption of DISC1 near the site of the translocation results in decreased DISC1 protein levels because of nonsense-mediated decay of long splice variants. This results in an increased level of canonical Wnt signaling in neural progenitor cells and altered expression of fate markers such as Foxg1 and Tbr2. These gene expression changes are rescued by antagonizing Wnt signaling in a critical developmental window, supporting the hypothesis that DISC1-dependent suppression of basal Wnt signaling influences the distribution of cell types generated during cortical development.

Synthesis of racemic [methyl-d3]-labeled cis- and trans-3'-hydroxycotinine

International Nuclear Information System (INIS)

Ravard, A.; Crooks, P.A.

1994-01-01

A method is described for the synthesis of the racemic [methyl-d 3 ] forms of the nicotine metabolites cis-3'-hydroxycotinine and trans-3'-hydroxycotinine. The key intermediate was [methyl-d 3 ]-N-methylhydroxylamine, obtained from a selective hydrogenation of d 3 -nitro-methane. This intermediate was converted to [methyl-d 3 ]-α-3-pyridyl-N-methylnitrone, which was condensed with methyl acrylate to give a mixture of isomeric isoxazolidines. The hydrogenolysis of this mixture afforded a 70:30 mixture of [methyl-d 3 ] cis- and trans-3'-hydroxycotinine, from which the pure cis-isomer could be isolated by recrystallization from acetone. [Methyl-d 3 ]-trans-3'-hydroxycotinine could be prepared in high yield from the cis-isomer via chiral inversion utilizing a Mitsunobu reaction, or by chromatographic separation from a mixture of the cis- and trans-3'-benzoyloxycotinine, followed by O-debenzoylation in methanolic NaOH. (author)

Ultraviolet inactivation of papain

International Nuclear Information System (INIS)

Baugher, J.F.; Grossweiner, L.I.

1975-01-01

Flash photolysis transient spectra (lambda > 250 nm) of aqueous papain showed that the initial products are the neutral tryptophan radical Trp (lambdasub(max) 510 nm), the tryptophan triplet state 3 Trp (lambdasub(max) 460 nm), the disulfide bridge electron adduct -SS - - (lambdasub(max) 420 nm) and the hydrated electron esub(aq) - . The -SS - - yield was not altered by nitrous oxide or air, indicating that the formation of this product does not involve electrons in the external medium. The original papain preparation was activated by irradiating under nitrogen. The action spectrum supports previous work attributing the low initial activity to blocking of cysteinyl site 25 with a mixed disulfide. Flask lamp irradiation in nitrogen led to activation at low starting activities and inactivation at higher starting activities, while only inactivation at the same quantum yield was observed with air saturation. The results are consistent with photoionization of an essential tryptophyl residue as the key inactivating step. (author)

Questions on maintenance of ecological safety in space of the CIS

International Nuclear Information System (INIS)

Maharramov, A.A.

2009-01-01

Disintegration of the USSR has led to disintegration uniform economic and legal space and it has led to occurrence of some problems in ecological sphere. In given article it is shown some directions of maintenance of ecological safety, agreements on this sphere and organizational mechanisms, forms of mutual relations of the CIS countries in this sphere. At the end it is shownthe basic directions on maintenance of ecological safety in framework of CIS and elements of development of mutual relations of the CIS countries

Evaluation of the antagonism of nicotine by mecamylamine and pempidine in the brain

International Nuclear Information System (INIS)

Martin, T.J.

1989-01-01

Antagonists have been crucial in the characterization of nicotine's pharmacology. Initial evidence for the existence of central nicotinic receptors was based on the fact that nicotine produced a number of behavioral effects that were antagonized by ganglionic blockers that crossed the blood-brain barrier, such as mecamylamine and pempidine. These compounds are thought to be noncompetitive antagonists due to the fact that they do not compete for agonist binding to brain homogenate in vitro. However, pharmacological evidence in support of noncompetitive antagonism is lacking. Dose-response curves for nicotine were determined in the presence of various doses of pempidine for depression of spontaneous activity and antinociception in mice. Pempidine was found to shift the dose response curves for these effects of nicotine in a manner consistent with noncompetitive antagonism. A number of mecamylamine analogs were investigated for antagonism of these central effects of nicotine as well. These studies revealed that the N-, 2-, and 3-methyls were crucial for optimal efficacy and potency and suggests that these compounds possess a specific mechanism of action, possibly involving a receptor. Furthermore, the structure-activity relationships for the mecamylamine analogs were found to be different than that previously reported for the agonists, suggesting that they do not act at the same site. The binding of [ 3 H]-L-nicotine and [ 3 H]-pempidine was studied in vitro to mouse brain homogentate and in situ to rat brain slices. The in situ binding of [ 3 H]-L-nicotine to rat brain slices was quantitated autoradiographically to discrete brain areas in the presence and absence of 1, 10 and 100 μM nicotine and pempidine. Pempidine did not effectively displace [ 3 H]-L-nicotine binding

Thermodynamic state ensemble models of cis-regulation.

Directory of Open Access Journals (Sweden)

Marc S Sherman

Full Text Available A major goal in computational biology is to develop models that accurately predict a gene's expression from its surrounding regulatory DNA. Here we present one class of such models, thermodynamic state ensemble models. We describe the biochemical derivation of the thermodynamic framework in simple terms, and lay out the mathematical components that comprise each model. These components include (1 the possible states of a promoter, where a state is defined as a particular arrangement of transcription factors bound to a DNA promoter, (2 the binding constants that describe the affinity of the protein-protein and protein-DNA interactions that occur in each state, and (3 whether each state is capable of transcribing. Using these components, we demonstrate how to compute a cis-regulatory function that encodes the probability of a promoter being active. Our intention is to provide enough detail so that readers with little background in thermodynamics can compose their own cis-regulatory functions. To facilitate this goal, we also describe a matrix form of the model that can be easily coded in any programming language. This formalism has great flexibility, which we show by illustrating how phenomena such as competition between transcription factors and cooperativity are readily incorporated into these models. Using this framework, we also demonstrate that Michaelis-like functions, another class of cis-regulatory models, are a subset of the thermodynamic framework with specific assumptions. By recasting Michaelis-like functions as thermodynamic functions, we emphasize the relationship between these models and delineate the specific circumstances representable by each approach. Application of thermodynamic state ensemble models is likely to be an important tool in unraveling the physical basis of combinatorial cis-regulation and in generating formalisms that accurately predict gene expression from DNA sequence.

Action of cis-dichlorobis (cyclopentylamine) platinum (2) (cis-PAD) on L5178Y cells of two strains inversely cross-sensitive to X-rays and UV-light. Part 3. Differential effects of caffeine

International Nuclear Information System (INIS)

Szumiel, I.

1977-01-01

Two strains of L5178Y murine lymphoma, inversely cross-sensitive to X-rays and UV-light, were shown previously to respond to treatment with an antitumour platinum complex, cis-PAD, in a similar manner as to UV. The difference in sensitivity to cis-PAD, found in L5178Y-R and L5178Y-S cells is not caused by a difference in ability to bind platinum complex. Enhancement of chromosomal damage and potentiation of lethal effect of cis-PAD by 0.75 mM caffeine were found in cis-PAD and UV-light-resistant L5178Y-S strain but not in cis-PAD and UV-light-sensitive L5178Y-R strain. These results suggest that the extreme sensitivity of L5178Y-R strain to cis-PAD and UV-light is caused to some extent by deficiency in a caffeine-sensitive post-replication repair system. (author)

Action of cis-dichlorobis (cyclopentylamine) platinum (2) (cis-PAD) on L5178Y cells of two strains inversely cross-sensitive to X-rays and UV-light. Part 1. Cytotoxicity

International Nuclear Information System (INIS)

Szumiel, I.

1977-01-01

The response to cis-PAD, an antitumour platinum complex, was studied in two strains of murine lymphoma L5178Y cross-sensitive to X-rays and UV light. Dose-survival relationship, DNA synthesis, formation of chromatid aberrations, progression through the cell cycle, and growth and viability changes after 1 h cis-PAD treatment at 37 0 C were examined and compared with respective effects of X-rays and UV-light. In both strains studied, cis-PAD causes immediate inhibition of progression through the cell cycle, reduced rate of DNA synthesis, delayed appearance of chromatid aberrations and delayed death. However, there is a marked difference in sensitivity to cis-PAD between L5178Y-S strain (D 0 ca.5.8 μg/ml) and L5178Y-R strain (D 0 ca. 2.5μg/ml). In both strains a close resemblance was found between dose-survival relationship after cis-PAD and UV-light treatment, respectively. (author)

Barcoded DNA-tag reporters for multiplex cis-regulatory analysis.

Directory of Open Access Journals (Sweden)

Jongmin Nam

Full Text Available Cis-regulatory DNA sequences causally mediate patterns of gene expression, but efficient experimental analysis of these control systems has remained challenging. Here we develop a new version of "barcoded" DNA-tag reporters, "Nanotags" that permit simultaneous quantitative analysis of up to 130 distinct cis-regulatory modules (CRMs. The activities of these reporters are measured in single experiments by the NanoString RNA counting method and other quantitative procedures. We demonstrate the efficiency of the Nanotag method by simultaneously measuring hourly temporal activities of 126 CRMs from 46 genes in the developing sea urchin embryo, otherwise a virtually impossible task. Nanotags are also used in gene perturbation experiments to reveal cis-regulatory responses of many CRMs at once. Nanotag methodology can be applied to many research areas, ranging from gene regulatory networks to functional and evolutionary genomics.

Alcohol-Induced Impairment of Balance is Antagonized by Energy Drinks.

Science.gov (United States)

Marczinski, Cecile A; Fillmore, Mark T; Stamates, Amy L; Maloney, Sarah F

2018-01-01

The acute administration of alcohol reliably impairs balance and motor coordination. While it is common for consumers to ingest alcohol with other stimulant drugs (e.g., caffeine, nicotine), little is known whether prototypical alcohol-induced balance impairments are altered by stimulant drugs. The purpose of this study was to examine whether the coadministration of a high-caffeine energy drink with alcohol can antagonize expected alcohol-induced increases in body sway. Sixteen social drinkers (of equal gender) participated in 4 separate double-blind dose administration sessions that involved consumption of alcohol and energy drinks, alone and in combination. Following dose administration, participants completed automated assessments of balance stability (both eyes open and eyes closed) measured using the Biosway Portable Balance System. Participants completed several subjective measures including self-reported ratings of sedation, stimulation, fatigue, and impairment. Blood pressure and pulse rate were recorded repeatedly. The acute administration of alcohol increased body sway, and the coadministration of energy drinks antagonized this impairment. When participants closed their eyes, alcohol-induced body sway was similar whether or not energy drinks were ingested. While alcohol administration increased ratings of sedation and fatigue, energy drink administration increased ratings of stimulation and reduced ratings of fatigue. Modest increases in systolic and diastolic blood pressure following energy drink administration were also observed. Visual assessment of balance impairment is frequently used to indicate that an individual has consumed too much alcohol (e.g., as part of police-standardized field sobriety testing or by a bartender assessing when someone should no longer be served more alcohol). The current findings suggest that energy drinks can antagonize alcohol-induced increases in body sway, indicating that future work is needed to determine whether this

Flumazenil antagonizes the central effects of zolpidem, an imidazopyridine hypnotic.

Science.gov (United States)

Patat, A; Naef, M M; van Gessel, E; Forster, A; Dubruc, C; Rosenzweig, P

1994-10-01

Zolpidem is a new imidazopyridine-hypnotic that selectively binds to the central omega 1-receptor subtype. A double-blind, randomized, three-way, crossover placebo-controlled study was carried out in nine healthy male volunteers to assess the possible antagonism of central nervous system--depressant effects of zolpidem by flumazenil. Subjects received zolpidem (0.21 mg/kg) or placebo, intravenously, followed 17 minutes later by flumazenil (0.04 mg/kg) or placebo. Vigilance and performance were assessed by a trained anesthetist with use of ciliary reflex, response to a verbal instruction, subjective sedation, a tracking task, and a free recall task. Zolpidem produced a clinically relevant hypnotic effect in five subjects and significantly impaired performance in all nine subjects up to 90 minutes after dosing. Flumazenil rapidly antagonized clinical sedation in the five subjects who were asleep and significantly reversed the performance decrement within 3 minutes, without any escape phenomenon. Flumazenil did not change zolpidem plasma concentrations, confirming the pharmacodynamic nature of the interaction. Flumazenil may thus be a safe and effective antidote in patients with zolpidem overdosage.

Development of cooperation of the CIS member states in the peaceful use of atomic energy

International Nuclear Information System (INIS)

Sobolev, A.Ye.

2012-01-01

Full text: Cooperation platform: Attraction of potential investors; Promotion of national goods and services; Pursuit of national and commercial interests. The Commission of the CIS Member States for the Peaceful Use of Atomic Energy is a nuclear cooperation body and the CIS intergovernmental coordinating and advisory authority. The Commission of the CIS Member States for the Peaceful Use of Atomic Energy coordinates and expands the spheres of cooperation. Members of the Commission- state-appointed heads of the authorized CIS member state bodies in the peaceful use of atomic energy; Secretariat is the working body of the Commission. Expert work groups formed within the CIS members States Commission: On the status of the draft Agreement on Coordination of Interstate Relations in the Peaceful Use of Atomic Energy in the CIS Territory; On the establishment of the CIS regional center for advanced training of medical physicists; Formation of an integrated system for the maintenance of safety of the nuclear research facilities. Issues of establishing the Coalition of the CIS Nuclear Research reactors; Formation of mechanisms for the convergence of the CIS member states legal and technical regulations in the peaceful use of atomic energy; Adaptation and introduction in the CIS members states of international standards in the field of using industrial radiation technologies and ensuring radiation safety; Basic forms of the CIS cooperation in ensuring economic security of projects for the peaceful use of atomic energy; Establishment of a system for the management of intellectual assets of the CIS members states; On the use of tele medical technologies of Ros atom State Cooperation- FMBA-MEPHI in diagnosis of oncologic diseases; Development of the major components of the Concept of Ensuring Nuclear, radiation and Radio ecological; Policy of the CIS Member States in the Peaceful Use of Atomic Energy; Joint implementation of the project to establish and implement a program of

Ultraviolet irradiation produces cytotoxic synergy and increased DNA interstrand crosslinking with cis- and trans-diamminedichloroplatinum(II)

International Nuclear Information System (INIS)

Swinnen, L.J.; Erickson, L.C.

1989-01-01

The excision-repair mechanism responsible for the removal of UV-induced thymine dimers may also play a role in the repair of cis-diamminedichloroplatinum(II) (cis-DDP)-induced DNA adducts in both bacteria and mammalian cells. It was hypothesized that UV dimers and cis-DDP adducts, when present simultaneously, might compete for a common repair system. Colony survival assays were performed in HT-29 human colon carcinoma cells exposed either to cis-DDP alone or to cis-DDP immediately followed by UV exposure. Progressively greater cytotoxic synergy with both increasing UV dose and cis-DDP dose was observed, to a point of saturation beyond which further toxicity was purely additive. An approximate doubling in DNA crosslink frequency, relative to cis-DDP alone, was found in cells exposed to cis-DDP plus UV. Since cis-DDP produces both inter- and intrastrand DNA crosslinks similar studies were performed with trans-DDP, which is incapable of producing intrastrand crosslinks, but does produce interstrand crosslinks. Cytotoxic synergy and increased interstrand crosslinking again resulted from the addition of UV exposure, but not to the same extent as seen with cis-DDP. (author)

Whole-body kinetics and dosimetry of cis-4-[18F]fluoro-l-proline

International Nuclear Information System (INIS)

Boerner, Anne R.; Langen, Karl-J.; Herzog, Hans; Hamacher, Kurt; Mueller-Mattheis, Volker; Schmitz, Thomas; Ackermann, Rolf; Coenen, Heinz H.

2001-01-01

The whole-body distribution of 4-cis[ 18 F]fluoro-L-proline (cis-FPro) was studied in six patients with urological tumors by PET. Based on the IMEDOSE and MIRDOSE procedures radiation absorbed doses were estimated from whole-body PET scans acquired at 1 and 3-5 h after i.v. injection of 400 MBq cis-FPro. Cis-FPro showed high retention in the renal cortex and a slight uptake in liver and pancreas. Urinary excretion ranged from 12 to 19% at 5 h p.i. Highest absorbed doses were found for the urinary bladder wall and the kidneys (44.1/44.0 μGy/MBq). The effective dose according to ICRP 60 was 15.1 μSv/MBq for adults. This leads to an effective dose of 6.0 mSv in a PET study using 400 MBq cis-FPro

Whole-body kinetics and dosimetry of cis-4-[(18)F]fluoro-L-proline.

Science.gov (United States)

Börner, A R; Langen, K J; Herzog, H; Hamacher, K; Müller-Mattheis, V; Schmitz, T; Ackermann, R; Coenen, H H

2001-04-01

The whole-body distribution of 4-cis[(18)F]fluoro-L-proline (cis-FPro) was studied in six patients with urological tumors by PET. Based on the IMEDOSE and MIRDOSE procedures radiation absorbed doses were estimated from whole-body PET scans acquired at 1 and 3-5 h after i.v. injection of 400 MBq cis-FPro. Cis-FPro showed high retention in the renal cortex and a slight uptake in liver and pancreas. Urinary excretion ranged from 12 to 19% at 5 h p.i. Highest absorbed doses were found for the urinary bladder wall and the kidneys (44.1/44.0 microGy/mbq). The effective dose according to ICRP 60 was 15.1 microSv/mbq for adults. This leads to an effective dose of 6.0 mSv in a PET study using 400 MBq cis-FPro.

Inactivation of enteroviruses in sewage with ozone

Energy Technology Data Exchange (ETDEWEB)

Ivanova, O.E.; Bogdanov, M.V.; Kazantseva, V.A.; Gabrilevskaia, L.N.; Kodkind, G.K.H.

The study of ozone inactivation of enteroviruses in sewage showed the presence in sewage of suspensions of organic origin and bacterial flora to influence the rate of inactivation. The inactivation rate of poliomyelitis virus in sewage free from organic suspension and bacterial flora was significantly higher than that in sewage containing such suspension and bacterial flora. The inactivation rate of enteroviruses was found not to depend upon the protein and salt composition and pH of sewage or strain appurtenance of viruses. The inactivation rate of enteroviruses directly depended upon the dose of ozone and time of contact with it. Differences in the resistance of different types of poliomyelitis virus, ECHO and Coxsackie viruses to the effect of ozone are likely exist. These differences are manifested within the range of relatively small doses of ozone. E. coli is more resistant to ozone than entero-viruses. The results of laboratory studies were used to choose the regimen of sanitation of urban sewage to be used in technological cycles of industrial enterprises.

Conjugated linoleic acid (CLA. Cis 9, trans 11 and trans 10, cis 12 isomer detection in crude and refined corn oils by capillary GC

Directory of Open Access Journals (Sweden)

Özlem Tokuşoğlu

2008-06-01

Full Text Available Conjugated linoleic acids (CLAs exhibit protective effects against various types of cancer and heart diseases. With the newly developed capillary gas chromatographic method (GC, cis9, trans11 and trans10, cis12 octadecadienoic acid isomers of CLA (C18:2 were determined in crude and refined corn oils as qualitative and quantitative measurements. Cis 9, trans11 C18:2 (c9, t11 CLA was the major CLA isomer in both oils. It was found that c9, t11 CLA was 0.62% of the total lipid in crude oil and 1.24% of the total lipid in refined oil. Using the refining process, the total CLA was 1.38% whereas that of crude corn oil was 0.62%. An approximate 2.2 fold increase in the total CLA was found in refined oil (n = 9 (p y = 2.782x + 0.046 (R2 = 0.9999] were performed (p El ácido linoleico conjugado (CLA parece exhibir efecto protector frente a enfermedades cardiovasculares y varios tipos de cáncer. En este trabajo, se establece un mátodo analítico mediante cromatografía de gases con columna capilar para la determinación cualitativa y cuantitativa de los isómeros cis 9,trans 11 y trans 10, cis 12 en aceites de maiz crudo y refinado. El isómero cis 9, trans11 C18:2 fue el mayoritario encontrándose en concentraciones de 0.62% en el aceite cru,do y de 1.24 % en el aceite refinado. La cantidad total de CLA encontrada en el aceite refinado (n = 9 (p 2 = 0.9999 y de recuperación [y = 2.782x+0.046 (R2 = 0.9999]. El método cromatográfico propuesto podría ser usado para el control de calidad de los aceites vegetales.

Evolution of Enzymatic Activities in the Enolase Superfamily: Stereochemically Distinct Mechanisms in Two Families of cis,cis-Muconate Lactonizing Enzymes

Energy Technology Data Exchange (ETDEWEB)

Sakai, A.; Fedorov, A; Fedorov, E; Schnoes, A; Glasner, M; Burley, S; Babbitt, P; Almo, S; Gerlt, J

2009-01-01

The mechanistically diverse enolase superfamily is a paradigm for elucidating Nature's strategies for divergent evolution of enzyme function. Each of the different reactions catalyzed by members of the superfamily is initiated by abstraction of the a-proton of a carboxylate substrate that is coordinated to an essential Mg2+. The muconate lactonizing enzyme (MLE) from Pseudomonas putida, a member of a family that catalyzes the syn-cycloisomerization of cis,cis-muconate to (4S)-muconolactone in the e-ketoadipate pathway, has provided critical insights into the structural bases for evolution of function within the superfamily. A second, divergent family of homologous MLEs that catalyzes anti-cycloisomerization has been identified. Structures of members of both families liganded with the common (4S)-muconolactone product (syn, Pseudomonas fluorescens, gi 70731221; anti, Mycobacterium smegmatis, gi 118470554) document that the conserved Lys at the end of the second e-strand in the (e/a)7e-barrel domain serves as the acid catalyst in both reactions. The different stereochemical courses (syn and anti) result from different structural strategies for determining substrate specificity: although the distal carboxylate group of the cis,cis-muconate substrate attacks the same face of the proximal double bond, opposite faces of the resulting enolate anion intermediate are presented to the conserved Lys acid catalyst. The discovery of two families of homologous, but stereochemically distinct, MLEs likely provides an example of 'pseudoconvergent' evolution of the same function from different homologous progenitors within the enolase superfamily, in which different spatial arrangements of active site functional groups and substrate specificity determinants support catalysis of the same reaction.

Evolution of Enzymatic Activities in the Enolase Superfamily: Stereochemically Distinct Mechanisms in Two Families of cis,cis-Muconate Lactonizing Enzymes†

Science.gov (United States)

Sakai, Ayano; Fedorov, Alexander A.; Fedorov, Elena V.; Schnoes, Alexandra M.; Glasner, Margaret E.; Brown, Shoshana; Rutter, Marc E.; Bain, Kevin; Chang, Shawn; Gheyi, Tarun; Sauder, J. Michael; Burley, Stephen K.; Babbitt, Patricia C.; Almo, Steven C.; Gerlt, John A.

2009-01-01

The mechanistically diverse enolase superfamily is a paradigm for elucidating Nature’s strategies for divergent evolution of enzyme function. Each of the different reactions catalyzed by members of the superfamily is initiated by abstraction of the α-proton of a carboxylate substrate that is coordinated to an essential Mg2+. The muconate lactonizing enzyme (MLE) from Pseudomonas putida, a member of a family that catalyzes the syn-cycloisomerization of cis,cis-muconate to (4S)-muconolactone in the β-ketoadipate pathway, has provided critical insights into the structural bases for evolution of function within the superfamily. A second, divergent family of homologues MLEs that catalyzes anti-cycloisomerization has been identified. Structures of members of both families liganded with the common (4S)-muconolactone product (syn, Pseudomonas fluorescens, GI:70731221; anti, Mycobacterium smegmatis, GI:118470554) document that the conserved Lys at the end of the second β-strand in the (β/α)7β-barrel domain serves as the acid catalyst in both reactions. The different stereochemical courses (syn and anti) result from different structural strategies for determining substrate specificity: although the distal carboxylate group of the cis,cis-muconate substrate attacks the same face of the proximal double bond, opposite faces of the resulting enolate anion intermediate are presented to the conserved Lys acid catalyst. The discovery of two families of homologous, but stereochemically distinct, MLEs likely provides an example of “pseudoconvergent” evolution of the same function from different homologous progenitors within the enolase superfamily, in which different spatial arrangements of active site functional groups and substrate specificity determinants support catalysis of the same reaction. PMID:19220063

Progranulin shows cytoprotective effects on trophoblast cells in vitro but does not antagonize TNF-α-induced apoptosis.

Science.gov (United States)

Stubert, Johannes; Waldmann, Kathrin; Dieterich, Max; Richter, Dagmar-Ulrike; Briese, Volker

2014-11-01

The glycoprotein progranulin directly binds to TNF-receptors and thereby can antagonize the inflammatory effects of TNF-α. Here we analyzed the impact of both cytokines on cytotoxicity and viability of trophoblast cells. Isolated villous first trimester human trophoblast cells and the human choriocarcinoma cell line BeWo were treated with recombinant human progranulin and TNF-α. Analyses were performed by LDH- and MTT-assay and measurement of caspase-8-activity. Progranulin treatment showed some cytoprotective effects on isolated trophoblast cells. However, TNF-α-induced apoptosis was not antagonized by addition of progranulin. Effects were similar, but more pronounced in BeWo cells. The cytoprotective activity of progranulin on trophoblast cells in vitro was only weak and of doubtful biologic relevance. It was not able to antagonize TNF-α. Future studies should focus on possible paracrine activities of progranulin.

Mycobacteria inactivation using Engineered Water Nanostructures (EWNS).

Science.gov (United States)

Pyrgiotakis, Georgios; McDevitt, James; Gao, Ya; Branco, Alan; Eleftheriadou, Mary; Lemos, Bernardo; Nardell, Edward; Demokritou, Philip

2014-08-01

Airborne transmitted pathogens such as Mycobacterium tuberculosis (Mtb) cause serious, often fatal infectious disease with enormous global health implications. Due to their unique cell wall and slow growth, mycobacteria are among the most resilient microbial forms. Herein we evaluate the ability of an emerging, chemical-free, nanotechnology-based method to inactivate M. parafortuitum (Mtb surrogate). This method is based on the transformation of atmospheric water vapor into engineered water nano-structures (EWNS) via electrospray. We demonstrate that the EWNS can interact with and inactivate airborne mycobacteria, reducing their concentration levels significantly. Additionally, EWNS can inactivate M. parafortuitum on surfaces eight times faster than the control. The mechanism of mycobacteria inactivation was also investigated in this study. It was demonstrated that the EWNS effectively deliver the reactive oxygen species, encapsulated during the electrospray process, to the bacteria oxidizing their cell membrane resulting into inactivation. Overall, this is a method with the potential to become an effective intervention technology in the battle against airborne infections. This study demonstrates the feasibility of mycobacterium inactivation in airborne form or on contact surfaces using electrospray activated water nano-structures. Given that the method is free of toxic chemicals, this might become an important tool in the prevention of mycobacterial infections, which are notoriously hard to treat. Copyright © 2014 Elsevier Inc. All rights reserved.

The value of bladder mapping and prostatic urethra biopsies for detection of carcinoma in situ (CIS).

Science.gov (United States)

Gudjónsson, Sigurdur; Bläckberg, Mats; Chebil, Gunilla; Jahnson, Staffan; Olsson, Hans; Bendahl, Pär-Ola; Månsson, Wiking; Liedberg, Fredrik

2012-07-01

It is well known that CIS is a major risk factor for muscle-invasive bladder cancer and that this entity can be difficult to diagnose. Taking cold-cup mapping biopsies from different areas of the bladder (BMAP) is commonly used in patients at risk of harbouring CIS. The diagnostic accuracy of this approach has not been assessed until now. By using the CIS found in the cystoprostatectomy specimen as an indicator of the true occurrence of CIS and comparing that with the findings of BMAP, it is clear that the sensitivity of BMAP to detect CIS when present is low and that negative findings should be considered unreliable. To assess the value of bladder mapping and prostatic urethra biopsies for detection of urothelial carcinoma in situ (CIS). CIS of the urinary bladder is a flat high-grade lesion of the mucosa associated with a significant risk of progression to muscle-invasive disease. CIS is difficult to identify on cystoscopy, and definite diagnosis requires histopathology. Traditionally, if CIS is suspected, multiple cold-cup biopsies are taken from the bladder mucosa, and resection biopsies are obtained from the prostatic urethra in males. This approach is often called bladder mapping (BMAP). The accuracy of BMAP as a diagnostic tool is not known. Male patients with bladder cancer scheduled for cystectomy underwent cold-cup bladder biopsies (sidewalls, posterior wall, dome, trigone), and resection biopsies were taken from the prostatic urethra. After cystectomy, the surgical specimen was investigated in a standardised manner and subsequently compared with the BMAP biopsies for the presence of CIS. The histopathology reports of 162 patients were analysed. CIS was detected in 46% of the cystoprostatectomy specimens, and multiple (≥2) CIS lesions were found in 30%. BMAP (cold-cup bladder biopsies + resection biopsies from the prostatic urethra) provided sensitivity of 51% for any CIS, and 55% for multiple CIS lesions. The cold-cup biopsies for CIS in the bladder

Columbia River Coordinated Information System (CIS), 1992-1993 Annual Report.

Energy Technology Data Exchange (ETDEWEB)

Rowe, Mike; Roger, Phillip B.; O' Connor, Dick

1993-11-01

The purposes of this report are to: (1) describe the project to date; (2) to document the work and accomplishments of the (CIS) project for Fiscal Year 1993; and (3) to provide a glimpse of future project direction. The concept of a Coordinated Information System (CIS) as an approach to meeting the growing needs for regionally standardized anadromous fish information.

Hybrid macrocycle formation and spiro annulation on cis-syn-cis-tricyclo[6.3.0.02,6]undeca-3,11-dione and its congeners via ring-closing metathesis

Directory of Open Access Journals (Sweden)

Sambasivarao Kotha

2015-07-01

Full Text Available We have developed a simple methodology to transform cis-syn-cis-triquinane derivative 2 into the diindole based macrocycle 6 involving Fischer indolization and ring-closing metathesis (RCM. Various spiro-polyquinane derivatives have been assembled via RCM as a key step.

Crystal structure of cis-anti-cis-dicyclohexane-18-crown-6 acetonitrile disolvate

Directory of Open Access Journals (Sweden)

Alexander Nazarenko

2015-07-01

Full Text Available The title compound (systematic name: cis-anti-cis-2,5,8,15,18,21-hexaoxatricyclo[20.4.0.09,14]hexacosane acetonitrile disolvate, C20H36O6·2CH3CN, crystallizes from an acetonitrile solution of dicyclohexane-18-crown-6 on evaporation. The molecule is arranged around a center of symmetry with half the crown ether molecule and one molecule of acetonitrile symmetry independent. All O—C—C—O torsion angles are gauche while all C—O—C—C angles are trans. The sequence of torsion angles is [(tg+t(tg−t]3; the geometry of oxygen atoms is close to pseudo-D3d with three atoms below and three atoms above the mean plane, with an average deviation of ±0.16 (1 Å from the mean plane. This geometry is identical to that observed in metal ion complexes of dicyclohexane-18-crown-6 but differs significantly from the conformation of a free unsolvated molecule. Each acetonitrile molecule connects to a crown ether molecule via two of its methyl group H atoms (C—H...O. Weaker interactions exist between the third H atom of the acetonitrile methyl group and an O atom of a neighbouring crown ether molecule (C—H...O; and between the N atom of the acetonitrile molecule and a H atom of another neighbouring crown ether molecule. All these intermolecular interactions create a three-dimensional network stabilizing the disolvate.

Effects of metals on enantioselective toxicity and biotransformation of cis-bifenthrin in zebrafish.

Science.gov (United States)

Yang, Ye; Ji, Dapeng; Huang, Xin; Zhang, Jianyun; Liu, Jing

2017-08-01

Co-occurrence of pyrethroids and metals in watersheds previously has been reported to pose great risk to aquatic species. Pyrethroids are a class of chiral insecticides that have been shown to have enantioselective toxicity and biotransformation. However, the influence of metals on enantioselectivity of pyrethroids has not yet been evaluated. In the present study, the effects of cadmium (Cd), copper (Cu), and lead (Pb) on the enantioselective toxicity and metabolism of cis-bifenthrin (cis-BF) were investigated in zebrafish at environmentally relevant concentrations. The addition of Cd, Cu, or Pb significantly increased the mortality of zebrafish in racemate and R-enantiomer of cis-BF-treated groups. In rac-cis-BF- or 1R-cis-BF-treated groups, the addition of Cd, Cu, or Pb caused a decrease in enantiomeric fraction (EF) and an increased ratio of R-enantiomer residues in zebrafish. In 1S-cis-BF-treated groups, coexposure to Cd led to a lower EF and decreased residue levels of S-enantiomer. In addition, coexposure to the 3 metals resulted in different biodegradation characteristics of each enantiomer accompanied with differential changes in the expression of cytochrome P450 (CYP)1, CYP2, and CYP3 genes, which might be responsible for the enantioselective biodegradation of cis-BF in zebrafish. These results suggest that the influence of coexistent metals should be considered in the ecological risk assessment of chiral pyrethroids in aquatic environments. Environ Toxicol Chem 2017;36:2139-2146. © 2017 SETAC. © 2017 SETAC.

The Role of Cis-Lunar Space in Future Global Space Exploration

Science.gov (United States)

Bobskill, Marianne R.; Lupisella, Mark L.

2012-01-01

Cis-lunar space offers affordable near-term opportunities to help pave the way for future global human exploration of deep space, acting as a bridge between present missions and future deep space missions. While missions in cis-lunar space have value unto themselves, they can also play an important role in enabling and reducing risk for future human missions to the Moon, Near-Earth Asteroids (NEAs), Mars, and other deep space destinations. The Cis-Lunar Destination Team of NASA's Human Spaceflight Architecture Team (HAT) has been analyzing cis-lunar destination activities and developing notional missions (or "destination Design Reference Missions" [DRMs]) for cis-lunar locations to inform roadmap and architecture development, transportation and destination elements definition, operations, and strategic knowledge gaps. The cis-lunar domain is defined as that area of deep space under the gravitational influence of the earth-moon system. This includes a set of earth-centered orbital locations in low earth orbit (LEO), geosynchronous earth orbit (GEO), highly elliptical and high earth orbits (HEO), earth-moon libration or "Lagrange" points (E-ML1 through E-ML5, and in particular, E-ML1 and E-ML2), and low lunar orbit (LLO). To help explore this large possibility space, we developed a set of high level cis-lunar mission concepts in the form of a large mission tree, defined primarily by mission duration, pre-deployment, type of mission, and location. The mission tree has provided an overall analytical context and has helped in developing more detailed design reference missions that are then intended to inform capabilities, operations, and architectures. With the mission tree as context, we will describe two destination DRMs to LEO and GEO, based on present human space exploration architectural considerations, as well as our recent work on defining mission activities that could be conducted with an EML1 or EML2 facility, the latter of which will be an emphasis of this

Mutualism and Antagonism: Ecological Interactions Among Bark Beetles, Mite and Fungi

Science.gov (United States)

K.D. Klepzig; J.C. Moser; M.J. Lombardero; M.P. Ayres; R.W. Hofstetter; C.J. Walkinshaw

2001-01-01

Insect-fungal complexes provide challenging and fascinating systems for the study of biotic interactions between plants. plant pathogens, insect vectors and other associated organisms. The types of interactions among these organisms (mutualism. antagonism. parasitism. phoresy. etc.) are as variable as the range of organisms involved (plants, fungi, insects. mites. etc...

Interleukin-1 Antagonism Decreases Cortisol Levels in Obese Individuals

OpenAIRE

Urwyler, Sandrine Andrea; Schuetz, Philipp; Ebrahimi, Fahim; Donath, Marc Y.; Christ-Crain, Mirjam

2017-01-01

Increased cortisol levels in obesity may contribute to the associated metabolic syndrome. In obesity, the activated innate immune system leads to increased interleukin (IL)-1β, which is known to stimulate the release of adrenocorticotropin hormone (ACTH).; We hypothesized that in obesity IL-1 antagonism would result in downregulation of the hypothalamo-pituitary-adrenal axis, leading to decreased cortisol levels.; In this prospective intervention study, we included 73 patients with obesity (b...

[Kinetics of catalase inactivation induced by ultrasonic cavitation].

Science.gov (United States)

Potapovich, M V; Eremin, A N; Metelitsa, D I

2003-01-01

Kinetic patterns of sonication-induced inactivation of bovine liver catalase (CAT) were studied in buffer solutions (pH 4-11) within the temperature range from 36 to 55 degrees C. Solutions of CAT were exposed to low-frequency (20.8 kHz) ultrasound (specific power, 48-62 W/cm2). The kinetics of CAT inactivation was characterized by effective first-order rate constants (s-1) of total inactivation (kin), thermal inactivation (*kin), and ultrasonic inactivation (kin(us)). In all cases, the following inequality was valid: kin > *kin. The value of kin(us) increased with the ultrasound power (range, 48-62 W/cm2) and exhibited a strong dependence on pH of the medium. On increasing the initial concentration of CAT (0.4-4.0 nM), kin(us) decreased. The three rate constants were minimum within the range of pH 6.5-8; their values increased considerably at pH 9. At 36-55 degrees C, temperature dependence of kin(us) was characterized by an activation energy (Eact) of 19.7 kcal/mol, whereas the value of Eact for CAT thermoinactivation was equal to 44.2 kcal/mol. Bovine serum and human serum albumins (BSA and HSA, respectively) inhibited sonication-induced CAT inactivation; complete prevention was observed at concentrations above 2.5 micrograms/ml. Dimethyl formamide (DMFA), a scavenger of hydroxyl radicals (HO.), prevented sonication-induced CAT inactivation at 10% (kin and *kin increased with the content of DMFA at concentrations in excess of 3%). The results obtained indicate that free radicals generated in the field of ultrasonic cavitation play a decisive role in the inactivation of CAT, which takes place when its solutions are exposed to low-frequency ultrasound. However, the efficiency of CAT inactivation by the radicals is determined by (1) the degree of association between the enzyme molecules in the reaction medium and (2) the composition thereof.

Investing in CIS: obstacles and strategies

International Nuclear Information System (INIS)

Anon.

1996-01-01

The CIS (Community of Independent States) needs the help of foreign investments to develop its huge hydrocarbon potentialities. Because of the uncertainties concerning the legal and fiscal context of their activities, the role of the international oil companies has remained limited so far. These problems were discussed in May 1996 during an important ''General Session'' of the OTC 96 congress. Proven and explored onshore oil reserves in Russia are enormous, in particular in Western and Eastern Siberia. However, the economically most interesting resources are located in the offshore zones of the Barents, Pechora and Kara seas and of Eastern Siberia and Okhotsk. This paper describes the last years decay of oil production in CIS and its causes, in particular the obstacles to foreign investments (exportation and transport taxes), the recent contracts and joint-ventures with American major companies (Exxon, Amoco..), and the situation of the Russian industry in petroleum engineering and field exploitation materials. (J.S.)

Coevolution within a transcriptional network by compensatory trans and cis mutations

KAUST Repository

Kuo, D.

2010-10-26

Transcriptional networks have been shown to evolve very rapidly, prompting questions as to how such changes arise and are tolerated. Recent comparisons of transcriptional networks across species have implicated variations in the cis-acting DNA sequences near genes as the main cause of divergence. What is less clear is how these changes interact with trans-acting changes occurring elsewhere in the genetic circuit. Here, we report the discovery of a system of compensatory trans and cis mutations in the yeast AP-1 transcriptional network that allows for conserved transcriptional regulation despite continued genetic change. We pinpoint a single species, the fungal pathogen Candida glabrata, in which a trans mutation has occurred very recently in a single AP-1 family member, distinguishing it from its Saccharomyces ortholog. Comparison of chromatin immunoprecipitation profiles between Candida and Saccharomyces shows that, despite their different DNA-binding domains, the AP-1 orthologs regulate a conserved block of genes. This conservation is enabled by concomitant changes in the cis-regulatory motifs upstream of each gene. Thus, both trans and cis mutations have perturbed the yeast AP-1 regulatory system in such a way as to compensate for one another. This demonstrates an example of “coevolution” between a DNA-binding transcription factor and its cis-regulatory site, reminiscent of the coevolution of protein binding partners.

CIS-based registration of quality of life in a single source approach.

Science.gov (United States)

Fritz, Fleur; Ständer, Sonja; Breil, Bernhard; Riek, Markus; Dugas, Martin

2011-04-21

Documenting quality of life (QoL) in routine medical care and using it both for treatment and for clinical research is not common, although such information is absolutely valuable for physicians and patients alike. We therefore aimed at developing an efficient method to integrate quality of life information into the clinical information system (CIS) and thus make it available for clinical care and secondary use. We piloted our method in three different medical departments, using five different QoL questionnaires. In this setting we used structured interviews and onsite observations to perform workflow and form analyses. The forms and pertinent data reports were implemented using the integrated tools of the local CIS. A web-based application for mobile devices was developed based on XML schemata to facilitate data import into the CIS. Data exports of the CIS were analysed with statistical software to perform an analysis of data quality. The quality of life questionnaires are now regularly documented by patients and physicians. The resulting data is available in the Electronic Health Record (EHR) and can be used for treatment purposes and communication as well as research functionalities. The completion of questionnaires by the patients themselves using a mobile device (iPad) and the import of the respective data into the CIS forms were successfully tested in a pilot installation. The quality of data is rendered high by the use of automatic score calculations as well as the automatic creation of forms for follow-up documentation. The QoL data was exported to research databases for use in scientific analysis. The CIS-based QoL is technically feasible, clinically accepted and provides an excellent quality of data for medical treatment and clinical research. Our approach with a commercial CIS and the web-based application is transferable to other sites.

Cationic antimicrobial peptides inactivate Shiga toxin-encoding bacteriophages

Science.gov (United States)

Del Cogliano, Manuel E.; Hollmann, Axel; Martinez, Melina; Semorile, Liliana; Ghiringhelli, Pablo D.; Maffía, Paulo C.; Bentancor, Leticia V.

2017-12-01

Shiga toxin (Stx) is the principal virulence factor during Shiga toxin-producing Escherichia coli (STEC) infections. We have previously reported the inactivation of bacteriophage encoding Stx after treatment with chitosan, a linear polysaccharide polymer with cationic properties. Cationic antimicrobial peptides (cAMPs) are short linear aminoacidic sequences, with a positive net charge, which display bactericidal or bacteriostatic activity against a wide range of bacterial species. They are promising novel antibiotics since they have shown bactericidal effects against multiresistant bacteria. To evaluate whether cationic properties are responsible for bacteriophage inactivation, we tested seven cationic peptides with proven antimicrobial activity as anti-bacteriophage agents, and one random sequence cationic peptide with no antimicrobial activity as a control. We observed bacteriophage inactivation after incubation with five cAMPs, but no inactivating activity was observed with the random sequence cationic peptide or with the non alpha helical cAMP Omiganan. Finally, to confirm peptide-bacteriophage interaction, zeta potential was analyzed by following changes on bacteriophage surface charges after peptide incubation. According to our results we could propose that: 1) direct interaction of peptides with phage is a necessary step for bacteriophage inactivation, 2) cationic properties are necessary but not sufficient for bacteriophage inactivation, and 3) inactivation by cationic peptides could be sequence (or structure) specific. Overall our data suggest that these peptides could be considered a new family of molecules potentially useful to decrease bacteriophage replication and Stx expression.

Cationic Antimicrobial Peptides Inactivate Shiga Toxin-Encoding Bacteriophages

Directory of Open Access Journals (Sweden)

Manuel E. Del Cogliano

2017-12-01

Full Text Available Shiga toxin (Stx is the principal virulence factor during Shiga toxin-producing Escherichia coli (STEC infections. We have previously reported the inactivation of bacteriophage encoding Stx after treatment with chitosan, a linear polysaccharide polymer with cationic properties. Cationic antimicrobial peptides (cAMPs are short linear aminoacidic sequences, with a positive net charge, which display bactericidal or bacteriostatic activity against a wide range of bacterial species. They are promising novel antibiotics since they have shown bactericidal effects against multiresistant bacteria. To evaluate whether cationic properties are responsible for bacteriophage inactivation, we tested seven cationic peptides with proven antimicrobial activity as anti-bacteriophage agents, and one random sequence cationic peptide with no antimicrobial activity as a control. We observed bacteriophage inactivation after incubation with five cAMPs, but no inactivating activity was observed with the random sequence cationic peptide or with the non-alpha helical cAMP Omiganan. Finally, to confirm peptide-bacteriophage interaction, zeta potential was analyzed by following changes on bacteriophage surface charges after peptide incubation. According to our results we could propose that: (1 direct interaction of peptides with phage is a necessary step for bacteriophage inactivation, (2 cationic properties are necessary but not sufficient for bacteriophage inactivation, and (3 inactivation by cationic peptides could be sequence (or structure specific. Overall our data suggest that these peptides could be considered a new family of molecules potentially useful to decrease bacteriophage replication and Stx expression.

Studies of Binary Complexes of Tripodal Ligand cis,cis-1,3,5-tris(methylaminocyclohexane with Cr(III and Fe(III

Directory of Open Access Journals (Sweden)

S. Esakki Muthu

2005-01-01

Full Text Available The formation of binary complexes of Cr(III and Fe(III with a tripodal ligand cis,cis-1,3,5-tris(methylaminocyclohexane (tmach (L has been investigated in solution. The overall stability constants of tmach with Cr(III and Fe(III were determined by potentiometric method at an ionic strength of 0.1 M NaClO4 at 25±1°C in aqueous medium. The formation of species like MLH25+, MLH4+, ML3+, ML(OH2+ and ML(OH3 were observed. Fe(III was found to form more stable complexes than Cr(III. Molecular mechanics calculations were performed to explain the mode of coordination in solution.

SoxB1-driven transcriptional network underlies neural-specific interpretation of morphogen signals.

Science.gov (United States)

Oosterveen, Tony; Kurdija, Sanja; Ensterö, Mats; Uhde, Christopher W; Bergsland, Maria; Sandberg, Magnus; Sandberg, Rickard; Muhr, Jonas; Ericson, Johan

2013-04-30

The reiterative deployment of a small cadre of morphogen signals underlies patterning and growth of most tissues during embyogenesis, but how such inductive events result in tissue-specific responses remains poorly understood. By characterizing cis-regulatory modules (CRMs) associated with genes regulated by Sonic hedgehog (Shh), retinoids, or bone morphogenetic proteins in the CNS, we provide evidence that the neural-specific interpretation of morphogen signaling reflects a direct integration of these pathways with SoxB1 proteins at the CRM level. Moreover, expression of SoxB1 proteins in the limb bud confers on mesodermal cells the potential to activate neural-specific target genes upon Shh, retinoid, or bone morphogenetic protein signaling, and the collocation of binding sites for SoxB1 and morphogen-mediatory transcription factors in CRMs faithfully predicts neural-specific gene activity. Thus, an unexpectedly simple transcriptional paradigm appears to conceptually explain the neural-specific interpretation of pleiotropic signaling during vertebrate development. Importantly, genes induced in a SoxB1-dependent manner appear to constitute repressive gene regulatory networks that are directly interlinked at the CRM level to constrain the regional expression of patterning genes. Accordingly, not only does the topology of SoxB1-driven gene regulatory networks provide a tissue-specific mode of gene activation, but it also determines the spatial expression pattern of target genes within the developing neural tube.

Structure of suicide-inactivated β-hydroxydecanoyl-thioester dehydrase

International Nuclear Information System (INIS)

Schwab, J.M.; Ho, C.K.; Li, W.B.; Townsend, C.A.; Salituro, G.M.

1986-01-01

β-Hydroxydecanoylthioester dehydrase, the key enzyme in biosynthesis of unsaturated fatty acids under anaerobic conditions, equilibrates thioesters of (R)-3-hydroxydecanoic acid, E-2-decenoic acid, and Z-3-decenoic acid. Dehydrase is irreversibly inactivated by the N-acetylcysteamine thioester of 3-decynoic acid (3-decynoyl-NAC), via dehydrase-catalyzed isomerization to 2,3-decadienoyl-NAC. To probe the relationship between normal catalysis and suicide inactivation, the structure of the inactivated enzyme has been studied. 3-[2- 13 C]Decynoyl-NAC was synthesized and incubated with dehydrase. 13 C NMR showed that attack of 2,3-decadienoyl-NAC by the active site histidine gives 3-histidinyl-3-decenoyl-NAC, which slowly rearranges to the more stable Δ 2 isomer. Model histidine-allene adducts have been made and characterized. Analysis of NMR data show that the C=C configuration of the decenoyl moiety of enzyme-bound inactivator is E. The suggestion that the mechanism of dehydrase inactivation parallels its normal mechanism of action is supported these findings

Modelling and application of the inactivation of microorganism

International Nuclear Information System (INIS)

Oğuzhan, P.; Yangılar, F.

2013-01-01

Prevention of consuming contaminated food with toxic microorganisms causing infections and consideration of food protection and new microbial inactivation methods are obligatory situations. Food microbiology is mainly related with unwanted microorganisms spoiling foods during processing and transporting stages and causing diseases. Determination of pathogen microorganisms is important for human health to define and prevent dangers and elongate shelf life. Inactivation of pathogen microorganisms can provide food security and reduce nutrient losses. Microbial inactivation which is using methods of food protection such as food safety and fresh. With this aim, various methods are used such as classical thermal processes (pasteurisation, sterilisation), pressured electrical field (PEF), ionised radiation, high pressure, ultrasonic waves and plasma sterilisation. Microbial inactivation modelling is a secure and effective method in food production. A new microbiological application can give useful results for risk assessment in food, inactivation of microorganisms and improvement of shelf life. Application and control methods should be developed and supported by scientific research and industrial applications

Single d(ApG)/cis-diamminedichloroplatinum(II) adduct-induced mutagenesis in Escherichia coli

International Nuclear Information System (INIS)

Burnouf, D.; Fuchs, R.P.P.; Gauthier, C.; Chottard, J.C.

1990-01-01

The mutation spectrum induced by the widely used antitumor drug cis-diamminedichloroplatinum(II) (cis-DDP) showed that cisDDP[d(ApG)] adducts, although they account for only 25% of the lesions formed are ∼5 times more mutagenic than the major GG adduct. The authors report the construction of vectors bearing a single cisDDP[d(ApG)] lesion and their use in mutagenesis experiments in Escherichia coli. The mutagenic processing of the lesion is found to depend strictly on induction of the SOS system of the bacterial host cells. In SOS-induced cells, mutation frequencies of 1-2% were detected. All these mutations are targeted to the 5' base of the adduct. Single A → T transversions are mainly observed (80%), whereas A → G transitions account for 10% of the total mutations. Tandem base-pair substitutions involving the adenine residue and the thymine residue immediately 5' to the adduct occur at a comparable frequency (10%). No selective loss of the strand bearing the platinum adduct was seen, suggesting that, in vivo, cisDDP[d(ApG)] adducts are not blocking lesions. The high mutation specificity of cisDDP-[d(ApG)]-induced mutagenesis is discussed in relation to structural data

Strand-specific RNA-seq reveals widespread occurrence of novel cis-natural antisense transcripts in rice

Directory of Open Access Journals (Sweden)

Lu Tingting

2012-12-01

Full Text Available Abstract Background Cis-natural antisense transcripts (cis-NATs are RNAs transcribed from the antisense strand of a gene locus, and are complementary to the RNA transcribed from the sense strand. Common techniques including microarray approach and analysis of transcriptome databases are the major ways to globally identify cis-NATs in various eukaryotic organisms. Genome-wide in silico analysis has identified a large number of cis-NATs that may generate endogenous short interfering RNAs (nat-siRNAs, which participate in important biogenesis mechanisms for transcriptional and post-transcriptional regulation in rice. However, the transcriptomes are yet to be deeply sequenced to comprehensively investigate cis-NATs. Results We applied high-throughput strand-specific complementary DNA sequencing technology (ssRNA-seq to deeply sequence mRNA for assessing sense and antisense transcripts that were derived under salt, drought and cold stresses, and normal conditions, in the model plant rice (Oryza sativa. Combined with RAP-DB genome annotation (the Rice Annotation Project Database build-5 data set, 76,013 transcripts corresponding to 45,844 unique gene loci were assembled, in which 4873 gene loci were newly identified. Of 3819 putative rice cis-NATs, 2292 were detected as expressed and giving rise to small RNAs from their overlapping regions through integrated analysis of ssRNA-seq data and small RNA data. Among them, 503 cis-NATs seemed to be associated with specific conditions. The deep sequence data from isolated epidermal cells of rice seedlings further showed that 54.0% of cis-NATs were expressed simultaneously in a population of homogenous cells. Nearly 9.7% of rice transcripts were involved in one-to-one or many-to-many cis-NATs formation. Furthermore, only 17.4-34.7% of 223 many-to-many cis-NAT groups were all expressed and generated nat-siRNAs, indicating that only some cis-NAT groups may be involved in complex regulatory networks. Conclusions

Antagonism between abscisic acid and gibberellins is partially mediated by ascorbic acid during seed germination in rice.

Science.gov (United States)

Ye, Nenghui; Zhang, Jianhua

2012-05-01

The antagonism between abscisic acid (ABA) and gibberellin (GA) plays a key role in controlling seed germination, but the mechanism of antagonism during this process is not known. In the associated study, we investigated the relationship among ABA, reactive oxygen species (ROS), ascorbic acid (ASC) and GA during rice seed germination. ROS production is reduced by ABA, which hence results in decreasing ASC accumulation during imbibition. GA accumulation was also suppressed by a reduced ROS and ASC level, whereas application of exogenous ASC can partially rescue seed germination from ABA treatment. Further results show that production of ASC, which acts as a substrate in GA biosynthesis, was significantly inhibited by lycorine which thus suppressed the accumulation of GA. Consequently, expression of GA biosynthesis genes was suppressed by the low levels of ROS and ASC in ABA-treated seeds. These studies reveal a new role for ASC in mediating the antagonism between ABA and GA during seed germination in rice.

Whole-body kinetics and dosimetry of cis-4-[{sup 18}F]fluoro-l-proline

Energy Technology Data Exchange (ETDEWEB)

Boerner, Anne R.; Langen, Karl-J. E-mail: k.j.langen@fz-juelich.de; Herzog, Hans; Hamacher, Kurt; Mueller-Mattheis, Volker; Schmitz, Thomas; Ackermann, Rolf; Coenen, Heinz H

2001-04-01

The whole-body distribution of 4-cis[{sup 18}F]fluoro-L-proline (cis-FPro) was studied in six patients with urological tumors by PET. Based on the IMEDOSE and MIRDOSE procedures radiation absorbed doses were estimated from whole-body PET scans acquired at 1 and 3-5 h after i.v. injection of 400 MBq cis-FPro. Cis-FPro showed high retention in the renal cortex and a slight uptake in liver and pancreas. Urinary excretion ranged from 12 to 19% at 5 h p.i. Highest absorbed doses were found for the urinary bladder wall and the kidneys (44.1/44.0 {mu}Gy/MBq). The effective dose according to ICRP 60 was 15.1 {mu}Sv/MBq for adults. This leads to an effective dose of 6.0 mSv in a PET study using 400 MBq cis-FPro.

Ethical Challenges of Educational Leadership in the Countries of the CIS

Science.gov (United States)

Zagoumennov, Iouri

2010-01-01

There is no school administrators' pre-service training in the CIS (Former USSR) countries. As for the in-service training, it has been traditionally focused on educational management. As a result, schools in the CIS countries are run as well-oiled machines but there is a big question mark over whether these machines are running in the right…

Dissecting neural pathways for forgetting in Drosophila olfactory aversive memory.

Science.gov (United States)

Shuai, Yichun; Hirokawa, Areekul; Ai, Yulian; Zhang, Min; Li, Wanhe; Zhong, Yi

2015-12-01

Recent studies have identified molecular pathways driving forgetting and supported the notion that forgetting is a biologically active process. The circuit mechanisms of forgetting, however, remain largely unknown. Here we report two sets of Drosophila neurons that account for the rapid forgetting of early olfactory aversive memory. We show that inactivating these neurons inhibits memory decay without altering learning, whereas activating them promotes forgetting. These neurons, including a cluster of dopaminergic neurons (PAM-β'1) and a pair of glutamatergic neurons (MBON-γ4>γ1γ2), terminate in distinct subdomains in the mushroom body and represent parallel neural pathways for regulating forgetting. Interestingly, although activity of these neurons is required for memory decay over time, they are not required for acute forgetting during reversal learning. Our results thus not only establish the presence of multiple neural pathways for forgetting in Drosophila but also suggest the existence of diverse circuit mechanisms of forgetting in different contexts.

Removal of detergents from SDS-inactivated dextransucrase

International Nuclear Information System (INIS)

Husman, D.W.; Mayer, R.M.

1986-01-01

Dextransucrase, which is rapidly inactivated by SDS, can be reactivated upon the addition of Triton X-100. Purification of the enzyme, in good yield and homogeneity, has been achieved by chromatography in the presence of SDS. The purified enzyme can be reactivated with Triton, but has large amounts of detergents. It was important to develop procedures for their removal. Density gradient centrifugation of SDS-inactivated or Triton-reactivated enzyme, treatment with Extracti-Gel D (Pierce) or chromatography on hydroxyl apatite (HA), have been examined for their effectiveness in providing detergent-free enzyme in good yield. Ultracentrifugation of SDS-inactivated protein provided limited recovery of active enzyme, but suggested that reactivation could be achieved by the simple removal of the detergent. While similar behavior was observed when the enzyme was eluted from Extracti-Gel, it was also shown that the limited recovery was a result of irreversible inactivation of the enzyme. Recovery could be improved if the enzyme was collected in solutions containing Triton, which has been reported to be a stabilizer. Chromatography of SDS-inactivated enzyme on HA also yielded active enzyme. Good recovery was obtained when Triton-reactivated enzyme was employed in these studies. The degree of detergent removal was determined by utilizing radiolabelled SDS and Triton X-100

IFITM Proteins Restrict HIV-1 Infection by Antagonizing the Envelope Glycoprotein

Directory of Open Access Journals (Sweden)

Jingyou Yu

2015-10-01

Full Text Available The interferon-induced transmembrane (IFITM proteins have been recently shown to restrict HIV-1 and other viruses. Here, we provide evidence that IFITM proteins, particularly IFITM2 and IFITM3, specifically antagonize the HIV-1 envelope glycoprotein (Env, thereby inhibiting viral infection. IFITM proteins interact with HIV-1 Env in viral producer cells, leading to impaired Env processing and virion incorporation. Notably, the level of IFITM incorporation into HIV-1 virions does not strictly correlate with the extent of inhibition. Prolonged passage of HIV-1 in IFITM-expressing T lymphocytes leads to emergence of Env mutants that overcome IFITM restriction. The ability of IFITMs to inhibit cell-to-cell infection can be extended to HIV-1 primary isolates, HIV-2 and SIVs; however, the extent of inhibition appears to be virus-strain dependent. Overall, our study uncovers a mechanism by which IFITM proteins specifically antagonize HIV-1 Env to restrict HIV-1 infection and provides insight into the specialized role of IFITMs in HIV infection.

Effect of endothelin antagonism on apnea frequency following chronic intermittent hypoxia.

Science.gov (United States)

Donovan, Lucas M; Liu, Yuzhen; Weiss, J Woodrow

2014-04-01

Chronic hypoxia increases the hypoxic ventilatory response (HVR). Augmented HVR contributes to central apneas seen in heart failure and complex sleep apnea. Endothelin receptor (ETR) antagonism decreases carotid body afferent activity following chronic intermittent hypoxia (CIH). We speculated ETR antagonism would reduce HVR and apneas following CIH. HVR and apneas were measured after exposure to CIH and room air sham (SHAM). ETR blocker Ambrisentan was administered via the chow of CIH-exposed animals from days 1 to 12 of CIH (CIH/AMB). A separate crossover group was exposed to CIH and fed normal chow (placebo) days 1-6, and Ambrisentan days 7-12 (CIH/PLA-AMB). SHAM and CIH/PLA animals were fed placebo days 1-12. The CIH/AMB and CIH/PLA-AMB rats had reduced HVR compared to CIH/PLA, similar HVR compared to sham exposed animals, and reduced apnea frequency compared to CIH/PLA animals. The reduced HVR and post-hypoxic apneas resulting from Ambrisentan administration suggests ETR antagonists may have utility in reducing central apneas following CIH. Copyright © 2014 Elsevier B.V. All rights reserved.

SRY-box-containing gene 2 regulation of nuclear receptor tailless (Tlx) transcription in adult neural stem cells.

Science.gov (United States)

Shimozaki, Koji; Zhang, Chun-Li; Suh, Hoonkyo; Denli, Ahmet M; Evans, Ronald M; Gage, Fred H

2012-02-17

Adult neurogenesis is maintained by self-renewable neural stem cells (NSCs). Their activity is regulated by multiple signaling pathways and key transcription factors. However, it has been unclear whether these factors interplay with each other at the molecular level. Here we show that SRY-box-containing gene 2 (Sox2) and nuclear receptor tailless (TLX) form a molecular network in adult NSCs. We observed that both Sox2 and TLX proteins bind to the upstream region of Tlx gene. Sox2 positively regulates Tlx expression, whereas the binding of TLX to its own promoter suppresses its transcriptional activity in luciferase reporter assays. Such TLX-mediated suppression can be antagonized by overexpressing wild-type Sox2 but not a mutant lacking the transcriptional activation domain. Furthermore, through regions involved in DNA-binding activity, Sox2 and TLX physically interact to form a complex on DNAs that contain a consensus binding site for TLX. Finally, depletion of Sox2 revealed the potential negative feedback loop of TLX expression that is antagonized by Sox2 in adult NSCs. These data suggest that Sox2 plays an important role in Tlx transcription in cultured adult NSCs.

SRY-box-containing Gene 2 Regulation of Nuclear Receptor Tailless (Tlx) Transcription in Adult Neural Stem Cells*

Science.gov (United States)

Shimozaki, Koji; Zhang, Chun-Li; Suh, Hoonkyo; Denli, Ahmet M.; Evans, Ronald M.; Gage, Fred H.

2012-01-01

Adult neurogenesis is maintained by self-renewable neural stem cells (NSCs). Their activity is regulated by multiple signaling pathways and key transcription factors. However, it has been unclear whether these factors interplay with each other at the molecular level. Here we show that SRY-box-containing gene 2 (Sox2) and nuclear receptor tailless (TLX) form a molecular network in adult NSCs. We observed that both Sox2 and TLX proteins bind to the upstream region of Tlx gene. Sox2 positively regulates Tlx expression, whereas the binding of TLX to its own promoter suppresses its transcriptional activity in luciferase reporter assays. Such TLX-mediated suppression can be antagonized by overexpressing wild-type Sox2 but not a mutant lacking the transcriptional activation domain. Furthermore, through regions involved in DNA-binding activity, Sox2 and TLX physically interact to form a complex on DNAs that contain a consensus binding site for TLX. Finally, depletion of Sox2 revealed the potential negative feedback loop of TLX expression that is antagonized by Sox2 in adult NSCs. These data suggest that Sox2 plays an important role in Tlx transcription in cultured adult NSCs. PMID:22194602

Cis-regulatory somatic mutations and gene-expression alteration in B-cell lymphomas.

Science.gov (United States)

Mathelier, Anthony; Lefebvre, Calvin; Zhang, Allen W; Arenillas, David J; Ding, Jiarui; Wasserman, Wyeth W; Shah, Sohrab P

2015-04-23

With the rapid increase of whole-genome sequencing of human cancers, an important opportunity to analyze and characterize somatic mutations lying within cis-regulatory regions has emerged. A focus on protein-coding regions to identify nonsense or missense mutations disruptive to protein structure and/or function has led to important insights; however, the impact on gene expression of mutations lying within cis-regulatory regions remains under-explored. We analyzed somatic mutations from 84 matched tumor-normal whole genomes from B-cell lymphomas with accompanying gene expression measurements to elucidate the extent to which these cancers are disrupted by cis-regulatory mutations. We characterize mutations overlapping a high quality set of well-annotated transcription factor binding sites (TFBSs), covering a similar portion of the genome as protein-coding exons. Our results indicate that cis-regulatory mutations overlapping predicted TFBSs are enriched in promoter regions of genes involved in apoptosis or growth/proliferation. By integrating gene expression data with mutation data, our computational approach culminates with identification of cis-regulatory mutations most likely to participate in dysregulation of the gene expression program. The impact can be measured along with protein-coding mutations to highlight key mutations disrupting gene expression and pathways in cancer. Our study yields specific genes with disrupted expression triggered by genomic mutations in either the coding or the regulatory space. It implies that mutated regulatory components of the genome contribute substantially to cancer pathways. Our analyses demonstrate that identifying genomically altered cis-regulatory elements coupled with analysis of gene expression data will augment biological interpretation of mutational landscapes of cancers.

Genome-wide haplotype analysis of cis expression quantitative trait loci in monocytes.

Directory of Open Access Journals (Sweden)

Sophie Garnier

Full Text Available In order to assess whether gene expression variability could be influenced by several SNPs acting in cis, either through additive or more complex haplotype effects, a systematic genome-wide search for cis haplotype expression quantitative trait loci (eQTL was conducted in a sample of 758 individuals, part of the Cardiogenics Transcriptomic Study, for which genome-wide monocyte expression and GWAS data were available. 19,805 RNA probes were assessed for cis haplotypic regulation through investigation of ~2,1 × 10(9 haplotypic combinations. 2,650 probes demonstrated haplotypic p-values >10(4-fold smaller than the best single SNP p-value. Replication of significant haplotype effects were tested for 412 probes for which SNPs (or proxies that defined the detected haplotypes were available in the Gutenberg Health Study composed of 1,374 individuals. At the Bonferroni correction level of 1.2 × 10(-4 (~0.05/412, 193 haplotypic signals replicated. 1000 G imputation was then conducted, and 105 haplotypic signals still remained more informative than imputed SNPs. In-depth analysis of these 105 cis eQTL revealed that at 76 loci genetic associations were compatible with additive effects of several SNPs, while for the 29 remaining regions data could be compatible with a more complex haplotypic pattern. As 24 of the 105 cis eQTL have previously been reported to be disease-associated loci, this work highlights the need for conducting haplotype-based and 1000 G imputed cis eQTL analysis before commencing functional studies at disease-associated loci.

Luciferase inactivation in the luminous marine bacterium Vibrio harveyi.

Science.gov (United States)

Reeve, C A; Baldwin, T O

1981-06-01

Luciferase was rapidly inactivated in stationary-phase cultures of the wild type of the luminous marine bacterium Vibrio harveyi, but was stable in stationary-phase cultures of mutants of V. harveyi that are nonluminous without exogenous aldehyde, termed the aldehyde-deficient mutants. The inactivation in the wild type was halted by cell lysis and was slowed or stopped by O2 deprivation or by addition of KCN and NaF or of chloramphenicol. If KCN and NaF or chloramphenicol were added to a culture before the onset of luciferase inactivation, then luciferase inactivation did not occur. However, if these inhibitors were added after the onset of luciferase inactivation, then luciferase inactivation continued for about 2 to 3 h before the inactivation process stopped. The onset of luciferase inactivation in early stationary-phase cultures of wild-type cell coincided with a slight drop in the intracellular adenosine 5'-triphosphate (ATP) level from a relatively constant log-phase value of 20 pmol of ATP per microgram of soluble cell protein. Addition of KCN and NaF to a culture shortly after this drop in ATP caused a rapid decrease in the ATP level to about 4 pmol of ATP per microgram whereas chloramphenicol added at this same time caused a transient increase in ATP level to about 25 pmol/microgram. The aldehyde-deficient mutant (M17) showed a relatively constant log-phase ATP level identical with that of the wild-type cells, but rather than decreasing in early stationary phase, the ATP level increased to a value twice that in log-phase cells. We suggest that the inactivation of luciferase is dependent on the synthesis of some factor which is produced during stationary phase and is itself unstable, and whose synthesis is blocked by chloramphenicol or cyanide plus fluoride.

Comparison of two different methods for inactivation of viruses in serum

DEFF Research Database (Denmark)

Preuss, T.; Kamstrup, Søren; Kyvsgaard, N.C.

1997-01-01

enterovirus (PEV) was inactivated within 3 h, The inactivation with electron-beam irradiation resulted in almost linear curves in a semilogarithmic plot of virus titer versus irradiation dose, reflecting a first-order inactivation, The rate of inactivation was almost twice as fast in the liquid samples...

Symbiont interactions in a tripartite mutualism: exploring the presence and impact of antagonism between two fungus-growing ant mutualists.

Directory of Open Access Journals (Sweden)

Michael Poulsen

Full Text Available Mutualistic associations are shaped by the interplay of cooperation and conflict among the partners involved, and it is becoming increasingly clear that within many mutualisms multiple partners simultaneously engage in beneficial interactions. Consequently, a more complete understanding of the dynamics within multipartite mutualism communities is essential for understanding the origin, specificity, and stability of mutualisms. Fungus-growing ants cultivate fungi for food and maintain antibiotic-producing Pseudonocardia actinobacteria on their cuticle that help defend the cultivar fungus from specialized parasites. Within both ant-fungus and ant-bacterium mutualisms, mixing of genetically distinct strains can lead to antagonistic interactions (i.e., competitive conflict, which may prevent the ants from rearing multiple strains of either of the mutualistic symbionts within individual colonies. The success of different ant-cultivar-bacterium combinations could ultimately be governed by antagonistic interactions between the two mutualists, either as inhibition of the cultivar by Pseudonocardia or vice versa. Here we explore cultivar-Pseudonocardia antagonism by evaluating in vitro interactions between strains of the two mutualists, and find frequent antagonistic interactions both from cultivars towards Pseudonocardia and vice versa. To test whether such in vitro antagonistic interactions affect ant colonies in vivo, we performed sub-colony experiments using species of Acromyrmex leaf-cutting ants. We created novel ant-fungus-bacterium pairings in which there was antagonism from one, both, or neither of the ants' microbial mutualists, and evaluated the effect of directional antagonism on cultivar biomass and Pseudonocardia abundance on the cuticle of workers within sub-colonies. Despite the presence of frequent in vitro growth suppression between cultivars and Pseudonocardia, antagonism from Pseudonocardia towards the cultivar did not reduce sub

Oxidation reactions of derivatives of cis-octalins promoted by thallium trinitrate (TTN)

International Nuclear Information System (INIS)

Ferraz, Helena M.C.; Carneiro, Vania M.T.; Vieira, Tiago O.; Silva Junior, Luiz F.

2008-01-01

The reaction of ten cis-octalins and cis-octalones with thallium trinitrate (TTN) leads to different products, depending mainly on the substitution pattern of the substrate. Functionalized cis-hydrindanes were obtained from the reaction of 1,2,3,4,4a,5,8,8a-octahydro- 4a-methylnaphthalene and of 1,2,3,4,4a,5,8,8a-octahydro-4a,7-dimethylnaphthalene with TTN in acetonitrile, whereas a cyclic ether was formed treating 1,2,3,4,4a,5,8,8a-octahydro-6,8a-dimethylnaphthalene-1-ol with TTN in trimethylorthoformate (TMOF). (author)

Antagonism of a (+)N-allylnormetazocine stimulus by (-)PPAP and several structurally related analogs.

Science.gov (United States)

Glennon, R A; Young, R; Herndon, J L

1993-08-01

Employing rats trained to discriminate 5 mg/kg of the benzomorphan opioid (+)N-allylnormetazocine [(+)NANM] from vehicle, tests of stimulus generalization and antagonism were conducted to determine the influence of several potential sigma-receptor ligands. It has been previously suggested that the (+)NANM stimulus may involve concurrent action at sigma- and phencyclidine (PCP) receptors. Although the low-affinity sigma-antagonist rimcazole was without stimulus-attenuating effect, three novel sigma-ligands--(-)PPAP, CNS 3018, and CNS 3093 (ID50 doses = 3.2, 6.7, and 4.5 mg/kg, respectively)--antagonized the (+)NANM stimulus in a dose-related fashion. The nonselective serotonergic agent 1-(3-trifluoromethyl)phenylpiperazine (TFMPP) produced partial generalization in (+)NANM-trained animals whereas buspirone, a 5-hydroxytryptamine1A (5-HT1A) agonist, attenuated (to 27% drug-appropriate responding) the (+)NANM stimulus. Because the prototypic 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) failed to attenuate the (+)NANM stimulus at pharmacologically relevant doses, it seems unlikely that the (+)NANM stimulus involves a 5-HT1A mechanism. TFMPP and buspirone display modest affinity for sigma-receptors and this may account for the present findings with these agents. The present results neither establish a role for sigma involvement in the stimulus properties of (+)NANM nor eliminate a role for PCP receptors. They do, however, demonstrate that sigma-ligands with little to no affinity for PCP receptors are capable of antagonizing the (+)NANM stimulus.

Neural stem cell-encoded temporal patterning delineates an early window of malignant susceptibility in Drosophila.

Science.gov (United States)

Narbonne-Reveau, Karine; Lanet, Elodie; Dillard, Caroline; Foppolo, Sophie; Chen, Ching-Huan; Parrinello, Hugues; Rialle, Stéphanie; Sokol, Nicholas S; Maurange, Cédric

2016-06-14

Pediatric neural tumors are often initiated during early development and can undergo very rapid transformation. However, the molecular basis of this early malignant susceptibility remains unknown. During Drosophila development, neural stem cells (NSCs) divide asymmetrically and generate intermediate progenitors that rapidly differentiate in neurons. Upon gene inactivation, these progeny can dedifferentiate and generate malignant tumors. Here, we find that intermediate progenitors are prone to malignancy only when born during an early window of development while expressing the transcription factor Chinmo, and the mRNA-binding proteins Imp/IGF2BP and Lin-28. These genes compose an oncogenic module that is coopted upon dedifferentiation of early-born intermediate progenitors to drive unlimited tumor growth. In late larvae, temporal transcription factor progression in NSCs silences the module, thereby limiting mitotic potential and terminating the window of malignant susceptibility. Thus, this study identifies the gene regulatory network that confers malignant potential to neural tumors with early developmental origins.

On the Concept of Cis-regulatory Information: From Sequence Motifs to Logic Functions

Science.gov (United States)

Tarpine, Ryan; Istrail, Sorin

The regulatory genome is about the “system level organization of the core genomic regulatory apparatus, and how this is the locus of causality underlying the twin phenomena of animal development and animal evolution” (E.H. Davidson. The Regulatory Genome: Gene Regulatory Networks in Development and Evolution, Academic Press, 2006). Information processing in the regulatory genome is done through regulatory states, defined as sets of transcription factors (sequence-specific DNA binding proteins which determine gene expression) that are expressed and active at the same time. The core information processing machinery consists of modular DNA sequence elements, called cis-modules, that interact with transcription factors. The cis-modules “read” the information contained in the regulatory state of the cell through transcription factor binding, “process” it, and directly or indirectly communicate with the basal transcription apparatus to determine gene expression. This endowment of each gene with the information-receiving capacity through their cis-regulatory modules is essential for the response to every possible regulatory state to which it might be exposed during all phases of the life cycle and in all cell types. We present here a set of challenges addressed by our CYRENE research project aimed at studying the cis-regulatory code of the regulatory genome. The CYRENE Project is devoted to (1) the construction of a database, the cis-Lexicon, containing comprehensive information across species about experimentally validated cis-regulatory modules; and (2) the software development of a next-generation genome browser, the cis-Browser, specialized for the regulatory genome. The presentation is anchored on three main computational challenges: the Gene Naming Problem, the Consensus Sequence Bottleneck Problem, and the Logic Function Inference Problem.

Inactivation of Lassa, Marburg, and Ebola viruses by gamma irradiation

International Nuclear Information System (INIS)

Elliott, L.H.; McCormick, J.B.; Johnson, K.M.

1982-01-01

Because of the cumbersome conditions experienced in a maximum containment laboratory, methods for inactivating highly pathogenic viruses were investigated. The infectivity of Lassa, Marburg, and Ebola viruses was inactivated without altering the immunological activity after radiation with 60 CO gamma rays. At 4 degrees C, Lassa virus was the most difficult to inactivate with a rate of 5.3 X 10(-6) log 50% tissue culture infective dose per rad of 60 CO radiation, as compared with 6.8 X 10(-6) log 50% tissue culture infective dose per rad for Ebola virus and 8.4 X 10(-6) log 50% tissue culture infective dose per rad for Marburg virus. Experimental inactivation curves, as well as curves giving the total radiation needed to inactivate a given concentration of any of the three viruses, are presented. The authors found this method of inactivation to be superior to UV light or beta-propiolactone inactivation and now routinely use it for preparation of material for protein-chemistry studies or for preparation of immunological reagents

Inactivation of Lassa, Marburg, and Ebola viruses by gamma irradiation

International Nuclear Information System (INIS)

Elliott, L.H.; McCormick, J.B.; Johnson, K.M.

1982-01-01

Because of the cumbersome conditions experienced in a maximum containment laboratory, methods for inactivating highly pathogenic viruses were investigated. The infectivity of Lassa, Marburg, and Ebola viruses was inactivated without altering the immunological activity after radiation with 60 Co gamma rays. At 4 degrees C, Lassa virus was the most difficult to inactivate with a rate of 5.3 X 10(-6) log 50% tissue culture infective dose per rad of 60 Co radiation, as compared with 6.8 X 10(-6) log 50% tissue culture infective dose per rad for Ebola virus and 8.4 X 10(-6) log 50% tissue culture infective dose per rad for Marburg virus. Experimental inactivation curves, as well as curves giving the total radiation needed to inactivate a given concentration of any of the three viruses, are presented. We found this method of inactivation to be superior to UV light or beta-propiolactone inactivation and now routinely use it for preparation of material for protein-chemistry studies or for preparation of immunological reagents

Melatonin antagonizes interleukin-18-mediated inhibition on neural stem cell proliferation and differentiation.

Science.gov (United States)

Li, Zheng; Li, Xingye; Chan, Matthew T V; Wu, William Ka Kei; Tan, DunXian; Shen, Jianxiong

2017-09-01

Neural stem cells (NSCs) are self-renewing, pluripotent and undifferentiated cells which have the potential to differentiate into neurons, oligodendrocytes and astrocytes. NSC therapy for tissue regeneration, thus, gains popularity. However, the low survivals rate of the transplanted cell impedes its utilities. In this study, we tested whether melatonin, a potent antioxidant, could promote the NSC proliferation and neuronal differentiation, especially, in the presence of the pro-inflammatory cytokine interleukin-18 (IL-18). Our results showed that melatonin per se indeed exhibited beneficial effects on NSCs and IL-18 inhibited NSC proliferation, neurosphere formation and their differentiation into neurons. All inhibitory effects of IL-18 on NSCs were significantly reduced by melatonin treatment. Moreover, melatonin application increased the production of both brain-derived and glial cell-derived neurotrophic factors (BDNF, GDNF) in IL-18-stimulated NSCs. It was observed that inhibition of BDNF or GDNF hindered the protective effects of melatonin on NSCs. A potentially protective mechanism of melatonin on the inhibition of NSC's differentiation caused IL-18 may attribute to the up-regulation of these two major neurotrophic factors, BNDF and GNDF. The findings indicate that melatonin may play an important role promoting the survival of NSCs in neuroinflammatory diseases. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Photodynamic inactivation of foodborne bacteria by eosin Y.

Science.gov (United States)

Bonin, E; Dos Santos, A R; Fiori da Silva, A; Ribeiro, L H; Favero, M E; Campanerut-Sá, P A Z; de Freitas, C F; Caetano, W; Hioka, N; Mikcha, J M G

2018-03-25

The aim of this study was evaluate the effect of photodynamic inactivation mediated by eosin Y in Salmonella enterica serotype Typhimurium ATCC 14028, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923 and Bacillus cereus ATCC 11778. Bacteria (10 7 CFU per ml) were incubated with eosin Y at concentrations ranging from 0·1 to 10 μmol l -1 , irradiated by green LED (λ max 490-570 nm) for 5, 10 and 15 min and the cellular viability was determined. Pseudomonas aeruginosa was completely inactivated when treated with 10 μmol l -1 eosin Y for 10 min. Treatments reduced B. cereus and Salm. Typhimurium counts to 2·7 log CFU per ml and 1·7 log CFU per ml, respectively. Escherichia coli counts were slightly reduced. Staphylococcus aureus presented the highest sensitivity, being completely inactivated by eosin Y at 5 μmol l -1 and 5 min of illumination. The reduction of cellular viability of photoinactivated Staph. aureus was also demonstrated by flow cytometry and morphological changes were observed by scanning electron microscopy. Eosin Y in combination with LED produced bacterial inactivation, being a potential candidate for photodynamic inactivation. This study evidenced the efficacy of photodynamic inactivation as a novel and promising alternative to bacterial control. © 2018 The Society for Applied Microbiology.

Organization of cis-acting regulatory elements in osmotic- and cold-stress-responsive promoters.

Science.gov (United States)

Yamaguchi-Shinozaki, Kazuko; Shinozaki, Kazuo

2005-02-01

cis-Acting regulatory elements are important molecular switches involved in the transcriptional regulation of a dynamic network of gene activities controlling various biological processes, including abiotic stress responses, hormone responses and developmental processes. In particular, understanding regulatory gene networks in stress response cascades depends on successful functional analyses of cis-acting elements. The ever-improving accuracy of transcriptome expression profiling has led to the identification of various combinations of cis-acting elements in the promoter regions of stress-inducible genes involved in stress and hormone responses. Here we discuss major cis-acting elements, such as the ABA-responsive element (ABRE) and the dehydration-responsive element/C-repeat (DRE/CRT), that are a vital part of ABA-dependent and ABA-independent gene expression in osmotic and cold stress responses.

Molecular mechanism of 9-cis-retinoic acid inhibition of adipogenesis in 3T3-L1 cells

International Nuclear Information System (INIS)

Sagara, Chiaki; Takahashi, Katsuhiko; Kagechika, Hiroyuki; Takahashi, Noriko

2013-01-01

Highlights: ► We examined the effects of 9-cis-RA on adipogenesis in mouse preadipocyte 3T3-L1. ► 9-cis-RA inhibited lipid accumulation in adipogenetically-induced 3T3-L1 cells. ► A RXR pan-antagonist suppressed the inhibitory effects of 9-cis-RA on adipogenesis. ► This antagonist had no effects on RXRα and PPARγ levels in 9-cis-RA-treated cells. ► 9-cis-RA-induced decrease in both RXRα and PPARγ was independent of RXR activation. -- Abstract: Retinoic acid (RA) signaling is mediated by specific nuclear hormone receptors. Here we examined the effects of 9-cis-RA on adipogenesis in mouse preadipocyte 3T3-L1 cells. 9-cis-RA inhibits the lipid accumulation of adipogenetically induced 3T3-L1 cells. The complex of retinoid X receptor α (RXRα) with peroxisome proliferator-activated receptor γ (PPARγ) is a major transcription factor in the process of adipogenesis, and the levels of these molecules were decreased by 9-cis-RA treatment. A RXR pan-antagonist suppressed 9-cis-RA’s inhibitory effects on adipogenesis, but not on the intracellular levels of both RXRα and PPARγ. These results suggest that 9-cis-RA could inhibit adipogenesis by activating RXR, and decrease both RXR and PPARγs levels in a RXR activation-independent manner

Antagonism of Sorafenib and Regorafenib actions by platelet factors in hepatocellular carcinoma cell lines

International Nuclear Information System (INIS)

D’Alessandro, Rosalba; Refolo, Maria G; Lippolis, Catia; Giannuzzi, Grazia; Carella, Nicola; Messa, Caterina; Cavallini, Aldo; Carr, Brian I

2014-01-01

Platelets are frequently altered in hepatocellular carcinoma (HCC) patients. Platelet lysates (hPL) can enhance HCC cell growth and decrease apoptosis. The aims were to evaluate whether hPL can modulate the actions of Sorafenib or Regorafenib, two clinical HCC multikinase antagonists. Several human HCC cell lines were grown in the presence and absence of Sorafenib or Regorafenib, with or without hPL. Growth was measured by MTT assay, apoptosis was assessed by Annexin V and by western blot, and autophagy and MAPK growth signaling were also measured by western blot, and migration and invasion were measured by standard in vitro assays. Both Sorafenib and Regorafenib-mediated inhibition of cell growth, migration and invasion were all antagonized by hPL. Drug-mediated apoptosis and decrease in phospho-ERK levels were both blocked by hPL, which also increased anti-apoptotic phospho-STAT, Bax and Bcl-xL levels. Preliminary data, obtained with epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I), included in hPL, revealed that these factors were able to antagonized Sorafenib in a proliferation assay, in particular when used in combination. Platelet factors can antagonize Sorafenib or Regorafenib-mediated growth inhibition and apoptosis in HCC cells. The modulation of platelet activity or numbers has the potential to enhance multikinase drug actions

Information Spreadsheet for Engines and Vehicles Compliance Information System (EV-CIS) User Registration

Science.gov (United States)

In this spreadsheet, user(s) provide their company’s manufacturer code, user contact information for EV-CIS, and user roles. This spreadsheet is used for the Company Authorizing Official (CAO), CROMERR Signer, and EV-CIS Submitters.

The synthesis and preliminary pharmacological evaluation of the racemic cis and trans 3-alkylfentanyl analogues

Directory of Open Access Journals (Sweden)

LJ. DOSEN-MICOVIC

2004-07-01

Full Text Available A general, five step method for the synthesis of 3-alkylfentanyl analogues (i.e., cis and trans 3-alkyl-4-anilidopiperidines 6.1–6.6 has been developed. The starting N-phenethyl-4-piperidone 1 was first converted into the cyclohexylimine derivative 2, a-deprotonated with butyllithium and the resulting imine anion efficiently monoalkylated with primary and secondary alkyl halides. After mild acid hydrolysis, the obtained 3-alkyl-4-piperidones 3.1–3.6 were isolated in good yields (79–85 %, then condensed with aniline to form imines 4.1–4.6. Subsequent reduction of the imines (LiAlH4/THF yielded cis/trans mixtures of 3-alkyl-4-anilinopiperidines 5.1–5.6. Quantitative separation of the diastereoisomers by column chromatography of Al2O3 gave pure cis 5.1–5.6 (29–51 % yield and trans 5.1–5.6 (19–27 % yield, with the cis/trans ratio in the range 7/3–6/4. The synthesis was concluded by N-acylation of the purified 5.1–5.6, with propionyl chloride, to afford cis and trans 3-alkyl-4-anilidopiperidines 6.1–6.6 (~95 % yield, as monooxalate salts. No enatioseparation was attempted at any stage. The relative cis/trans stereochemistry was provisionally assigned from the 1H-NMR spectra. Of the twelve synthesized 3-alkylfentanyls, ten compounds (two known and eight novel derivatives, all as the monooxalate salts were preliminarily tested as analgesics in rats, comparing the potency to fentanyl. Except for the known (±-cis-3-Me fentanyl 6.1cis, (8 × fentanyl, and the novel (±-cis-3-Et fentanyl 6.2cis, (1.5 × fentanyl, all of the others were less active than fentanyl or inactive. Some tentative conclusions on the structure-activity relationship (SAR in this series of derivatives have been made.

Inactivation of Mycobacterium avium with free chlorine.

Science.gov (United States)

Luh, Jeanne; Mariñas, Benito J

2007-07-15

The inactivation kinetics of Mycobacterium avium with free chlorine was characterized by two stages: an initial phase at a relatively fast rate followed by a slower second stage of pseudo first-order kinetics. The inactivation rate of each stage was approximately the same for all experiments performed at a certain condition of pH and temperature; however, variability was observed for the disinfectant exposure at which the transition between the two stages occurred. This variability was not a function of the initial disinfectant concentration, the initial bacterial density, or the bacterial stock. However, the transition to the second stage varied more significantly at high temperatures (30 degrees C), while lower variability was observed at lower temperatures (5 and 20 degrees C). Experiments conducted at pH values in the range of 6-9 revealed that the inactivation of M. avium was primarily due to hypochlorous acid, with little contribution from hypochlorite ion within this pH range. The inactivation kinetics was represented with a two-population model. The activation energies for the resulting pseudo first-order rate constants for the populations with fast and slow kinetics were 100.3 and 96.5 kJ/mol, respectively. The magnitude of these values suggested that for waters of relatively high pH and low temperatures, little inactivation of M. avium would be achieved within treatment plants, providing a seeding source for distribution systems.

Inactivating the infralimbic but not prelimbic medial prefrontal cortex facilitates the extinction of appetitive Pavlovian conditioning in Long-Evans rats.

Science.gov (United States)

Mendoza, J; Sanio, C; Chaudhri, N

2015-02-01

The infralimbic medial prefrontal cortex (IL) has been posited as a common node in distinct neural circuits that mediate the extinction of appetitive and aversive conditioning. However, appetitive extinction is typically assessed using instrumental conditioning procedures, whereas the extinction of aversive conditioning is customarily studied using Pavlovian assays. The role of the IL in the extinction of appetitive Pavlovian conditioning remains underexplored. We investigated the involvement of the IL and prelimbic medial prefrontal cortex (PrL) in appetitive extinction in Pavlovian and instrumental conditioning assays in male, Long-Evans rats. Following acquisition, a gamma-aminobutyric acid agonist solution (0.03 nmol muscimol; 0.3 nmol baclofen; 0.3 μl/side) was bilaterally microinfused into the IL or PrL to pharmacologically inactivate each region before the first extinction session. Compared to saline, PrL inactivation did not affect the acquisition of extinction or the recall of extinction memory 24-h later. IL inactivation caused a more rapid extinction of Pavlovian conditioning, but had no effect on the extinction of instrumental conditioning or extinction recall. IL inactivation during a Pavlovian conditioning session in which conditioned stimulus (CS) trials were paired with sucrose did not affect CS-elicited behaviour, but increased responding during intervals that did not contain the CS. The same manipulation did not impact lever pressing for sucrose. These findings suggest that the IL may normally maintain Pavlovian conditioned responding when an anticipated appetitive CS is unexpectedly withheld, and that this region has distinct roles in the expression of Pavlovian conditioning when an appetitive unconditioned stimulus is either presented or omitted. Copyright © 2014 Elsevier Inc. All rights reserved.

Identification of the 11-cis-specific retinyl-ester synthase in retinal Müller cells as multifunctional O-acyltransferase (MFAT)

Science.gov (United States)

Kaylor, Joanna J.; Cook, Jeremy D.; Makshanoff, Jacob; Bischoff, Nicholas; Yong, Jennifer; Travis, Gabriel H.

2014-01-01

Absorption of a photon by a rhodopsin or cone-opsin pigment isomerizes its 11-cis-retinaldehyde (11-cis-RAL) chromophore to all-trans-retinaldehyde (all-trans-RAL), which dissociates after a brief period of activation. Light sensitivity is restored to the resulting apo-opsin when it recombines with another 11-cis-RAL. Conversion of all-trans-RAL to 11-cis-RAL is carried out by an enzyme pathway called the visual cycle in cells of the retinal pigment epithelium. A second visual cycle is present in Müller cells of the retina. The retinol isomerase for this noncanonical pathway is dihydroceramide desaturase (DES1), which catalyzes equilibrium isomerization of retinol. Because 11-cis-retinol (11-cis-ROL) constitutes only a small fraction of total retinols in an equilibrium mixture, a subsequent step involving selective removal of 11-cis-ROL is required to drive synthesis of 11-cis-retinoids for production of visual chromophore. Selective esterification of 11-cis-ROL is one possibility. Crude homogenates of chicken retinas rapidly convert all-trans-ROL to 11-cis-retinyl esters (11-cis-REs) with minimal formation of other retinyl-ester isomers. This enzymatic activity implies the existence of an 11-cis-specific retinyl-ester synthase in Müller cells. Here, we evaluated multifunctional O-acyltransferase (MFAT) as a candidate for this 11-cis-RE-synthase. MFAT exhibited much higher catalytic efficiency as a synthase of 11-cis-REs versus other retinyl-ester isomers. Further, we show that MFAT is expressed in Müller cells. Finally, homogenates of cells coexpressing DES1 and MFAT catalyzed the conversion of all-trans-ROL to 11-cis-RP, similar to what we observed with chicken-retina homogenates. MFAT is therefore an excellent candidate for the retinyl-ester synthase that cooperates with DES1 to drive synthesis of 11-cis-retinoids by mass action. PMID:24799687

Detection of trans-cis flips and peptide-plane flips in protein structures

NARCIS (Netherlands)

Touw, W.G.; Joosten, R.P.; Vriend, G.

2015-01-01

A coordinate-based method is presented to detect peptide bonds that need correction either by a peptide-plane flip or by a trans-cis inversion of the peptide bond. When applied to the whole Protein Data Bank, the method predicts 4617 trans-cis flips and many thousands of hitherto unknown

Inactivation of the infragranular striate cortex broadens orientation tuning of supragranular visual neurons in the cat.

Science.gov (United States)

Allison, J D; Bonds, A B

1994-01-01

Intracortical inhibition is believed to enhance the orientation tuning of striate cortical neurons, but the origin of this inhibition is unclear. To examine the possible influence of ascending inhibitory projections from the infragranular layers of striate cortex on the orientation selectivity of neurons in the supragranular layers, we measured the spatiotemporal response properties of 32 supragranular neurons in the cat before, during, and after neural activity in the infragranular layers beneath the recorded cells was inactivated by iontophoretic administration of GABA. During GABA iontophoresis, the orientation tuning bandwidth of 15 (46.9%) supragranular neurons broadened as a result of increases in response amplitude to stimuli oriented about +/- 20 degrees away from the preferred stimulus angle. The mean (+/- SD) baseline orientation tuning bandwidth (half width at half height) of these neurons was 13.08 +/- 2.3 degrees. Their mean tuning bandwidth during inactivation of the infragranular layers increased to 19.59 +/- 2.54 degrees, an increase of 49.7%. The mean percentage increase in orientation tuning bandwidth of the individual neurons was 47.4%. Four neurons exhibited symmetrical changes in their orientation tuning functions, while 11 neurons displayed asymmetrical changes. The change in form of the orientation tuning functions appeared to depend on the relative vertical alignment of the recorded neuron and the infragranular region of inactivation. Neurons located in close vertical register with the inactivated infragranular tissue exhibited symmetric changes in their orientation tuning functions. The neurons exhibiting asymmetric changes in their orientation tuning functions were located just outside the vertical register. Eight of these 11 neurons also demonstrated a mean shift of 6.67 +/- 5.77 degrees in their preferred stimulus orientation. The magnitude of change in the orientation tuning functions increased as the delivery of GABA was prolonged

Inactivation of viruses in municipal effluent by chlorine.

OpenAIRE

Hajenian, H. G.; Butler, M.

1980-01-01

The influence of pH and temperature on the efficiency of chlorine inactivation of two unrelated picornaviruses in a typical urban wastewater effluent was examined. Temperature, unlike pH, had relatively little effect on the rate of inactivation. The pH effect was complex and the two viruses differed. The f2 coliphage was more sensitive to chlorine at low pH, but at all values there was a threshold above which additional chlorine resulted in very rapid inactivation. The amount of chlorine requ...

A study of the relative importance of the peroxiredoxin-, catalase-, and glutathione-dependent systems in neural peroxide metabolism.

Science.gov (United States)

Mitozo, Péricles Arruda; de Souza, Luiz Felipe; Loch-Neckel, Gecioni; Flesch, Samira; Maris, Angelica Francesca; Figueiredo, Cláudia Pinto; Dos Santos, Adair Roberto Soares; Farina, Marcelo; Dafre, Alcir Luiz

2011-07-01

Cells are endowed with several overlapping peroxide-degrading systems whose relative importance is a matter of debate. In this study, three different sources of neural cells (rat hippocampal slices, rat C6 glioma cells, and mouse N2a neuroblastoma cells) were used as models to understand the relative contributions of individual peroxide-degrading systems. After a pretreatment (30 min) with specific inhibitors, each system was challenged with either H₂O₂ or cumene hydroperoxide (CuOOH), both at 100 μM. Hippocampal slices, C6 cells, and N2a cells showed a decrease in the H₂O₂ decomposition rate (23-28%) by a pretreatment with the catalase inhibitor aminotriazole. The inhibition of glutathione reductase (GR) by BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) significantly decreased H₂O₂ and CuOOH decomposition rates (31-77%). Inhibition of catalase was not as effective as BCNU at decreasing cell viability (MTT assay) and cell permeability or at increasing DNA damage (comet test). Impairing the thioredoxin (Trx)-dependent peroxiredoxin (Prx) recycling by thioredoxin reductase (TrxR) inhibition with auranofin neither potentiated peroxide toxicity nor decreased the peroxide-decomposition rate. The results indicate that neural peroxidatic systems depending on Trx/TrxR for recycling are not as important as those depending on GSH/GR. Dimer formation, which leads to Prx2 inactivation, was observed in hippocampal slices and N2a cells treated with H₂O₂, but not in C6 cells. However, Prx-SO₃ formation, another form of Prx inactivation, was observed in all neural cell types tested, indicating that redox-mediated signaling pathways can be modulated in neural cells. These differences in Prx2 dimerization suggest specific redox regulation mechanisms in glia-derived (C6) compared to neuron-derived (N2a) cells and hippocampal slices. Copyright © 2011 Elsevier Inc. All rights reserved.

PAA, WSH, and CIS Overview Self-Study #47656

Energy Technology Data Exchange (ETDEWEB)

Schroeder, Rachel Anne [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2017-09-14

This course presents an overview of the Department of Energy’s (DOE’s) regulatory requirements relevant to the Price-Anderson Amendments Act (PAAA, also referred to as nuclear safety), worker safety and health (WSH), and classified information security (CIS) that are enforceable under the DOE enforcement program; describes the DOE enforcement process; and provides an overview of Los Alamos National Laboratory’s (LANL’s) internal compliance program relative to these DOE regulatory requirements. The LANL PAAA Program is responsible for maintaining LANL’s internal compliance program, which ensures the prompt identification, screening, and reporting of noncompliances to DOE regulatory requirements pertaining to nuclear safety, WSH, and CIS to build the strongest mitigation position for the Laboratory with respect to civil or other penalties.

Neural underpinnings of distortions in the experience of time across senses

Directory of Open Access Journals (Sweden)

Deborah L. Harrington

2011-07-01

Full Text Available Auditory signals (A are perceived as lasting longer than visual signals (V of the same physical duration when they are compared together. Despite considerable debate about how this illusion arises psychologically, the neural underpinnings have not been studied. We used functional magnetic resonance imaging (fMRI to investigate the neural bases of audiovisual temporal distortions and more generally, intersensory timing. Adults underwent fMRI while judging the relative duration of successively presented standard interval (SI-comparison interval (CI pairs, which were unimodal (A-A, V-V or crossmodal (V-A, A-V. Mechanisms of time dilation and compression were identified by comparing the two crossmodal pairs. Mechanisms of intersensory timing were identified by comparing the unimodal and crossmodal conditions. The behavioral results showed that auditory CIs were perceived as lasting longer than visual CIs. There were three novel fMRI results. First, time dilation and compression were distinguished by differential activation of higher sensory areas (superior temporal, posterior insula, middle occipital, which typically showed stronger effective connectivity when time was dilated (V-A. Second, when time was compressed (A-V activation was greater in frontal cognitive-control centers, which guide decision making. These areas did not exhibit effective connectivity. Third, intrasensory timing was distinguished from intersensory timing partly by decreased striatal and increased superior parietal activation. These regions showed stronger connectivity with visual, memory, and cognitive-control centers during intersensory timing. Altogether, the results indicate that time dilation and compression arise from the connectivity strength of higher sensory systems with other areas. Conversely, more extensive network interactions are needed with core timing (striatum and attention (superior parietal centers to integrate time codes for intersensory signals.

Antagonism between penicillin and erythromycin against Streptococcus pneumoniae in vitro and in vivo

DEFF Research Database (Denmark)

Johansen, H K; Jensen, T G; Dessau, R B

2000-01-01

The combination of beta-lactam antibiotics and macrolides is often recommended for the initial empirical treatment of acute pneumonia in order to obtain activity against the most important pathogens. Theoretically, this combination may be inexpedient, as the bacteriostatic agent may antagonize th...

FoxO3A promotes metabolic adaptation to hypoxia by antagonizing Myc function

OpenAIRE

Jensen, Kim Steen; Binderup, Tina; Jensen, Klaus Thorleif; Therkelsen, Ib; Borup, Rehannah; Nilsson, Elise; Multhaupt, Hinke; Bouchard, Caroline; Quistorff, Bjørn; Kjær, Andreas; Landberg, Göran; Staller, Peter

2011-01-01

This paper characterizes FoxO3A as required for hypoxic suppression of mitochondrial mass, oxygen consumption, and ROS production. Mechanistically, FoxO3A is shown to promote hypoxic cell survival by directly antagonizing c-Myc at nuclear encoded mitochondrial genes.

Physical inactivation and stabilization of sludges

International Nuclear Information System (INIS)

Alexandre, D.

1979-07-01

High temperature conditioning of sludge is a stabilization process that insures sterilization. Both thermal pasteurization and irradiation are inactivation processes. Viruses and parasites are inactivated at 70-80 0 C. Total bacterial destruction requires higher temperatures and/or detention time. Radio sensitivity of pathogens and pertinent treatment parameters are examined. If sludge is to be land disposed, disinfection requires irradiation doses ranging 500 Krad; if cattle feeding is considered, the required dose is 1 Mrad

New probabilistic risk assessment of ethylhexyl methoxycinnamate: Comparing the genotoxic effects of trans- and cis-EHMC.

Science.gov (United States)

Nečasová, Anežka; Bányiová, Katarína; Literák, Jaromír; Čupr, Pavel

2017-02-01

Ethylhexyl methoxycinnamate (EHMC) is a widely used UV filter present in a large number of personal care products (PCPs). Under normal conditions, EHMC occurs in a mixture of two isomers: trans-EHMC and cis-EHMC in a ratio of 99:1. When exposed to sunlight, the trans isomer is transformed to the less stable cis isomer and the efficiency of the UV filter is reduced. To date, the toxicological effects of the cis-EHMC isomer remain largely unknown. We developed a completely new method for preparing cis-EHMC. An EHMC technical mixture was irradiated using a UV lamp and 98% pure cis-EHMC was isolated from the irradiated solution using column chromatography. The genotoxic effects of the isolated cis-EHMC isomer and the nonirradiated trans-EHMC were subsequently measured using two bioassays (SOS chromotest and UmuC test). In the case of trans-EHMC, significant genotoxicity was observed using both bioassays at the highest concentrations (0.5 - 4 mg mL -1 ). In the case of cis-EHMC, significant genotoxicity was only detected using the UmuC test at concentrations of 0.25 - 1 mg mL -1 . Based on these results, the NOEC was calculated for both cis- and trans-EHMC, 0.038 and 0.064 mg mL -1 , respectively. Risk assessment of dermal, oral and inhalation exposure to PCPs containing EHMC was carried out for a female population using probabilistic simulation and by using Quantitative in vitro to in vivo extrapolation (QIVIVE). The risk of cis-EHMC was found to be ∼1.7 times greater than trans-EHMC. In the case of cis-EHMC, a hazard index of 1 was exceeded in the 92nd percentile. Based on the observed differences between the isomers, EHMC application in PCPs requires detailed reassessment. Further exploration of the toxicological effects and properties of cis-EHMC is needed in order to correctly predict risks posed to humans and the environment. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 569-580, 2017. © 2016 Wiley Periodicals, Inc.

Cramp-fasciculation syndrome in patients with and without neural autoantibodies.

Science.gov (United States)

Liewluck, Teerin; Klein, Christopher J; Jones, Lyell K

2014-03-01

We investigated the clinical, electrophysiological and neural autoantibody characteristics in cramp-fasciculation syndrome (CFS) patients. We reviewed Mayo Clinic records from 2000 to 2011 to identify clinically defined CFS patients who underwent neural autoantibody testing. Stored sera of patients who tested positive for antibodies to voltage-gated potassium channel complex (VGKC complex) were analyzed further for leucine-rich glioma-inactivated 1 (LGI1) or contactin-associated protein-2 immunoglobulin G (CASPR2-IgG) antibodies. Thirty-seven patients were identified. Twelve were seropositive for neural autoantibodies. Clinical manifestations were similar in seropositive and seronegative patients, although central and autonomic neuronal hyperexcitability symptoms were more common in seropositive cases. No patients had a malignancy. Repetitive tibial nerve stimulation at 10 Hz revealed longer afterdischarges in seropositive patients. Two of 7 patients with VGKC-complex autoimmunity demonstrated LGI1 or CASPR2-IgG antibodies. Only 2 of 12 seropositive patients required immunotherapy. VGKC-complex autoimmunity occurs in a minority of CFS patients. Antibody positivity was associated with extramuscular manifestations, typically without malignancy. Target antigens within the VGKC complex remain unknown in most patients. Published 2013 by Wiley Periodicals, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.

Inactivation of complement by Loxosceles reclusa spider venom.

Science.gov (United States)

Gebel, H M; Finke, J H; Elgert, K D; Cambell, B J; Barrett, J T

1979-07-01

Zymosan depletion of serum complement in guinea pigs rendered them highly resistant to lesion by Loxosceles reclusa spider venom. Guinea pigs deficient in C4 of the complement system are as sensitive to the venom as normal guinea pigs. The injection of 35 micrograms of whole recluse venom intradermally into guinea pigs lowered their complement level by 35.7%. Brown recluse spider venom in concentrations as slight as 0.02 micrograms protein/ml can totally inactivate one CH50 of guinea pig complement in vitro. Bee, scorpion, and other spider venoms had no influence on the hemolytic titer of complement. Fractionation of recluse spider venom by Sephadex G-200 filtration separated the complement-inactivating property of the venom into three major regions which could be distinguished on the basis of heat stability as well as size. None was neutralized by antivenom. Polyacrylamide gel electrophoresis of venom resolved the complement inactivators into five fractions. Complement inactivated by whole venom or the Sephadex fractions could be restored to hemolytic activity by supplements of fresh serum but not by heat-inactivated serum, pure C3, pure C5, or C3 and C5 in combination.

Randomized Trials Comparing Inactivated Vaccine after Medium- or High-titer Measles Vaccine with Standard Titer Measles Vaccine after Inactivated Vaccine

DEFF Research Database (Denmark)

Aaby, Peter; Ravn, Henrik; Benn, Christine S.

2016-01-01

Background: Observational studies have suggested that girls have higher mortality if their most recent immunization is an inactivated vaccine rather than a live vaccine. We therefore reanalyzed 5 randomized trials of early measles vaccine (MV) in which it was possible to compare an inactivated va...

Germination and Inactivation of Alicyclobacillus acidoterrestris Spores Induced by Moderate Hydrostatic Pressure.

Science.gov (United States)

Sokołowska, Barbara; Skapska, Sylwia; Fonberg-Broczek, Monika; Niezgoda, Jolanta; Porebska, Izabela; Dekowska, Agnieszka; Rzoska, Sylwester J

2015-01-01

Given the importance of spoilage caused by Alicyclobacillus acidoterrestris for the fruit juice industry, the objective of this work was to study the germination and inactivation of A. acidoterrestris spores induced by moderate hydrostatic pressure. Hydrostatic pressure treatment can induce the germination and inactivation of A. acidoterrestris spores. At low pH, spore germination of up to 3.59-3.75 log and inactivation of 1.85-2.04 log was observed in a low pressure window (200-300 MPa) applied at 50 degrees C for 20 min. Neutral pH suppressed inactivation, the number of spores inactivated at pH 7.0 was only 0.24-1.06 log. The pressurization temperature significantly affected spore germination and inactivation. The degree of germination in apple juice after pressurization for 30 min with 200 MPa at 20 degrees C was 2.04 log, with only 0.61 log of spores being inactivated, while at 70 degrees C spore germination was 5.94 log and inactivation 4.72 log. This temperature strongly stimulated germination and inactivation under higher (500 MPa) than lower (200 MPa) pressure. When the oscillatory mode was used, the degree of germination and inactivation was slightly higher than at continuous mode. The degree of germination and inactivation was inversely proportional to the soluble solids content and was lowest in concentrated apple juice.

Inactivation of human and simian rotaviruses by ozone

Energy Technology Data Exchange (ETDEWEB)

Vaughn, J.M.; Chen, Y.S.; Lindburg, K.; Morales, D.

1987-09-01

The inactivation of simian rotavirus Sa-11 and human rotavirus type 2 (Wa) by ozone was compared at 4/sup 0/C by using single-particle virus stocks. Although the human strain was clearly more sensitive, both virus types were rapidly inactivated by ozone concentrations of 0.25 mg/liter or greater at all pH levels tested. Comparison of the virucidal activity of ozone with that of chlorine in identical experiments indicated little significant difference in rotavirus-inactivating efficiencies when the disinfectants were used at concentrations of 0.25 mg/liter or greater.

A CIS (Clinical Information System) Quality Evaluation Tool for Nursing Care Services

Science.gov (United States)

Lee, Seon Ah

2010-01-01

The purpose of this study was to develop a tool to evaluate the quality of a clinical information system (CIS) conceived by nurses and conduct a pilot test with the developed tool as an initial assessment. CIS quality is required for successful implementation in information technology (IT) environments. The study started with the realization that…

Vasoactive intestinal peptide is a local mediator in a gut-brain neural axis activating intestinal gluconeogenesis.

Science.gov (United States)

De Vadder, F; Plessier, F; Gautier-Stein, A; Mithieux, G

2015-03-01

Intestinal gluconeogenesis (IGN) promotes metabolic benefits through activation of a gut-brain neural axis. However, the local mediator activating gluconeogenic genes in the enterocytes remains unknown. We show that (i) vasoactive intestinal peptide (VIP) signaling through VPAC1 receptor activates the intestinal glucose-6-phosphatase gene in vivo, (ii) the activation of IGN by propionate is counteracted by VPAC1 antagonism, and (iii) VIP-positive intrinsic neurons in the submucosal plexus are increased under the action of propionate. These data support the role of VIP as a local neuromodulator released by intrinsic enteric neurons and responsible for the induction of IGN through a VPAC1 receptor-dependent mechanism in enterocytes. © 2015 John Wiley & Sons Ltd.

Inhibition of protein synthesis does not antagonize induction of UV-induced sister-chromatid exchange in xeroderma pigmentosum cells

International Nuclear Information System (INIS)

Sono, Akira; Sakaguchi, Kengo.

1988-01-01

Cycloheximide strongly antagonizes the induction of sisterchromatid exchanges by ethyl methanesulfonate or mitomycin C in human skin fibroblast and xeroderma pigmentosum cells (group A). Analogous behavior has been observed in several other species including Chinese hamster and plant cells. This report documents an exception to that pattern: cycloheximide fails to antagonize UV-induced sister chromatid exchange in xeroderma pigmentosum cells, whereas it does in normal human skin fibroblast cells. A genetic defect in these cells is postulated to alter the UV-mediated DNA recombination process. (author)

Investment in the CEE/CIS region

International Nuclear Information System (INIS)

Lemierre, J.

2002-01-01

The energy investments in the Central and Eastern European region and the Commonwealth of Independent States (CIS) region are discussed in this Keynote Address. The message is addressed to regulators and governments. The restructuring of old industries to save energy is highlighted. The regulatory system must undergo a substantial reform. Another message is placed for investors in the energy field. (R.P.)

High pressure inactivation of Brettanomyces bruxellensis in red wine.

Science.gov (United States)

van Wyk, Sanelle; Silva, Filipa V M

2017-05-01

Brettanomyces bruxellensis ("Brett") is a major spoilage concern for the wine industry worldwide, leading to undesirable sensory properties. Sulphur dioxide, is currently the preferred method for wine preservation. However, due to its negative effects on consumers, the use of new alternative non-thermal technologies are increasingly being investigated. The aim of this study was to determine and model the effect of high pressure processing (HPP) conditions and yeast strain on the inactivation of "Brett" in Cabernet Sauvignon wine. Processing at 200 MPa for 3 min resulted in 5.8 log reductions. However higher pressure is recommended to achieve high throughput in the wine industry, for example >6.0 log reductions were achieved after 400 MPa for 5 s. The inactivation of B. bruxellensis is pressure and time dependent, with increased treatment time and pressure leading to increased yeast inactivation. It was also found that yeast strain had a significant effect on HPP inactivation, with AWRI 1499 being the most resistant strain. The Weibull model successfully described the HPP "Brett" inactivation. HPP is a viable alternative for the inactivation of B. bruxellensis in wine, with the potential to reduce the industry's reliance on sulphur dioxide. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chlorophyll mediated photodynamic inactivation of blue laser on Streptococcus mutans

Science.gov (United States)

Astuti, Suryani Dyah; Zaidan, A.; Setiawati, Ernie Maduratna; Suhariningsih

2016-03-01

Photodynamic inactivation is an inactivation method in microbial pathogens that utilize light and photosensitizer. This study was conducted to investigate photodynamic inactivation effects of low intensity laser exposure with various dose energy on Streptococcus mutans bacteria. The photodynamic inactivation was achieved with the addition of chlorophyll as photosensitizers. To determine the survival percentage of Streptococcus mutans bacteria after laser exposure, the total plate count method was used. For this study, the wavelength of the laser is 405 nm and variables of energy doses are 1.44, 2.87, 4.31, 5.74, 7.18, and 8.61 in J/cm2. The results show that exposure to laser with energy dose of 7.18 J/cm2 has the best photodynamic inactivation with a decrease of 78% in Streptococcus

Forced Normalization: Antagonism Between Epilepsy and Psychosis.

Science.gov (United States)

Kawakami, Yasuhiko; Itoh, Yasuhiko

2017-05-01

The antagonism between epilepsy and psychosis has been discussed for a long time. Landolt coined the term "forced normalization" in the 1950s to describe psychotic episodes associated with the remission of seizures and disappearance of epileptiform activity on electroencephalograms in individuals with epilepsy. Since then, neurologists and psychiatrists have been intrigued by this phenomenon. However, although collaborative clinical studies and basic experimental researches have been performed, the mechanism of forced normalization remains unknown. In this review article, we present a historical overview of the concept of forced normalization, and discuss potential pathogenic mechanisms and clinical diagnosis. We also discuss the role of dopamine, which appears to be a key factor in the mechanism of forced normalization. Copyright © 2017 Elsevier Inc. All rights reserved.

Differential Effects of Inactivation of Discrete Regions of Medial Prefrontal Cortex on Memory Consolidation of Moderate and Intense Inhibitory Avoidance Training

Directory of Open Access Journals (Sweden)

María E. Torres-García

2017-11-01

Full Text Available It has been found that the medial prefrontal cortex (mPFC is involved in memory encoding of aversive events, such as inhibitory avoidance (IA training. Dissociable roles have been described for different mPFC subregions regarding various memory processes, wherein the anterior cingulate cortex (ACC, prelimbic cortex (PL, and infralimbic cortex (IL are involved in acquisition, retrieval, and extinction of aversive events, respectively. On the other hand, it has been demonstrated that intense training impedes the effects on memory of treatments that typically interfere with memory consolidation. The aim of this work was to determine if there are differential effects on memory induced by reversible inactivation of neural activity of ACC, PL, or IL produced by tetrodotoxin (TTX in rats trained in IA using moderate (1.0 mA and intense (3.0 mA foot-shocks. We found that inactivation of ACC has no effects on memory consolidation, regardless of intensity of training. PL inactivation impairs memory consolidation in the 1.0 mA group, while no effect on consolidation was produced in the 3.0 mA group. In the case of IL, a remarkable amnestic effect in LTM was observed in both training conditions. However, state-dependency can explain the amnestic effect of TTX found in the 3.0 mA IL group. In order to circumvent this effect, TTX was injected into IL immediately after training (thus avoiding state-dependency. The behavioral results are equivalent to those found after PL inactivation. Therefore, these findings provide evidence that PL and IL, but not ACC, mediate LTM of IA only in moderate training.

Selective augmentation of striatal functional connectivity following NMDA receptor antagonism: implications for psychosis.

Science.gov (United States)

Dandash, Orwa; Harrison, Ben J; Adapa, Ram; Gaillard, Raphael; Giorlando, Francesco; Wood, Stephen J; Fletcher, Paul C; Fornito, Alex

2015-02-01

The psychotomimetic effect of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine is thought to arise from a functional modulation of the brain's fronto-striato-thalamic (FST) circuits. Animal models suggest a pronounced effect on ventral 'limbic' FST systems, although recent work in patients with psychosis and high-risk individuals suggests specific alterations of dorsal 'associative' FST circuits. Here, we used functional magnetic resonance imaging to investigate the effects of a subanesthetic dose of ketamine on measures of functional connectivity as indexed by the temporal coherence of spontaneous neural activity in both dorsal and ventral FST circuits, as well as their symptom correlates. We adopted a placebo-controlled, double-blind, randomized, repeated-measures design in which 19 healthy participants received either an intravenous saline infusion or a racemic mixture of ketamine (100 ng/ml) separated by at least 1 week. Compared with placebo, ketamine increased functional connectivity between the dorsal caudate and both the thalamus and midbrain bilaterally. Ketamine additionally increased functional connectivity of the ventral striatum/nucleus accumbens and ventromedial prefrontal cortex. Both connectivity increases significantly correlated with the psychosis-like and dissociative symptoms under ketamine. Importantly, dorsal caudate connectivity with the ventrolateral thalamus and subthalamic nucleus showed inverse correlation with ketamine-induced symptomatology, pointing to a possible resilience role to disturbances in FST circuits. Although consistent with the role of FST in mediating psychosis, these findings contrast with previous research in clinical samples by suggesting that acute NMDAR antagonism may lead to psychosis-like experiences via a mechanism that is distinct from that implicated in frank psychotic illness.

First start toward nuclear disarmament: CIS openness and compliance. Research report, August 1991-April 1992

Energy Technology Data Exchange (ETDEWEB)

Casteel, B.

1992-04-01

In the last six months we have seen significant changes in the Soviet Union which have radically altered that way we have conducted business. Now, it is no longer the Soviet Union, but the Commonwealth of Independent States (CIS). We are now making wholesale unilateral cuts in our defense structure as the CIS is viewed as our friend and no longer the Evil Empire. We are supplying the CIS with food, loan credits, and even offering assistance to help them destroy nuclear weapons. Even though the world has changed, the CIS remains the only country on the face of the earth capable of destroying the United States in a nuclear holocaust.

Inactivation of RNA Viruses by Gamma Irradiation: A Study on Mitigating Factors

Directory of Open Access Journals (Sweden)

Adam J. Hume

2016-07-01

Full Text Available Effective inactivation of biosafety level 4 (BSL-4 pathogens is vital in order to study these agents safely. Gamma irradiation is a commonly used method for the inactivation of BSL-4 viruses, which among other advantages, facilitates the study of inactivated yet morphologically intact virions. The reported values for susceptibility of viruses to inactivation by gamma irradiation are sometimes inconsistent, likely due to differences in experimental protocols. We analyzed the effects of common sample attributes on the inactivation of a recombinant vesicular stomatitis virus expressing the Zaire ebolavirus glycoprotein and green fluorescent protein. Using this surrogate virus, we found that sample volume and protein content of the sample modulated viral inactivation by gamma irradiation but that air volume within the sample container and the addition of external disinfectant surrounding the sample did not. These data identify several factors which alter viral susceptibility to inactivation and highlight the usefulness of lower biosafety level surrogate viruses for such studies. Our results underscore the need to validate inactivation protocols of BSL-4 pathogens using “worst-case scenario” procedures to ensure complete sample inactivation.

X inactivation in females with X-linked Charcot-Marie-Tooth disease.

LENUS (Irish Health Repository)

Murphy, Sinéad M

2012-07-01

X-linked Charcot-Marie-Tooth disease (CMT1X) is the second most common inherited neuropathy, caused by mutations in gap junction beta-1 (GJB1). Males have a uniformly moderately severe phenotype while females have a variable phenotype, suggested to be due to X inactivation. We aimed to assess X inactivation pattern in females with CMT1X and correlate this with phenotype using the CMT examination score to determine whether the X inactivation pattern accounted for the variable phenotype in females with CMT1X. We determined X inactivation pattern in 67 females with CMT1X and 24 controls using the androgen receptor assay. We were able to determine which X chromosome carried the GJB1 mutation in 30 females. There was no difference in X inactivation pattern between patients and controls. In addition, there was no correlation between X inactivation pattern in blood and phenotype. A possible explanation for these findings is that the X inactivation pattern in Schwann cells rather than in blood may explain the variable phenotype in females with CMT1X.

Benzodiazepine antagonism by harmane and other beta-carbolines in vitro and in vivo.

Science.gov (United States)

Rommelspacher, H; Nanz, C; Borbe, H O; Fehske, K J; Müller, W E; Wollert, U

1981-03-26

Harmane and other related beta-carbolines are putative endogenous ligands of the benzodiazepine receptor. Since the compounds are potent convulsants they may have agonist activities at the benzodiazepine receptor while the benzodiazepines may be antagonists. This hypothesis was proved by comparing the in vivo and in vitro antagonism of benzodiazepines by harmane and other beta-carbolines. Harmane is clearly a competitive inhibitor of benzodiazepine receptor binding in vitro. Moreover, harmane-induced convulsions can be inhibited reversibly by diazepam in a manner which is consistent with the assumption of competitive antagonism in vivo. For some beta-carboline derivatives a correlation was found between the affinity for the benzodiazepine receptor in vitro and the convulsive potency in vivo. Thus, the data reported suggest that harmane or other related beta-carbolines are putative endogenous agonists of the benzodiazepine receptor. This suggestion is further supported by the observation that diazepam is equally potent in inhibiting harmane- or picrotoxin-induced convulsions, indicating a convulsive mechanism within the GABA receptor-benzodiazepine receptor system.

Cis-urocanic acid, a sunlight-induced immunosuppressive factor, activates immune suppression via the 5-HT2A receptor

Science.gov (United States)

Walterscheid, Jeffrey P.; Nghiem, Dat X.; Kazimi, Nasser; Nutt, Leta K.; McConkey, David J.; Norval, Mary; Ullrich, Stephen E.

2006-01-01

Exposure to UV radiation induces skin cancer and suppresses the immune response. To induce immune suppression, the electromagnetic energy of UV radiation must be absorbed by an epidermal photoreceptor and converted into a biologically recognizable signal. Two photoreceptors have been recognized: DNA and trans-urocanic acid (UCA). Trans-UCA is normally found in the outermost layer of skin and isomerizes to the cis isomer upon exposure to UV radiation. Although UCA was identified as a UV photoreceptor years ago, and many have documented its ability to induce immune suppression, its exact mode of action remains elusive. Particularly vexing has been the identity of the molecular pathway by which cis-UCA mediates immune suppression. Here we provide evidence that cis-UCA binds to the serotonin [5-hydroxytryptamine (5-HT)] receptor with relatively high affinity (Kd = 4.6 nM). Anti-cis-UCA antibody precipitates radiolabeled 5-HT, and the binding is inhibited by excess 5-HT and/or excess cis-UCA. Similarly, anti-5-HT antibody precipitates radiolabeled cis-UCA, and the binding is inhibited by excess 5-HT or excess cis-UCA. Calcium mobilization was activated when a mouse fibroblast line, stably transfected with the human 5-HT2A receptor, was treated with cis-UCA. Cis-UCA-induced calcium mobilization was blocked with a selective 5-HT2A receptor antagonist. UV- and cis-UCA-induced immune suppression was blocked by antiserotonin antibodies or by treating the mice with 5-HT2A receptor antagonists. Our findings identify cis-UCA as a serotonin receptor ligand and indicate that the immunosuppressive effects of cis-UCA and UV radiation are mediated by activation of the 5-HT2A receptor. PMID:17085585

Injection anaesthesia with fentanyl-midazolam-medetomidine in adult female mice: importance of antagonization and perioperative care.

Science.gov (United States)

Fleischmann, Thea; Jirkof, Paulin; Henke, Julia; Arras, Margarete; Cesarovic, Nikola

2016-08-01

Injection anaesthesia is commonly used in laboratory mice; however, a disadvantage is that post-anaesthesia recovery phases are long. Here, we investigated the potential for shortening the recovery phase after injection anaesthesia with fentanyl-midazolam-medetomidine by antagonization with naloxone-flumazenil-atipamezole. In order to monitor side-effects, the depth of anaesthesia, heart rate (HR), core body temperature (BT) and concentration of blood gases, as well as reflex responses, were assessed during a 50 min anaesthesia. Mice were allowed to recover from the anaesthesia in their home cages either with or without antagonization, while HR, core BT and spontaneous home cage behaviours were recorded for 24 h. Mice lost righting reflex at 330 ± 47 s after intraperitoneal injection of fentanyl-midazolam-medetomidine. During anaesthesia, HR averaged 225 ± 23 beats/min, respiratory rate and core BT reached steady state at 131 ± 15 breaths/min and 34.3 ± 0.25℃, respectively. Positive pedal withdrawal reflex, movement triggered by tail pinch and by toe pinch, still occurred in 25%, 31.2% and 100% of animals, respectively. Arterial blood gas analysis revealed acidosis, hypoxia, hypercapnia and a marked increase in glucose concentration. After anaesthesia reversal by injection with naloxone-flumazenil-atipamezole, animals regained consciousness after 110 ± 18 s and swiftly returned to physiological baseline values, yet they displayed diminished levels of locomotion and disrupted circadian rhythm. Without antagonization, mice showed marked hypothermia (22 ± 1.9℃) and bradycardia (119 ± 69 beats/min) for several hours. Fentanyl-midazolam-medetomidine provided reliable anaesthesia in mice with reasonable intra-anaesthetic side-effects. Post-anaesthetic period and related adverse effects were both reduced substantially by antagonization with naloxone-flumazenil-atipamezole. © The Author(s) 2016.

Mxi1 and Mxi1-0 Antagonize N-Myc Function and Independently Mediate Apoptosis in Neuroblastoma

Directory of Open Access Journals (Sweden)

David A. Erichsen

2015-02-01

Full Text Available Neuroblastoma (NB is the third most common malignancy of childhood, and outcomes for children with advanced disease remain poor; amplification of the MYCN gene portends a particularly poor prognosis. Mxi1 antagonizes N-Myc by competing for binding to Max and E-boxes. Unlike N-Myc, Mxi1 mediates transcriptional repression and suppresses cell proliferation. Mxi1 and Mxi1-0 (an alternatively transcribed Mxi1 isoform share identical Max and DNA binding domains but differ in amino-terminal sequences. Because of the conservation of these critical binding domains, we hypothesized that Mxi1-0 antagonizes N-Myc activity similar to Mxi1. SHEP NB cells and SHEP cells stably transfected with MYCN (SHEP/MYCN were transiently transfected with vectors containing full-length Mxi1, full-length Mxi1-0, or the common Mxi domain encoded by exons 2 to 6 (ex2-6. After incubation in low serum, parental SHEP/MYCN cell numbers were reduced compared with SHEP cells. Activated caspase-3 staining and DNA fragmentation ELISA confirmed that SHEP/MYCN cells undergo apoptosis in low serum, while SHEP/MYCN cells transfected with Mxi1 or Mxi1-0 do not. However, SHEP/MYCN cells transfected with Mxi1 or Mxi1-0 and grown in normal serum showed proliferation rates similar to SHEP cells. Mxi ex2-6 did not affect cell number in low or normal serum, suggesting that amino terminal domains of Mxi1 and Mxi1-0 are critical for antagonism. In the absence of N-Myc, Mxi1 and Mxi1-0 induce apoptosis independently through the caspase-8–dependent extrinsic pathway, while N-Myc activates the caspase-9–dependent intrinsic pathway. Together, these data indicate that Mxi1 and Mxi1-0 antagonize N-Myc but also independently impact NB cell survival.

Inactivation of prion infectivity by ionizing rays

Energy Technology Data Exchange (ETDEWEB)

Gominet, M. [Ionisos, ZI les Chatinieres, F01120 Dagneux (France); Vadrot, C.; Austruy, G. [Paris V University, Central Pharmacy of Hospitals, 4 avenue de l' Observatoire, F-75006, Paris (France); Darbord, J.C. [Paris V University, Central Pharmacy of Hospitals, 4 avenue de l' Observatoire, F-75006, Paris (France)], E-mail: darbord@pharmacie.univ-paris5.fr

2007-11-15

Inactivation of prion deposits on medical devices or prion contamination in pharmaceutical raw materials is considered as impossible by using gamma irradiation. Early, the guideline WHO/CDS/CSR/APH/2000 has described irradiation as an ineffective process. But, in 2003, S. Miekka et al. noted radiation inactivation of prions in a particular application to purify human albumin, shown by the physical denaturation of the infectious protein (PrP). The aim of our study was to determine the inactivation of prions with a scrapie model (strain C506M3) by irradiating standardised preparations. Results: Gamma irradiation was partially effective, showing a 4-5 log reduction on exposure to 50 kGy. A characteristic effect-dose curve was not observed (25, 50 and 100 kGy), only an increase in the incubation period of the murine disease (229 days with 25 kGy to 290 days with 100 kGy) compared with 170 days without irradiation. Since the inactivation was not a total one, the observed effect is significant. It is proposed that further work be undertaken with the model to investigate the application of gamma radiation known levels of prion contamination.

Inactivation of prion infectivity by ionizing rays

International Nuclear Information System (INIS)

Gominet, M.; Vadrot, C.; Austruy, G.; Darbord, J.C.

2007-01-01

Inactivation of prion deposits on medical devices or prion contamination in pharmaceutical raw materials is considered as impossible by using gamma irradiation. Early, the guideline WHO/CDS/CSR/APH/2000 has described irradiation as an ineffective process. But, in 2003, S. Miekka et al. noted radiation inactivation of prions in a particular application to purify human albumin, shown by the physical denaturation of the infectious protein (PrP). The aim of our study was to determine the inactivation of prions with a scrapie model (strain C506M3) by irradiating standardised preparations. Results: Gamma irradiation was partially effective, showing a 4-5 log reduction on exposure to 50 kGy. A characteristic effect-dose curve was not observed (25, 50 and 100 kGy), only an increase in the incubation period of the murine disease (229 days with 25 kGy to 290 days with 100 kGy) compared with 170 days without irradiation. Since the inactivation was not a total one, the observed effect is significant. It is proposed that further work be undertaken with the model to investigate the application of gamma radiation known levels of prion contamination

Detection of trans–cis flips and peptide-plane flips in protein structures

Energy Technology Data Exchange (ETDEWEB)

Touw, Wouter G., E-mail: wouter.touw@radboudumc.nl [Radboud University Medical Center, Geert Grooteplein-Zuid 26-28, 6525 GA Nijmegen (Netherlands); Joosten, Robbie P. [Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Vriend, Gert, E-mail: wouter.touw@radboudumc.nl [Radboud University Medical Center, Geert Grooteplein-Zuid 26-28, 6525 GA Nijmegen (Netherlands)

2015-07-28

A method is presented to detect peptide bonds that need either a trans–cis flip or a peptide-plane flip. A coordinate-based method is presented to detect peptide bonds that need correction either by a peptide-plane flip or by a trans–cis inversion of the peptide bond. When applied to the whole Protein Data Bank, the method predicts 4617 trans–cis flips and many thousands of hitherto unknown peptide-plane flips. A few examples are highlighted for which a correction of the peptide-plane geometry leads to a correction of the understanding of the structure–function relation. All data, including 1088 manually validated cases, are freely available and the method is available from a web server, a web-service interface and through WHAT-CHECK.

Detection of trans–cis flips and peptide-plane flips in protein structures

International Nuclear Information System (INIS)

Touw, Wouter G.; Joosten, Robbie P.; Vriend, Gert

2015-01-01

A method is presented to detect peptide bonds that need either a trans–cis flip or a peptide-plane flip. A coordinate-based method is presented to detect peptide bonds that need correction either by a peptide-plane flip or by a trans–cis inversion of the peptide bond. When applied to the whole Protein Data Bank, the method predicts 4617 trans–cis flips and many thousands of hitherto unknown peptide-plane flips. A few examples are highlighted for which a correction of the peptide-plane geometry leads to a correction of the understanding of the structure–function relation. All data, including 1088 manually validated cases, are freely available and the method is available from a web server, a web-service interface and through WHAT-CHECK

Thermal and high pressure inactivation kinetics of blueberry peroxidase.

Science.gov (United States)

Terefe, Netsanet Shiferaw; Delon, Antoine; Versteeg, Cornelis

2017-10-01

This study for the first time investigated the stability and inactivation kinetics of blueberry peroxidase in model systems (McIlvaine buffer, pH=3.6, the typical pH of blueberry juice) during thermal (40-80°C) and combined high pressure-thermal processing (0.1-690MPa, 30-90°C). At 70-80°C, the thermal inactivation kinetics was best described by a biphasic model with ∼61% labile and ∼39% stable fractions at temperature between 70 and 75°C. High pressure inhibited the inactivation of the enzyme with no inactivation at pressures as high as 690MPa and temperatures less than 50°C. The inactivation kinetics of the enzyme at 60-70°C, and pressures higher than 500MPa was best described by a first order biphasic model with ∼25% labile fraction and 75% stable fraction. The activation energy values at atmospheric pressure were 548.6kJ/mol and 324.5kJ/mol respectively for the stable and the labile fractions. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

cis-Tetrachlorido-bis(indazole)osmium(iv) and its osmium(iii) analogues: paving the way towards the cis-isomer of the ruthenium anticancer drugs KP1019 and/or NKP1339

KAUST Repository

Bü chel, Gabriel E.; Kossatz, Susanne; Sadique, Ahmad; Rapta, Peter; Zalibera, Michal; Bucinsky, Lukas; Komorovsky, Stanislav; Telser, Joshua; Eppinger, Jö rg; Reiner, Thomas; Arion, Vladimir B.

2017-01-01

The relationship between cis-trans isomerism and anticancer activity has been mainly addressed for square-planar metal complexes, in particular, for platinum(II), e.g., cis- and trans-[PtCl2(NH3)(2)], and a number of related compounds, of which, however, only cis-counterparts are in clinical use today. For octahedral metal complexes, this effect of geometrical isomerism on anticancer activity has not been investigated systematically, mainly because the relevant isomers are still unavailable. An example of such an octahedral complex is trans-[RuCl4(Hind)(2)](-), which is in clinical trials now as its indazolium (KP1019) or sodium salt (NKP1339), but the corresponding cis-isomers remain inaccessible. We report the synthesis of Na[cis-(OsCl4)-Cl-III(kappa N2-1H-ind)(2)] . (Na[1]) suggesting a route to the cis-isomer of NKP1339. The procedure involves heating (H(2)ind)[(OsCl5)-Cl-IV(kappa N1-2H-ind)] in a high boiling point organic solvent resulting in an Anderson rearrangement with the formation of cis-[(OsCl4)-Cl-IV(kappa N2-1H-ind)(2)] ([1]) in high yield. The transformation is accompanied by an indazole coordination mode switch from kappa N1 to kappa N2 and stabilization of the 1H-indazole tautomer. Fully reversible spectroelectrochemical reduction of [1] in acetonitrile at 0.46 V vs. NHE is accompanied by a change in electronic absorption bands indicating the formation of cis-[(OsCl4)-Cl-III(kappa N2-1H-ind)(2)](-) ([1](-)). Chemical reduction of [1] in methanol with NaBH4 followed by addition of nBu(4)NCl afforded the osmium(III) complex nBu(4)N[cis-(OsCl4)-Cl-III(kappa N2-1H-ind)(2)] (nBu(4)N [1]). A metathesis reaction of nBu(4)N[1] with an ion exchange resin led to the isolation of the water-soluble salt Na[1]. The X-ray diffraction crystal structure of [1] . Me2CO was determined and compared with that of trans-[(OsCl4)-Cl-IV(kappa N2-1H-ind)(2)] . 2Me(2)SO (2 . 2Me(2)SO), also prepared in this work. EPR spectroscopy was performed on the Os-III complexes and

cis-Tetrachlorido-bis(indazole)osmium(iv) and its osmium(iii) analogues: paving the way towards the cis-isomer of the ruthenium anticancer drugs KP1019 and/or NKP1339

KAUST Repository

Büchel, Gabriel E.

2017-08-15

The relationship between cis-trans isomerism and anticancer activity has been mainly addressed for square-planar metal complexes, in particular, for platinum(II), e.g., cis- and trans-[PtCl2(NH3)(2)], and a number of related compounds, of which, however, only cis-counterparts are in clinical use today. For octahedral metal complexes, this effect of geometrical isomerism on anticancer activity has not been investigated systematically, mainly because the relevant isomers are still unavailable. An example of such an octahedral complex is trans-[RuCl4(Hind)(2)](-), which is in clinical trials now as its indazolium (KP1019) or sodium salt (NKP1339), but the corresponding cis-isomers remain inaccessible. We report the synthesis of Na[cis-(OsCl4)-Cl-III(kappa N2-1H-ind)(2)] . (Na[1]) suggesting a route to the cis-isomer of NKP1339. The procedure involves heating (H(2)ind)[(OsCl5)-Cl-IV(kappa N1-2H-ind)] in a high boiling point organic solvent resulting in an Anderson rearrangement with the formation of cis-[(OsCl4)-Cl-IV(kappa N2-1H-ind)(2)] ([1]) in high yield. The transformation is accompanied by an indazole coordination mode switch from kappa N1 to kappa N2 and stabilization of the 1H-indazole tautomer. Fully reversible spectroelectrochemical reduction of [1] in acetonitrile at 0.46 V vs. NHE is accompanied by a change in electronic absorption bands indicating the formation of cis-[(OsCl4)-Cl-III(kappa N2-1H-ind)(2)](-) ([1](-)). Chemical reduction of [1] in methanol with NaBH4 followed by addition of nBu(4)NCl afforded the osmium(III) complex nBu(4)N[cis-(OsCl4)-Cl-III(kappa N2-1H-ind)(2)] (nBu(4)N [1]). A metathesis reaction of nBu(4)N[1] with an ion exchange resin led to the isolation of the water-soluble salt Na[1]. The X-ray diffraction crystal structure of [1] . Me2CO was determined and compared with that of trans-[(OsCl4)-Cl-IV(kappa N2-1H-ind)(2)] . 2Me(2)SO (2 . 2Me(2)SO), also prepared in this work. EPR spectroscopy was performed on the Os-III complexes and

cisTEM, user-friendly software for single-particle image processing

Science.gov (United States)

2018-01-01

We have developed new open-source software called cisTEM (computational imaging system for transmission electron microscopy) for the processing of data for high-resolution electron cryo-microscopy and single-particle averaging. cisTEM features a graphical user interface that is used to submit jobs, monitor their progress, and display results. It implements a full processing pipeline including movie processing, image defocus determination, automatic particle picking, 2D classification, ab-initio 3D map generation from random parameters, 3D classification, and high-resolution refinement and reconstruction. Some of these steps implement newly-developed algorithms; others were adapted from previously published algorithms. The software is optimized to enable processing of typical datasets (2000 micrographs, 200 k – 300 k particles) on a high-end, CPU-based workstation in half a day or less, comparable to GPU-accelerated processing. Jobs can also be scheduled on large computer clusters using flexible run profiles that can be adapted for most computing environments. cisTEM is available for download from cistem.org. PMID:29513216

cisTEM, user-friendly software for single-particle image processing.

Science.gov (United States)

Grant, Timothy; Rohou, Alexis; Grigorieff, Nikolaus

2018-03-07

We have developed new open-source software called cis TEM (computational imaging system for transmission electron microscopy) for the processing of data for high-resolution electron cryo-microscopy and single-particle averaging. cis TEM features a graphical user interface that is used to submit jobs, monitor their progress, and display results. It implements a full processing pipeline including movie processing, image defocus determination, automatic particle picking, 2D classification, ab-initio 3D map generation from random parameters, 3D classification, and high-resolution refinement and reconstruction. Some of these steps implement newly-developed algorithms; others were adapted from previously published algorithms. The software is optimized to enable processing of typical datasets (2000 micrographs, 200 k - 300 k particles) on a high-end, CPU-based workstation in half a day or less, comparable to GPU-accelerated processing. Jobs can also be scheduled on large computer clusters using flexible run profiles that can be adapted for most computing environments. cis TEM is available for download from cistem.org. © 2018, Grant et al.

Viscometric study of high-cis polybutadiene in toluene solution

International Nuclear Information System (INIS)

Mwllo, Ivana L.; Coutinho, Fernanda M.B.; Delpech, Marcia C.; Albino, Fernanda F.M.

2006-01-01

Viscometric measurements, in toluene solution at 30 deg C, were performed with high-cis polybutadiene synthesized by neodymium based catalyst. Six different equations were used to calculate intrinsic viscosities and viscosimetric constant values: Huggins, Kraemer, Martin and Schulz-Blaschke by graphic extrapolation, and Solomon-Ciuta, Deb-Chanterjee and again Schulz- Blaschke, through a single point determination. The molecular weight of the polymers was also determined applying Mark-Houwink-Sakurada equation using the values of intrinsic viscosity obtained by the six equations. The values of intrinsic viscosity and viscosity-average molecular weight obtained by the two methods were compared in order to verify the validity of the single point determination for high-cis polybutadiene. (author)

Thermal inactivation kinetics of β-galactosidase during bread baking.

Science.gov (United States)

Zhang, Lu; Chen, Xiao Dong; Boom, Remko M; Schutyser, Maarten A I

2017-06-15

In this study, β-galactosidase was utilized as a model enzyme to investigate the mechanism of enzyme inactivation during bread baking. Thermal inactivation of β-galactosidase was investigated in a wheat flour/water system at varying temperature-moisture content combinations, and in bread during baking at 175 or 205°C. In the wheat flour/water system, the thermostability of β-galactosidase increased with decreased moisture content, and a kinetic model was accurately fitted to the corresponding inactivation data (R 2 =0.99). Interestingly, the residual enzyme activity in the bread crust (about 30%) was hundredfold higher than that in the crumb (about 0.3%) after baking, despite the higher temperature in the crust throughout baking. This result suggested that the reduced moisture content in the crust increased the thermostability of the enzyme. Subsequently, the kinetic model reasonably predicted the enzyme inactivation in the crumb using the same parameters derived from the wheat flour/water system. However, the model predicted a lower residual enzyme activity in the crust compared with the experimental result, which indicated that the structure of the crust may influence the enzyme inactivation mechanism during baking. The results reported can provide a quantitative understanding of the thermal inactivation kinetics of enzyme during baking, which is essential to better retain enzymatic activity in bakery products supplemented with heat-sensitive enzymes. Copyright © 2017 Elsevier Ltd. All rights reserved.

A CREB-Sirt1-Hes1 Circuitry Mediates Neural Stem Cell Response to Glucose Availability

Directory of Open Access Journals (Sweden)

Salvatore Fusco

2016-02-01

Full Text Available Summary: Adult neurogenesis plays increasingly recognized roles in brain homeostasis and repair and is profoundly affected by energy balance and nutrients. We found that the expression of Hes-1 (hairy and enhancer of split 1 is modulated in neural stem and progenitor cells (NSCs by extracellular glucose through the coordinated action of CREB (cyclic AMP responsive element binding protein and Sirt-1 (Sirtuin 1, two cellular nutrient sensors. Excess glucose reduced CREB-activated Hes-1 expression and results in impaired cell proliferation. CREB-deficient NSCs expanded poorly in vitro and did not respond to glucose availability. Elevated glucose also promoted Sirt-1-dependent repression of the Hes-1 promoter. Conversely, in low glucose, CREB replaced Sirt-1 on the chromatin associated with the Hes-1 promoter enhancing Hes-1 expression and cell proliferation. Thus, the glucose-regulated antagonism between CREB and Sirt-1 for Hes-1 transcription participates in the metabolic regulation of neurogenesis. : Using a combination of in vitro and in vivo studies, Fusco et al. find that excess glucose impairs the self-renewal capacity of neural stem cells through a molecular circuit that involves the transcription factor CREB and Sirtuin 1. The authors suggest that this circuitry may link nutrient excess with neurodegeneration and brain aging. Keywords: neural stem cells, adult neurogenesis, CREB, Sirt-1, nutrients, metabolism, diabetes

Protection against the clastogenic effect of CIS-PLATINUM by WR-2721, ATP and Vitamin C

International Nuclear Information System (INIS)

Rupova, I.; Yagova, A.

1993-01-01

The mutagenic effect of antineoplastic drug Cis-Platinum has been assessed by the frequency of micronuclei in polychromatic erythrocytes (PE) in the mouse bone marrow at time intervals of 24, 48 and 73 h. The maximal clastogenic effect of 2 mg/kg of Cis-Platinum has been found at 24 h interval after treatment (3.6%). The protection against mutagenic activity of Cis-Platinum has been studied by pretreatment of the mice with the thiophosphate compound WR-2721, adenosine triphosphate (ATP) and Vitamin C alone or in combinations at the time of maximal response. The radioprotector WR-2721 exerts a high anti-mutagenic activity when applied prior to Cis-Platinum (2.2%; p 0.05). (author)

The role of 11-cis-retinyl esters in vertebrate cone vision.

Science.gov (United States)

Babino, Darwin; Perkins, Brian D; Kindermann, Aljoscha; Oberhauser, Vitus; von Lintig, Johannes

2015-01-01

A cycle of cis-to-trans isomerization of the chromophore is intrinsic to vertebrate vision where rod and cone photoreceptors mediate dim- and bright-light vision, respectively. Daylight illumination can greatly exceed the rate at which the photoproduct can be recycled back to the chromophore by the canonical visual cycle. Thus, an additional supply pathway(s) must exist to sustain cone-dependent vision. Two-photon microscopy revealed that the eyes of the zebrafish (Danio rerio) contain high levels of 11-cis-retinyl esters (11-REs) within the retinal pigment epithelium. HPLC analyses demonstrate that 11-REs are bleached by bright light and regenerated in the dark. Pharmacologic treatment with all-trans-retinylamine (Ret-NH2), a potent and specific inhibitor of the trans-to-cis reisomerization reaction of the canonical visual cycle, impeded the regeneration of 11-REs. Intervention with 11-cis-retinol restored the regeneration of 11-REs in the presence of all-trans-Ret-NH2. We used the XOPS:mCFP transgenic zebrafish line with a functional cone-only retina to directly demonstrate that this 11-RE cycle is critical to maintain vision under bright-light conditions. Thus, our analyses reveal that a dark-generated pool of 11-REs helps to supply photoreceptors with the chromophore under the varying light conditions present in natural environments. © FASEB.

Bacterial Seed Endophytes of Domesticated Cucurbits Antagonize Fungal and Oomycete Pathogens Including Powdery Mildew

Science.gov (United States)

Khalaf, Eman M.; Raizada, Manish N.

2018-01-01

The cucurbit vegetables, including cucumbers, melons and pumpkins, have been cultivated for thousands of years without fungicides. However, their seed germination stage is prone to be infected by soil-borne fungal and oomycete pathogens. Endophytes are symbionts that reside inside plant tissues including seeds. Seed endophytes are founders of the juvenile plant microbiome and can promote host defense at seed germination and later stages. We previously isolated 169 bacterial endophytes associated with seeds of diverse cultivated cucurbits. We hypothesized that these endophytes can antagonize major fungal and oomycete pathogens. Here we tested the endophytes for in vitro antagonism (dual culture assays) against important soil-borne pathogens (Rhizoctonia solani, Fusarium graminearum, Phytophthora capsici, Pythium aphanideratum). The endophytes were also assayed in planta (leaf disk and detached leaf bioassays) for antagonism against a foliar pathogen of global importance, Podosphaera fuliginea, the causative agent of cucurbit powdery mildew. The endophytes were further tested in vitro for secretion of volatile organic compounds (VOCs) known to induce plant defense. Extracellular ribonuclease activity was also tested, as a subset of pathogenesis-related (PR) proteins of plant hosts implicated in suppression of fungal pathogens, displays ribonuclease activity. An unexpected majority of the endophytes (70%, 118/169) exhibited antagonism to the five phytopathogens, of which 68% (50/73) of in vitro antagonists belong to the genera Bacillus and Paenibacillus. All Lactococcus and Pantoea endophytes exhibited anti-oomycete activity. However, amongst the most effective inoculants against Podosphaera fuliginea were Pediococcus and Pantoea endophytes. Interestingly, 67% (113/169) of endophytes emitted host defense inducing VOCs (acetoin/diacetyl) and 62% (104/169) secreted extracellular ribonucleases in vitro, respectively. These results show that seeds of cultivated cucurbits

Bacterial Seed Endophytes of Domesticated Cucurbits Antagonize Fungal and Oomycete Pathogens Including Powdery Mildew

Directory of Open Access Journals (Sweden)

Eman M. Khalaf

2018-02-01

Full Text Available The cucurbit vegetables, including cucumbers, melons and pumpkins, have been cultivated for thousands of years without fungicides. However, their seed germination stage is prone to be infected by soil-borne fungal and oomycete pathogens. Endophytes are symbionts that reside inside plant tissues including seeds. Seed endophytes are founders of the juvenile plant microbiome and can promote host defense at seed germination and later stages. We previously isolated 169 bacterial endophytes associated with seeds of diverse cultivated cucurbits. We hypothesized that these endophytes can antagonize major fungal and oomycete pathogens. Here we tested the endophytes for in vitro antagonism (dual culture assays against important soil-borne pathogens (Rhizoctonia solani, Fusarium graminearum, Phytophthora capsici, Pythium aphanideratum. The endophytes were also assayed in planta (leaf disk and detached leaf bioassays for antagonism against a foliar pathogen of global importance, Podosphaera fuliginea, the causative agent of cucurbit powdery mildew. The endophytes were further tested in vitro for secretion of volatile organic compounds (VOCs known to induce plant defense. Extracellular ribonuclease activity was also tested, as a subset of pathogenesis-related (PR proteins of plant hosts implicated in suppression of fungal pathogens, displays ribonuclease activity. An unexpected majority of the endophytes (70%, 118/169 exhibited antagonism to the five phytopathogens, of which 68% (50/73 of in vitro antagonists belong to the genera Bacillus and Paenibacillus. All Lactococcus and Pantoea endophytes exhibited anti-oomycete activity. However, amongst the most effective inoculants against Podosphaera fuliginea were Pediococcus and Pantoea endophytes. Interestingly, 67% (113/169 of endophytes emitted host defense inducing VOCs (acetoin/diacetyl and 62% (104/169 secreted extracellular ribonucleases in vitro, respectively. These results show that seeds of cultivated

Bacterial Seed Endophytes of Domesticated Cucurbits Antagonize Fungal and Oomycete Pathogens Including Powdery Mildew

Directory of Open Access Journals (Sweden)

Eman M. Khalaf

2018-02-01

Full Text Available The cucurbit vegetables, including cucumbers, melons and pumpkins, have been cultivated for thousands of years without fungicides. However, their seed germination stage is prone to be infected by soil-borne fungal and oomycete pathogens. Endophytes are symbionts that reside inside plant tissues including seeds. Seed endophytes are founders of the juvenile plant microbiome and can promote host defense at seed germination and later stages. We previously isolated 169 bacterial endophytes associated with seeds of diverse cultivated cucurbits. We hypothesized that these endophytes can antagonize major fungal and oomycete pathogens. Here we tested the endophytes for in vitro antagonism (dual culture assays against important soil-borne pathogens (Rhizoctonia solani, Fusarium graminearum, Phytophthora capsici, Pythium aphanidermatum. The endophytes were also assayed in planta (leaf disk and detached leaf bioassays for antagonism against a foliar pathogen of global importance, Podosphaera fuliginea, the causative agent of cucurbit powdery mildew. The endophytes were further tested in vitro for secretion of volatile organic compounds (VOCs known to induce plant defense. Extracellular ribonuclease activity was also tested, as a subset of pathogenesis-related (PR proteins of plant hosts implicated in suppression of fungal pathogens, displays ribonuclease activity. An unexpected majority of the endophytes (70%, 118/169 exhibited antagonism to the five phytopathogens, of which 68% (50/73 of in vitro antagonists belong to the genera Bacillus and Paenibacillus. All Lactococcus and Pantoea endophytes exhibited anti-oomycete activity. However, amongst the most effective inoculants against Podosphaera fuliginea were Pediococcus and Pantoea endophytes. Interestingly, 67% (113/169 of endophytes emitted host defense inducing VOCs (acetoin/diacetyl and 62% (104/169 secreted extracellular ribonucleases in vitro, respectively. These results show that seeds of cultivated

Modeling-independent elucidation of inactivation pathways in recombinant and native A-type Kv channels

Science.gov (United States)

Fineberg, Jeffrey D.; Ritter, David M.

2012-01-01

A-type voltage-gated K+ (Kv) channels self-regulate their activity by inactivating directly from the open state (open-state inactivation [OSI]) or by inactivating before they open (closed-state inactivation [CSI]). To determine the inactivation pathways, it is often necessary to apply several pulse protocols, pore blockers, single-channel recording, and kinetic modeling. However, intrinsic hurdles may preclude the standardized application of these methods. Here, we implemented a simple method inspired by earlier studies of Na+ channels to analyze macroscopic inactivation and conclusively deduce the pathways of inactivation of recombinant and native A-type Kv channels. We investigated two distinct A-type Kv channels expressed heterologously (Kv3.4 and Kv4.2 with accessory subunits) and their native counterparts in dorsal root ganglion and cerebellar granule neurons. This approach applies two conventional pulse protocols to examine inactivation induced by (a) a simple step (single-pulse inactivation) and (b) a conditioning step (double-pulse inactivation). Consistent with OSI, the rate of Kv3.4 inactivation (i.e., the negative first derivative of double-pulse inactivation) precisely superimposes on the profile of the Kv3.4 current evoked by a single pulse because the channels must open to inactivate. In contrast, the rate of Kv4.2 inactivation is asynchronous, already changing at earlier times relative to the profile of the Kv4.2 current evoked by a single pulse. Thus, Kv4.2 inactivation occurs uncoupled from channel opening, indicating CSI. Furthermore, the inactivation time constant versus voltage relation of Kv3.4 decreases monotonically with depolarization and levels off, whereas that of Kv4.2 exhibits a J-shape profile. We also manipulated the inactivation phenotype by changing the subunit composition and show how CSI and CSI combined with OSI might affect spiking properties in a full computational model of the hippocampal CA1 neuron. This work unambiguously

Cigarette smoke-induced cell death of a spermatocyte cell line can be prevented by inactivating the Aryl hydrocarbon receptor

Science.gov (United States)

Esakky, P; Hansen, D A; Drury, A M; Cusumano, A; Moley, K H

2015-01-01

Cigarette smoke exposure causes germ cell death during spermatogenesis. Our earlier studies demonstrated that cigarette smoke condensate (CSC) causes spermatocyte cell death in vivo and growth arrest of the mouse spermatocyte cell line (GC-2spd(ts)) in vitro via the aryl hydrocarbon receptor (AHR). We hypothesize here that inactivation of AHR could prevent the CSC-induced cell death in spermatocytes. We demonstrate that CSC exposure generates oxidative stress, which differentially regulates mitochondrial apoptosis in GC-2spd(ts) and wild type (WT) and AHR knockout (AHR-KO) mouse embryonic fibroblasts (MEFs). SiRNA-mediated silencing of Ahr augments the extent of CSC-mediated cellular damage while complementing the AHR-knockout condition. Pharmacological inhibition using the AHR-antagonist (CH223191) modulates the CSC-altered expression of apoptotic proteins and significantly abrogates DNA fragmentation though the cleavage of PARP appears AHR independent. Pretreatment with CH223191 at concentrations above 50 μM significantly prevents the CSC-induced activation of caspase-3/7 and externalization of phosphatidylserine in the plasma membrane. However, MAPK inhibitors alone or together with CH223191 could not prevent the membrane damage upon CSC addition and the caspase-3/7 activation and membrane damage in AHR-deficient MEF indicates the interplay of multiple cell signaling and cytoprotective ability of AHR. Thus the data obtained on one hand signifies the protective role of AHR in maintaining normal cellular homeostasis and the other, could be a potential prophylactic therapeutic target to promote cell survival and growth under cigarette smoke exposed environment by receptor antagonism via CH223191-like mechanism. Antagonist-mediated inactivation of the aryl hydrocarbon receptor blocks downstream events leading to cigarette smoke-induced cell death of a spermatocyte cell line. PMID:27551479

Comparative genome sequencing of Drosophila pseudoobscura: Chromosomal, gene, and cis-element evolution

DEFF Research Database (Denmark)

Richards, Stephen; Liu, Yue; Bettencourt, Brian R.

2005-01-01

years (Myr) since the pseudoobscura/melanogaster divergence. Genes expressed in the testes had higher amino acid sequence divergence than the genome-wide average, consistent with the rapid evolution of sex-specific proteins. Cis-regulatory sequences are more conserved than random and nearby sequences......We have sequenced the genome of a second Drosophila species, Drosophila pseudoobscura, and compared this to the genome sequence of Drosophila melanogaster, a primary model organism. Throughout evolution the vast majority of Drosophila genes have remained on the same chromosome arm, but within each...... between the species-but the difference is slight, suggesting that the evolution of cis-regulatory elements is flexible. Overall, a pattern of repeat-mediated chromosomal rearrangement, and high coadaptation of both male genes and cis-regulatory sequences emerges as important themes of genome divergence...

In vivo impact of Dlx3 conditional inactivation in Neural Crest-Derived Craniofacial Bones

Science.gov (United States)

Duverger, Olivier; Isaac, Juliane; Zah, Angela; Hwang, Joonsung; Berdal, Ariane; Lian, Jane B.; Morasso, Maria I.

2012-01-01

Mutations in DLX3 in humans lead to defects in craniofacial and appendicular bones, yet the in vivo activity related to Dlx3 function during normal skeletal development have not been fully elucidated. Here we used a conditional knockout approach to analyze the effects of neural crest deletion of Dlx3 on craniofacial bones development. At birth, mutant mice exhibit a normal overall positioning of the skull bones, but a change in the shape of the calvaria was observed. Molecular analysis of the genes affected in the frontal bones and mandibles from these mice identified several bone markers known to affect bone development, with a strong prediction for increased bone formation and mineralization in vivo. Interestingly, while a subset of these genes were similarly affected in frontal bones and mandibles (Sost, Mepe, Bglap, Alp, Ibsp, Agt), several genes, including Lect1 and Calca, were specifically affected in frontal bones. Consistent with these molecular alterations, cells isolated from the frontal bone of mutant mice exhibited increased differentiation and mineralization capacities ex vivo, supporting cell autonomous defects in neural crest cells. However, adult mutant animals exhibited decreased bone mineral density in both mandibles and calvaria, as well as a significant increase in bone porosity. Together, these observations suggest that mature osteoblasts in the adult respond to signals that regulate adult bone mass and remodeling. This study provides new downstream targets for Dlx3 in craniofacial bone, and gives additional evidence of the complex regulation of bone formation and homeostasis in the adult skeleton. PMID:22886599

Thermal inactivation of enzymes and pathogens in biosamples for MS analysis.

Science.gov (United States)

Ahnoff, Martin; Cazares, Lisa H; Sköld, Karl

2015-01-01

Protein denaturation is the common basis for enzyme inactivation and inactivation of pathogens, necessary for preservation and safe handling of biosamples for downstream analysis. While heat-stabilization technology has been used in proteomic and peptidomic research since its introduction in 2009, the advantages of using the technique for simultaneous pathogen inactivation have only recently been addressed. The time required for enzyme inactivation by heat (≈1 min) is short compared with chemical treatments, and inactivation is irreversible in contrast to freezing. Heat stabilization thus facilitates mass spectrometric studies of biomolecules with a fast conversion rate, and expands the chemical space of potential biomarkers to include more short-lived entities, such as phosphorylated proteins, in tissue samples as well as whole-blood (dried blood sample) samples.

KINETICS OF SUBSTITUTION OF CIS-BIS(MALONATO ...

African Journals Online (AJOL)

Preferred Customer

In this process, it indicated that the substitution reaction occurs through an Ia mechanism in the ... isotopic water exchange and other anation processes. ... The potassium salt of cis-bis(malonato)diaquochromate(III) was prepared by a reported [26] ... of the synthesized metal complex showed maxima at 415 nm (ε = 41.6 M-1 ...

Disruption of Cell-to-Cell Signaling Does Not Abolish the Antagonism of Phaeobacter gallaeciensis toward the Fish Pathogen Vibrio anguillarum in Algal Systems

DEFF Research Database (Denmark)

Prol García, María Jesús; D'Alvise, Paul; Gram, Lone

2013-01-01

Quorum sensing (QS) regulates Phaeobacter gallaeciensis antagonism in broth systems; however, we demonstrate here that QS is not important for antagonism in algal cultures. QS mutants reduced Vibrio anguillarum to the same extent as the wild type. Consequently, a combination of probiotic Phaeobac...... Phaeobacter and QS inhibitors is a feasible strategy for aquaculture disease control....

Effects of prefrontal cortical inactivation on neural activity in the ventral tegmental area

Science.gov (United States)

Jo, Yong Sang; Lee, Jane; Mizumori, Sheri J.Y.

2013-01-01

Dopamine (DA) cells have been suggested to signal discrepancies between expected and actual rewards in reinforcement learning. DA cells in the ventral tegmental area (VTA) receive direct projections from the medial prefrontal cortex (mPFC), a structure that is known as one of the brain areas that represent expected future rewards. To investigate whether the mPFC contributes to generating reward prediction error signals of DA cells, we recorded VTA cells from rats foraging for different amounts of reward in a spatial working memory task. Our results showed that DA cells initially responded after the acquisition of rewards, but over training, they exhibited phasic responses when rats detected sensory cues originating from the rewards before obtaining them. We also observed two separate groups of non-DA cells that were activated in expectation of upcoming rewards or during reward consumption. Bilateral injections of muscimol, a GABAA agonist, into the mPFC significantly decreased the non-DA activity that encoded reward expectation. By contrast, the same manipulation of the mPFC elevated DA responses to reward-predicting cues. However, neither DA nor non-DA responses that were elicited after reward acquisition were affected by mPFC inactivation. These results suggest that the mPFC provides the information about expected rewards to the VTA, and its functional loss elevates DA responses to reward-predicting cues by altering expectations about forthcoming rewards. PMID:23658156

Participation of Peoples’ Friendship University of Russia in the activities of CIS Network University

Directory of Open Access Journals (Sweden)

S A Kovalenko

2014-12-01

Full Text Available The article analyzes processes in the sphere of humanitarian cooperation in the CIS region and PFUR contribution to the development of educational area as a key of success in strengthening intercultural relations and academic mobility in the CIS countries.

cis-Apa: a practical linker for the microwave-assisted preparation of cyclic pseudopeptides via RCM cyclative cleavage.

Science.gov (United States)

Baron, Alice; Verdié, Pascal; Martinez, Jean; Lamaty, Frédéric

2011-02-04

A new linker cis-5-aminopent-3-enoic acid (cis-Apa) was prepared for the synthesis of cyclic pseudopeptides by cyclization-cleavage by using ring-closing methatesis (RCM). We developed a new synthetic pathway for the preparation of the cis-Apa linker that was tested in the cyclization-cleavage process of different RGD peptide sequences. Different macrocyclic peptidomimetics were prepared by using this integrated microwave-assisted method, showing that the readily available cis-Apa amino acid is well adapted as a linker in the cyclization-cleavage process.

Enzymatic and free radical formation of cis- and trans- epoxyeicosatrienoic acids in vitro and in vivo.

Science.gov (United States)

Aliwarga, Theresa; Raccor, Brianne S; Lemaitre, Rozenn N; Sotoodehnia, Nona; Gharib, Sina A; Xu, Libin; Totah, Rheem A

2017-11-01

Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid (AA) oxidation that have important cardioprotective and signaling properties. AA is an ω-6 polyunsaturated fatty acid (PUFA) that is prone to autoxidation. Although hydroperoxides and isoprostanes are major autoxidation products of AA, EETs are also formed from the largely overlooked peroxyl radical addition mechanism. While autoxidation yields both cis- and trans-EETs, cytochrome P450 (CYP) epoxygenases have been shown to exclusively catalyze the formation of all regioisomer cis-EETs, on each of the double bonds. In plasma and red blood cell (RBC) membranes, cis- and trans-EETs have been observed, and both have multiple physiological functions. We developed a sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay that separates cis- and trans- isomers of EETs and applied it to determine the relative distribution of cis- vs. trans-EETs in reaction mixtures of AA subjected to free radical oxidation in benzene and liposomes in vitro. We also determined the in vivo distribution of EETs in several tissues, including human and mouse heart, and RBC membranes. We then measured EET levels in heart and RBC of young mice compared to old. Formation of EETs in free radical reactions of AA in benzene and in liposomes exhibited time- and AA concentration-dependent increase and trans-EET levels were higher than cis-EETs under both conditions. In contrast, cis-EET levels were overall higher in biological samples. In general, trans-EETs increased with mouse age more than cis-EETs. We propose a mechanism for the non-enzymatic formation of cis- and trans-EETs involving addition of the peroxyl radical to one of AA's double bonds followed by bond rotation and intramolecular homolytic substitution (S H i). Enzymatic formation of cis-EETs by cytochrome P450 most likely occurs via a one-step concerted mechanism that does not allow bond rotation. The ability to accurately measure

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

Science.gov (United States)

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

2006-06-01

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

Inactivation as a new regulatory mechanism for neuronal Kv7 channels

DEFF Research Database (Denmark)

Jensen, Henrik Sindal; Grunnet, Morten; Olesen, Søren-Peter

2007-01-01

neuronal channels and are important for controlling excitability. Kv7.1 channels have been considered the only Kv7 channels to undergo inactivation upon depolarization. However, here we demonstrate that inactivation is also an intrinsic property of Kv7.4 and Kv7.5 channels, which inactivate to a larger...

9-cis-retinoic acid represses estrogen-induced expression of the very low density apolipoprotein II gene.

Science.gov (United States)

Schippers, I J; Kloppenburg, M; Snippe, L; Ab, G

1994-11-01

The chicken very low density apolipoprotein II (apoVLDLII) gene is estrogen-inducible and specifically expressed in liver. We examined the possible involvement of the retinoid X receptor (RXR) and its ligand 9-cis-retinoic acid (9-cis-RA) in the activation of the apoVLDLII promoter. We first concentrated on a potential RXR recognition site, which deviates at only one position from a perfect direct A/GGGTCA repeat spaced by one nucleotide (DR-1) and was earlier identified as a common HNF-4/COUP-TF recognition site. However, band shift analysis revealed that this imperfect DR-1 motif does not interact with RXR alpha-homodimers. In accordance with this observation we found that this regulatory element does not mediate transactivation through RXR alpha in the presence of 9-cis-RA. However, our experiments revealed another, unexpected, effect of 9-cis-RA. Instead of stimulating, 9-cis-RA attenuated estrogen-induced expression of transfected estrogen-responsive VLDL-CAT reporter plasmids. This repression appeared to take place through the main estrogen response element (ERE) of the gene. Importantly, 9-cis-RA also strongly repressed the estrogen-induced expression of the endogenous apoVLDLII gene in cultured chicken hepatoma cells.

Manganese catalyzed cis-dihydroxylation of electron deficient alkenes with H(2)O(2).

Science.gov (United States)

Saisaha, Pattama; Pijper, Dirk; van Summeren, Ruben P; Hoen, Rob; Smit, Christian; de Boer, Johannes W; Hage, Ronald; Alsters, Paul L; Feringa, Ben L; Browne, Wesley R

2010-10-07

A practical method for the multigram scale selective cis-dihydroxylation of electron deficient alkenes such as diethyl fumarate and N-alkyl and N-aryl-maleimides using H(2)O(2) is described. High turnovers (>1000) can be achieved with this efficient manganese based catalyst system, prepared in situ from a manganese salt, pyridine-2-carboxylic acid, a ketone and a base, under ambient conditions. Under optimized conditions, for diethyl fumarate at least 1000 turnovers could be achieved with only 1.5 equiv. of H(2)O(2) with d/l-diethyl tartrate (cis-diol product) as the sole product. For electron rich alkenes, such as cis-cyclooctene, this catalyst provides for efficient epoxidation.

Quantum chromodynamics as the sequential fragmenting with inactivation

International Nuclear Information System (INIS)

Botet, R.

1996-01-01

We investigate the relation between the modified leading log approximation of the perturbative QCD and the sequential binary fragmentation process. We will show that in the absence of inactivation, this process is equivalent to the QCD gluodynamics. The inactivation term yields a precise prescription of how to include the hadronization in the QCD equations. (authors)

Scale down of the inactivated polio vaccine production process

NARCIS (Netherlands)

Thomassen, Y.E.; Oever, van 't R.; Vinke, C.M.; Spiekstra, A.; Wijffels, R.H.; Pol, van der L.A.; Bakker, W.A.M.

2013-01-01

The anticipated increase in the demand for inactivated polio vaccines resulting from the success in the polio eradication program requires an increase in production capacity and cost price reduction of the current inactivated polio vaccine production processes. Improvement of existing production

[Antagonism against Beauveria bassiana by lipopeptide metabolites produced by entophyte Bacillus amyloliquefaciens strain SWB16].

Science.gov (United States)

Wang, Jingjie; Zhao, Dongyang; Liu, Yonggui; Ao, Xiang; Fan, Rui; Duan, Zhengqiao; Liu, Yanping; Chen, Qianqian; Jin, Zhixiong; Wan, Yongji

2014-07-04

We screened bacterial strains that have strong antagonism against Beauveria bassiana, an important pathogen of silkworm industry, and detected the antagonistic activity of lipopeptide metabolites. We identified bacterium SWB16 by morphological observation, physiological and biochemical experiments, 16SrRNA, and gyrA gene sequence analysis, tested antagonistic activity of strain SWB16 against Beauveria bassiana by measuring the inhibition zone diameter using filter paper diffusion method (Kirby-Bauer method), obtained lipopeptide metabolites of the strain using methanol extraction and observed the antagonism of strain SWB16 lipopeptide extracts against the conidia and hyphae of Beauveria bassiana, detected main ingredients and genes of lipopeptide metabolites by high-performance liquid chromatography-mass spectrometry and PCR amplification. SWB16 isolated from tissue of plant Dioscorea zingiberensis C. H. Wright belongs to Bacillus amyloliquefaciens and showed high antagonistic activity to Beauveria bassiana, and the lipopeptide extracts of isolate SWB16 exhibited significant inhibition to conidial germination and mycelial growth of Beauveria bassiana. The result of mass spectrometric detection indicated main component of the lipopeptide metabolites were fengcin and iturin, and genes fenB, ituA involved in the synthesis of them were amplified in the genome. Bacillus amyloliquefaciens strain SWB16 could produce lipopeptide antibiotics with strong antagonism to the entomopathogenic fungus Beauveria bassiana, and the results suggested that strain SWB16 has potential application value for controlling white muscardine of economic insects including silkworm.

Cytolytic T lymphocyte responses to metabolically inactivated stimulator cells. I. Metabolic inactivation impairs both CD and LD antigen signals

International Nuclear Information System (INIS)

Kelso, A.; Boyle, W.

1982-01-01

The effects of metabolic inactivation of spleen cells on antigen presentation to precursors of alloreactive cytolytic T lymphocytes (T/sub c/) were examined. By serological methods, populations inactivated by ultraviolet irradiation, glutaraldehyde fixation or plasma membrane isolation were found to retain normal levels of H-2K/D and Ia antigens. However, comparison of the antigen doses required to stimulate secondary T/sub c/ responses in mixed leukocyte culture showed that the inactivated preparations were approximately 10-fold less immunogenic than X-irradiated spleen cells. Their total inability to stimulate primary cytolytic responses pointed to at least a 100-fold impairment of immunogenicity for unprimed T/sub c/ precursors in the case of uv-irradiated and glutaraldehyde-treated stimulator cells, and at least a 10-fold impairment for membrane fragments. Experiments showing that the capacity of cell monolayers to absorb precursor T/sub c/ from unprimed spleen populations was reduced following uv-irradiation or glutaraldehyde treatment provided direct evidence that this loss of immunogenicity was due in part to suboptimal antigen presentation to precursor T/sub c/. It is concluded that, in addition to the traditional view that these treatments damage the ''LD'' signal to helper T lymphocytes, metabolic inactivation also impairs recognition of ''CD'' determinants by precursor T/sub c/

Discovery of cis-elements between sorghum and rice using co-expression and evolutionary conservation

Directory of Open Access Journals (Sweden)

Haberer Georg

2009-06-01

Full Text Available Abstract Background The spatiotemporal regulation of gene expression largely depends on the presence and absence of cis-regulatory sites in the promoter. In the economically highly important grass family, our knowledge of transcription factor binding sites and transcriptional networks is still very limited. With the completion of the sorghum genome and the available rice genome sequence, comparative promoter analyses now allow genome-scale detection of conserved cis-elements. Results In this study, we identified thousands of phylogenetic footprints conserved between orthologous rice and sorghum upstream regions that are supported by co-expression information derived from three different rice expression data sets. In a complementary approach, cis-motifs were discovered by their highly conserved co-occurrence in syntenic promoter pairs. Sequence conservation and matches to known plant motifs support our findings. Expression similarities of gene pairs positively correlate with the number of motifs that are shared by gene pairs and corroborate the importance of similar promoter architectures for concerted regulation. This strongly suggests that these motifs function in the regulation of transcript levels in rice and, presumably also in sorghum. Conclusion Our work provides the first large-scale collection of cis-elements for rice and sorghum and can serve as a paradigm for cis-element analysis through comparative genomics in grasses in general.

Quantum chromodynamics as the sequential fragmenting with inactivation

Energy Technology Data Exchange (ETDEWEB)

Botet, R. [Paris-11 Univ., 91 - Orsay (France). Lab. de Physique des Solides; Ploszajczak, M. [Grand Accelerateur National d`Ions Lourds (GANIL), 14 - Caen (France)

1996-12-31

We investigate the relation between the modified leading log approximation of the perturbative QCD and the sequential binary fragmentation process. We will show that in the absence of inactivation, this process is equivalent to the QCD gluodynamics. The inactivation term yields a precise prescription of how to include the hadronization in the QCD equations. (authors). 15 refs.

The assessment of efficacy of porcine reproductive respiratory syndrome virus inactivated vaccine based on the viral quantity and inactivation methods

Directory of Open Access Journals (Sweden)

Lee Byeongchun

2011-06-01

Full Text Available Abstract Background There have been many efforts to develop efficient vaccines for the control of porcine reproductive and respiratory syndrome virus (PRRSV. Although inactivated PRRSV vaccines are preferred for their safety, they are weak at inducing humoral immune responses and controlling field PRRSV infection, especially when heterologous viruses are involved. Results In all groups, the sample to positive (S/P ratio of IDEXX ELISA and the virus neutralization (VN titer remained negative until challenge. While viremia did not reduce in the vaccinated groups, the IDEXX-ELISA-specific immunoglobulin G increased more rapidly and to significantly greater levels 7 days after the challenge in all the vaccinated groups compared to the non-vaccinated groups (p 6 PFU/mL PRRSV vaccine-inoculated and binary ethylenimine (BEI-inactivated groups 22 days after challenge (p Conclusions The inactivated vaccine failed to show the humoral immunity, but it showed different immune response after the challenge compared to mock group. Although the 106 PFU/mL-vaccinated and BEI-inactivated groups showed significantly greater VN titers 22 days after challenge, all the groups were already negative for viremia.

Does gestrinone antagonize the effects of estrogen on endometrial implants upon the peritoneum of rats?

Directory of Open Access Journals (Sweden)

Vera Lúcia Rodrigues Lobo

2008-01-01

Full Text Available OBJECTIVE: To evaluate the effects of estrogen treatment in combination with gestrinone on an experimental rat model of endometriosis. METHODS: Uterine transplants were attached to the peritoneum of female Wistar rats via a surgical autotransplantation technique. The implanted area was measured during the proestrus phase and after hormonal treatment. We performed morphometric analysis and examined the macroscopic and morphometric alterations of endometrial implants after hormonal treatment in ovariectomized rats. RESULTS: The high dose of estrogen caused macroscopic increases in the endometrial implant group compared with other groups, which were similar to increases in the proestrus phase. The low dose showed morphometric development of implants, such as an increase in number of endometrial glands, leukocyte infiltration and mitosis. Gestrinone antagonized both doses of estrogen. CONCLUSION: Our findings suggest that gestrinone antagonizes estrogen's effects on rat peritoneal endometrial implants.

The roles of the various plasma agents in the inactivation of bacteria

International Nuclear Information System (INIS)

Lu Xinpei; Xiong Qing; Tang Zhiyuan; Xiong Zhilan; Hu Jing; Jiang Zhonghe; Pan Yuan; Ye Tao; Cao Yingguang; Sun Ziyong

2008-01-01

The roles of various plasma agents in the inactivation of bacteria have recently been investigated. However, up to now, the effect of the charged particles on the inactivation of bacteria is not well understood. In this paper, an atmospheric pressure plasma jet device, which generates a cold plasma plume carrying a peak current of 300 mA, is used to investigate the role of the charged particles in the inactivation process. It is found that the charged particles play a minor role in the inactivation process when He/N 2 (3%) is used as working gas. On the other hand, when He/O 2 (3%) is used, the charged particles are expected to play an important role in the inactivation of bacteria. Further analysis shows that the negative ions O 2 - might be the charged particles that are playing the role. Besides, it is found that the active species, including O, O 3 , and metastable state O 2 *, can play a crucial role in the inactivation of the bacteria. However, the excited He*, N 2 C 3 Π u , and N 2 + B 2 Σ u + have no significant direct effect on the inactivation of bacteria. It is also concluded that heat and UV play no or minor role in the inactivation process

Future CIS Manufacturing Technology Development: Final Report, 8 July 1998--17 October 2001

Energy Technology Data Exchange (ETDEWEB)

Anderson, T. J.; Crisalle, O. D.; Li, S. S.; Holloway, P. H.

2003-06-01

The University of Florida served as the basis for educating 12 graduate students in the area of photovoltaics engineering and research with a focus on thin-film CIS manufacturing technologies. A critical assessment of the thermodynamic data and of the phase diagrams for the Cu-Se and In-Se binary systems were carried out. We investigated the use of two novel precursor structures that used stacked In-Se and Cu-Se binary layers instead of conventional elemental layers, followed by rapid thermal processing (RTP) to produce CIS films. We investigated the evolution of electrical and microstructural properties of sputter-deposited ZnO:Al thin films. An assessment of the thermodynamics of the pseudobinary Cu2Se-Ga2Se3 system was done by using available experimental data, as well as an empirical method for estimating interactions in semiconductor solid solutions. Optimization studies were conducted to characterize the RTP of binary bilayer precursors for CIS synthesis using a newly acquired AG Associates Heatpulse furnace. Progress was made on the calculation of the 500C isothermal section of the phase diagram of the ternary Cu-In-Se system. Pursuit of developing alternative buffer layers for Cd-free CIS-based solar cells using a chemical-bath deposition (CBD) process has resulted in specific recipes for deposition. A rigorous model has been derived to predict the metal mass fluxes produced by conical thermal effusion sources. A two-dimensional model of the heat transfer was developed to model the substrate temperature distribution in the UF PMEE Reactor that features a rotating platen/substrates and effusion sources. We have grown and characterized polycrystalline CIS epitaxial films on single-crystal GaAs substrates under conditions that enhance the influence of surface effects on the resulting films and their properties. Progress was made on the study of CIS and CGS single-crystal growth, along with accompanying morphological and compositional characterizations. We have

Mechanism of Cd2+-coordination during Slow Inactivation in Potassium Channels

Science.gov (United States)

Raghuraman, H.; Cordero-Morales, Julio F.; Jogini, Vishwanath; Pan, Albert C.; Kollewe, Astrid; Roux, Benoît; Perozo, Eduardo

2013-01-01

Summary In K+ channels, rearrangements of the pore outer-vestibule have been associated with C-type inactivation gating. Paradoxically, the crystal structure of Open/C-type inactivated KcsA suggest these movements to be modest in magnitude. Here, we show that under physiological conditions, the KcsA outer-vestibule undergoes relatively large dynamic rearrangements upon inactivation. External Cd2+ enhances the rate of C-type inactivation in an outer-vestibule cysteine mutant (Y82C) via metal-bridge formation. This effect is not present in a non-inactivating mutant (E71A/Y82C). Tandem dimer and tandem tetramer constructs of equivalent cysteine mutants in KcsA and Shaker K+ channels demonstrate that these Cd2+ metal bridges are formed only between adjacent subunits. This is well supported by molecular dynamics simulations. Based on the crystal structure of Cd2+-bound Y82C-KcsA in the closed state, together with EPR distance measurements in the KcsA outer-vestibule, we suggest that subunits must dynamically come in close proximity as the channels undergo inactivation. PMID:22771214

Quantitative analysis of wet-heat inactivation in bovine spongiform encephalopathy

International Nuclear Information System (INIS)

Matsuura, Yuichi; Ishikawa, Yukiko; Bo, Xiao; Murayama, Yuichi; Yokoyama, Takashi; Somerville, Robert A.; Kitamoto, Tetsuyuki; Mohri, Shirou

2013-01-01

Highlights: ► We quantitatively analyzed wet-heat inactivation of the BSE agent. ► Infectivity of the BSE macerate did not survive 155 °C wet-heat treatment. ► Once the sample was dehydrated, infectivity was observed even at 170 °C. ► A quantitative PMCA assay was used to evaluate the degree of BSE inactivation. - Abstract: The bovine spongiform encephalopathy (BSE) agent is resistant to conventional microbial inactivation procedures and thus threatens the safety of cattle products and by-products. To obtain information necessary to assess BSE inactivation, we performed quantitative analysis of wet-heat inactivation of infectivity in BSE-infected cattle spinal cords. Using a highly sensitive bioassay, we found that infectivity in BSE cattle macerates fell with increase in temperatures from 133 °C to 150 °C and was not detected in the samples subjected to temperatures above 155 °C. In dry cattle tissues, infectivity was detected even at 170 °C. Thus, BSE infectivity reduces with increase in wet-heat temperatures but is less affected when tissues are dehydrated prior to the wet-heat treatment. The results of the quantitative protein misfolding cyclic amplification assay also demonstrated that the level of the protease-resistant prion protein fell below the bioassay detection limit by wet-heat at 155 °C and higher and could help assess BSE inactivation. Our results show that BSE infectivity is strongly resistant to wet-heat inactivation and that it is necessary to pay attention to BSE decontamination in recycled cattle by-products

Quantitative analysis of wet-heat inactivation in bovine spongiform encephalopathy

Energy Technology Data Exchange (ETDEWEB)

Matsuura, Yuichi; Ishikawa, Yukiko; Bo, Xiao; Murayama, Yuichi; Yokoyama, Takashi [Prion Disease Research Center, National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856 (Japan); Somerville, Robert A. [The Roslin Institute and Royal (Dick) School of Veterinary Studies, Roslin, Midlothian, EH25 9PS (United Kingdom); Kitamoto, Tetsuyuki [Division of CJD Science and Technology, Department of Prion Research, Center for Translational and Advanced Animal Research on Human Diseases, Tohoku University Graduate School of Medicine, 2-1 Seiryo, Aoba, Sendai 980-8575 (Japan); Mohri, Shirou, E-mail: shirou@affrc.go.jp [Prion Disease Research Center, National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856 (Japan)

2013-03-01

Highlights: ► We quantitatively analyzed wet-heat inactivation of the BSE agent. ► Infectivity of the BSE macerate did not survive 155 °C wet-heat treatment. ► Once the sample was dehydrated, infectivity was observed even at 170 °C. ► A quantitative PMCA assay was used to evaluate the degree of BSE inactivation. - Abstract: The bovine spongiform encephalopathy (BSE) agent is resistant to conventional microbial inactivation procedures and thus threatens the safety of cattle products and by-products. To obtain information necessary to assess BSE inactivation, we performed quantitative analysis of wet-heat inactivation of infectivity in BSE-infected cattle spinal cords. Using a highly sensitive bioassay, we found that infectivity in BSE cattle macerates fell with increase in temperatures from 133 °C to 150 °C and was not detected in the samples subjected to temperatures above 155 °C. In dry cattle tissues, infectivity was detected even at 170 °C. Thus, BSE infectivity reduces with increase in wet-heat temperatures but is less affected when tissues are dehydrated prior to the wet-heat treatment. The results of the quantitative protein misfolding cyclic amplification assay also demonstrated that the level of the protease-resistant prion protein fell below the bioassay detection limit by wet-heat at 155 °C and higher and could help assess BSE inactivation. Our results show that BSE infectivity is strongly resistant to wet-heat inactivation and that it is necessary to pay attention to BSE decontamination in recycled cattle by-products.

THE ANTIGENIC POTENCY OF EPIDEMIC INFLUENZA VIRUS FOLLOWING INACTIVATION BY ULTRAVIOLET RADIATION

Science.gov (United States)

Salk, Jonas E.; Lavin, G. I.; Francis, Thomas

1940-01-01

A study of the antigenic potency of influenza virus inactivated by ultraviolet radiation has been made. Virus so inactivated is still capable of functioning as an immunizing agent when given to mice by the intraperitoneal route. In high concentrations inactivated virus appears to be nearly as effective as active virus but when quantitative comparisons of the immunity induced by different dilutions are made, it is seen that a hundredfold loss in immunizing capacity occurs during inactivation. Virus in suspensions prepared from the lungs of infected mice is inactivated more rapidly than virus in tissue culture medium. A standard for the comparison of vaccines of epidemic influenza virus is proposed. PMID:19871057

FCJ-156 Hacking the Social: Internet Memes, Identity Antagonism, and the Logic of Lulz.

Directory of Open Access Journals (Sweden)

Ryan M. Milner

2013-12-01

Full Text Available 4chan and reddit are participatory media collectives undergirded by a “logic of lulz” that favours distanced irony and critique. It often works at the expense of core identity categories like race and gender. However, the logic need not be entirely counterproductive to public discourse. Provided that diverse identities find voice instead of exclusion, these sites may facilitate vibrant, agonistic discussion instead of disenfranchising antagonism. In order to assess this potential for productive agonism, I undertook a critical discourse analysis of these collectives. Emphasising the image memes they produce, I evaluated discourses on race and gender. Both race and gender representations were dominated by familiar stereotypes and partial representations. However, while dissenting perspectives on race were repressed or excluded, dissenting perspectives on gender were vocalised and contested. The ‘logic of lulz’ facilitated both dominance and counter, each articulated with heavy reliance on irony and critique. This logic ambiguously balanced agonism and antagonism, but contestation provided sharper engagement than repression.

Fullerene C60 and graphene photosensibiles for photodynamic virus inactivation

Science.gov (United States)

Belousova, I.; Hvorostovsky, A.; Kiselev, V.; Zarubaev, V.; Kiselev, O.; Piotrovsky, L.; Anfimov, P.; Krisko, T.; Muraviova, T.; Rylkov, V.; Starodubzev, A.; Sirotkin, A.; Grishkanich, A.; Kudashev, I.; Kancer, A.; Kustikova, M.; Bykovskaya, E.; Mayurova, A.; Stupnikov, A.; Ruzankina, J.; Afanasyev, M.; Lukyanov, N.; Redka, D.; Paklinov, N.

2018-02-01

A solid-phase photosensitizer based on aggregated C60 fullerene and graphene oxide for photodynamic inactivation of pathogens in biological fluids was studied. The most promising technologies of inactivation include the photodynamic effect, which consists in the inactivation of infectious agents by active oxygen forms (including singlet oxygen), formed when light is activated by the photosensitizer introduced into the plasma. Research shows features of solid-phase systems based on graphene and fullerene C60 oxide, which is a combination of an effective inactivating pathogens (for example, influenza viruses) reactive oxygen species formed upon irradiation of the photosensitizer in aqueous and biological fluids, a high photostability fullerene coatings and the possibility of full recovery photosensitizer from the biological environment after the photodynamic action.

Agonism and antagonism at the insulin receptor

DEFF Research Database (Denmark)

Knudsen, Louise; Hansen, Bo Falck; Jensen, Pia

2012-01-01

Insulin can trigger metabolic as well as mitogenic effects, the latter being pharmaceutically undesirable. An understanding of the structure/function relationships between insulin receptor (IR) binding and mitogenic/metabolic signalling would greatly facilitate the preclinical development of new...... insulin analogues. The occurrence of ligand agonism and antagonism is well described for G protein-coupled receptors (GPCRs) and other receptors but in general, with the exception of antibodies, not for receptor tyrosine kinases (RTKs). In the case of the IR, no natural ligand or insulin analogue has been...... shown to exhibit antagonistic properties, with the exception of a crosslinked insulin dimer (B29-B'29). However, synthetic monomeric or dimeric peptides targeting sites 1 or 2 of the IR were shown to be either agonists or antagonists. We found here that the S961 peptide, previously described to be an IR...

Thermal inactivation kinetics of β-galactosidase during bread baking

NARCIS (Netherlands)

Zhang, L.; Chen, Xiao Dong; Boom, R.M.; Schutyser, M.A.I.

2017-01-01

In this study, β-galactosidase was utilized as a model enzyme to investigate the mechanism of enzyme inactivation during bread baking. Thermal inactivation of β-galactosidase was investigated in a wheat flour/water system at varying temperature-moisture content combinations, and in bread during

Ebola Virus Inactivation by Detergents Is Annulled in Serum

NARCIS (Netherlands)

van Kampen, Jeroen J. A.; Tintu, Andrei; Russcher, Henk; Fraaij, Pieter L. A.; Reusken, Chantal B. E. M.; Rijken, Mikel; van Hellemond, Jaap J.; van Genderen, Perry J. J.; Koelewijn, Rob; de Jong, Menno D.; Haddock, Elaine; Fischer, Robert J.; Munster, Vincent J.; Koopmans, Marion P. G.

2017-01-01

Treatment of blood samples from hemorrhagic fever virus (HFV)-infected patients with 0.1% detergents has been recommended for virus inactivation and subsequent safe laboratory testing. However, data on virus inactivation by this procedure are lacking. Here we show the effect of this procedure on

Interaction of cis-[Ru(DMSO)4Cl2] with acetate-ion in solutions

International Nuclear Information System (INIS)

Buslaeva, T.M.; Rudnitskaya, O.V.; Kabanova, A.G.; Fedorova, G.A.

2000-01-01

Solutions of cis-[Ru(DMSO) 4 Cl 2 ] in water and alcohols in the presence of CH 3 COONa in dependence on concentration and relation of reagents are studied. It is shown that introduction of acetate-ion in solution of cis-[Ru(DMSO) 4 Cl 2 ] in methanol directs to formation of fac-[Ru(DMSO) 3 Cl 3 ] - which can be separated as sodium salt insoluble in methanol. It is necessary to mention that spectrum of solution of cis-[Ru(DMSO) 4 Cl 2 ] in methanol varies in time but these changes are insignificant in comparison with changes taking place in the presence of CH 3 COONa. Compound Na[Ru(DMSO) 3 (CH 3 COO) 2 Cl] is prepared and characterized spectrally for the first time [ru

Embryonic exposure to cis-bifenthrin enantioselectively induces the transcription of genes related to oxidative stress, apoptosis and immunotoxicity in zebrafish (Danio rerio).

Science.gov (United States)

Jin, Yuanxiang; Pan, Xiuhong; Cao, Limin; Ma, Bufang; Fu, Zhengwei

2013-02-01

Cis-bifenthrin (cis-BF) is used widely for agricultural and non-agricultural purpose. Thus, cis-BF is one of the most frequently detected insecticides in the aquatic ecosystem. As a chiral pesticide, the commercial cis-BF contained two enantiomers including 1R-cis-BF and 1S-cis-BF. However, the difference in inducing oxidative stress, apoptosis and immunotoxicity by the two enantiomers in zebrafish still remains unclear. In the present study, the zebrafish were exposed to environmental concentrations of cis-BF, 1R-cis-BF and 1S-cis-BF during the embryos developmental stage. We observed that the mRNA levels of the most genes related to oxidative stress, apoptosis and immunotoxicity including Cu/Zn-superoxide dismutase (Cu/Zn-Sod), catalase (Cat), P53, murine double minute 2 (Mdm2), B-cell lymphoma/leukaemia-2 gene (Bcl2), Bcl2 associated X protein (Bax), apoptotic protease activating factor-1 (Apaf1), Caspase 9 (Cas9), Caspase 3 (Cas3), interleukin-1 beta (IL-1β) and interleukin-8(Il-8) were much higher in 1S-cis-BF treated group than those in cis-BF or 1R-cis-BF treated ones, suggesting that 1S-cis-BF has higher risk to induced oxidative stress, apoptosis and immunotoxicity than 1R-cis-BF in zebrafish. The information presented in this study will help with elucidating the differences and environmental risk of the two enantiomers of cis-BF-induced toxicity in aquatic organisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

Rapid Bedside Inactivation of Ebola Virus for Safe Nucleic Acid Tests

DEFF Research Database (Denmark)

Rosenstierne, Maiken Worsøe; Karlberg, Helen; Bragstad, Karoline

2016-01-01

Rapid bedside inactivation of Ebola virus would be a solution for the safety of medical and technical staff, risk containment, sample transport, and high-throughput or rapid diagnostic testing during an outbreak. We show that the commercially available Magna Pure lysis/binding buffer used...... for nucleic acid extraction inactivates Ebola virus. A rapid bedside inactivation method for nucleic acid tests is obtained by simply adding Magna Pure lysis/binding buffer directly into vacuum blood collection EDTA tubes using a thin needle and syringe prior to sampling. The ready-to-use inactivation vacuum...... tubes are stable for more than 4 months, and Ebola virus RNA is preserved in the Magna Pure lysis/binding buffer for at least 5 weeks independent of the storage temperature. We also show that Ebola virus RNA can be manually extracted from Magna Pure lysis/binding buffer-inactivated samples using...

INVESTIGATION OF THE SOLVENT FREE ISOMERISATION OF cis ...

African Journals Online (AJOL)

Preferred Customer

The rate of the solid state isomerisation of cis-Mo(CO)4(PPh3)2 was .... R = reflectance, k = absorption coefficient, s = scattering coefficient, c = concentration of the .... total loss of 75 % mass, which is assumed to be due to loss of the two PPh3 ...

[Antagonism in vitro among phytopathogenic and saprobic fungi from horticultural soils].

Science.gov (United States)

Alippi, H E; Monaco, C

1990-01-01

Two methods were tested in order to determine the existence of in vitro antagonism among saprobic and pathogenic fungi. These microorganisms were the most common isolates from horticultural soils of La Plata (Buenos Aires). Trichoderma harzianum; T. koningii and Penicillium sp. were antagonistic to all the pathogenic fungi tested, Fusarium solani; F. oxysporum; Alternaria solani; Colletotrichum sp. and Sclerotium rolfsii Spicaria sp., Paecilomyces sp. and Chaetomiun sp. were antagonistic only to Colletotrichum sp. and Fusarium solani.

Dicer activity in neural crest cells is essential for craniofacial organogenesis and pharyngeal arch artery morphogenesis

Science.gov (United States)

Nie, Xuguang; Wang, Qin; Jiao, Kai

2014-01-01

MicroRNAs (miRNAs) play important roles in regulating gene expression during numerous biological/pathological processes. Dicer encodes an RNase III endonuclease that is essential for generating most, if not all, functional miRNAs. In this work, we applied a conditional gene inactivation approach to examine the function of Dicer during neural crest cell (NCC) development. Mice with NCC-specific inactivation of Dicer died perinatally. Cranial and cardiac NCC migration into target tissues was not affected by Dicer disruption, but their subsequent development was disturbed. NCC derivatives and their associated mesoderm-derived cells displayed massive apoptosis, leading to severe abnormalities during craniofacial morphogenesis and organogenesis. In addition, the 4th pharyngeal arch artery (PAA) remodeling was affected, resulting in interrupted aortic arch artery type B (IAA-B) in mutant animals. Taken together, our results show that Dicer activity in NCCs is essential for craniofacial development and pharyngeal arch artery morphogenesis. PMID:21256960

cis-4-[{sup 18}F]-Fluoro-L-proline fails to detect peripheral tumors in humans

Energy Technology Data Exchange (ETDEWEB)

Stoffels, Gabriele; Pauleit, Dirk [Institute of Neuroscience and Biophysics-Medicine, Research Centre Juelich, D-52425 Juelich, FRG (Germany); Haas, Rainer; Kobbe, Guido [Department of Oncology, Hematology, and Clinical Immunology, Heinrich-Heine-University Duesseldorf, FRG (Germany); Salber, Dagmar [C. and O. Vogt Institute of Brain Research, Heinrich-Heine-University Duesseldorf, FRG (Germany); Hamacher, Kurt; Coenen, Heinz H. [Institute of Neuroscience and Biophysics - Nuclear Chemistry, Research Centre Juelich, Juelich, FRG (Germany); Langen, Karl-Josef [Institute of Neuroscience and Biophysics-Medicine, Research Centre Juelich, D-52425 Juelich, FRG (Germany)], E-mail: k.j.langen@fz-juelich.de

2008-11-15

System A amino acid transport is increased in transformed and malignant cells. The amino acid 4-cis[{sup 18}F]fluoro-L-proline (cis-[{sup 18}F]FPro) has been shown to be a substrate of the System A amino acid carrier. In this pilot study, we investigated the diagnostic potential of cis-[{sup 18}F]FPro in patients with various tumors in comparison with [{sup 18}F]fluorodeoxyglucose-positron emission tomography (FDG-PET). Methods: Eight patients (seven females, one male, age range 43-77 years) with large primary, recurrent or metastatic tumors of different histologies were included in this study. One patient had a recurrent non-Hodgkin lymphoma; two patients, metastatic colon or rectal cancer; one, a metastatic endometrial cancer; one, a multiple myeloma; one, an Ewing sarcoma; one, a metastatic breast cancer and one, a gastrointestinal stromal tumor. PET scans of the trunk were acquired at 1 h after intravenous injection of 400 MBq cis-[{sup 18}F]FPro and compared to PET scans with [{sup 18}F]FDG. Results: None of the tumors or metastatic lesions in this series of patients demonstrated relevant uptake of cis-[{sup 18}F]FPro. In contrast, all tumors with exception of the multiple myeloma showed an intensive uptake of [{sup 18}F]FDG. The mean standardized uptake value of cis-[{sup 18}F]FPro in the tumor or metastases was significantly lower than that of [{sup 18}F]FDG uptake (1.7{+-}0.6 vs. 5.7{+-}3.0; n=8; P<.01). Conclusion: Although other System A-specific tracers have shown relevant tumor uptake, cis-[{sup 18}F]FPro fails to detect most types of human tumors. Based on these results, we cannot recommend a further evaluation of this tracer as a tumor-seeking agent.

Extraction of metals such as Pu, U and Sr with an organic solvent or a solid phase containing a cis-syn-cis isomer of the crown ether DCH18C6

International Nuclear Information System (INIS)

Guy, A.; Foos, J.; Lemaire, M.; Guyon, V.; Chomel, R.; Doutreluigne, P.; Le Roy, H.

1991-01-01

The cis-syn-cis isomer of the crown ether DCH18C6 is used in solution in an organic diluent such as benzonitrile or dichlorethane, or on a solid phase such as silica. The use of this isomer increases the extraction ratio of plutonium and strontium of solution from spent fuel reprocessing or from aqueous effluents containing Sr or Pu [fr

Determination of the valence-band offset of CdS/CIS solar cell devices by target factor analysis

Energy Technology Data Exchange (ETDEWEB)

Niles, D.W.; Contreras, M.; Ramanathan, K.; Noufi, R. [National Renewable Energy Lab., Golden, CO (United States)

1996-05-01

X-ray photoemission spectroscopy (XPS) is used to determine and compare the valence-band offsets ({Delta}E{sub v}) for CdS grown by chemical bath deposition on single-crystal and thin-film CuInSe{sub 2} (CIS). The thin-film CIS device was suitable for photovoltaic energy production. By sputtering through the CdS/CIS interface and reducing the depth profile with target factor analysis, the magnitude of {Delta}E{sub v} was determined to be {Delta}E{sub v} = 1.06 {+-} 0.15 eV for both the single-crystal and thin-film interfaces. This determination of {Delta}E{sub v} is about 0.25 eV larger than many previously reported estimations CdS grown by physical vapor deposition on CIS and helps explain the record performance of CdS/CIS photovoltaic devices.

Study of biodistribution of lipidic nanospheres charged with cis-diaminedichloroplatinum (II) and labelled with radioactive nuclei of Indium-111; Estudio de biodistribucion de nanoesferas lipidicas cargadas con cis-diaminodicloroplatino (II) y marcadas con nucleos radioactivos de Indio-111

Energy Technology Data Exchange (ETDEWEB)

Lopez R, V.; Juarez O, C.; Medina L, A. [Unidad de Investigacion Biomedica en Cancer INCAN-UNAM, Mexico D.F. (Mexico); Perez C, E.; Garcia L, P. [Instituto nacional de cancerologia, Mexico D.F. (Mexico)

2007-07-01

The general objective of the study was to evaluate the lipidic nanospheres biodistribution charged with cis-diaminedichloroplatinum (II) (cis-DDP) and labelled with radioactive nuclei of Indium-111 (Lip-Cis-in-111) in Wistar rats and in a tumoral model of CaCu. The conclusions were: 1. The system Lip-Cis-in-111 it presents a very fast elimination probably, to a fast recognition response of the reticuloendothelial system (RES). 2. It is planned to make modifications to the formulation to increase the quantity of the hydrophilic polymer (PEG), so that its time of residence in the blood is bigger and allow a bigger accumulation in the tumor. (Author)

Cis- and trans-perfluorodecalin: Infrared spectra, radiative efficiency and global warming potential

Science.gov (United States)

Le Bris, Karine; DeZeeuw, Jasmine; Godin, Paul J.; Strong, Kimberly

2017-12-01

Perfluorodecalin (PFD) is a molecule used in various medical applications for its capacity to dissolve gases. This potent greenhouse gas was detected for the first time in the atmosphere in 2005. We present infrared absorption cross-section spectra of a pure vapour of cis- and trans-perfluorodecalin at a resolution of 0.1 cm-1. Measurements were performed in the 560-3000 cm-1 spectral range using Fourier transform spectroscopy. The spectra have been compared with previous experimental data and theoretical calculations by density functional theory. The new experimental absorption cross-sections have been used to calculate a lifetime-corrected radiative efficiency at 300 K of 0.62 W m-2 ppb-1 and 0.57 W.m-2.ppb-1 for the cis and trans isomers respectively. This leads to a 100-year time horizon global warming potential of 8030 for cis-PFD and 7440 for trans-PFD.

Managing the competitiveness in CIS countries and Ukraine: the goal and conditions

Directory of Open Access Journals (Sweden)

Anna KUKHARUK

2017-06-01

Full Text Available The study is focused on the analysis of conditions for business development and the industrial enterprises’ competitiveness formation in Commonwealth of Independent States (CIS. The study is based on several concepts – sustainable development, macroeconomic stability, “green economy”, and competitiveness. The article analyses the level of macroeconomic instability in a sample of CIS countries and Ukraine following the statistical approach and using the variation coefficient. The authors suggest calculating the indicators of stable development (SD-indicator and business simplicity (SB-indicator based on the international analytical reports data. Several CIS countries are visualized in SD and SB coordinates. The study defines the countries where the conditions for business competitiveness are to be improved due to the comparatively higher level of macroeconomic instability. The article will be interesting to scientists whose subject of research is the competitiveness of enterprises or the economic instability phenomena.

Inactivation of human and simian rotaviruses by chlorine dioxide

Energy Technology Data Exchange (ETDEWEB)

Chen, Yu-Shiaw (Brookhaven National Lab., Upton, NY (USA)); Vaughn, J.M. (Univ. of New England College of Medicine, Biddeford, ME (USA))

1990-05-01

The inactivation of single-particle stocks of human (type 2, Wa) and simian (SA-11) rotaviruses by chlorine dioxide was investigated. Experiments were conducted at 4{degree}C in a standard phosphate-carbonate buffer. Both virus types were rapidly inactivated, within 20 s under alkaline conditions, when chlorine dioxide concentrations ranging from 0.05 to 0.2 mg/liter were used. Similar reductions of 10{sup 5}-fold in infectivity required additional exposure time of 120 s at 0.2 mg/liter for Wa and at 0.5 mg/liter for SA-11, respectively, at pH 6.0. The inactivation of both virus types was moderate a neutral pH, and the sensitivities to chlorine dioxide were similar. The observed enhancement of virucidal efficiency with increasing pH was contrary to earlier findings with chlorine- and ozone-treated rotavirus particles, where efficiencies decreased with increasing alkalinity. Comparison of 99.9% virus inactivation times revealed ozone to be the most effective virucidal agent among these three disinfectants.

Deletion of OTX2 in neural ectoderm delays anterior pituitary development

Science.gov (United States)

Mortensen, Amanda H.; Schade, Vanessa; Lamonerie, Thomas; Camper, Sally A.

2015-01-01

OTX2 is a homeodomain transcription factor that is necessary for normal head development in mouse and man. Heterozygosity for loss-of-function alleles causes an incompletely penetrant, haploinsufficiency disorder. Affected individuals exhibit a spectrum of features that range from developmental defects in eye and/or pituitary development to acephaly. To investigate the mechanism underlying the pituitary defects, we used different cre lines to inactivate Otx2 in early head development and in the prospective anterior and posterior lobes. Mice homozygous for Otx2 deficiency in early head development and pituitary oral ectoderm exhibit craniofacial defects and pituitary gland dysmorphology, but normal pituitary cell specification. The morphological defects mimic those observed in humans and mice with OTX2 heterozygous mutations. Mice homozygous for Otx2 deficiency in the pituitary neural ectoderm exhibited altered patterning of gene expression and ablation of FGF signaling. The posterior pituitary lobe and stalk, which normally arise from neural ectoderm, were extremely hypoplastic. Otx2 expression was intact in Rathke's pouch, the precursor to the anterior lobe, but the anterior lobe was hypoplastic. The lack of FGF signaling from the neural ectoderm was sufficient to impair anterior lobe growth, but not the differentiation of hormone-producing cells. This study demonstrates that Otx2 expression in the neural ectoderm is important intrinsically for the development of the posterior lobe and pituitary stalk, and it has significant extrinsic effects on anterior pituitary growth. Otx2 expression early in head development is important for establishing normal craniofacial features including development of the brain, eyes and pituitary gland. PMID:25315894

Strategy to inactivate Clostridium perfringens spores in meat products.

Science.gov (United States)

Akhtar, Saeed; Paredes-Sabja, Daniel; Torres, J Antonio; Sarker, Mahfuzur R

2009-05-01

The current study aimed to develop an inactivation strategy for Clostridium perfringens spores in meat through a combination of spore activation at low pressure (100-200 MPa, 7 min) and elevated temperature (80 degrees C, 10 min); spore germination at high temperatures (55, 60 or 65 degrees C); and inactivation of germinated spores with elevated temperatures (80 and 90 degrees C, 10 and 20 min) and high pressure (586 MPa, at 23 and 73 degrees C, 10 min). Low pressures (100-200 MPa) were insufficient to efficiently activate C. perfringens spores for germination. However, C. perfringens spores were efficiently activated with elevated temperature (80 degrees C, 10 min), and germinated at temperatures lethal for vegetative cells (>or= 55 degrees C) when incubated for 60 min with a mixture of L-asparagine and KCl (AK) in phosphate buffer (pH 7) and in poultry meat. Inactivation of spores (approximately 4 decimal reduction) in meat by elevated temperatures (80-90 degrees C for 20 min) required a long germination period (55 degrees C for 60 min). However, similar inactivation level was reached with shorter germination period (55 degrees C for 15 min) when spore contaminated-meat was treated with pressure-assisted thermal processing (568 MPa, 73 degrees C, 10 min). Therefore, the most efficient strategy to inactivate C. perfringens spores in poultry meat containing 50 mM AK consisted: (i) a primary heat treatment (80 degrees C, 10 min) to pasteurize and denature the meat proteins and to activate C. perfringens spores for germination; (ii) cooling of the product to 55 degrees C in about 20 min and further incubation at 55 degrees C for about 15 min for spore germination; and (iii) inactivation of germinated spores by pressure-assisted thermal processing (586 MPa at 73 degrees C for 10 min). Collectively, this study demonstrates the feasibility of an alternative and novel strategy to inactivate C. perfringens spores in meat products formulated with germinants specific for C

The radiation inactivation of glutamate and isocitrate dehydrogenases

International Nuclear Information System (INIS)

El Failat, R.R.A.

1980-12-01

The reaction of free radicals produced by ionizing radiation with the enzymes glutamate dehydrogenase (GDH) and NADP + -specific isocitrate dehydrogenase (ICDH) have been studied by steady-state and pulse radiolysis techniques. In de-aerated GDH solutions, hydroxyl radicals have been found to be the most efficient of the primary radicals generated from water in causing inactivation. The effect of reaction with the enzyme of selective free radicals (SCN) 2 - , (Br) 2 - and (I) 2 - on its activity has also been studied. In neutral solutions, the order of inactivating effectiveness is (I) 2 - > (Br) 2 - > (SCN) 2 - . In the case of the thiocyanate radical anion (SCN) 2 - , the inactivation efficiency is found to depend on KSCN concentration. The radiation inactivation of GDH at both neutral and alkaline pH is accompanied by the loss of sulphydryl groups. Pulse radiolysis was also used to determine the rate constants and the transient absorption spectra following the reaction of the free radicals with GDH. 60 Co-γ-radiolysis and pulse radiolysis were also used to study the effect of ionizing radiation on the activity of ICDH. The results obtained were similar to those of GDH. (author)

The inactivation of papain by high LET radiations

International Nuclear Information System (INIS)

Bisby, R.H.; Cundall, R.B.; Sims, H.E.; Burns, W.G.

1984-01-01

The effect of varying LET over a wide range (0.2-1570 eV/nm) on the radiation-induced inactivation of the enzyme papain in dilute aqueous solution has been investigated. Measurements of total, reparable and non-reparable inactivation G values in oxygen, nitrous oxide and argon saturated solutions have allowed the contributions to inactivation from radicals and hydrogen peroxide to be evaluated. At high LET the results demonstrate an increasing component due to reaction of the superoxide radical, formed from oxygen produced in the track as a primary radiolysis product. This effect was not observed in our previous study with ribonuclease due to the insensitivity of ribonuclease to inactivation by superoxide and hydrogen peroxide. The results obtained with papain clearly demonstrate a maximum in G(H 2 O 2 ) at an LET of equivalent to 140 eV/nm. Generation of O 2 within the track as a primary radiolysis product at high LET now appears to be confirmed as an important mechanism leading to reduction in the oxygen enhancement ratio for cellular systems exposed to high LET radiations (Baverstock and Burns 1981). (author)

Extinction antagonizes olfactory memory at the subcellular level.

Science.gov (United States)

Schwaerzel, Martin; Heisenberg, Martin; Zars, Troy

2002-08-29

Memory loss occurs by diverse mechanisms, as different time constants of performance decrement and sensitivities to experimental manipulations suggest. While the phenomena of memory decay, interference, and extinction are well established behaviorally, little is known about them at the circuit or molecular level. In Drosophila, odorant memories lasting up to 3 hr can be localized to mushroom body Kenyon cells, a single neuronal level in the olfactory pathway. The plasticity underlying this memory trace can be induced without Kenyon cell synaptic output. Experimental extinction, i.e., presentation of the conditioned stimulus without the reinforcer, reduces memory performance and does so at the same circuit level as memory formation. Thus, unreinforced presentation of learned odorants antagonizes intracellularly the signaling cascade underlying memory formation.

Regulation of MIR165/166 by class II and class III homeodomain leucine zipper proteins establishes leaf polarity

DEFF Research Database (Denmark)

Merelo, Paz; Ram, Hathi; Caggiano, Monica Pia

2016-01-01

A defining feature of plant leaves is their flattened shape. This shape depends on an antagonism between the genes that specify adaxial (top) and abaxial (bottom) tissue identity; however, the molecular nature of this antagonism remains poorly understood. Class III homeodomain leucine zipper (HD-...... show that class III and class II HD-ZIP proteins act together to repress MIR165/166 via a conserved cis-element in their promoters. Organ morphology and tissue patterning in plants, therefore, depend on a bidirectional repressive circuit involving a set of miRNAs and its targets....

7 CFR 272.10 - ADP/CIS Model Plan.

Science.gov (United States)

2010-01-01

... 7 Agriculture 4 2010-01-01 2010-01-01 false ADP/CIS Model Plan. 272.10 Section 272.10 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE... benefit computation (including but not limited to all household members' names, addresses, dates of birth...

Evolution of Cis-Regulatory Elements and Regulatory Networks in Duplicated Genes of Arabidopsis.

Science.gov (United States)

Arsovski, Andrej A; Pradinuk, Julian; Guo, Xu Qiu; Wang, Sishuo; Adams, Keith L

2015-12-01

Plant genomes contain large numbers of duplicated genes that contribute to the evolution of new functions. Following duplication, genes can exhibit divergence in their coding sequence and their expression patterns. Changes in the cis-regulatory element landscape can result in changes in gene expression patterns. High-throughput methods developed recently can identify potential cis-regulatory elements on a genome-wide scale. Here, we use a recent comprehensive data set of DNase I sequencing-identified cis-regulatory binding sites (footprints) at single-base-pair resolution to compare binding sites and network connectivity in duplicated gene pairs in Arabidopsis (Arabidopsis thaliana). We found that duplicated gene pairs vary greatly in their cis-regulatory element architecture, resulting in changes in regulatory network connectivity. Whole-genome duplicates (WGDs) have approximately twice as many footprints in their promoters left by potential regulatory proteins than do tandem duplicates (TDs). The WGDs have a greater average number of footprint differences between paralogs than TDs. The footprints, in turn, result in more regulatory network connections between WGDs and other genes, forming denser, more complex regulatory networks than shown by TDs. When comparing regulatory connections between duplicates, WGDs had more pairs in which the two genes are either partially or fully diverged in their network connections, but fewer genes with no network connections than the TDs. There is evidence of younger TDs and WGDs having fewer unique connections compared with older duplicates. This study provides insights into cis-regulatory element evolution and network divergence in duplicated genes. © 2015 American Society of Plant Biologists. All Rights Reserved.

Design and mechanism of tetrahydrothiophene-based γ-aminobutyric acid aminotransferase inactivators.

Science.gov (United States)

Le, Hoang V; Hawker, Dustin D; Wu, Rui; Doud, Emma; Widom, Julia; Sanishvili, Ruslan; Liu, Dali; Kelleher, Neil L; Silverman, Richard B

2015-04-08

Low levels of γ-aminobutyric acid (GABA), one of two major neurotransmitters that regulate brain neuronal activity, are associated with many neurological disorders, such as epilepsy, Parkinson's disease, Alzheimer's disease, Huntington's disease, and cocaine addiction. One of the main methods to raise the GABA level in human brain is to use small molecules that cross the blood-brain barrier and inhibit the activity of γ-aminobutyric acid aminotransferase (GABA-AT), the enzyme that degrades GABA. We have designed a series of conformationally restricted tetrahydrothiophene-based GABA analogues with a properly positioned leaving group that could facilitate a ring-opening mechanism, leading to inactivation of GABA-AT. One compound in the series is 8 times more efficient an inactivator of GABA-AT than vigabatrin, the only FDA-approved inactivator of GABA-AT. Our mechanistic studies show that the compound inactivates GABA-AT by a new mechanism. The metabolite resulting from inactivation does not covalently bind to amino acid residues of GABA-AT but stays in the active site via H-bonding interactions with Arg-192, a π-π interaction with Phe-189, and a weak nonbonded S···O═C interaction with Glu-270, thereby inactivating the enzyme.

Design and Mechanism of Tetrahydrothiophene-Based γ-Aminobutyric Acid Aminotransferase Inactivators

Energy Technology Data Exchange (ETDEWEB)

Le, Hoang V. [Departments; Hawker, Dustin D. [Departments; Wu, Rui [Department; Doud, Emma [Departments; Widom, Julia [Departments; Sanishvili, Ruslan [X-ray; Liu, Dali [Department; Kelleher, Neil L. [Departments; Silverman, Richard B. [Departments

2015-03-25

Low levels of gamma-aminobutyric acid (GABA), one of two major neurotransmitters that regulate brain neuronal activity, are associated with many neurological disorders, such as epilepsy, Parkinsons disease, Alzheimers disease, Huntingtons disease, and cocaine addiction. One of the main methods to raise the GABA level in human brain is to use small molecules that cross the bloodbrain barrier and inhibit the activity of gamma-aminobutyric acid aminotransferase (GABA-AT), the enzyme that degrades GABA. We have designed a series of conformationally restricted tetrahydrothiophene-based GABA analogues with a properly positioned leaving group that could facilitate a ring-opening mechanism, leading to inactivation of GABA-AT. One compound in the series is 8 times more efficient an inactivator of GABA-AT than vigabatrin, the only FDA-approved inactivator of GABA-AT. Our mechanistic studies show that the compound inactivates GABA-AT by a new mechanism. The metabolite resulting from inactivation does not covalently bind to amino acid residues of GABA-AT but stays in the active site via H-bonding interactions with Arg-192, a pi-pi interaction with Phe-189, and a weak nonbonded (SO)-O-...=C interaction with Glu-270, thereby inactivating the enzyme.

Synthesis of 1-[13CD3]-9-cis-retinoic acid

International Nuclear Information System (INIS)

Bennani, Y.L.

1995-01-01

1-[ 13 CD 3 ]-9-cis-Retinoic acid was prepared in 8 steps from 2,6-dimethylcyclohexanone. Alkylation of 2,6-dimethylcyclohexanone under LiHMDS/MnBr 2 / 13 CD 3 I gave the corresponding labeled 2-[ 13 CD 3 ]-2,2,6-trimethylcyclohexanone 4 in good yield. Further functionalization of 4 to 6-[ 13 CD 3 ]-β-cyclocitral 6 proceeded through a Shapiro reaction. Aldehyde 6 was condensed with ethyl 3,3-dimethylacrylate to afford the corresponding bicyclic pyranone 7. Reduction of 7 to lactol 8, followed by acid-catalyzed ring opening gave the 9-cis-aldehyde 9. Wittig-Horner olefination and saponification afforded the title compound in good overall yield and in excellent isotopic purity. (Author)

Identifying cis-regulatory modules by combining comparative and compositional analysis of DNA.

Science.gov (United States)

Pierstorff, Nora; Bergman, Casey M; Wiehe, Thomas

2006-12-01

Predicting cis-regulatory modules (CRMs) in higher eukaryotes is a challenging computational task. Commonly used methods to predict CRMs based on the signal of transcription factor binding sites (TFBS) are limited by prior information about transcription factor specificity. More general methods that bypass the reliance on TFBS models are needed for comprehensive CRM prediction. We have developed a method to predict CRMs called CisPlusFinder that identifies high density regions of perfect local ungapped sequences (PLUSs) based on multiple species conservation. By assuming that PLUSs contain core TFBS motifs that are locally overrepresented, the method attempts to capture the expected features of CRM structure and evolution. Applied to a benchmark dataset of CRMs involved in early Drosophila development, CisPlusFinder predicts more annotated CRMs than all other methods tested. Using the REDfly database, we find that some 'false positive' predictions in the benchmark dataset correspond to recently annotated CRMs. Our work demonstrates that CRM prediction methods that combine comparative genomic data with statistical properties of DNA may achieve reasonable performance when applied genome-wide in the absence of an a priori set of known TFBS motifs. The program CisPlusFinder can be downloaded at http://jakob.genetik.uni-koeln.de/bioinformatik/people/nora/nora.html. All software is licensed under the Lesser GNU Public License (LGPL).

Ionizing radiation sources management in the Commonwealth of Independent States - CIS

International Nuclear Information System (INIS)

Iskra, A.; Bufetova, M.

2006-01-01

Ionizing radiation sources cover a broad band of power: from powerful NPP reactors and research reactors to portable radioisotope ionizing radiation sources applied in medicine, agriculture, industry and in the energy supply systems of remote facilities. At present, scales and use field of radionuclide sources in the CIS have the tendency to increase. In this connection, the issues of ionizing radiation sources management safety at all stages of their life cycle, from production to treatment, have been of a great importance. The materials on ionizing radiation sources inventory and treatment in the CIS (Russia, Armenia, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Tajikistan and Ukraine) are presented in the report. It is shown that in some republics, there is difficulty in ionizing radiation sources accounting and control system; the national regulatory and legal framework bases regulating activity on radioactive sources use, localization and treatment require update. Many problems are connected with the sources beyond state accounting. The problem of ionizing radiation sources use safety is complicated by the growing activity of various terrorist groups. The opportunity to use ionizing radiation sources with terrorism goals requires the application of defined systems of security and physical protection at all stages of their management. For this purpose a collective, with all CIS countries, organization of radioactive sources accounting and control as well as countermeasures on their illegal transportation and use are necessary. In this connection, the information collection regarding situation with providing of ionizing radiation sources safety, conditions of equipment and storage facilities, radioactive materials accounting and control system in the CIS countries is vitally needed

Gamma-irradiation to inactivate thioglucosidase of crucifers

International Nuclear Information System (INIS)

Lessman, K.J.; McCaslin, B.D.

1987-01-01

The crucifers contain glucosinolates which through enzymatic hydrolysis give rise to toxicants that limit the use of oil-free meal obtainable from this plant family. Seeds from three crucifers were used to test gamma irradiation to inactivate enzyme systems as a step toward detoxification. Seeds of Crambe abyssinica Hochst (crambe), ground seeds of Sinapis alba L. (mustard), and seeds of Brassica napus L. (rape) were subjected to gamma-irradiation (6.25, 12.5, 25.0 and 50.4 Mrad) to inactivate thioglucosidase and/or destroy glucosinolates. Samples of ground seeds, their oil-free meals, previously irradiated ground seeds and their oil-free meals were assayed for glucose, a product of enzymatic hydrolysis of glucosinolates present in the crucifer seeds. The 50.4 Mrad exposure inactivated thioglucosidase but did not destroy glucosinolates. The fatty acid contents of extracted oils were affected. The amino acid profile of defatted crambe protein meal was affected, while that of white mustard was not

Lipase inactivation in wheat germ by gamma irradiation

International Nuclear Information System (INIS)

Jha, Pankaj Kumar; Kudachikar, V.B.; Kumar, Sourav

2013-01-01

An attempt was made to improve the shelf life of wheat germ by optimizing processing conditions involving γ-irradiation. Studies were carried out to investigate the effect of γ-irradiation (0–30 kGy doses) on the chemical composition of wheat germ with respect to variation in moisture, total ash, crude fat, free fatty acid, protein and lipase activity. The results demonstrate that shelf stability of wheat germ was achieved by inactivation of lipase at doses of γ-irradiation greater than 12 kGy. - Highlights: Ø γ-irradiation was found to inactivate Lipase present in Wheat Germ. Ø The treatment did not result in significant changes in Total Ash, Moisture and Protein Content of Wheat Germ. Ø The irradiation at 30 kGy resulted in 31.2 % inactivation of Lipase in Wheat Germ

The pulsed light inactivation of veterinary relevant microbial biofilms ...

African Journals Online (AJOL)

Results show that both Cryptosporidium and Giardia attach to biofilms in large numbers (100-1000 oo/cysts) in as little as 72 hours. Pulsed light successfully inactivated all test species (Listeria, Salmonella, Bacillus, Escherichia) in planktonic and biofilm form with an increase in inactivation for every increase in UV dose.

Targeting cytokine signaling checkpoint CIS activates NK cells to protect from tumor initiation and metastasis

Science.gov (United States)

Putz, Eva M.; Guillerey, Camille; Kos, Kevin; Stannard, Kimberley; Miles, Kim; Delconte, Rebecca B.; Nicholson, Sandra E.; Huntington, Nicholas D.; Smyth, Mark J.

2017-01-01

ABSTRACT The cytokine-induced SH2-containing protein CIS belongs to the suppressor of cytokine signaling (SOCS) protein family. Here, we show the critical role of CIS in suppressing natural killer (NK) cell control of tumor initiation and metastasis. Cish-deficient mice were highly resistant to methylcholanthrene-induced sarcoma formation and protected from lung metastasis of B16F10 melanoma and RM-1 prostate carcinoma cells. In contrast, the growth of primary subcutaneous tumors, including those expressing the foreign antigen OVA, was unchanged in Cish-deficient mice. The combination of Cish deficiency and relevant targeted and immuno-therapies such as combined BRAF and MEK inhibitors, immune checkpoint blockade antibodies, IL-2 and type I interferon revealed further improved control of metastasis. The data clearly indicate that targeting CIS promotes NK cell antitumor functions and CIS holds great promise as a novel target in NK cell immunotherapy. PMID:28344878

Capsid protein oxidation in feline calicivirus using an electrochemical inactivation treatment

Energy Technology Data Exchange (ETDEWEB)

Shionoiri, Nozomi; Nogariya, Osamu; Tanaka, Masayoshi; Matsunaga, Tadashi; Tanaka, Tsuyoshi, E-mail: tsuyo@cc.tuat.ac.jp

2015-02-11

Highlights: • Feline calicivirus was inactivated electrochemically by a factor of >5 log. • The electrochemical treatment was performed at 0.9 V (vs. Ag/AgCl) for 15 min. • Electrochemical treatment caused oxidation of viral proteins. • Oxidation of viral proteins can lead to loss of viral structural integrity. - Abstract: Pathogenic viral infections are an international public health concern, and viral disinfection has received increasing attention. Electrochemical treatment has been used for treatment of water contaminated by bacteria for several decades, and although in recent years several reports have investigated viral inactivation kinetics, the mode of action of viral inactivation by electrochemical treatment remains unclear. Here, we demonstrated the inactivation of feline calicivirus (FCV), a surrogate for human noroviruses, by electrochemical treatment in a developed flow-cell equipped with a screen-printed electrode. The viral infectivity titer was reduced by over 5 orders of magnitude after 15 min of treatment at 0.9 V vs. Ag/AgCl. Proteomic study of electrochemically inactivated virus revealed oxidation of peptides located in the viral particles; oxidation was not observed in the non-treated sample. Furthermore, transmission electron microscopy revealed that viral particles in the treated sample had irregular structures. These results suggest that electrochemical treatment inactivates FCV via oxidation of peptides in the structural region, causing structural deformation of virus particles. This first report of viral protein damage through electrochemical treatment will contribute to broadening the understanding of viral inactivation mechanisms.

The Tetherin Antagonism of the Ebola Virus Glycoprotein Requires an Intact Receptor-Binding Domain and Can Be Blocked by GP1-Specific Antibodies.

Science.gov (United States)

Brinkmann, Constantin; Nehlmeier, Inga; Walendy-Gnirß, Kerstin; Nehls, Julia; González Hernández, Mariana; Hoffmann, Markus; Qiu, Xiangguo; Takada, Ayato; Schindler, Michael; Pöhlmann, Stefan

2016-12-15

The glycoprotein of Ebola virus (EBOV GP), a member of the family Filoviridae, facilitates viral entry into target cells. In addition, EBOV GP antagonizes the antiviral activity of the host cell protein tetherin, which may otherwise restrict EBOV release from infected cells. However, it is unclear how EBOV GP antagonizes tetherin, and it is unknown whether the GP of Lloviu virus (LLOV), a filovirus found in dead bats in Northern Spain, also counteracts tetherin. Here, we show that LLOV GP antagonizes tetherin, indicating that tetherin may not impede LLOV spread in human cells. Moreover, we demonstrate that appropriate processing of N-glycans in tetherin/GP-coexpressing cells is required for tetherin counteraction by EBOV GP. Furthermore, we show that an intact receptor-binding domain (RBD) in the GP1 subunit of EBOV GP is a prerequisite for tetherin counteraction. In contrast, blockade of Niemann-Pick disease type C1 (NPC1), a cellular binding partner of the RBD, did not interfere with tetherin antagonism. Finally, we provide evidence that an antibody directed against GP1, which protects mice from a lethal EBOV challenge, may block GP-dependent tetherin antagonism. Our data, in conjunction with previous reports, indicate that tetherin antagonism is conserved among the GPs of all known filoviruses and demonstrate that the GP1 subunit of EBOV GP plays a central role in tetherin antagonism. Filoviruses are reemerging pathogens that constitute a public health threat. Understanding how Ebola virus (EBOV), a highly pathogenic filovirus responsible for the 2013-2016 Ebola virus disease epidemic in western Africa, counteracts antiviral effectors of the innate immune system might help to define novel targets for antiviral intervention. Similarly, determining whether Lloviu virus (LLOV), a filovirus detected in bats in northern Spain, is inhibited by innate antiviral effectors in human cells might help to determine whether the virus constitutes a threat to humans. The

Oil industry perspective on investment: in the CIS/Russia

International Nuclear Information System (INIS)

Boulos, A.J.

1994-01-01

Despite the existance of abundant petroleum reserves in the CIS, oil production is decreasing through lack of sophisticated equipment, advanced technology and capital to fully exploit existing and now depleting oil fields and to open up new ones. The oil industry is in need of restructuring and substantial investment if it is to meet increasing domestic demand. Positive moves are being made within the CIS to create an attractive investment climate and encourage the setting up of joint ventures with foreign companies. The types of joint venture agreements that could be used are examined and the challenges and opportunities provided by such ventures are discussed. Notwithstanding serious problems, particularly those relating to political stability and the creation of a suitable legal framework, it is concluded that significant and promising opportunities exist for joint ventures in the oil and gas sectors. (UK)

EU-CIS joint study project 2. Intervention criteria in CIS, risk assessments and non-radiological factors in decision-making

Energy Technology Data Exchange (ETDEWEB)

Hedemann Jensen, P. [Risoe National Lab., Roskilde (Denmark); Demin, V.F. [Russian Reserch Centre `Kurchatov Inst.`, Moscow (Russian Federation); Konstantinov, Y.O. [Research Inst. of Radiation Hygiene, St. Petersburg (Russian Federation); Likhtarev, I.A. [Ukrainian Scientific Centre for Radiation Medicine, Kiev (Ukraine); Rolevich, I.V. [Chernobyl State Commiettee, Minsk (Belarus); Schneider, T. [Centre d`etudes sur l`Evaluation de la Protection dans le domaine Nucleaire, CEPN, Paris (France)

1996-05-01

An extensive radiation risk estimation methodology has recently been developed in Russia and used for estimates of risk in exposed populations in the republics of Russia, Belarus and Ukraine. Results based on demographic data for the three republics are presented and compared with risk estimates from the EU risk model ASQRAD. The intervention criteria in the CIS republics have been evolving since the Chernobyl accident. The development of criteria in each of the three republics has been analysed and the CIS-Criteria have been compared to international guidance on intervention. After a nuclear or radiological emergency both radiological and non-radiological protection factors will influence the level of protective actions being introduced. The role of non-radiological protection factors in the overall optimization of health protection is addressed. It is argued that optimization of the overall health protection is not a question of developing radiation radiation protection philosophy to fully include socio-psychological factors. It is rather a question of including these factors - in parallel with the radiological protection factors - in cooperation between radiation protection experts and psychological specialists under the responsibility of the decision maker. (au) 19 tabs., 10 ills., 45 refs.

EU-CIS joint study project 2. Intervention criteria in CIS, risk assessments and non-radiological factors in decision-making

International Nuclear Information System (INIS)

Hedemann Jensen, P.; Demin, V.F.; Konstantinov, Y.O.; Likhtarev, I.A.; Rolevich, I.V.; Schneider, T.

1996-05-01

An extensive radiation risk estimation methodology has recently been developed in Russia and used for estimates of risk in exposed populations in the republics of Russia, Belarus and Ukraine. Results based on demographic data for the three republics are presented and compared with risk estimates from the EU risk model ASQRAD. The intervention criteria in the CIS republics have been evolving since the Chernobyl accident. The development of criteria in each of the three republics has been analysed and the CIS-Criteria have been compared to international guidance on intervention. After a nuclear or radiological emergency both radiological and non-radiological protection factors will influence the level of protective actions being introduced. The role of non-radiological protection factors in the overall optimization of health protection is addressed. It is argued that optimization of the overall health protection is not a question of developing radiation radiation protection philosophy to fully include socio-psychological factors. It is rather a question of including these factors - in parallel with the radiological protection factors - in cooperation between radiation protection experts and psychological specialists under the responsibility of the decision maker. (au) 19 tabs., 10 ills., 45 refs

Cis-, intra-, subgenesis, genome editing as modern technologies for modifying the crop genomes (review

Directory of Open Access Journals (Sweden)

Н. Е. Волкова

2016-02-01

Full Text Available Purpose. Reviewing the literature on modern technologies of genetic modification of crop genomes. Results. The current state of genetically modified plants creation is analyzed. The information on cis-, intra- and subgenic plants and their comparison with transgenic crops is given. Examples of cis- and intragenesis application for improving characteristics of crops are provided. Such state-of-the-art technology of crop genome modification as genome editing is considered. Conclusions. Technologies for producing cis-, intra-, subgenic plants are rapidly developing and resulting in crops of the 21st century that can solve the problem of food provision for a constantly growing world population with the least contrary to the public interest.

Inactivation of Heterosigma akashiwo in ballast water by circular orifice plate-generated hydrodynamic cavitation.

Science.gov (United States)

Feng, Daolun; Zhao, Jie; Liu, Tian

2016-01-01

The discharge of alien ballast water is a well-known, major reason for marine species invasion. Here, circular orifice plate-generated hydrodynamic cavitation was used to inactivate Heterosigma akashiwo in ballast water. In comparison with single- and multihole orifice plates, the conical-hole orifice plate yielded the highest inactivation percentage, 51.12%, and consumed only 6.84% energy (based on a 50% inactivation percentage). Repeating treatment, either using double series-connection or circling inactivation, elevated the inactivation percentage, yet consumed much more energy. The results indicate that conical-hole-generated hydrodynamic cavitation shows great potential as a pre-inactivation method for ballast water treatment.

Factors affecting the In Vitro inactivation of adolase by x-rays

Energy Technology Data Exchange (ETDEWEB)

Quintiliani, M.; Boccacci, M.

1962-08-15

The influence of urea and of various protective compounds on the in vitro inactivation of aldolase by x rays was studied. Low concentrations of urea protect the enzyme from the inactivation, whereas high concentrations, able to induce an unfolding of the protein molecule, increase the degree inactivation by a given dose of radiation. Cysteamine, cystamine, aminoethyl-isothio-uronium, and glutathione, all protect the aldolase in solution from the inactivation by x rays. Cystamine is as protective as cysteamine, in equimolecular concentrations, when high inactivation levels are reached. No protection can be demonstrated when the aldolase, after incubation with the tested compounds, is precipitated and redissolved in a new medium before irradiation. Nevertheless, with S/sup 35/ labeled cystamine, it can be demonstrated that at least seven residues of cysteamine are bound to each aldolase molecule. The protective power of glutathione is reduced by a factor of about 0.2 in the presence of 4 M urea. The possible implications of these findings are discussed. (auth)

Mechanistic and kinetic aspects of microbial inactivation in food irradiation processes

International Nuclear Information System (INIS)

Tukenmez, I.

2004-01-01

Full text: A proper reaction mechanism was searched by analyzing the inactivation processes of microorganisms during food irradiation by ionizing radiation. By employing transition-state theory, it was assumed that the overall inactivation process involves a reversible sub-lethal stress and repair reactions to form reversibly injured cell or sensitized cell, which then undergoes irreversible injury leading to dead cell. A shoulder in low dose range in survival kinetics was associated with the repair process. Depending on the postulated mechanism, kinetic model equations were derived. The kinetics of cell inactivation by irradiation was expressed as depending on irradiation dose. By using experimental data in the developed model the inactivation parameters including threshold dose, radiation yield, decimal reduction dose and minimum sterilization dose were evaluated and microbial inactivation by irradiation was simulated by using the numerical values of the parameters. Developed model and model parameters may be used for the process control and the assessment of product quality in radiation preservation of food

A molecular switch driving inactivation in the cardiac K+ channel HERG.

Directory of Open Access Journals (Sweden)

David A Köpfer

Full Text Available K(+ channels control transmembrane action potentials by gating open or closed in response to external stimuli. Inactivation gating, involving a conformational change at the K(+ selectivity filter, has recently been recognized as a major K(+ channel regulatory mechanism. In the K(+ channel hERG, inactivation controls the length of the human cardiac action potential. Mutations impairing hERG inactivation cause life-threatening cardiac arrhythmia, which also occur as undesired side effects of drugs. In this paper, we report atomistic molecular dynamics simulations, complemented by mutational and electrophysiological studies, which suggest that the selectivity filter adopts a collapsed conformation in the inactivated state of hERG. The selectivity filter is gated by an intricate hydrogen bond network around residues S620 and N629. Mutations of this hydrogen bond network are shown to cause inactivation deficiency in electrophysiological measurements. In addition, drug-related conformational changes around the central cavity and pore helix provide a functional mechanism for newly discovered hERG activators.

Comparison of glycerolisation with cryopreservation methods on HIV-1 inactivation

International Nuclear Information System (INIS)

Van Baare, J.; Pagnon, J.; Cameron, P.; Vardaxis, N.; Middlekoop, E.; Crowe, S.

1999-01-01

Cryopreservation and glycerolisation are two successful long-term preservation methods for human cadaveric donor skin, which is used in the treatment of bum patients. High concentrations of glycerol has been shown to be antibacterial and virucidal. Because fear of possible transmission of HIV-1 following allograft transplantation, this study was undertaken to investigate whether HIV can be effectively eliminated from skin explants. HIV-1 Ba-L, which has been shown to infect monocytes in skin explants and also dendritic cells, was. For the experiments we used cell-free virus, exogenously HIV infected peripheral blood mononuclear cells (PBMCs) and exogenously HIV infected cadaver split skin. Different concentrations of glycerol at various temperatures and the glycerolisation procedure as used by the Euro Skin Bank were used to determine the effects on HIV-1 Ba-L infectivity. For the cryopreservation technique we used 10% DMSO and a controlled rate freezer. HIV-1 Ba-L transfer was determined by adding uninfected PBMCs to the infected material and reverse transcriptase was measured. Cell-free HIV-1 Ba-L was not inactivated by 50% glycerol but was effectively inactivated within 30 minutes by 70% and 85% glycerol at 4 degree C, room temperature and 37 degree C. In contrast, cell-free HIV-1 Ba-L was not inactivated by cryopreservation. Most importantly, we have shown that HIV-1 Ba-L present in split skin is inactivated by incubating skin in 70% glycerol for three hours at 37-C. HIV in exogenously infected skin was not inactivated by cryopreservation. High concentrations of glycerol effectively inactivates free HIV-1 Ba-L and intracellular HIV-1 Ba-L. Also the current glycerolisation procedure carried out by the Euro Skin Bank effectively inactivates infectious virus. However, the cryopreservation technique did not show any reduction in HIV-1 Ba-L infectivity

An in vivo comparison of cis- and trans-[{sup 18}F]mefway in the nonhuman primate

Energy Technology Data Exchange (ETDEWEB)

Wooten, Dustin, E-mail: dwooten@wisc.edu [Department of Medical Physics, Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, WI 53705 (United States); Hillmer, Ansel; Murali, Dhanabalan; Barnhart, Todd [Department of Medical Physics, Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, WI 53705 (United States); Schneider, Mary L. [Department of Kinesiology, University of Wisconsin-Madison, Madison, WI 53706 (United States); Mukherjee, Jogeshwar [Preclinical Imaging Center, Department of Psychiatry and Human Behavior, University of California-Irvine, Irvine 92697 (United States); Christian, Bradley T. [Department of Medical Physics, Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, WI 53705 (United States)

2011-10-15

Introduction: [{sup 18}F]Mefway is a serotonin 5-HT{sub 1A} PET radiotracer with high specificity and favorable in vivo imaging properties. The chemical structure of [{sup 18}F]mefway permits {sup 18}F labeling in either the cis or trans positions at the 4-cyclohexyl site. We have previously reported on the in vivo kinetics of trans-[{sup 18}F]mefway in the nonhuman primate. In this work, we compare the in vivo binding of cis-[{sup 18}F]mefway and trans-[{sup 18}F]mefway to evaluate the properties of cis-[{sup 18}F]mefway for 5-HT{sub 1A} PET imaging. Methods: The cis- and trans-[{sup 18}F]mefway tracers were synthesized via nucleophilic substitution with their respective tosyl precursors. Two monkeys (one male, one female) were given bolus injections of both cis- and trans-labeled [{sup 18}F]mefway in separate experiments. Dynamic scans were acquired for 90 min with a microPET P4 scanner. Time-activity curves were extracted in the areas of the mesial temporal cortex (MTC), anterior cingulate gyrus (aCG), insular cortex (IC), raphe nuclei (RN) and cerebellum (CB). The in vivo behavior of the radiotracers was compared based upon the nondisplaceable binding potential (BP{sub ND}) using the CB as a reference region. Results: Averaged over the two subjects, BP{sub ND} values were as follows: MTC: 7.7, 0.58; aCG: 4.95, 0.32; IC: 3.27, 0.2; and RN: 3.05, 0.13, for trans-[{sup 18}F]mefway and cis-[{sup 18}F]mefway, respectively. Conclusion: The cis-labeled [{sup 18}F]mefway tracer has low specific binding throughout the 5-HT{sub 1A} regions of the brain compared to trans-[{sup 18}F]mefway, suggesting that the target-to-background binding of cis-[{sup 18}F]mefway may limit its use for in vivo assessment of 5-HT{sub 1A} binding.

Optimising the inactivation of grape juice spoilage organisms by pulse electric fields.

Science.gov (United States)

Marsellés-Fontanet, A Robert; Puig, Anna; Olmos, Paola; Mínguez-Sanz, Santiago; Martín-Belloso, Olga

2009-04-15

The effect of some pulsed electric field (PEF) processing parameters (electric field strength, pulse frequency and treatment time), on a mixture of microorganisms (Kloeckera apiculata, Saccharomyces cerevisiae, Lactobacillus plantarum, Lactobacillus hilgardii and Gluconobacter oxydans) typically present in grape juice and wine were evaluated. An experimental design based on response surface methodology (RSM) was used and results were also compared with those of a factorially designed experiment. The relationship between the levels of inactivation of microorganisms and the energy applied to the grape juice was analysed. Yeast and bacteria were inactivated by the PEF treatments, with reductions that ranged from 2.24 to 3.94 log units. All PEF parameters affected microbial inactivation. Optimal inactivation of the mixture of spoilage microorganisms was predicted by the RSM models at 35.0 kV cm(-1) with 303 Hz pulse width for 1 ms. Inactivation was greater for yeasts than for bacteria, as was predicted by the RSM. The maximum efficacy of the PEF treatment for inactivation of microorganisms in grape juice was observed around 1500 MJ L(-1) for all the microorganisms investigated. The RSM could be used in the fruit juice industry to optimise the inactivation of spoilage microorganisms by PEF.

Epigenetic inactivation of CHFR in human tumors.

Science.gov (United States)

Toyota, Minoru; Sasaki, Yasushi; Satoh, Ayumi; Ogi, Kazuhiro; Kikuchi, Takefumi; Suzuki, Hiromu; Mita, Hiroaki; Tanaka, Nobuyuki; Itoh, Fumio; Issa, Jean-Pierre J; Jair, Kam-Wing; Schuebel, Kornel E; Imai, Kohzoh; Tokino, Takashi

2003-06-24

Cell-cycle checkpoints controlling the orderly progression through mitosis are frequently disrupted in human cancers. One such checkpoint, entry into metaphase, is regulated by the CHFR gene encoding a protein possessing forkhead-associated and RING finger domains as well as ubiquitin-ligase activity. Although defects in this checkpoint have been described, the molecular basis and prevalence of CHFR inactivation in human tumors are still not fully understood. To address this question, we analyzed the pattern of CHFR expression in a number of human cancer cell lines and primary tumors. We found CpG methylation-dependent silencing of CHFR expression in 45% of cancer cell lines, 40% of primary colorectal cancers, 53% of colorectal adenomas, and 30% of primary head and neck cancers. Expression of CHFR was precisely correlated with both CpG methylation and deacetylation of histones H3 and H4 in the CpG-rich regulatory region. Moreover, CpG methylation and thus silencing of CHFR depended on the activities of two DNA methyltransferases, DNMT1 and DNMT3b, as their genetic inactivation restored CHFR expression. Finally, cells with CHFR methylation had an intrinsically high mitotic index when treated with microtubule inhibitor. This means that cells in which CHFR was epigenetically inactivated constitute loss-of-function alleles for mitotic checkpoint control. Taken together, these findings shed light on a pathway by which mitotic checkpoint is bypassed in cancer cells and suggest that inactivation of checkpoint genes is much more widespread than previously suspected.

UK-18,892: resistance to modification by aminoglycoside-inactivating enzymes.

Science.gov (United States)

Andrews, R J; Brammer, K W; Cheeseman, H E; Jevons, S

1978-12-01

UK-18,892, a new semisynthetic aminoglycoside, was active against bacteria possessing aminoglycoside-inactivating enzymes, with the exception of some known to possess AAC(6') or AAD(4') enzymes. This activity has been rationalized by using cell-free extracts of bacteria containing known inactivating enzymes, where it was shown that UK-18,892 was not a substrate for the APH(3'), AAD(2''), AAC(3), and AAC(2') enzymes. It was also demonstrated that UK-18,892 protected mice against lethal infections caused by organisms possessing aminoglycoside-inactivating enzymes.

Structural Elucidation of cis / trans Dicaffeoylquinic Acid Photoisomerization Using Ion Mobility Spectrometry-Mass Spectrometry

Energy Technology Data Exchange (ETDEWEB)

Zheng, Xueyun; Renslow, Ryan S.; Makola, Mpho M.; Webb, Ian K.; Deng, Liulin; Thomas, Dennis G.; Govind, Niranjan; Ibrahim, Yehia M.; Kabanda, Mwadham M.; Dubery, Ian A.; Heyman, Heino M.; Smith, Richard D.; Madala, Ntakadzeni E.; Baker, Erin S.

2017-03-15

Due to the recently uncovered health benefits and anti-HIV activities of dicaffeoylquinic acids (diCQAs), understanding their structures and functions is of great interest for drug discovery efforts. DiCQAs are analytically challenging to identify and quantify since they commonly exist as a diverse mixture of positional and geometric (cis/trans) isomers. In this work, we utilized ion mobility spectrometry coupled with mass spectrometry to separate the various isomers before and after UV irradiation. The experimental collision cross sections were then compared with theoretical structures to differentiate and identify the diCQA isomers. Our analyses found that naturally the diCQAs existed predominantly as trans/trans isomers, but after 3 h of UV irradiation, cis/cis, cis/trans, trans/cis, and trans/trans isomers were all present in the mixture. This is the first report of successful differentiation of cis/trans diCQA isomers individually, which shows the great promise of IMS coupled with theoretical calculations for determining the structure and activity relationships of different isomers in drug discovery studies.

9-cis-retinoic acid increases apolipoprotein AI secretion and mRNA expression in HepG2 cells.

Science.gov (United States)

Haghpassand, M; Moberly, J B

1995-10-01

HepG2 cells were studied as a model for regulation of hepatic apolipoprotein AI (apo AI) secretion and gene expression by 9-cis-retinoic acid. HepG2 cells cultured on plastic dishes were exposed to 9-cis-retinoic acid (9-cis-RA) for 48 h with a complete media change at 24 h. Apo AI mass in cultured media was determined by ELISA, by quantitative immunoblotting and by steady-state 35S-methionine labeling. Messenger RNA levels were determined by RNase protection using probes for apo AI and the housekeeping gene, glyceraldehyde 3-phosphate dehydrogenase (G3PDH). 9-cis-RA increased secretion of apo AI by 52% at doses of 10 and 1 microM (6.3 +/- 0.6 vs. 4.2 +/- 0.3; P G3PDH mRNA was slightly decreased (14%, P < 0.05). Thus, 9-cis-RA stimulates apo AI expression in HepG2 cells, suggesting a role for retinoids in activating endogenous apo AI gene expression.

Inactivation and stability of viral diagnostic reagents treated by gamma radiation

International Nuclear Information System (INIS)

White, L.A.; Freeman, C.Y.; Hall, H.E.; Forrester, B.D.

1990-01-01

The objective of this study was to apply the pertinent findings from gamma inactivation of virus infectivity to the production of high quality diagnostic reagents. A Gammacell 220 was used to subject 38 viruses grown in either susceptible tissue cultures or embryonated chicken eggs to various doses of gamma radiation from a cobalt-60 source. The radiation required to reduce viral infectivity was 0.42 to 3.7 megarads (Mrad). The effect of gamma treatment on the antigenic reactivity of reagents for the complement fixation (CF), hemagglutination (HA) and neuraminadase assays was determined. Influenza antigens inactivated with 1.7 Mrad displayed comparable potency, sensitivity, specificity and stability to those inactivated by standard procedures with beta-propiolactone (BPL). Significant inactivation of influenza N1 and B neuraminidase occurred with >2.4 Mrad radiation at temperatures above 4 0 C. All 38 viruses were inactivated, and CF or HA antigens were prepared successfully. Antigenic potency remained stable with all antigens for 3 years and with 83% after 5 years storage. Influenza HA antigens evaluated after 9 years of storage demonstrated 86% stability. Gamma radiation is safer than chemical inactivation procedures and is a reliable and effective replacement for BPL in preparing diagnostic reagents. (author)

Inactivation and stability of viral diagnostic reagents treated by gamma radiation

Energy Technology Data Exchange (ETDEWEB)

White, L A; Freeman, C Y; Hall, H E; Forrester, B D [Department of Health and Human Services, Atlanta, GA (USA)

1990-10-01

The objective of this study was to apply the pertinent findings from gamma inactivation of virus infectivity to the production of high quality diagnostic reagents. A Gammacell 220 was used to subject 38 viruses grown in either susceptible tissue cultures or embryonated chicken eggs to various doses of gamma radiation from a cobalt-60 source. The radiation required to reduce viral infectivity was 0.42 to 3.7 megarads (Mrad). The effect of gamma treatment on the antigenic reactivity of reagents for the complement fixation (CF), hemagglutination (HA) and neuraminadase assays was determined. Influenza antigens inactivated with 1.7 Mrad displayed comparable potency, sensitivity, specificity and stability to those inactivated by standard procedures with beta-propiolactone (BPL). Significant inactivation of influenza N1 and B neuraminidase occurred with >2.4 Mrad radiation at temperatures above 4{sup 0}C. All 38 viruses were inactivated, and CF or HA antigens were prepared successfully. Antigenic potency remained stable with all antigens for 3 years and with 83% after 5 years storage. Influenza HA antigens evaluated after 9 years of storage demonstrated 86% stability. Gamma radiation is safer than chemical inactivation procedures and is a reliable and effective replacement for BPL in preparing diagnostic reagents. (author).

Development of inactivated-local isolate vaccine for infectious bronchitis

Directory of Open Access Journals (Sweden)

Darminto

1999-06-01

Full Text Available Infectious bronchitis (IB is an acute highly contagious viral respiratory disease of poultry caused by coronavirus. The disease causes high mortality in young chicks, reduce body weight gain in broilers and remarkable drop in egg production. IB can only be controlled by vaccination, but due to the antigenic variation among serotypes of IB viruses, the effective IB vaccine should be prepared from local isolates. The aim of this research is to develop inactivated IB vaccine derived from local IB isolates. Local isolates of IB viruses designated as I-37, I-269 and PTS-III were propagated respectively in specific pathogen free (SPF chicken eggs, the viruses then were inactivated by formaline at final concentration of 1:1,000. Subsequently, the inactivated viruses were mixed and emulsified in oil emulsion adjuvant with sorbitant mono-oleic as an emulsifier. The vaccine then was tested for its safety, potency and efficacy in broiler chickens. Birds inoculated twice with a two-week interval by inactivated vaccine did not show any adverse reaction, either systemic or local reaction. The inoculated birds developed antibody responses with high titre, while antibody of the control birds remain negative. In addition, efficacy test which was conducted in broilers demonstrated that birds vaccinated by live-commercial vaccine and boosted three weeks later by Balitvet inactivated vaccine showed high level of antibody production which provided high level of protection against challenged virus (76% against I-37, 92% against I-269 and 68% against PTS-III challenge viruses. From this study, it can be concluded that inactivated local IB vaccine is considered to be safe, potent and efficacious. The vaccine stimulates high titre of antibody responses, which provide high level of protection against challenged viruses.

A single cis element maintains repression of the key developmental regulator Gata2.

Directory of Open Access Journals (Sweden)

Jonathan W Snow

2010-09-01

Full Text Available In development, lineage-restricted transcription factors simultaneously promote differentiation while repressing alternative fates. Molecular dissection of this process has been challenging as transcription factor loci are regulated by many trans-acting factors functioning through dispersed cis elements. It is not understood whether these elements function collectively to confer transcriptional regulation, or individually to control specific aspects of activation or repression, such as initiation versus maintenance. Here, we have analyzed cis element regulation of the critical hematopoietic factor Gata2, which is expressed in early precursors and repressed as GATA-1 levels rise during terminal differentiation. We engineered mice lacking a single cis element -1.8 kb upstream of the Gata2 transcriptional start site. Although Gata2 is normally repressed in late-stage erythroblasts, the -1.8 kb mutation unexpectedly resulted in reactivated Gata2 transcription, blocked differentiation, and an aberrant lineage-specific gene expression pattern. Our findings demonstrate that the -1.8 kb site selectively maintains repression, confers a specific histone modification pattern and expels RNA Polymerase II from the locus. These studies reveal how an individual cis element establishes a normal developmental program via regulating specific steps in the mechanism by which a critical transcription factor is repressed.

The chicken Z chromosome is enriched for genes with preferential expression in ovarian somatic cells

Czech Academy of Sciences Publication Activity Database

Mořkovský, L.; Storchová, R.; Plachý, Jiří; Ivánek, Robert; Divina, Petr; Hejnar, Jiří

2010-01-01

Roč. 70, č. 2 (2010), s. 129-136 ISSN 0022-2844 Institutional research plan: CEZ:AV0Z50520514 Keywords : Z chromosome * meiotic sex chromosome inactivation * sex ual antagonisms Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.311, year: 2010

Modelling fungal solid-state fermentation: The role of inactivation kinetics

NARCIS (Netherlands)

Smits, J.P.; Sonsbeek, H.M. van; Knol, W.; Tramper, J.; Geelhoed, W.; Peeters, M.; Rinzema, A.

1999-01-01

The theoretical mathematical models described in this paper are used to evaluate the effects of fungal biomass inactivation kinetics on a non- isothermal tray solid-state fermentation (SSF). The inactivation kinetics, derived from previously reported experiments done under isothermal conditions and

A specific inactivator of mammalian C'4 isolated from nurse shark (Ginglymostoma cirratum) serum.

Science.gov (United States)

Jensen, J A

1969-08-01

A material which specifically inactivates mammalian C'4 was isolated from low ionic strength precipitates of nurse shark serum. The C'4 inactivator was not detected in whole serum. The conditions of its generation and its immunoelectrophoretic behavior seem to indicate that it is an enzymatically formed cleavage product of a precursor contained in whole shark serum. The inactivator was partially purified and characterized. It had an S-value of 3.3 (sucrose gradient) which was in agreement with its retardation on gel filtration, was stable between pH 5.0 and 10.0, had a half-life of 5 min at 56 degrees C, pH 7.5, was inactivated by trypsin and was nontoxic. Its powerful anticomplementary activity in vitro and in vivo was solely due to the rapid inactivation of C'4; no other complement components were affected. No cofactor requirement was observed for the equally rapid inactivation of highly purified human and guinea pig C'4. The kinetics of C'4 inactivation and TAME hydrolysis, the greater anodic mobility of inactivated human C'4, and the influence of temperature on the rate of inactivation suggest that the inactivator is an enzyme and C'4 its substrate. This conclusion was supported by the more recent detection of a split product of C'4. Intravenous administration of the C'4 inactivator could prevent lethal Forssman shock and suppress the Arthus reaction in guinea pigs; it prolonged significantly the rejection time of renal xenografts but had no detectable effect on passive cutaneous anaphylaxis. Anaphylatoxin could be generated in C'4 depleted guinea pig serum with the cobra venom factor, but not with immune precipitates. The possible relationship between C'1 esterase and the C'4 inactivator is discussed on the basis of similarities and dissimilarities.

Impaired neurogenesis, learning and memory and low seizure threshold associated with loss of neural precursor cell survivin

Directory of Open Access Journals (Sweden)

Eisch Amelia

2010-01-01

Full Text Available Abstract Background Survivin is a unique member of the inhibitor of apoptosis protein (IAP family in that it exhibits antiapoptotic properties and also promotes the cell cycle and mediates mitosis as a chromosome passenger protein. Survivin is highly expressed in neural precursor cells in the brain, yet its function there has not been elucidated. Results To examine the role of neural precursor cell survivin, we first showed that survivin is normally expressed in periventricular neurogenic regions in the embryo, becoming restricted postnatally to proliferating and migrating NPCs in the key neurogenic sites, the subventricular zone (SVZ and the subgranular zone (SGZ. We then used a conditional gene inactivation strategy to delete the survivin gene prenatally in those neurogenic regions. Lack of embryonic NPC survivin results in viable, fertile mice (SurvivinCamcre with reduced numbers of SVZ NPCs, absent rostral migratory stream, and olfactory bulb hypoplasia. The phenotype can be partially rescued, as intracerebroventricular gene delivery of survivin during embryonic development increases olfactory bulb neurogenesis, detected postnatally. SurvivinCamcre brains have fewer cortical inhibitory interneurons, contributing to enhanced sensitivity to seizures, and profound deficits in memory and learning. Conclusions The findings highlight the critical role that survivin plays during neural development, deficiencies of which dramatically impact on postnatal neural function.

Cis-Natural Antisense Transcripts Are Mainly Co-expressed with Their Sense Transcripts and Primarily Related to Energy Metabolic Pathways during Muscle Development.

Science.gov (United States)

Zhao, Yunxia; Hou, Ye; Zhao, Changzhi; Liu, Fei; Luan, Yu; Jing, Lu; Li, Xinyun; Zhu, Mengjin; Zhao, Shuhong

2016-01-01

Cis-natural antisense transcripts (cis-NATs) are a new class of RNAs identified in various species. However, the biological functions of cis-NATs are largely unknown. In this study, we investigated the transcriptional characteristics and functions of cis-NATs in the muscle tissue of lean Landrace and indigenous fatty Lantang pigs. In total, 3,306 cis-NATs of 2,469 annotated genes were identified in the muscle tissue of pigs. More than 1,300 cis-NATs correlated with their sense genes at the transcriptional level, and approximately 80% of them were co-expressed in the two breeds. Furthermore, over 1,200 differentially expressed cis-NATs were identified during muscle development. Function annotation showed that the cis-NATs participated in muscle development mainly by co-expressing with genes involved in energy metabolic pathways, including citrate cycle (TCA cycle), glycolysis or gluconeogenesis, mitochondrial activation and so on. Moreover, these cis-NATs and their sense genes abruptly increased at the transition from the late fetal stages to the early postnatal stages and then decreased along with muscle development. In conclusion, the cis-NATs in the muscle tissue of pigs were identified and determined to be mainly co-expressed with their sense genes. The co-expressed cis-NATs and their sense gene were primarily related to energy metabolic pathways during muscle development in pigs. Our results offered novel evidence on the roles of cis-NATs during the muscle development of pigs.

Artificial neural network applying for justification of tractors undercarriages parameters

Directory of Open Access Journals (Sweden)

V. A. Kuz’Min

2017-01-01

Full Text Available One of the most important properties that determine undercarriage layout on design stage is the soil compaction effect. Existing domestic standards of undercarriages impact to soil do not meet modern agricultural requirements completely. The authors justify the need for analysis of traction and transportation machines travel systems and recommendations for these parameters applied to machines that are on design or modernization stage. The database of crawler agricultural tractors particularly in such parameters as traction class and basic operational weight, engine power rating, average ground pressure, square of track basic branch surface area was modeled. Meanwhile the considered machines were divided into two groups by producing countries: Europe/North America and Russian Federation/CIS. The main graphical dependences for every group of machines are plotted, and the conforming analytical dependences within the ranges with greatest concentration of machines are generated. To make the procedure of obtaining parameters of the soil panning by tractors easier it is expedient to use the program tool - artificial neural network (or perceptron. It is necessary to apply to the solution of this task multilayered perceptron - neutron network of direct distribution of signals (without feedback. To carry out the analysis of parameters of running systems taking into account parameters of the soil panning by them and to recommend the choice of these parameters for newly created machines. The program code of artificial neural network is developed. On the basis of the created base of tractors the artificial neural network was created and tested. Accumulated error was not more than 5 percent. These data indicate the results accuracy and tool reliability. It is possible by operating initial design-data base and using the designed artificial neural network to define missing parameters.

Inactivation of carbenicillin by some radioresistant mutant strains

International Nuclear Information System (INIS)

Zahiera, T.S.; Mahmoud, M.I.; Bashandy, A.A.

1990-01-01

Sensitivity test of five bacterial species to carbenicillin was performed microbiologically. The bacterial species were previously isolated from high level radiation environment. All the studied species could either highly decrease the antibiotic activity or even inactivate it completely. Detailed study of the inactivation of carbenicillin by the radioresistant mutant strains B. Laterosporus, B. firmus and M. roseus was performed, in the present study. Using high performace liquid chromatography technique. The gram-positive m. roseus mutant strain seemed to be the most active mutant in degrading the antibiotic. The left over of the antibiotic attained a value of 9% of the original amount after 14 day incubation of the antibiotic with this mutant strain, while the value of the left over reached 36% and 32% after the same period of incubation with the mutants B. laterosporus and B. firmus respectively. In the case of bacillus species, the degradation of the antibiotic started at the same moment when it was added to the bacterial cultures. This fact may indicate that the inactivation of the studied antibiotic by these bacillus species was due to extracellular enzymes extracted rapidly in the surrounding medium. In the case of M. roseus the inactivation process started later. after the addition of the antibiotic to the mutant culture

Complement C5a receptor antagonism by protamine and poly-L-Arg on human leukocytes.

Science.gov (United States)

Olsen, U B; Selmer, J; Kahl, J U

1988-01-01

It is shown that protamine selectively and dose-dependently inhibits complement C5a-induced leukocyte responses such as histamine release from basophils, chemiluminescence and beta-glucuronidase release from neutrophils. Protamine produces parallel rightward displacements of the C5a dose-response curves. The inhibitory capacity of the polypeptide is reversible and disappears following repeated washing of exposed cells. In neutrophils poly-L-Arg similarly and specifically antagonizes C5a-induced chemiluminescence and enzyme release. This polymer alone, however, degranulates basophils and neutrophils, leading to histamine and enzyme release, respectively. It is concluded that on human neutrophils the arginine-rich polycations protamine and poly-L-Arg exhibit a competitive C5a receptor antagonism. In addition, protamine inhibits the C5a receptors on basophils. It is hypothesized that molecular conformations of the arginine-rich polycations might bind reversibly to, and block negatively charged groups at the C5a-receptor sites.

Calcitonin gene-related peptide antagonism and cluster headache

DEFF Research Database (Denmark)

Ashina, Håkan; Newman, Lawrence; Ashina, Sait

2017-01-01

Calcitonin gene-related peptide (CGRP) is a key signaling molecule involved in migraine pathophysiology. Efficacy of CGRP monoclonal antibodies and antagonists in migraine treatment has fueled an increasing interest in the prospect of treating cluster headache (CH) with CGRP antagonism. The exact...... role of CGRP and its mechanism of action in CH have not been fully clarified. A search for original studies and randomized controlled trials (RCTs) published in English was performed in PubMed and in ClinicalTrials.gov . The search term used was "cluster headache and calcitonin gene related peptide......" and "primary headaches and calcitonin gene related peptide." Reference lists of identified articles were also searched for additional relevant papers. Human experimental studies have reported elevated plasma CGRP levels during both spontaneous and glyceryl trinitrate-induced cluster attacks. CGRP may play...

ANTAGONISM OF A. VIRIDANS TO CONDITIONALLY - PATHOGENIC MICROFLORA OF THE NOSE AND OROPHARYNX OF CHILDREN WITH CARDIAC PATOLOGY

Directory of Open Access Journals (Sweden)

Stepansky D.O.

2015-12-01

Full Text Available Introduction. Search for harmless and simultaneously effective probiotics, which could be successfully used for treatment and prevention of infectious deseases, is currently important. A. viridans is of particular interest, as it is representative of the normal microflora of human with broad spectrum of antibacterial action. The use of this microorganism has a number of advantages: the absence of side effects on the body; high adhesive abilities; resistance to lysozyme in saliva; the ability of use in patients, sensitized to antibiotics and chemotherapeutic drugs; stimulation effects on the human immune system. Material and methods. The purpose of the study was to investigate the antagonism of A. viridans № 167 and autostrains of aerococcuses, isolated at patients, to conditionally - pathogenic microflora of the nose and oropharynx of children with cardiac patology. At the first stage of the study the microflora of the of the nose and oropharynx of 2 investigated categories was examined – 40 children 4-14 years with cardiac patology and 40 healthy children 4-5 years old. The second stage of work was to study the effect of A. viridans on the explored strains. Results and discussion. A. viridans manifests the antagonism to all studied strains of gram-positive and gram-negative microorganisms, except C. albisans. A. viridans antagonistic activity to staphylococci (10 + 3 mm and streptococci (10 + 2mm is at the approximately same level. It is interesting to compare the antagonism of aerococcuses to clinical isolates of S. pyogenes and similar strains from carriers (healthy children category. Impact of aerococcuses on P. mirabilis strain appeared at the highest level. Autosimbionts of A. viridans, isolated from healthy children, are more antagonistic to CPM strains, isolated from these children, than autostrains of A. viridans, isolated from children with with cardiac patology, and higher than the museum strain of A. viridans № 167 antagonism

37 CFR 11.11 - Administrative suspension, inactivation, resignation, and readmission.

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Administrative suspension, inactivation, resignation, and readmission. 11.11 Section 11.11 Patents, Trademarks, and Copyrights UNITED... Other Non-Patent Law § 11.11 Administrative suspension, inactivation, resignation, and readmission. (a...

Immunogenicity of UV-inactivated measles virus

International Nuclear Information System (INIS)

Zahorska, R.; Mazur, N.; Korbecki, M.

1978-01-01

By means of the antigen extinction limit test it was shown that a triple dose vaccination of guinea pigs with UV-inactivated measles virus gave better results, than a single dose vaccination which was proved by the very low immunogenicity index. For both vaccination schemes (single and triple) the immune response was only sligthly influenced by a change of dose from 10 5 to 10 6 HadU 50 /ml or by the addition of aluminum adjuvant. In the antigen extinction limit test the antibody levels were determined by two methods (HIT and NT) the results of which were statistically equivalent. The UV-inactivated measles virus was also found to induce hemolysis-inhibiting antibodies. (orig.) [de

Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis.

Science.gov (United States)

Yang, Fan; Wang, Jiebiao; Pierce, Brandon L; Chen, Lin S

2017-11-01

The impact of inherited genetic variation on gene expression in humans is well-established. The majority of known expression quantitative trait loci (eQTLs) impact expression of local genes ( cis -eQTLs). More research is needed to identify effects of genetic variation on distant genes ( trans -eQTLs) and understand their biological mechanisms. One common trans -eQTLs mechanism is "mediation" by a local ( cis ) transcript. Thus, mediation analysis can be applied to genome-wide SNP and expression data in order to identify transcripts that are " cis -mediators" of trans -eQTLs, including those " cis -hubs" involved in regulation of many trans -genes. Identifying such mediators helps us understand regulatory networks and suggests biological mechanisms underlying trans -eQTLs, both of which are relevant for understanding susceptibility to complex diseases. The multitissue expression data from the Genotype-Tissue Expression (GTEx) program provides a unique opportunity to study cis -mediation across human tissue types. However, the presence of complex hidden confounding effects in biological systems can make mediation analyses challenging and prone to confounding bias, particularly when conducted among diverse samples. To address this problem, we propose a new method: Genomic Mediation analysis with Adaptive Confounding adjustment (GMAC). It enables the search of a very large pool of variables, and adaptively selects potential confounding variables for each mediation test. Analyses of simulated data and GTEx data demonstrate that the adaptive selection of confounders by GMAC improves the power and precision of mediation analysis. Application of GMAC to GTEx data provides new insights into the observed patterns of cis -hubs and trans -eQTL regulation across tissue types. © 2017 Yang et al.; Published by Cold Spring Harbor Laboratory Press.

Influenza (flu) vaccine (Inactivated or Recombinant): What you need to know

Science.gov (United States)

... taken in its entirety from the CDC Inactivated Influenza Vaccine Information Statement (VIS) www.cdc.gov/vaccines/hcp/vis/vis-statements/flu.html CDC review information for Inactivated Influenza VIS: ...

Inactivation disinfection property of Moringa Oleifera seed extract: optimization and kinetic studies

Science.gov (United States)

Idris, M. A.; Jami, M. S.; Hammed, A. M.

2017-05-01

This paper presents the statistical optimization study of disinfection inactivation parameters of defatted Moringa oleifera seed extract on Pseudomonas aeruginosa bacterial cells. Three level factorial design was used to estimate the optimum range and the kinetics of the inactivation process was also carried. The inactivation process involved comparing different disinfection models of Chicks-Watson, Collins-Selleck and Homs models. The results from analysis of variance (ANOVA) of the statistical optimization process revealed that only contact time was significant. The optimum disinfection range of the seed extract was 125 mg/L, 30 minutes and 120rpm agitation. At the optimum dose, the inactivation kinetics followed the Collin-Selleck model with coefficient of determination (R2) of 0.6320. This study is the first of its kind in determining the inactivation kinetics of pseudomonas aeruginosa using the defatted seed extract.

Inactivation Effect of Antibiotic-Resistant Gene Using Chlorine Disinfection

Directory of Open Access Journals (Sweden)

Takashi Furukawa

2017-07-01

Full Text Available The aim of this study was to elucidate the inactivation effects on the antibiotic-resistance gene (vanA of vancomycin-resistant enterococci (VRE using chlorination, a disinfection method widely used in various water treatment facilities. Suspensions of VRE were prepared by adding VRE to phosphate-buffered saline, or the sterilized secondary effluent of a wastewater treatment plant. The inactivation experiments were carried out at several chlorine concentrations and stirring time. Enterococci concentration and presence of vanA were determined. The enterococci concentration decreased as chlorine concentrations and stirring times increased, with more than 7.0 log reduction occurring under the following conditions: 40 min stirring at 0.5 mg Cl2/L, 20 min stirring at 1.0 mg Cl2/L, and 3 min stirring at 3.0 mg Cl2/L. In the inactivation experiment using VRE suspended in secondary effluent, the culturable enterococci required much higher chlorine concentration and longer treatment time for complete disinfection than the cases of suspension of VRE. However, vanA was detected in all chlorinated suspensions of VRE, even in samples where no enterococcal colonies were present on the medium agar plate. The chlorine disinfection was not able to destroy antibiotic-resistance genes, though it can inactivate and decrease bacterial counts of antibiotic-resistant bacteria (ARB. Therefore, it was suggested that remaining ARB and/or antibiotic-resistance gene in inactivated bacterial cells after chlorine disinfection tank could be discharged into water environments.

CB1 receptor antagonism increases hippocampal acetylcholine release: site and mechanism of action.

Science.gov (United States)

Degroot, Aldemar; Köfalvi, Attila; Wade, Mark R; Davis, Richard J; Rodrigues, Ricardo J; Rebola, Nelson; Cunha, Rodrigo A; Nomikos, George G

2006-10-01

Evidence indicates that blockade of cannabinoid receptors increases acetylcholine (ACh) release in brain cortical regions. Although it is assumed that this type of effect is mediated through CB1 receptor (CB1R) antagonism, several in vitro functional studies recently have suggested non-CB1R involvement. In addition, neither the precise neuroanatomical site nor the exact mechanisms underlying this effect are known. We thoroughly examined these issues using a combination of systemic and local administration of CB1R antagonists, different methods of in vivo microdialysis, CB1R knockout (KO) mice, tissue measurements of ACh, and immunochemistry. First, we showed that systemic injections of the CB1R antagonists N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR-141716A) and N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) dose-dependently increased hippocampal ACh efflux. Likewise, local hippocampal, but not septal, infusions of SR141716A or AM251 increased hippocampal ACh release. It is noteworthy that the stimulatory effects of systemically administered CB1R antagonists on hippocampal ACh release were completely abolished in CB1R KO mice. CB1R KO mice had similar basal but higher stress-enhanced hippocampal ACh levels compared with wild-type controls. It is interesting that dopamine D1 receptor antagonism counteracted the stimulatory effect of CB1R blockade on hippocampal ACh levels. Finally, immunohistochemical methods revealed that a high proportion of CB1R-positive nerve terminals were found in hippocampus and confirmed the colocalization of CB1 receptors with cholinergic and dopaminergic nerve terminals. In conclusion, hippocampal ACh release may specifically be controlled through CB1Rs located on both cholinergic and dopaminergic neuronal projections, and CB1R antagonism increases hippocampal ACh release, probably through both a direct

Radical inactivation of a biological sulphydryl molecule

International Nuclear Information System (INIS)

Lin, W.S.; Lal, M.; Gaucher, G.M.; Armstrong, D.A.

1977-01-01

Reactive species produced from the free radical-induced chain oxidation of low molecular weight sulphydryl-containing molecules in aerated solutions deactivate the sulphydryl-containing enzyme papain, forming both reparable mixed disulphides and non-reparable products. This inactivation is highly efficient for penicillamine and glutathione, but almost negligible with cysteine, which is a protector of papain for [cysteine] / [papain] >= 5 under all conditions used. In the case of glutathione, superoxide dismutase caused only a small reduction in the inactivation and peroxide yields were small, implying that the deactivating species are not .O 2 - but RSOO. radicals or products from them. For penicillamine, however, dimutase was highly effective and the peroxide yields were relatively large, demonstrating that .O 2 - or a radical with similar capabilities for forming H 2 O 2 and being deactivated by dismutase was involved. Although in the presence of dismutase penicillamine is a better protector of non-reparable papain inactivation than glutathione, it suffers from a deficiency in that the papain-penicillamine mixed disulphide, which is always formed, cannot be repaired by spontaneous reaction with RSH molecules. (author)

Planning "and" Sprinting: Use of a Hybrid Project Management Methodology within a CIS Capstone Course

Science.gov (United States)

Baird, Aaron; Riggins, Frederick J.

2012-01-01

An increasing number of information systems projects in industry are managed using hybrid project management methodologies, but this shift in project management methods is not fully represented in our CIS curriculums. CIS capstone courses often include an applied project that is managed with traditional project management methods (plan first,…

Exposure of maternal mice to cis-bifenthrin enantioselectively disrupts the transcription of genes related to testosterone synthesis in male offspring.

Science.gov (United States)

Jin, Yuanxiang; Wang, Jiangcong; Sun, Xueqing; Ye, Yang; Xu, Minjie; Wang, Jianai; Chen, Shaoping; Fu, Zhengwei

2013-12-01

The commercial bifenthrin (BF) contains two cis isomers. In the present study, a dose of 15mg/kg of 1R-cis-BF or 1S-cis-BF was orally administered for 3 weeks to female mice before or during pregnancy. Then, the expression of steroidogenesis related genes which were considered as effective biomarkers of endocrine disruption were analyzed in the male offspring. Maternal exposure to 1S-cis-BF during pregnancy significantly reduced the mRNA levels of peripheral benzodiazepine receptor (PBR) and steroidogenic acute regulatory protein (StAR) in the testes of 3- or 6-week old male offspring. In addition, a significant decrease of cytochrome P450 17α-hydroxysteroid dehydrogenase (P450-17α) was also observed in the testes of 6-week old male offspring when dams were treated with 1S-cis-BF during pregnancy but not before pregnancy. Moreover, the scavenger receptor class B type 1 (SRB1) and cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc) decreased significantly in the testes of 6-week old male offspring when dams were treated with 1S-cis-BF during and before pregnancy. Thus, oral administration of the maternal mice to cis-BF for 3 weeks, particularly during pregnancy, resulted in endocrine disruption in the male offspring, with the 1S-cis-BF causing more significant alterations than the 1R-cis-BF form. Copyright © 2013 Elsevier Inc. All rights reserved.

Pulsed dielectric barrier discharge for Bacillus subtilis inactivation in water

Science.gov (United States)

Hernández-Arias, A. N.; Rodríguez-Méndez, B. G.; López-Callejas, R.; Valencia-Alvarado, R.; Mercado-Cabrera, A.; Peña-Eguiluz, R.; Barocio, S. R.; Muñoz-Castro, A. E.; de la Piedad Beneitez, A.

2012-06-01

The inactivation of Bacillus subtilis bacteria in water has been experimentally studied by means of a pulsed dielectric barrier discharge (PDBD) in a coaxial reactor endowed with an alumina dielectric. The plasma source is capable of operating at atmospheric pressure with gas, water or hybrid gas-liquid media at adjustable 25 kV pulses, 30 μs long and at a 500 Hz frequency. In order to evaluate the inactivation efficiency of the system, a set of experiments were designed on the basis of oxygen flow control. The initial data have showed a significant bacterial rate reduction of 103-107 CFU/mL. Additional results proved that applying an oxygen flow for a few seconds during the PDBD treatment inactivates the Bacillus subtilis population with 99.99% effectiveness. As a reference, without gas flow but with the same exposure times, this percentage is reduced to ~90%. The analysis of the relationship between inactivation rate and chemical species in the discharge has been carried out using optical emission spectroscopy as to identifying the main reactive species. Reactive oxygen species such as atomic oxygen and ozone tuned out to be the dominant germicidal species. Some proposed inactivation mechanisms of this technique are discussed.

Pulsed dielectric barrier discharge for Bacillus subtilis inactivation in water

International Nuclear Information System (INIS)

Hernández-Arias, A N; López-Callejas, R; De la Piedad Beneitez, A; Rodríguez-Méndez, B G; Valencia-Alvarado, R; Mercado-Cabrera, A; Peña-Eguiluz, R; Barocio, S R; Muñoz-Castro, A E

2012-01-01

The inactivation of Bacillus subtilis bacteria in water has been experimentally studied by means of a pulsed dielectric barrier discharge (PDBD) in a coaxial reactor endowed with an alumina dielectric. The plasma source is capable of operating at atmospheric pressure with gas, water or hybrid gas-liquid media at adjustable 25 kV pulses, 30 μs long and at a 500 Hz frequency. In order to evaluate the inactivation efficiency of the system, a set of experiments were designed on the basis of oxygen flow control. The initial data have showed a significant bacterial rate reduction of 10 3 -10 7 CFU/mL. Additional results proved that applying an oxygen flow for a few seconds during the PDBD treatment inactivates the Bacillus subtilis population with 99.99% effectiveness. As a reference, without gas flow but with the same exposure times, this percentage is reduced to ∼90%. The analysis of the relationship between inactivation rate and chemical species in the discharge has been carried out using optical emission spectroscopy as to identifying the main reactive species. Reactive oxygen species such as atomic oxygen and ozone tuned out to be the dominant germicidal species. Some proposed inactivation mechanisms of this technique are discussed.

Enhanced cis-platinum ototoxicity in children with brain tumours who have received simultaneous or prior cranial irradiation

International Nuclear Information System (INIS)

Walker, D.A.; Pillow, J.; Waters, K.D.; Keir, E.

1989-01-01

We report on four children who received cis-platinum simultaneously with, or in one case 10 months after, cranial irradiation and experienced exaggerated ototoxicity affecting all audible frequencies. The hearing loss was severe, affecting the critical areas for speech perception, and necessitated the provision of bilateral hearing aids. The audiograms of these patients are shown and compared to those of four children who had received cis-platinum as part of their treatment for neuroblastoma but without cranial irradiation. The precipitation of the exaggerated hearing loss with the administration of cis-platinum in one patient 10 months after finishing cranial irradiation suggests that care should be taken in the timing of cis-platinum administration in relation to concurrent or previous cranial irradiation

Annual report of the project CIS-03-95, `evaluation of actinide nuclear data`

Energy Technology Data Exchange (ETDEWEB)

Maslov, V.M. [Radiation Physics and Chemistry Problems Inst., Minsk-Sosny (Belarus)

1997-03-01

The evaluation of neutron data for {sup 243}Cm, {sup 245}Cm and {sup 246}Cm is made in the energy region from 10-5 eV up to 20 MeV. The results of the evaluation are compiled in the ENDF/B-VI format. This work is performed under the Project Agreement CIS-03-95 with the International Science and Technology Center (Moscow). This is the annual report of the project CIS-03-95. (author)

Calmodulin and calcium differentially regulate the neuronal Nav1.1 voltage-dependent sodium channel

Energy Technology Data Exchange (ETDEWEB)

Gaudioso, Christelle; Carlier, Edmond; Youssouf, Fahamoe [INSERM U641, Institut Jean Roche, Marseille F-13344 (France); Universite de la Mediterranee, Faculte de Medecine Secteur Nord, IFR 11, Marseille F-13344 (France); Clare, Jeffrey J. [Eaton Pharma Consulting, Eaton Socon, Cambridgeshire PE19 8EF (United Kingdom); Debanne, Dominique [INSERM U641, Institut Jean Roche, Marseille F-13344 (France); Universite de la Mediterranee, Faculte de Medecine Secteur Nord, IFR 11, Marseille F-13344 (France); Alcaraz, Gisele, E-mail: gisele.alcaraz@univmed.fr [INSERM U641, Institut Jean Roche, Marseille F-13344 (France); Universite de la Mediterranee, Faculte de Medecine Secteur Nord, IFR 11, Marseille F-13344 (France)

2011-07-29

Highlights: {yields} Both Ca{sup ++}-Calmodulin (CaM) and Ca{sup ++}-free CaM bind to the C-terminal region of Nav1.1. {yields} Ca{sup ++} and CaM have both opposite and convergent effects on I{sub Nav1.1}. {yields} Ca{sup ++}-CaM modulates I{sub Nav1.1} amplitude. {yields} CaM hyperpolarizes the voltage-dependence of activation, and increases the inactivation rate. {yields} Ca{sup ++} alone antagonizes CaM for both effects, and depolarizes the voltage-dependence of inactivation. -- Abstract: Mutations in the neuronal Nav1.1 voltage-gated sodium channel are responsible for mild to severe epileptic syndromes. The ubiquitous calcium sensor calmodulin (CaM) bound to rat brain Nav1.1 and to the human Nav1.1 channel expressed by a stably transfected HEK-293 cell line. The C-terminal region of the channel, as a fusion protein or in the yeast two-hybrid system, interacted with CaM via a consensus C-terminal motif, the IQ domain. Patch clamp experiments on HEK1.1 cells showed that CaM overexpression increased peak current in a calcium-dependent way. CaM had no effect on the voltage-dependence of fast inactivation, and accelerated the inactivation kinetics. Elevating Ca{sup ++} depolarized the voltage-dependence of fast inactivation and slowed down the fast inactivation kinetics, and for high concentrations this effect competed with the acceleration induced by CaM alone. Similarly, the depolarizing action of calcium antagonized the hyperpolarizing shift of the voltage-dependence of activation due to CaM overexpression. Fluorescence spectroscopy measurements suggested that Ca{sup ++} could bind the Nav1.1 C-terminal region with micromolar affinity.

Inactivation of E. Coli in Water Using Photocatalytic, Nanostructured Films Synthesized by Aerosol Routes

Directory of Open Access Journals (Sweden)

Pratim Biswas

2013-03-01

Full Text Available TiO2 nanostructured films were synthesized by an aerosol chemical vapor deposition (ACVD method with different controlled morphologies: columnar, granular, and branched structures for the photocatalytic inactivation of Escherichia coli (E. coli in water. Effects of film morphology and external applied voltage on inactivation rate were investigated. As-prepared films were characterized using scanning electron microscopy (SEM, transmission electron microscopy (TEM, X-ray diffractometry (XRD, and UV-VIS. Photocatalytic and photoelectrochemical inactivation of E. coli using as-prepared TiO2 films were performed under irradiation of UVA light (note: UVA has a low efficiency to inactivate E. coli. Inactivation rate constants for each case were obtained from their respective inactivation curve through a 2 h incubation period. Photocatalytic inactivation rate constants of E. coli are 0.02/min (using columnar films, and 0.08/min (using branched films. The inactivation rate constant for the columnar film was enhanced by 330% by applied voltage on the film while that for the branched film was increased only by 30%. Photocatalytic microbial inactivation rate of the columnar and the branched films were also compared taking into account their different surface areas. Since the majority of the UV radiation that reaches the Earth’s surface is UVA, this study provides an opportunity to use sunlight to efficiently decontaminate drinking water.

Stem-Cell Inactivation on Transplantation of Haemopoietic Cell Suspensions from Genetically Different Donors

Energy Technology Data Exchange (ETDEWEB)

Petrov, R. V. [Institute of Biophysics, Ministry of Public Health of the USSR, Moscow, USSR (Russian Federation)

1969-07-15

The transplantation of a mixture of haemopoietic or lymphoid cells from two genetically different mice into lethally irradiated F{sub 1} recipients results in marked or total inactivation of the colony-forming units of the graft. This phenomenon is observed following transplantation of mixtures of spleen cells or bone-marrow cells from animals of different genotypes: CBA + C57BL, A + CBA, A + C57BL, C3H + C57BL, CBA + (CBA x C57BL) F{sub 1}. Maximum inactivation is observed when lymph-node cells of one genotype are transplanted with spleen or bone-marrow cells of another genotype. Use of non-syngenic kidney cells or lymphoid cells inactivated by irradiation as one component of the mixture shows that inactivation of genetically heterogeneous stem cells requires the participation of viable lymphoid cells. The inactivation phenomenon is also observed with Jerne's method. This shows that inactivation affects not only colony-forming cells but also the immunologically competent precursors of antibody-producing cells. (author)

Inactivation of influenza A virus H1N1 by disinfection process.

Science.gov (United States)

Jeong, Eun Kyo; Bae, Jung Eun; Kim, In Seop

2010-06-01

Because any patient, health care worker, or visitor is capable of transmitting influenza to susceptible persons within hospitals, hospital-acquired influenza has been a clinical concern. Disinfection and cleaning of medical equipment, surgical instruments, and hospital environment are important measures to prevent transmission of influenza virus from hospitals to individuals. This study was conducted to evaluate the efficacy of disinfection processes, which can be easily operated at hospitals, in inactivating influenza A virus H1N1 (H1N1). The effects of 0.1 mol/L NaOH, 70% ethanol, 70% 1-propanol, solvent/detergent (S/D) using 0.3% tri (n-butyl)-phosphate and 1.0% Triton X-100, heat, and ethylene oxide (EO) treatments in inactivating H1N1 were determined. Inactivation of H1N1 was kinetically determined by the treatment of disinfectants to virus solution. Also, a surface test method, which involved drying an amount of virus on a surface and then applying the inactivation methods for 1 minute of contact time, was used to determine the virucidal activity. H1N1 was completely inactivated to undetectable levels in 1 minute of 70% ethanol, 70% 1-propanol, and solvent/detergent treatments in the surface tests as well as in the suspension tests. H1N1 was completely inactivated in 1 minute of 0.1 mol/L NaOH treatment in the suspension tests and also effectively inactivated in the surface tests with the log reduction factor of 3.7. H1N1 was inactivated to undetectable levels within 5 minutes, 2.5 minutes, and 1 minute of heat treatment at 70, 80, and 90 degrees C, respectively in the suspension tests. Also, H1N1 was completely inactivated by EO treatment in the surface tests. Common disinfectants, heat, and EO tested in this study were effective at inactivating H1N1. These results would be helpful in implementing effective disinfecting measures to prevent hospital-acquired infections. Copyright 2010 Association for Professionals in Infection Control and Epidemiology, Inc

Curcumin attenuates harmful effects of arsenic on neural stem/progenitor cells

Directory of Open Access Journals (Sweden)

Ali Jahanbazi Jahan-Abad

2017-06-01

Full Text Available Objective: Arsenic, an environmental pollutant, decreases neuronal migration as well as cellular maturation and inhibits the proliferation of neural progenitor cells. Curcumin has been described as an antioxidant and neuroprotective agent with strong therapeutic potential in some neurological disorders. Human adipose-derived stem cells (hADSCs, a source of multipotent stem cells, can self-renew and differentiate into neural cells. The aim of the present study was to investigate the preventive effect of curcumin against arsenic toxic effects on the viability, telomerase activity, and apoptosis of neural stem/progenitor cells (NSPCs derived from hADSCs. Materials and Methods: The characteristics of human adipose tissue were identified by immunocytochemistry for surface markers namely, CD105, CD73, and CD90. Using neurosphere assay, hADSCs were differentiated into neuronal cells. To characterize neural cells, expression of nestin, SOX2, MAP2, and GFAP were assessed by immunocytochemistry. Cytotoxicity and viability of NSPCs were evaluated by MTT assay. Reactive oxygen species (ROS generated by arsenic exposure, were measured and caspase 3/7 activity and caspase-3 processing as well as the telomerase activity were determined. Results: The isolated hADSCs positively expressed CD105, CD73, and CD90. Nestin, Sox2, GFAP, and MAP2 were expressed in the neurospheres derived from hADSCs. Curcumin/arsenic co-treatment significantly increased telomerase activity of NSPCs compared to arsenic group. Furthermore, curcumin significantly reduced arsenic-induced apoptosis (via inactivation of caspases as well as arsenic-associated ROS generation. Conclusion: Our findings revealed that curcumin has the potential to prevent harmful effects of arsenic on neurogenesis.

Studies on the inactivation of human parvovirus 4.

Science.gov (United States)

Baylis, Sally A; Tuke, Philip W; Miyagawa, Eiji; Blümel, Johannes

2013-10-01

Human parvovirus 4 (PARV4) is a novel parvovirus, which like parvovirus B19 (B19V) can be a contaminant of plasma pools used to prepare plasma-derived medicinal products. Inactivation studies of B19V have shown that it is more sensitive to virus inactivation strategies than animal parvoviruses. However, inactivation of PARV4 has not yet been specifically addressed. Treatment of parvoviruses by heat or low-pH conditions causes externalization of the virus genome. Using nuclease treatment combined with real-time polymerase chain reaction, the extent of virus DNA externalization was used as an indirect measure of the inactivation of PARV4, B19V, and minute virus of mice (MVM) by pasteurization of albumin and by low-pH treatment. Infectivity studies were performed in parallel for B19V and MVM. PARV4 showed greater resistance to pasteurization and low-pH treatment than B19V, although PARV4 was not as resistant as MVM. There was a 2- to 3-log reduction of encapsidated PARV4 DNA after pasteurization and low-pH treatment. In contrast, B19V was effectively inactivated while MVM was stable under these conditions. Divalent cations were found to have a stabilizing effect on PARV4 capsids. In the absence of divalent cations, even at neutral pH, there was a reduction of PARV4 titer, an effect not observed for B19V or MVM. In the case of heat treatment and incubation at low pH, PARV4 shows intermediate resistance when compared to B19V and MVM. Divalent cations seem important for stabilizing PARV4 virus particles. © 2013 American Association of Blood Banks.

cis-Dichloridobis(1,10-phenanthrolinechromium(III chloride

Directory of Open Access Journals (Sweden)

Xiaoli Gao

2011-02-01

Full Text Available In the title complex, [CrCl2(C12H8N22]Cl, the CrIII ion is situated on a twofold rotation axis and displays a slightly distorted octahedral CrCl2N4 coordination geometry. The Cr environment is composed of a cis arrangement of two 1,10-phenanthroline and two chloride ligands. The chloride counter-anion exhibits half-occupation and is equally disordered over two positions.

Pathogenic adaptation of intracellular bacteria by rewiring a cis-regulatory input function.

Science.gov (United States)

Osborne, Suzanne E; Walthers, Don; Tomljenovic, Ana M; Mulder, David T; Silphaduang, Uma; Duong, Nancy; Lowden, Michael J; Wickham, Mark E; Waller, Ross F; Kenney, Linda J; Coombes, Brian K

2009-03-10

The acquisition of DNA by horizontal gene transfer enables bacteria to adapt to previously unexploited ecological niches. Although horizontal gene transfer and mutation of protein-coding sequences are well-recognized forms of pathogen evolution, the evolutionary significance of cis-regulatory mutations in creating phenotypic diversity through altered transcriptional outputs is not known. We show the significance of regulatory mutation for pathogen evolution by mapping and then rewiring a cis-regulatory module controlling a gene required for murine typhoid. Acquisition of a binding site for the Salmonella pathogenicity island-2 regulator, SsrB, enabled the srfN gene, ancestral to the Salmonella genus, to play a role in pathoadaptation of S. typhimurium to a host animal. We identified the evolved cis-regulatory module and quantified the fitness gain that this regulatory output accrues for the bacterium using competitive infections of host animals. Our findings highlight a mechanism of pathogen evolution involving regulatory mutation that is selected because of the fitness advantage the new regulatory output provides the incipient clones.

The Eag domain regulates the voltage-dependent inactivation of rat Eag1 K+ channels.

Directory of Open Access Journals (Sweden)

Ting-Feng Lin

Full Text Available Eag (Kv10 and Erg (Kv11 belong to two distinct subfamilies of the ether-à-go-go K+ channel family (KCNH. While Erg channels are characterized by an inward-rectifying current-voltage relationship that results from a C-type inactivation, mammalian Eag channels display little or no voltage-dependent inactivation. Although the amino (N-terminal region such as the eag domain is not required for the C-type inactivation of Erg channels, an N-terminal deletion in mouse Eag1 has been shown to produce a voltage-dependent inactivation. To further discern the role of the eag domain in the inactivation of Eag1 channels, we generated N-terminal chimeras between rat Eag (rEag1 and human Erg (hERG1 channels that involved swapping the eag domain alone or the complete cytoplasmic N-terminal region. Functional analyses indicated that introduction of the homologous hERG1 eag domain led to both a fast phase and a slow phase of channel inactivation in the rEag1 chimeras. By contrast, the inactivation features were retained in the reverse hERG1 chimeras. Furthermore, an eag domain-lacking rEag1 deletion mutant also showed the fast phase of inactivation that was notably attenuated upon co-expression with the rEag1 eag domain fragment, but not with the hERG1 eag domain fragment. Additionally, we have identified a point mutation in the S4-S5 linker region of rEag1 that resulted in a similar inactivation phenotype. Biophysical analyses of these mutant constructs suggested that the inactivation gating of rEag1 was distinctly different from that of hERG1. Overall, our findings are consistent with the notion that the eag domain plays a critical role in regulating the inactivation gating of rEag1. We propose that the eag domain may destabilize or mask an inherent voltage-dependent inactivation of rEag1 K+ channels.

Small molecule antagonism of oxysterol-induced Epstein-Barr virus induced gene 2 (EBI2) activation

DEFF Research Database (Denmark)

Benned-Jensen, Tau; Madsen, Christian M; Arfelt, Kristine N

2013-01-01

The Epstein-Barr virus induced gene 2 (EBI2) was recently identified as the first oxysterol-activated 7TM receptor. EBI2 is essential for B cell trafficking within lymphoid tissues and thus the humoral immune response in general. Here we characterize the antagonism of the non-peptide molecule GSK...

Studies on disappearance and inactivation of viruses in sewage, 2

International Nuclear Information System (INIS)

Yano, Kazuyoshi; Yabuuchi, Kiyoshi; Taguchi, Fumiaki.

1985-01-01

Methods of inactivating viruses in wastewater were studied. Polio visuses were added to the distilled water until the number of viruses reached 10sup(6.8) TCID 50 /ml, and liquid layer was 2 mm. The inactivation rate of viruses was determined at each time of ultraviolet (U.V.) irradiation (from 0.425 x 10 4 μw/cm 2 to 10.0 x 10 4 μw/cm 2 ). A linear correlation was seen between the inactivation rate of viruses and the time of U.V. irradiation obtained from logarithmic transformation. The irradiation time required for inactivation of 99.9% viruses was 15 sec when U.V. intensity was 10.0 x 10 4 μw/cm 2 and 9.6 min when it was 0.423 x 10 4 μw/cm 2 . When the U.V. intensity was 0.425 x 10 4 μw/cm 2 , the time required for inactivation was dependent on the number of viruses (120 sec in cases of 10sup(3.8) TCID 50 /ml of viruses and 720 sec in cases of 10sup(7.8) TCID 50 /ml of viruses). When viruses were added to the distilled water until the number reached 10sup(5.8) TCID 50 /ml, and the depth of water was designated as 2 mm, 10 cm, and 15 cm, the U.V. permeability was more than 89% at any depth of water, and a sixteen-min U.V. irradiation inactivated more than 99.99% of viruses. When polio viruses were added to triple step-treated water until the number reached 10sup(5.3) TCID 50 /ml, the irradiation time required for inactivation of more than 99.99% was one min when the U.V. intensity was 10.0 x 10 4 μw/cm 2 and 20 min when it was 0.425 x 10 4 μw/cm 2 . (Namekawa, K.)

Efficient Bacteria Inactivation by Ultrasound in Municipal Wastewater

Directory of Open Access Journals (Sweden)

Leonel Ernesto Amabilis-Sosa

2018-04-01

Full Text Available The reuse of treated wastewaters could contribute to reducing water stress. In this research, ultrasound application on bacterial inactivation in municipal wastewater (MWW was evaluated. Total and fecal coliforms were used as standard fecal indicators; volatile suspended solids (VSS were analyzed too. Samples were taken from the effluent of secondary clarifiers. In addition, inactivation tests were carried out on pure cultures of E. coli (EC and B. subtilis (BS. Sonication was performed at 20 kHz, 35% amplitude and 600 W/L for 15, 30 and 45 min. After 15 min of sonication, bacterial density was reduced by 1.85 Log10 MPN/100 mL for EC and 3.16 Log10 CFU/mL for BS. After 30 min, no CFU/mL of BS were observed in MWW and, after 45 min, the reduction of total and fecal coliforms was practically 6.45 Log10 MPN/100mL. Inactivation mechanism was made by cavitation, which causes irreversible damage to the cell wall. Although high bacterial densities were employed, percentages of inactivation >99% were reached at 45 min. This research contributes to the implementation of ultrasound as a disinfection technique with high potential due to its high efficiency without producing byproducts. In fact, the water meets the guidelines for reuse in direct human contact services.

Computational exploration of cis-regulatory modules in rhythmic expression data using the "Exploration of Distinctive CREs and CRMs" (EDCC) and "CRM Network Generator" (CNG) programs.

Science.gov (United States)

Bekiaris, Pavlos Stephanos; Tekath, Tobias; Staiger, Dorothee; Danisman, Selahattin

2018-01-01

Understanding the effect of cis-regulatory elements (CRE) and clusters of CREs, which are called cis-regulatory modules (CRM), in eukaryotic gene expression is a challenge of computational biology. We developed two programs that allow simple, fast and reliable analysis of candidate CREs and CRMs that may affect specific gene expression and that determine positional features between individual CREs within a CRM. The first program, "Exploration of Distinctive CREs and CRMs" (EDCC), correlates candidate CREs and CRMs with specific gene expression patterns. For pairs of CREs, EDCC also determines positional preferences of the single CREs in relation to each other and to the transcriptional start site. The second program, "CRM Network Generator" (CNG), prioritizes these positional preferences using a neural network and thus allows unbiased rating of the positional preferences that were determined by EDCC. We tested these programs with data from a microarray study of circadian gene expression in Arabidopsis thaliana. Analyzing more than 1.5 million pairwise CRE combinations, we found 22 candidate combinations, of which several contained known clock promoter elements together with elements that had not been identified as relevant to circadian gene expression before. CNG analysis further identified positional preferences of these CRE pairs, hinting at positional information that may be relevant for circadian gene expression. Future wet lab experiments will have to determine which of these combinations confer daytime specific circadian gene expression.

Identification of unique cis-element pattern on simulated microgravity treated Arabidopsis by in silico and gene expression

Science.gov (United States)

Soh, Hyuncheol; Choi, Yongsang; Lee, Taek-Kyun; Yeo, Up-Dong; Han, Kyeongsik; Auh, Chungkyun; Lee, Sukchan

2012-08-01

Arabidopsis gene expression microarray (44 K) was used to detect genes highly induced under simulated microgravity stress (SMS). Ten SMS-inducible genes were selected from the microarray data and these 10 genes were found to be abundantly expressed in 3-week-old plants. Nine out of the 10 SMS-inducible genes were also expressed in response to the three abiotic stresses of drought, touch, and wounding in 3-week-old Arabidopsis plants respectively. However, WRKY46 was elevated only in response to SMS. Six other WRKY genes did not respond to SMS. To clarify the characteristics of the genes expressed at high levels in response to SMS, 20 cis-elements in the promoters of the 40 selected genes including the 10 SMS-inducible genes, the 6 WRKY genes, and abiotic stress-inducible genes were analyzed and their spatial positions on each promoter were determined. Four cis-elements (M/T-G-T-P from MYB1AT or TATABOX5, GT1CONSENSUS, TATABOX5, and POLASIG1) showed a unique spatial arrangement in most SMS-inducible genes including WRKY46. Therefore the M/T-G-T-P cis-element patterns identified in the promoter of WRKY46 may play important roles in regulating gene expression in response to SMS. The presences of the cis-element patterns suggest that the order or spatial positioning of certain groups of cis-elements is more important than the existence or numbers of specific cis-elements. Taken together, our data indicate that WRKY46 is a novel SMS inducible transcription factor and the unique spatial arrangement of cis-elements shown in WRKY46 promoter may play an important role for its response to SMS.

Photocytotoxic trans-diam(m)ine platinum(IV) diazido complexes more potent than their cis isomers.

Science.gov (United States)

Farrer, Nicola J; Woods, Julie A; Munk, Vivienne P; Mackay, Fiona S; Sadler, Peter J

2010-02-15

The photocytotoxicity of a series of anticancer trans-dihydroxido [Pt(N(3))(2)(OH)(2)(NH(3))(X)] (X = alkyl or aryl amine) platinum(IV) diazido complexes has been examined, and the influence of cis-trans isomerism has been investigated. A series of photoactivatable Pt(IV)-azido complexes has been synthesized: The synthesis, characterization, and photocytotoxicity of six mixed-ligand ammine/amine Pt(IV) diazido complexes, cis,trans,cis-[Pt(N(3))(2)(OH)(2)(NH(3))(X)] where X = propylamine (4c), butylamine (5c), or pentylamine (6c) and aromatic complexes where X = pyridine (7c), 2-methylpyridine (8c), or 3-methylpyridine (9c) are reported. Six all-trans isomers have also been studied where X = methylamine (2t), ethylamine (3t), 2-methylpyridine (8t), 4-methylpyridine (10t), 3-methylpyridine (9t), and 2-bromo-3-methylpyridine (11t). All of the complexes exhibit intense azide-to-Pt(IV) LMCT bands (ca. 290 nm for trans and ca. 260 nm for cis). When irradiated with UVA light (365 nm), the Pt(IV) complexes undergo photoreduction to Pt(II) species, as monitored by UV-vis spectroscopy. The trans isomers of complexes containing aliphatic or aromatic amines were more photocytotoxic than their cis isomers. One of the cis complexes (9c) was nonphotocytotoxic despite undergoing photoreduction. Substitution of NH(3) ligands by MeNH(2) or EtNH(2) results in more potent photocytotoxicity for the all-trans complexes. The complexes were all nontoxic toward human keratinocytes (HaCaT) and A2780 human ovarian cancer cells in the dark, apart from the 3-methylpyridine (9t), 2-bromo-3-methylpyridine (11t), and 4-methylpyridine (10t) derivatives.

Inactivation of bacteria in sewage sludge by gamma radiation

International Nuclear Information System (INIS)

Pandya, G.A.; Kapila, Smita; Kelkar, V.B.; Negi, Shobha; Modi, V.V.

1987-01-01

The survival of certain bacterial cultures suspended in sewage sludge and exposed to gamma-radiation was studied. The inactivation patterns of most of the organisms were significantly different when irradiation was performed using sewage samples collected in the summer and monsoon seasons. The summer sample collected from the anaerobic digester afforded significant protection to both Gram negative and Gram positive organisms. This was evident by the increase in dose required to bring about a 6 log cycle reduction in viable count of the bacterial cultures, when suspended in sewage samples instead of phosphate buffer. The observations made using monsoon digester samples were quite different. This sewage sludge greatly enhanced inactivation by gamma-radiation in most cases. The effects of certain chemicals on the inactivation patterns of two organisms - Salmonella typhi and Shigella flexneri - were examined. Arsenate, mercury and lead salts sensitised S. typhi, while barium acetate and sodium sulphide protected this culture against gamma-radiation. In the case of Sh. flexneri, barium acetate and iodacetamide proved to be radioprotectors. The effects of some chemicals on the inactivation pattern of Sh. flexneri cells irradiated in sludge are also discussed. (author)

Dusp16 Deficiency Causes Congenital Obstructive Hydrocephalus and Brain Overgrowth by Expansion of the Neural Progenitor Pool

Directory of Open Access Journals (Sweden)

Ksenija Zega

2017-11-01

Full Text Available Hydrocephalus can occur in children alone or in combination with other neurodevelopmental disorders that are often associated with brain overgrowth. Despite the severity of these disorders, the molecular and cellular mechanisms underlying these pathologies and their comorbidity are poorly understood. Here, we studied the consequences of genetically inactivating in mice dual-specificity phosphatase 16 (Dusp16, which is known to negatively regulate mitogen-activated protein kinases (MAPKs and which has never previously been implicated in brain development and disorders. Mouse mutants lacking a functional Dusp16 gene (Dusp16−/− developed fully-penetrant congenital obstructive hydrocephalus together with brain overgrowth. The midbrain aqueduct in Dusp16−/− mutants was obstructed during mid-gestation by an expansion of neural progenitors, and during later gestational stages by neurons resulting in a blockage of cerebrospinal fluid (CSF outflow. In contrast, the roof plate and ependymal cells developed normally. We identified a delayed cell cycle exit of neural progenitors in Dusp16−/− mutants as a cause of progenitor overproliferation during mid-gestation. At later gestational stages, this expanded neural progenitor pool generated an increased number of neurons associated with enlarged brain volume. Taken together, we found that Dusp16 plays a critical role in neurogenesis by balancing neural progenitor cell proliferation and neural differentiation. Moreover our results suggest that a lack of functional Dusp16 could play a central role in the molecular mechanisms linking brain overgrowth and hydrocephalus.

Isolation, Characterization and Identification of Environmental Bacterial Isolates with Screening for Antagonism Against Three Bacterial Targets

Science.gov (United States)

2017-04-01

ISOLATES WITH SCREENING FOR ANTAGONISM AGAINST THREE BACTERIAL TARGETS 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...Identification of environmental isolates followed the flowchart from “Bergey’s Manual of Determinative Bacteriology” (Holt et al. 1994), which

Active-site-directed inactivation of Aspergillus oryzae beta-galactosidase with beta-D-galactopyranosylmethyl-p-nitrophenyltriazene.

Science.gov (United States)

Mega, T; Nishijima, T; Ikenaka, T

1990-04-01

beta-D-Galactopyranosylmethyl-p-nitrophenyltriazene (beta-GalMNT), a specific inhibitor of beta-galactosidase, was isolated as crystals by HPLC and its chemical and physicochemical characteristics were examined. Aspergillus oryzae beta-galactosidase was inactivated by the compound. We studied the inhibition mechanism in detail. The inhibitor was hydrolyzed by the enzyme to p-nitroaniline and an active intermediate (beta-galactopyranosylmethyl carbonium or beta-galactopyranosylmethyldiazonium), which inactivated the enzyme. The efficiency of inactivation of the enzyme (the ratio of moles of inactivated enzyme to moles of beta-GalMNT hydrolyzed by the enzyme) was 3%; the efficiency of Escherichia coli beta-galactosidase was 49%. In spite of the low efficiency, the rate of inactivation of A. oryzae enzyme was not very different from that of the E. coli enzyme, because the former hydrolyzed beta-GalMNT faster than the latter did. A. oryzae beta-galactosidase was also inactivated by p-chlorophenyl, p-tolyl, and m-nitrophenyl derivatives of beta-galactopyranosylmethyltriazene. However, E. coli beta-galactosidase was not inactivated by these triazene derivatives. The results showed that the inactivation of A. oryzae and E. coli beta-galactosidases by beta-GalMNT was an enzyme-activated and active-site-directed irreversible inactivation. The possibility of inactivation by intermediates produced nonenzymatically was ruled out for E. coli, but not for the A. oryzae enzyme.

Density functional theory study of structural and electronic properties of trans and cis structures of thiothixene as a nano-drug.

Science.gov (United States)

Noori Tahneh, Akram; Bagheri Novir, Samaneh; Balali, Ebrahim

2017-11-25

The geometrical structure, electronic and optical properties, electronic absorption spectra, vibrational frequencies, natural charge distribution, MEP analysis and thermodynamic properties of the trans and cis structures of the drug thiothixene were investigated using density functional theory (DFT) and time-dependent DFT (TDDFT) methods with the B3LYP hybrid functional and 6-311 + G(d,p) basis set. The results of the calculations demonstrate that the cis structure of thiothixene has appropriate quantum properties that can act as an active medicine. The relative energies of trans and cis structures of thiothixene shows that the cis structure is more stable than the trans structure, with a small energy difference. TDDFT calculations show that the cis structure of thiothixene has the best absorption properties. The calculated NLO properties show that the NLO properties of the cis structure of thiothixene are higher than the trans structure, and the fact that the chemical hardness of the cis structure is lower than that of the trans structure that indicates that the reactivity and charge transfer of the cis isomer of thiothixene is higher than that of trans thiothixene. The molecular electrostatic potential (MEP) maps of both structures of thiothixene demonstrate that the oxygen atoms of the molecule are appropriate areas for electrophilic reactions. The vibrational frequencies of the two conformations of thiothixene demonstrate that both structures of thiothixene have almost similar modes of vibrations. The calculated thermodynamic parameters show that these quantities increase with enhancing temperature due to the enhancement of molecular vibrational intensities with temperature. Graphical abstract Trans/Cis isomerization of thiothixene drug.

Hydrogenation of fluoroarenes: Direct access to all-cis-(multi)fluorinated cycloalkanes.

Science.gov (United States)

Wiesenfeldt, Mario P; Nairoukh, Zackaria; Li, Wei; Glorius, Frank

2017-09-01

All-c is -multifluorinated cycloalkanes exhibit intriguing electronic properties. In particular, they display extremely high dipole moments perpendicular to the aliphatic ring, making them highly desired motifs in material science. Very few such motifs have been prepared, as their syntheses require multistep sequences from diastereoselectively prefunctionalized precursors. Herein we report a synthetic strategy to access these valuable materials via the rhodium-cyclic (alkyl)(amino)carbene (CAAC)-catalyzed hydrogenation of readily available fluorinated arenes in hexane. This route enables the scalable single-step preparation of an abundance of multisubstituted and multifluorinated cycloalkanes, including all- cis -1,2,3,4,5,6-hexafluorocyclohexane as well as cis-configured fluorinated aliphatic heterocycles. Copyright © 2017, American Association for the Advancement of Science.

Nanoscale Structural and Mechanical Analysis of Bacillus anthracis Spores Inactivated with Rapid Dry Heating

Science.gov (United States)

Felker, Daniel L.; Burggraf, Larry W.

2014-01-01

Effective killing of Bacillus anthracis spores is of paramount importance to antibioterrorism, food safety, environmental protection, and the medical device industry. Thus, a deeper understanding of the mechanisms of spore resistance and inactivation is highly desired for developing new strategies or improving the known methods for spore destruction. Previous studies have shown that spore inactivation mechanisms differ considerably depending upon the killing agents, such as heat (wet heat, dry heat), UV, ionizing radiation, and chemicals. It is believed that wet heat kills spores by inactivating critical enzymes, while dry heat kills spores by damaging their DNA. Many studies have focused on the biochemical aspects of spore inactivation by dry heat; few have investigated structural damages and changes in spore mechanical properties. In this study, we have inactivated Bacillus anthracis spores with rapid dry heating and performed nanoscale topographical and mechanical analysis of inactivated spores using atomic force microscopy (AFM). Our results revealed significant changes in spore morphology and nanomechanical properties after heat inactivation. In addition, we also found that these changes were different under different heating conditions that produced similar inactivation probabilities (high temperature for short exposure time versus low temperature for long exposure time). We attributed the differences to the differential thermal and mechanical stresses in the spore. The buildup of internal thermal and mechanical stresses may become prominent only in ultrafast, high-temperature heat inactivation when the experimental timescale is too short for heat-generated vapor to efficiently escape from the spore. Our results thus provide direct, visual evidences of the importance of thermal stresses and heat and mass transfer to spore inactivation by very rapid dry heating. PMID:24375142

Use of In Situ-Generated Dimethyldioxirane for Inactivation of Biological Agents

National Research Council Canada - National Science Library

Wallace, William H; Bushway, Karen E; Miller, Susan D; Delcomyn, Carrie A; Renard, Jean J; Henley, Michael V

2005-01-01

...) at neutral pH, was investigated for inactivation of biological warfare agent simulants. The DMDO solution inactivated bacterial spores, fungal spores, vegetative bacterial cells, viruses, and protein by 7 orders of magnitude in less than 10 min...

High pressure processing's potential to inactivate norovirus and other fooodborne viruses

Science.gov (United States)

High pressure processing (HPP) can inactivate human norovirus. However, all viruses are not equally susceptible to HPP. Pressure treatment parameters such as required pressure levels, initial pressurization temperatures, and pressurization times substantially affect inactivation. How food matrix ...

Method of inactivating reproducible forms of mycoplasma in biological preparations

International Nuclear Information System (INIS)

Veber, P.; Jurmanova, K.; Lesko, J.; Hana, L.; Veber, V.

1978-01-01

Inactivation of mycoplasms in biological materials was achieved using gamma radiation with a dose rate of 1x10 4 to 5x10 6 rads/h for 1 to 250 hours. The technique is advantageous for allowing the inactivation of the final form of products (tablets, vaccines, etc.). (J.P.)

Antigenic characterization of a formalin-inactivated poliovirus vaccine derived from live-attenuated Sabin strains.

Science.gov (United States)

Tano, Yoshio; Shimizu, Hiroyuki; Martin, Javier; Nishimura, Yorihiro; Simizu, Bunsiti; Miyamura, Tatsuo

2007-10-10

A candidate inactivated poliovirus vaccine derived from live-attenuated Sabin strains (sIPV), which are used in the oral poliovirus vaccine (OPV), was prepared in a large-production scale. The modification of viral antigenic epitopes during the formalin inactivation process was investigated by capture ELISA assays using type-specific and antigenic site-specific monoclonal antibodies (MoAbs). The major antigenic site 1 was modified during the formalin inactivation of Sabin 1. Antigenic sites 1-3 were slightly modified during the formalin inactivation of Sabin 2 strain. Sites 1 and 3 were altered on inactivated Sabin 3 virus. These alterations were different to those shown by wild-type Saukett strain, used in conventional IPV (cIPV). It has been previously reported that type 1 sIPV showed higher immunogenicity to type 1 cIPV whereas types 2 and 3 sIPV induced lower level of immunogenicity than their cIPV counterparts. Our results suggest that the differences in epitope structure after formalin inactivation may account, at least in part, for the observed differences in immunogenicity between Sabin and wild-type inactivated poliovaccines.

A cisão biopolítica originária em Giorgio Agamben

Directory of Open Access Journals (Sweden)

Estenio Ericson Botelho de Azevedo

2016-12-01

Full Text Available Este artigo pretende reconstituir a concepção de Biopolítica em Giorgio Agamben. Em diálogo com Hannah Arendt, o pensador italiano retoma a distinção entre zoé e bios, todavia considerando-a a cisão biopolítica originária. Essa cisão funda uma relação de inclusão excludente (exceptio presente em toda relação do Poder Soberano com a vida nua, de modo que esta se encontra excluída da vida política e ao mesmo tempo é nela incluída de forma subalterna. Essa cisão é posta pela própria Soberania política; por isso, para Agamben, o Poder Soberano é essencialmente, desde os gregos, um Biopoder. Com base nessa tese, delineiam-se suas aproximações e seus distanciamentos da perspectiva da Biopolítica inaugurada por Michel Foucault.

Fringe proteins modulate Notch-ligand cis and trans interactions to specify signaling states.

Science.gov (United States)

LeBon, Lauren; Lee, Tom V; Sprinzak, David; Jafar-Nejad, Hamed; Elowitz, Michael B

2014-09-25

The Notch signaling pathway consists of multiple types of receptors and ligands, whose interactions can be tuned by Fringe glycosyltransferases. A major challenge is to determine how these components control the specificity and directionality of Notch signaling in developmental contexts. Here, we analyzed same-cell (cis) Notch-ligand interactions for Notch1, Dll1, and Jag1, and their dependence on Fringe protein expression in mammalian cells. We found that Dll1 and Jag1 can cis-inhibit Notch1, and Fringe proteins modulate these interactions in a way that parallels their effects on trans interactions. Fringe similarly modulated Notch-ligand cis interactions during Drosophila development. Based on these and previously identified interactions, we show how the design of the Notch signaling pathway leads to a restricted repertoire of signaling states that promote heterotypic signaling between distinct cell types, providing insight into the design principles of the Notch signaling system, and the specific developmental process of Drosophila dorsal-ventral boundary formation.

Chlorine inactivation of fungal spores on cereal grains.

Science.gov (United States)

Andrews, S; Pardoel, D; Harun, A; Treloar, T

1997-04-01

Although 0.4% chlorine for 2 min has been recommended for surface disinfection of food samples before direct plating for fungal enumeration, this procedure may not be adequate for highly contaminated products. The effectiveness of a range of chlorine solutions was investigated using barley samples artificially contaminated with four different concentrations of Aspergillus flavus. A. niger, A. ochraceus, Eurotium repens, Penicillium brevicompactum P. chrysogenum and Cladosporium cladosporioides. At initial contamination levels greater than 10(4)/g, 0.4% chlorine did not inactivate sufficient spores to produce less than 20% contamination. Of the test fungi, ascospores of E. repens were the most resistant to chlorine inactivation, whereas the conidia of C. cladosporioides were the most sensitive. Rinsing the samples with 70% ethanol improved the effectiveness of the recommended surface disinfection procedure. However, some ethanol appears to permeate into the grains and may inactivate sensitive internal fungi, although a minimal effect only was observed on wheat infected with Alternaria.

Inactivation of alcohol dehydrogenase (ADH) by ferryl derivatives of human hemoglobin.

Science.gov (United States)

Kowalczyk, Aleksandra; Puchała, Mieczysław; Wesołowska, Katarzyna; Serafin, Eligiusz

2007-01-01

In this paper, inactivation of alcohol dehydrogenase (ADH) by products of reactions of H2O2 with metHb has been studied. Inactivation of the enzyme was studied in two systems corresponding to two kinetic stages of the reaction. In the first system H2O2 was added to the mixture of metHb and ADH [the (metHb+ADH)+H2O2] system (ADH was present in the system since the moment of addition of H2O2 i. e. since the very beginning of the reaction of metHb with H2O2). In the second system ADH was added to the system 5 min after the initiation of the reaction of H2O2 with metHb [the (metHb+H2O2)5 min+ADH] system. In the first case all the products of reaction of H2O2 with metHb (non-peroxyl and peroxyl radicals and non-radical products, viz. hydroperoxides and *HbFe(IV)=O) could react with the enzyme causing its inactivation. In the second system, enzyme reacted almost exclusively with non-radical products (though a small contribution of reactions with peroxyl radicals cannot be excluded). ADH inactivation was observed in both system. Hydrogen peroxide alone did not inactivate ADH at the concentrations employed evidencing that enzyme inactivation was due exclusively to products of reaction of H2O2 with metHb. The rate and extent of ADH inactivation were much higher in the first than in the second system. The dependence of ADH activity on the time of incubation with ferryl derivatives of Hb can be described by a sum of three exponentials in the first system and two exponentials in the second system. Reactions of appropriate forms of the ferryl derivatives of hemoglobin have been tentatively ascribed to these exponentials. The extent of the enzyme inactivation in the second system was dependent on the proton concentration, being at the highest at pH 7.4 and negligible at pH 6.0. The reaction of H2O2 with metHb resulted in the formation of cross-links of Hb subunits (dimers and trimers). The amount of the dimers formed was much lower in the first system i. e. when the radical

Inactivation of viruses in labile blood derivatives. II. Physical methods

International Nuclear Information System (INIS)

Horowitz, B.; Wiebe, M.E.; Lippin, A.; Vandersande, J.; Stryker, M.H.

1985-01-01

The thermal inactivation of viruses in labile blood derivatives was evaluated by addition of marker viruses (VSV, Sindbis, Sendai, EMC) to anti-hemophilic factor (AHF) concentrates. The rate of virus inactivation at 60 degrees C was decreased by at least 100- to 700-fold by inclusion of 2.75 M glycine and 50 percent sucrose, or 3.0 M potassium citrate, additives which contribute to retention of protein biologic activity. Nonetheless, at least 10(4) infectious units of each virus was inactivated within 10 hours. Increasing the temperature from 60 to 70 or 80 degrees C caused a 90 percent or greater loss in AHF activity. An even greater decline in the rate of virus inactivation was observed on heating AHF in the lyophilized state, although no loss in AHF activity was observed after 72 hours of heating at 60 degrees C. Several of the proteins present in lyophilized AHF concentrates displayed an altered electrophoretic mobility as a result of exposure to 60 degrees C for 24 hours. Exposure of lyophilized AHF to irradiation from a cobalt 60 source resulted in an acceptable yield of AHF at 1.0, but not at 2.0, megarads. At 1 megarad, greater than or equal to 6.0 logs of VSV and 3.3 logs of Sindbis virus were inactivated

Efficiency of superoxide anions in the inactivation of selected dehydrogenases

International Nuclear Information System (INIS)

Rodacka, Aleksandra; Serafin, Eligiusz; Puchala, Mieczyslaw

2010-01-01

The most ubiquitous of the primary reactive oxygen species, formed in all aerobes, is the superoxide free radical. It is believed that the superoxide anion radical shows low reactivity and in oxidative stress it is regarded mainly as an initiator of more reactive species such as · OH and ONOO - . In this paper, the effectiveness of inactivation of selected enzymes by radiation-generated superoxide radicals in comparison with the effectiveness of the other products of water radiolysis is examined. We investigate three enzymes: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), alcohol dehydrogenase (ADH) and lactate dehydrogenase (LDH). We show that the direct contribution of the superoxide anion radical to GAPDH and ADH inactivation is significant. The effectiveness of the superoxide anion in the inactivation of GAPDH and ADG was only 2.4 and 2.8 times smaller, respectively, in comparison with hydroxyl radical. LDH was practically not inactivated by the superoxide anion. Despite the fact that the studied dehydrogenases belong to the same class of enzymes (oxidoreductases), all have a similar molecular weight and are tetramers, their susceptibility to free-radical damage varies. The differences in the radiosensitivity of the enzymes are not determined by the basic structural parameters analyzed. A significant role in inactivation susceptibility is played by the type of amino acid residues and their localization within enzyme molecules.

Efficiency of superoxide anions in the inactivation of selected dehydrogenases

Energy Technology Data Exchange (ETDEWEB)

Rodacka, Aleksandra, E-mail: olakow@biol.uni.lodz.p [Department of Molecular Biophysics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Serafin, Eligiusz, E-mail: serafin@biol.uni.lodz.p [Laboratory of Computer and Analytical Techniques, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Puchala, Mieczyslaw, E-mail: puchala@biol.uni.lodz.p [Department of Molecular Biophysics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland)

2010-09-15

The most ubiquitous of the primary reactive oxygen species, formed in all aerobes, is the superoxide free radical. It is believed that the superoxide anion radical shows low reactivity and in oxidative stress it is regarded mainly as an initiator of more reactive species such as {sup {center_dot}}OH and ONOO{sup -}. In this paper, the effectiveness of inactivation of selected enzymes by radiation-generated superoxide radicals in comparison with the effectiveness of the other products of water radiolysis is examined. We investigate three enzymes: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), alcohol dehydrogenase (ADH) and lactate dehydrogenase (LDH). We show that the direct contribution of the superoxide anion radical to GAPDH and ADH inactivation is significant. The effectiveness of the superoxide anion in the inactivation of GAPDH and ADG was only 2.4 and 2.8 times smaller, respectively, in comparison with hydroxyl radical. LDH was practically not inactivated by the superoxide anion. Despite the fact that the studied dehydrogenases belong to the same class of enzymes (oxidoreductases), all have a similar molecular weight and are tetramers, their susceptibility to free-radical damage varies. The differences in the radiosensitivity of the enzymes are not determined by the basic structural parameters analyzed. A significant role in inactivation susceptibility is played by the type of amino acid residues and their localization within enzyme molecules.

Acute Vhl gene inactivation induces cardiac HIF-dependent erythropoietin gene expression.

Directory of Open Access Journals (Sweden)

Marta Miró-Murillo

Full Text Available Von Hippel Lindau (Vhl gene inactivation results in embryonic lethality. The consequences of its inactivation in adult mice, and of the ensuing activation of the hypoxia-inducible factors (HIFs, have been explored mainly in a tissue-specific manner. This mid-gestation lethality can be also circumvented by using a floxed Vhl allele in combination with an ubiquitous tamoxifen-inducible recombinase Cre-ER(T2. Here, we characterize a widespread reduction in Vhl gene expression in Vhl(floxed-UBC-Cre-ER(T2 adult mice after dietary tamoxifen administration, a convenient route of administration that has yet to be fully characterized for global gene inactivation. Vhl gene inactivation rapidly resulted in a marked splenomegaly and skin erythema, accompanied by renal and hepatic induction of the erythropoietin (Epo gene, indicative of the in vivo activation of the oxygen sensing HIF pathway. We show that acute Vhl gene inactivation also induced Epo gene expression in the heart, revealing cardiac tissue to be an extra-renal source of EPO. Indeed, primary cardiomyocytes and HL-1 cardiac cells both induce Epo gene expression when exposed to low O(2 tension in a HIF-dependent manner. Thus, as well as demonstrating the potential of dietary tamoxifen administration for gene inactivation studies in UBC-Cre-ER(T2 mouse lines, this data provides evidence of a cardiac oxygen-sensing VHL/HIF/EPO pathway in adult mice.

Direct demonstration of NCAM cis-dimerization and inhibitory effect of palmitoylation using the BRET2 technique

DEFF Research Database (Denmark)

Kulahin, Nikolaj; Grunnet, Lars Groth; Lundh, Morten

2011-01-01

, cis-dimerization in living cells has not been shown directly and the role of the cytoplasmic part in NCAM dimerization is poorly understood. Here, we used the bioluminescence resonance energy transfer (BRET(2)) technique to directly demonstrate that full-length NCAM cis-homodimerizes in living cells...

Histamine H3 receptors and its antagonism as a novel mechanism for antipsychotic effect: a current preclinical & clinical perspective.

Science.gov (United States)

Mahmood, Danish

2016-10-01

Histamine H 3 receptors are present as autoreceptors on histaminergic neurons and as heteroreceptors on nonhistaminergic neurones. They control the release and synthesis of histamine and several other key neurotransmitters in the brain. H 3 antagonism may be a novel approach to develop a new class of antipsychotic medications given the gathering evidence reporting therapeutic efficacy in several central nervous system disorders. Several medications such as cariprazine, lurasidone, LY214002, bexarotene, rasagiline, raloxifene, BL-1020 and ITI-070 are being developed to treat the negative symptoms and cognitive impairments of schizophrenia. These medications works through diverse mechanisms which include agonism at metabotropic glutamate receptor (mGluR2/3), partial agonism at dopamine D 2 , D 3 and serotonin 5-HT 1A receptors, antagonism at D 2 , 5-HT 2A, 5-HT 2B and 5-HT 7 receptors, combined dopamine antagonism with GABA agonist activity, inhibition of monoamine oxidase-B, modulation of oestrogen receptor, and activation of nuclear retinoid X receptor. However, still specific safe therapy for psychosis remains at large. Schizophrenia is a severe neuropsychiatric disorder result both from hyper- and hypo-dopaminergic transmission causing positive and negative symptoms, respectively. Pharmacological stimulation of dopamine release in the prefrontal cortex has been a viable approach in treating negative symptoms and cognitive deficits of schizophrenia symptoms that are currently not well treated and continue to represent significant unmet medical challenges. Administration of H 3 antagonists/inverse agonists increase extracellular dopamine concentrations in rat prefrontal cortex, but not in the striatum suggesting that antagonism via H 3 receptor may be a potential target for treating negative symptoms and cognitive deficits associated with schizophrenia. Further, insights are emerging into the potential role of histamine H 3 receptors as a target of antiobesity

Dynamical transitions in a pollination-herbivory interaction: a conflict between mutualism and antagonism.

Directory of Open Access Journals (Sweden)

Tomás A Revilla

Full Text Available Plant-pollinator associations are often seen as purely mutualistic, while in reality they can be more complex. Indeed they may also display a diverse array of antagonistic interactions, such as competition and victim-exploiter interactions. In some cases mutualistic and antagonistic interactions are carried-out by the same species but at different life-stages. As a consequence, population structure affects the balance of inter-specific associations, a topic that is receiving increased attention. In this paper, we developed a model that captures the basic features of the interaction between a flowering plant and an insect with a larval stage that feeds on the plant's vegetative tissues (e.g. leaves and an adult pollinator stage. Our model is able to display a rich set of dynamics, the most remarkable of which involves victim-exploiter oscillations that allow plants to attain abundances above their carrying capacities and the periodic alternation between states dominated by mutualism or antagonism. Our study indicates that changes in the insect's life cycle can modify the balance between mutualism and antagonism, causing important qualitative changes in the interaction dynamics. These changes in the life cycle could be caused by a variety of external drivers, such as temperature, plant nutrients, pesticides and changes in the diet of adult pollinators.

Inactivation of γ-aminobutyric acid aminotransferase by γ-ethynyl- and γ-vinyl GABA

International Nuclear Information System (INIS)

Silverman, R.B.; Burke, J.R.; Nanavati, S.M.

1989-01-01

γ-Ethynyl- and γ-vinyl GABA (vigabatrin) are anticonvulsant agents that have been shown to be mechanism-based inactivators of γ-aminobutyric acid aminotransferase (GABA-T). The inactivation mechanisms of these compounds have been investigated. Inactivation of GABA-T by [ 3 H]γ-ethynyl GABA led to the incorporation of 1.0 equiv of 3 H into the enzyme which is not released by enzyme denaturation. Inactivation by γ-ethynyl GABA of GABA-T reconstituted with [ 3 H]PLP followed by denaturation resulted in release of 3 H as PLP. Eight different possible adducts are consistent with that result. Experiments have been carried out to differentiate these possibilities. Similar studies have been carried out with γ-vinyl GABA. Inactivation by [ 14 C]γ-vinyl GABA resulted in the incorporation of 1.0 equiv of 14 C per active site. Unlike the case with γ-ethynyl GABA, γ-vinyl GABA inactivation of GABA-T reconstituted with [ 3 H]PLP followed by denaturation resulted in release of 3 H as PMP

PBPK modeling of the cis- and trans-permethrin isomers and their major urinary metabolites in rats

Energy Technology Data Exchange (ETDEWEB)

Willemin, Marie-Emilie [Institut National de l' Environnement Industriel et des Risques (INERIS), Unité Modèles pour l' Ecotoxicologie et la Toxicologie (METO), Parc ALATA BP2, 60550, Verneuil en Halatte (France); Sorbonne University, Université de Technologie de Compiègne, CNRS, UMR 7338 Biomechanics and Bioengineering, Centre de recherche Royallieu CS 60319,60203 Compiègnee Cedex (France); Desmots, Sophie [Institut National de l' Environnement Industriel et des Risques (INERIS), Unité Toxicologie Expérimentale (TOXI), Parc ALATA BP2, 60550, Verneuil en Halatte (France); Le Grand, Rozenn [Centre Hospitalo-Universitaire de Limoges, Service de Pharmacologie et de Toxicologie — Pharmacovigilance, 2, avenue Martin Luther King, 87042 Limoges (France); Lestremau, François [Institut National de l' Environnement Industriel et des Risques (INERIS), Unité Innovation pour la Mesure (NOVA), Parc ALATA BP2, 60550, Verneuil en Halatte (France); Zeman, Florence A. [Institut National de l' Environnement Industriel et des Risques (INERIS), Unité Modèles pour l' Ecotoxicologie et la Toxicologie (METO), Parc ALATA BP2, 60550, Verneuil en Halatte (France); Leclerc, Eric [Sorbonne University, Université de Technologie de Compiègne, CNRS, UMR 7338 Biomechanics and Bioengineering, Centre de recherche Royallieu CS 60319,60203 Compiègnee Cedex (France); Moesch, Christian [Centre Hospitalo-Universitaire de Limoges, Service de Pharmacologie et de Toxicologie — Pharmacovigilance, 2, avenue Martin Luther King, 87042 Limoges (France); and others

2016-03-01

Permethrin, a pyrethroid insecticide, is suspected to induce neuronal and hormonal disturbances in humans. The widespread exposure of the populations has been confirmed by the detection of the urinary metabolites of permethrin in biomonitoring studies. Permethrin is a chiral molecule presenting two forms, the cis and the trans isomers. Because in vitro studies indicated a metabolic interaction between the trans and cis isomers of permethrin, we adapted and calibrated a PBPK model for trans- and cis-permethrin separately in rats. The model also describes the toxicokinetics of three urinary metabolites, cis- and trans-3-(2,2 dichlorovinyl)-2,2-dimethyl-(1-cyclopropane) carboxylic acid (cis- and trans-DCCA), 3-phenoxybenzoic acid (3-PBA) and 4′OH-phenoxybenzoic acid (4′-OH-PBA). In vivo experiments performed in Sprague–Dawley rats were used to calibrate the PBPK model in a Bayesian framework. The model captured well the toxicokinetics of permethrin isomers and their metabolites including the rapid absorption, the accumulation in fat, the extensive metabolism of the parent compounds, and the rapid elimination of metabolites in urine. Average hepatic clearances in rats were estimated to be 2.4 and 5.7 L/h/kg for cis- and trans-permethrin, respectively. High concentrations of the metabolite 4′-OH-PBA were measured in urine compared to cis- and trans-DCCA and 3-PBA. The confidence in the extended PBPK model was then confirmed by good predictions of published experimental data obtained using the isomers mixture. The extended PBPK model could be extrapolated to humans to predict the internal dose of exposure to permethrin from biomonitoring data in urine. - Highlights: • A PBPK model of isomers of permethrin and its urinary metabolites was developed. • A quantitative link was established for permethrin and its biomarkers of exposure. • The bayesian framework allows getting confidence interval on the estimated parameters. • The PBPK model can be extrapolated

PBPK modeling of the cis- and trans-permethrin isomers and their major urinary metabolites in rats

International Nuclear Information System (INIS)

Willemin, Marie-Emilie; Desmots, Sophie; Le Grand, Rozenn; Lestremau, François; Zeman, Florence A.; Leclerc, Eric; Moesch, Christian

2016-01-01

Permethrin, a pyrethroid insecticide, is suspected to induce neuronal and hormonal disturbances in humans. The widespread exposure of the populations has been confirmed by the detection of the urinary metabolites of permethrin in biomonitoring studies. Permethrin is a chiral molecule presenting two forms, the cis and the trans isomers. Because in vitro studies indicated a metabolic interaction between the trans and cis isomers of permethrin, we adapted and calibrated a PBPK model for trans- and cis-permethrin separately in rats. The model also describes the toxicokinetics of three urinary metabolites, cis- and trans-3-(2,2 dichlorovinyl)-2,2-dimethyl-(1-cyclopropane) carboxylic acid (cis- and trans-DCCA), 3-phenoxybenzoic acid (3-PBA) and 4′OH-phenoxybenzoic acid (4′-OH-PBA). In vivo experiments performed in Sprague–Dawley rats were used to calibrate the PBPK model in a Bayesian framework. The model captured well the toxicokinetics of permethrin isomers and their metabolites including the rapid absorption, the accumulation in fat, the extensive metabolism of the parent compounds, and the rapid elimination of metabolites in urine. Average hepatic clearances in rats were estimated to be 2.4 and 5.7 L/h/kg for cis- and trans-permethrin, respectively. High concentrations of the metabolite 4′-OH-PBA were measured in urine compared to cis- and trans-DCCA and 3-PBA. The confidence in the extended PBPK model was then confirmed by good predictions of published experimental data obtained using the isomers mixture. The extended PBPK model could be extrapolated to humans to predict the internal dose of exposure to permethrin from biomonitoring data in urine. - Highlights: • A PBPK model of isomers of permethrin and its urinary metabolites was developed. • A quantitative link was established for permethrin and its biomarkers of exposure. • The bayesian framework allows getting confidence interval on the estimated parameters. • The PBPK model can be extrapolated

Inactivation of catalase by free radicals derived from oxygen via gamma radiolysis

International Nuclear Information System (INIS)

Malhaire, J.P.; Gardes-Albert, M.; Ferradini, C.; Sabourault, D.; Ribiere, C.

1991-01-01

The inactivation of catalase (10 -5 mol/l) by OH· or OH·/O 2 - · free radicals, at pH 7.4, has been investigated using γ radiolysis with doses up to 9000 Gy. Maxima initial G-values of catalase inactivation have been determined. These values are inferior to those of the free radicals OH· and O 2 - · produced by water radiolysis. Nevertheless, the presence of O 2 /O 2 - · enhances the inactivation due to OH· radicals. The general shape of the inactivation curves as a function of the radiation dose is biphasic: an initial rapid phase (from 0 to ∼ 500 Gy) followed by a slow phase (from ∼ 500 to 9000 Gy). The addition of H 2 O 2 at the beginning of irradiation decreases the inactivation yield by OH· radicals. This phenomenon could be due to the formation of compound-I (catalase-H 2 O 2 ) which would be less sensitive towards OH· radicals than catalase. In the presence of 0.1 mol/l ethanol, catalase (5 x 10 -6 mol/l) is not inactived by O 2 - · and RO 2 · (from ethanol) radicals for an irradiation dose of 2000 Gy, implying a complete protecting effect by ethanol [fr

Incorporation of deuterium-labeled trans- and cis-13-octadecenoic acids in human plasma lipids

International Nuclear Information System (INIS)

Emken, E.A.; Adlof, R.O.; Rohwedder, W.K.; Gulley, R.M.

1983-01-01

The absorption and distribution of deuterated trans- and cis-13-octadecenoic acid (13t-18:1 and 13c-18:1) in plasma lipids were compared to deuterated cis-9-octadecenoic acid (9c-18:1) in two young adult male subjects. A mixture of triglycerides was fed in a multiple-labeled experiment where each triglyceride contained a fatty acid labeled with a different number of deuterium atoms. Analysis of human plasma lipids by mass spectroscopy allowed the distribution of the two 13-octadecenoic acid isomers to be directly compared to cis-9-octadecenoic acid. Plasma lipids selectively excluded both the 13t-18:1 and 13c-18:1 isomers relative to 9c-18:1 in all neutral and phospholipid fractions. Discrimination against incorporation of the 13t-18:1 isomer into plasma cholesteryl ester and 2-acyl phosphatidylcholine was nearly absolute. The 1-acyl phosphatidylcholine fraction exhibited a large positive selectivity for the 13t-18:1 isomer. Differences in the relative distribution of the trans and cis 13-18:1 isomers vs. 9c-18:1 in the various lipoprotein lipid classes were found. Analysis of the chylomicron triglyceride component of the plasma lipids indicated all three fatty acids were equally well absorbed

Thermal decomposition and isomerization of cis-permethrin and beta-cypermethrin in the solid phase.

Science.gov (United States)

González Audino, Paola; Licastro, Susana A; Zerba, Eduardo

2002-02-01

The stability to heart of cis-permethrin and beta-cypermethrin in the solid phase was studied and the decomposition products identified. Samples heated at 210 degrees C in an oven in the dark showed that, in the absence of potassium chlorate (the salt present in smoke-generating formulations of these pyrethroids), cis-permethrin was not isomerized, although in the presence of that salt, decomposition was greater and thermal isomerization occurred. Other salts of the type KXO3 or NaXO3, with X being halogen or nitrogen, also led to a considerable thermal isomerization. Heating the insecticides in solution in the presence of potassium chlorate did not produce isomerization in any of the solvents assayed. Salt-catalysed thermal cis-trans isomerization was also found for other pyrethroids derived from permethrinic or deltamethrinic acid but not for those derived from chrysanthemic acid. The main thermal degradation processes of cis-permethrin and beta-cypermethrin decomposition when potassium chlorate was present were cyclopropane isomerization, ester cleavage and subsequent oxidation of the resulting products. Permethrinic acid, 3-phenoxybenzyle chloride, alcohol, aldehyde and acid were identified in both cases, as well as 3-phenoxybenzyl cyanide from beta-cypermethrin. A similar decomposition pattern occurred after combustion of pyrethroid fumigant formulations.

Synthesis and bacterial metabolism of cis- and trans-2-alkyl analogues of sodium cyclamate.

Science.gov (United States)

Wiley, R A; Pearson, D A; Schmidt, V; Wesche, S B; Roxon, J J

1983-07-01

Sodium cyclamate is an effective artificial sweetner, which has been banned from the U.SD. market because of alleged carcinogenic properties. It appears that cyclohexylamine, liberated from cyclamate as a result of bacterial mtabolism, is the proximate carcinogen. In an effort to elucidate the extent to which analogues of cyclamate would enter into the bacterial metabolic pathway, as well as any stereochemical requirements which might exist, several 2-alkaly analogues of sodium cyclamate were prepared. It was found that trans-N-(2-methylcyclohexyl)sulfamate (trans-2a) and trans-N-(2-ethylcyclohexyl)sulfamate were hydrolyzed by freshly collected fecal suspensions from rats fed cyclamate, but not from control rats, at the same rate as cyclamate itself. trans-N-(2-Isopropylcyclohexyl)sulfamate (trans-2c) was not hydrolyzed at all. Surprisingly, two of the analogous cis compounds (cis-2a and cis-2c, respectively) were hydrolyzed by fecal suspensions from control, as well as from cyclamate-fed, rats. Moreover, cis-2a was hydrolyzed by incubating it in medium only. Thus, it is apparent that stereochemical influences on the chemical properties of these compounds are substantial. These results do not appear to point the way toward a safe, nonmetabolizable sweetening agent.

Neural Networks and Their Applications for the Oil Industry Les réseaux neuronaux et leurs applications pour l'industrie pétrolière

Directory of Open Access Journals (Sweden)

Fogelman-Soulie F.

2006-11-01

Full Text Available Neural Networks can be used in many different areas of problems related to Petroleum Exploration and Production. There already exist well defined classes of applications, together with appropriate Neural Networks architectures. Detailed theoretical results allow to monitor and evaluate the results obtained by Neural Networks. Sophisticated applications will certainly require the use of multi-modular architectures. Les réseaux neuronaux peuvent être utilisés pour de nombreux problèmes dans les domaines de l'exploration et la production de pétrole. Il existe d'ores et déjà des classes d'applications bien définies, pour lesquelles on connaît les architectures neuronales les plus adaptées. Des résultats théoriques précis permettent de contrôler et d'évaluer les performances obtenues avec les réseaux neuronaux. Les applications complexes demanderont certainement la mise en oeuvre d'architectures multi-modulaires.

Siemens solar CIS photovoltaic module and system performance at the National Renewable Energy Laboratory

Energy Technology Data Exchange (ETDEWEB)

Strand, T.; Kroposki, B.; Hansen, R. [National Renewable Energy Lab., Golden, CO (United States); Willett, D. [Siemens Solar Industries, Camarillo, CA (United States)

1996-05-01

This paper evaluates the individual module and array performance of Siemens Solar Industries copper indium diselenide (CIS) polycrystalline thin-film technology. This is accomplished by studying module and array performance over time. Preliminary temperature coefficients for maximum power, maximum-power voltage, maximum-power current, open-circuit voltage, short-circuit current, and fill factor are determined at both the module and array level. These coefficients are used to correct module/array performance to 25{degrees}C to evaluate stability. The authors show that CIS exhibits a strong inverse correlation between array power and back-of-module temperature. This is due mainly to the narrow bandgap of the CIS material, which results in a strong inverse correlation between voltage and temperature. They also show that the temperature-corrected module and array performance has been relatively stable over the evaluation interval ({approx}2 years).

Combined removal of a BTEX, TCE, and cis-DCE mixture using Pseudomonas sp. immobilized on scrap tyres.

Science.gov (United States)

Lu, Qihong; de Toledo, Renata Alves; Xie, Fei; Li, Junhui; Shim, Hojae

2015-09-01

The simultaneous aerobic removal of a mixture of benzene, toluene, ethylbenzene, and o,m,p-xylene (BTEX); cis-dichloroethylene (cis-DCE); and trichloroethylene (TCE) from the artificially contaminated water using an indigenous bacterial isolate identified as Pseudomonas plecoglossicida immobilized on waste scrap tyres was investigated. Suspended and immobilized conditions were compared for the removal of these volatile organic compounds. For the immobilized system, toluene, benzene, and ethylbenzene were completely removed, while the highest removal efficiencies of 99.0 ± 0.1, 96.8 ± 0.3, 73.6 ± 2.5, and 61.6 ± 0.9% were obtained for o-xylene, m,p-xylene, TCE, and cis-DCE, respectively. The sorption kinetics of contaminants towards tyre surface was also evaluated, and the sorption capacity generally followed the order of toluene > benzene > m,p-xylene > o-xylene > ethylbenzene > TCE > cis-DCE. Scrap tyres showed a good capability for the simultaneous sorption and bioremoval of BTEX/cis-DCE/TCE mixture, implying a promising waste material for the removal of contaminant mixture from industrial wastewater or contaminated groundwater.

Inactivation of bacteria in sewage sludge by ionizing radiation, heat, and thermoradiation

International Nuclear Information System (INIS)

Brandon, J.R.; Langley, S.L.

1976-01-01

For purposes of animal feeding or fertilizer usage on edible crops, sewage sludge must be free of pathogenic organisms. Bacterial inactivation by a combination of heat and irradiation is shown to be effective. These results must be viewed in conjunction with those from studies of parasite egg inactivation, virus inactivation, and physical-chemical benefits in order to make a fair assessment of the value of the thermoradiation treatment compared to other possible sludge treatment processes

A Survey of Current Computer Information Science (CIS) Students.

Science.gov (United States)

Los Rios Community Coll. District, Sacramento, CA. Office of Institutional Research.

This document is a survey designed to be completed by current students of Computer Information Science (CIS) in the Los Rios Community College District (LRCCD), which consists of three community colleges: American River College, Cosumnes River College, and Sacramento City College. The students are asked about their educational goals and how…

Separation and identification of beta-carotene and its cis isomers by high pressure liquid chromatography (HPLC); Separacion e identificacion del beta-caroteno y sus isomeros cis por cromatografia liquida de alta resolucion (HPLC)

Energy Technology Data Exchange (ETDEWEB)

Carrillo de Padilla, F [Universidad Central de Venezuela (UCV), Facultad de Farmacia, Catedra de Analisis de Alimentos, Caracas (Venezuela)

1996-07-01

The separation and identification by HPLC of the cis isomers of beta-carotene was studied. A 1.26 mg/ml beta-carotene solution previously isomerized with iodine as a catalyst, was eluted with 2% acetone in hexane, from a Ca(OH)2 chromatographic column in three bands. The fractions were identified by spectrophotometry and the retention times of 2.05, 2.4 and 2.8 min for the 13 cis, all-trans, and 9 cis beta-carotene isomers, determined by HPLC, with 1% acetone in hexane as Mobil phase. 22.13 mg % of all-trans beta-carotene were found in a sample of canned carrots. It is recommended the analyses of a greater number of samples, the determination of the method's sensitivity, reproducibility, and the use of a standard of reference of a response factor for calculations.

cis-chlorobenzene dihydrodiol dehydrogenase (TcbB) from Pseudomonas sp. strain P51, expressed in Escherichia coli DH5alpha(pTCB149), catalyzes enantioselective dehydrogenase reactions.

Science.gov (United States)

Raschke, H; Fleischmann, T; Van Der Meer, J R; Kohler, H P

1999-12-01

cis-Chlorobenzene dihydrodiol dehydrogenase (CDD) from Pseudomonas sp. strain P51, cloned into Escherichia coli DH5alpha(pTCB149) was able to oxidize cis-dihydrodihydroxy derivatives (cis-dihydrodiols) of dihydronaphthalene, indene, and four para-substituted toluenes to the corresponding catechols. During the incubation of a nonracemic mixture of cis-1,2-indandiol, only the (+)-cis-(1R,2S) enantiomer was oxidized; the (-)-cis-(S,2R) enantiomer remained unchanged. CDD oxidized both enantiomers of cis-1,2-dihydroxy-1,2,3, 4-tetrahydronaphthalene, but oxidation of the (+)-cis-(1S,2R) enantiomer was delayed until the (-)-cis-(1R,2S) enantiomer was completely depleted. When incubated with nonracemic mixtures of para-substituted cis-toluene dihydrodiols, CDD always oxidized the major enantiomer at a higher rate than the minor enantiomer. When incubated with racemic 1-indanol, CDD enantioselectively transformed the (+)-(1S) enantiomer to 1-indanone. This stereoselective transformation shows that CDD also acted as an alcohol dehydrogenase. Additionally, CDD was able to oxidize (+)-cis-(1R,2S)-dihydroxy-1, 2-dihydronaphthalene, (+)-cis-monochlorobiphenyl dihydrodiols, and (+)-cis-toluene dihydrodiol to the corresponding catechols.

cis-Chlorobenzene Dihydrodiol Dehydrogenase (TcbB) from Pseudomonas sp. Strain P51, Expressed in Escherichia coli DH5α(pTCB149), Catalyzes Enantioselective Dehydrogenase Reactions

Science.gov (United States)

Raschke, Henning; Fleischmann, Thomas; Van Der Meer, Jan Roelof; Kohler, Hans-Peter E.

1999-01-01

cis-Chlorobenzene dihydrodiol dehydrogenase (CDD) from Pseudomonas sp. strain P51, cloned into Escherichia coli DH5α(pTCB149) was able to oxidize cis-dihydrodihydroxy derivatives (cis-dihydrodiols) of dihydronaphthalene, indene, and four para-substituted toluenes to the corresponding catechols. During the incubation of a nonracemic mixture of cis-1,2-indandiol, only the (+)-cis-(1R,2S) enantiomer was oxidized; the (−)-cis-(S,2R) enantiomer remained unchanged. CDD oxidized both enantiomers of cis-1,2-dihydroxy-1,2,3,4-tetrahydronaphthalene, but oxidation of the (+)-cis-(1S,2R) enantiomer was delayed until the (−)-cis-(1R,2S) enantiomer was completely depleted. When incubated with nonracemic mixtures of para-substituted cis-toluene dihydrodiols, CDD always oxidized the major enantiomer at a higher rate than the minor enantiomer. When incubated with racemic 1-indanol, CDD enantioselectively transformed the (+)-(1S) enantiomer to 1-indanone. This stereoselective transformation shows that CDD also acted as an alcohol dehydrogenase. Additionally, CDD was able to oxidize (+)-cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene, (+)-cis-monochlorobiphenyl dihydrodiols, and (+)-cis-toluene dihydrodiol to the corresponding catechols. PMID:10583971

Cis-Chlorobenzene dihydrodiol dehydrogenase (TcbB) from Pseudomonas sp. strain P51, expressed in Escherichia coli DH5{alpha}(pTCB149), catalyzes enantioselective dehydrogenase reactions

Energy Technology Data Exchange (ETDEWEB)

Raschke, H.; Fleischmann, T.; Meer, J.R. van der; Kohler, H.P.E.

1999-12-01

cis-Chlorobenzene dihydrodiol dehydrogenase (CDD) from Pseudomonas sp. strain P51, cloned into Escherichia coli DH5{alpha}(pTCB149) was able to oxidize cis-dihydrodihydroxy derivatives (cis-dihydrodiols) of dihydronaphthalene, indene, and four para-substituted toluenes to the corresponding catechols. During the incubation of a nonracemic mixture of cis-1,2-indandiol, only the (+)-cis-(1R,2S) enantiomer was oxidized; the (-)-cis-(S,2R) enantiomer remained unchanged, CDD oxidized both enantiomers of cis-1,2-dihydroxy-1,2,3,4-tetrahydronaphthalene, but oxidation of the (+)-cis-(1S,2R) enantiomer was delayed until the (-)-cis-(1R,2S) enantiomer was completely depleted. When incubated with nonracemic mixtures of para-substituted cis-toluene dihydrodiols, CDD always oxidized the major enantiomer at a higher rate than the minor enantiomer. When incubated with racemic 1-indanol, CDD enantioselectively transformed the (+)-(1S) enatiomer to 1-indanone. This stereoselective transformation shows that CDD also acted as an alcohol dehydrogenase. Additionally, CDD was able to oxidize (+)-cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene, (+)-cis-monochlorobiphenyl dihydrodiols, and (+)-cis-toluene dihydrodiol to the corresponding catechols.

Synthesis of cis - and trans-diisothiocyanato-bis(NHC) complexes of nickel(II) and applications in the Kumada-Corriu reaction

KAUST Repository

Jothibasu, Ramasamy

2010-09-13

Metathetical reaction of AgSCN with a series of trans-dihalido-bis(carbene) nickel(II) complexes in CH3CN readily afforded the novel diisothiocyanato-bis(carbene) complexes [Ni(NCS)2(NHC)2] (trans-2a, NHC = 1,3-diisopropylbenzimidazolin-2-ylidene; trans-2b, NHC = 1,3-diisobutylbenzimidazolin-2-ylidene; trans-2c, NHC = 1,3- dibenzylbenzimidazolin-2-ylidene; cis-2d, NHC = 1,3-di(2-propenyl) benzimidazolin-2-ylidene; cis-2e, NHC = 1-propyl-3-methylbenzimidazolin-2- ylidene) as greenish-yellow powders in moderate to good yields. While dihalido-bis(carbene) Ni(II) complexes exclusively form trans-complexes, a trans-cis isomerization occurs upon halido-isothiocyanato exchange with complexes bearing less bulky carbene ligands, i.e., cis-2d/e. DFT calculations indicated that this isomerization can be attributed to a reduced energy difference between trans- and cis-isomers of diisothiocyanato complexes. All complexes have been characterized by multinuclear NMR spectroscopy, ESI mass spectrometry, and X-ray diffraction analysis. A catalytic study revealed that cis-complexes generally exhibit greater activities in the Kumada-Corriu coupling reaction. © 2010 American Chemical Society.

Ethical aspects in clinical trials in the CIS, in particular the setting up of ethical committees.

Science.gov (United States)

Kubar, Olga

2005-01-01

The ethical aspects of clinical trials in the CIS are based on the development of systematic ethical review and ethical insight and responsibility on the part of researchers, sponsors, and government agencies and society. This is the main purpose of the Forum for Ethics Committees in the Commonwealth of Independent States (FECCIS) whose establishment and activities are focused on the integration of the CIS into the world system of biomedical research with regard to safeguarding ethical standards of human rights protection and harmonization of regulative and methodological space to safeguard protection of human rights and the dignity of biomedical research participants in the CIS.

Study of biodistribution of lipidic nanospheres charged with cis-diaminedichloroplatinum (II) and labelled with radioactive nuclei of Indium-111

International Nuclear Information System (INIS)

Lopez R, V.; Juarez O, C.; Medina L, A.; Perez C, E.; Garcia L, P.

2007-01-01

The general objective of the study was to evaluate the lipidic nanospheres biodistribution charged with cis-diaminedichloroplatinum (II) (cis-DDP) and labelled with radioactive nuclei of Indium-111 (Lip-Cis-in-111) in Wistar rats and in a tumoral model of CaCu. The conclusions were: 1. The system Lip-Cis-in-111 it presents a very fast elimination probably, to a fast recognition response of the reticuloendothelial system (RES). 2. It is planned to make modifications to the formulation to increase the quantity of the hydrophilic polymer (PEG), so that its time of residence in the blood is bigger and allow a bigger accumulation in the tumor. (Author)

Light-driven photosensitizer uptake increases Candida albicans photodynamic inactivation.

Science.gov (United States)

Romano, Renan A; Pratavieira, Sebastião; Silva, Ana P da; Kurachi, Cristina; Guimarães, Francisco E G

2017-11-01

Photodynamic Inactivation (PDI) is based on the use of a photosensitizer (PS) and light that results mainly in the production of reactive oxygen species, aiming to produce microorganism cell death. PS incubation time and light dose are key protocol parameters that influence PDI response; the correct choice of them can increase the efficiency of inactivation. The results of this study show that a minor change in the PDI protocol, namely light-driven incubation leads to a higher photosensitizer and more uniform cell uptake inside the irradiated zone. Furthermore, as the uptake increases, the damage caused by PDI also increases. The proposed light-driven incubation prior to the inactivation illumination dose has advantages when compared to the traditional PDI treatments since it can be more selective and effective. Using a violet light as pre-illumination (light-driven incubation) source and a red-light system as PDI source, it was possible to demonstrate that when compared to the traditional protocol of dark incubation, the pre-illuminated cell culture showed an inactivation increase of 7 log units. These in vitro results performed in Candida albicans cells may result in the introduction of a new protocol for PDI. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Inactivation of acetylcholinesterase by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride.

Science.gov (United States)

Zang, Lun-Yi; Misra, Hara P

2003-12-01

The neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to reversibly inhibit the activity of acetylcholinesterase. The inactivation of the enzyme was detected by monitoring the accumulation of yellow color produced from the reaction between thiocholine and dithiobisnitrobenzoate ion. The kinetic parameter, Km for the substrate (acetylthiocholine), was found to be 0.216 mM and Ki for MPTP inactivation of acetylcholinesterase was found to be 2.14 mM. The inactivation of enzyme by MPTP was found to be dose-dependent. It was found that MPTP is neither a substrate of AChE nor the time-dependent inactivator. The studies of reaction kinetics indicate the inactivation of AChE to be a linear mixed-type inhibition. The dilution assays indicate that MPTP is a reversible inhibitor for AChE. These data suggest that once MPTP enters the basal ganglia of the brain, it can inactivate the acetylcholinesterase enzyme and thereby increase the acetylcholine level in the basal ganglia of brain, leading to potential cell dysfunction. It appears that the nigrostriatal toxicity by MPTP leading to Parkinson's disease-like syndrome may, in part, be mediated via the acetylcholinesterase inactivation.

Metallic conductivity in a disordered charge-transfer salt derived from cis-BET-TTF

Energy Technology Data Exchange (ETDEWEB)

Rovira, C. [Inst. de Ciencia de Materials de Barcelona (CSIC) (Spain); Tarres, J. [Inst. de Ciencia de Materials de Barcelona (CSIC) (Spain); Ribera, E. [Inst. de Ciencia de Materials de Barcelona (CSIC) (Spain); Veciana, J. [Inst. de Ciencia de Materials de Barcelona (CSIC) (Spain); Canadell, E. [Inst. de Ciencia de Materials de Barcelona (CSIC) (Spain); Molins, E. [Inst. de Ciencia de Materials de Barcelona (CSIC) (Spain); Mas, M. [Inst. de Ciencia de Materials de Barcelona (CSIC) (Spain); Laukhin, V. [Inst. de Ciencia de Materials de Barcelona (CSIC) (Spain)]|[Rossijskaya Akademiya Nauk, Chernogolovka (Russian Federation). Inst. Khimicheskoj Fiziki; Doublet, M.L. [Lab. de Structure et Dynamique (CNRS), Univ. de Montpellier 2 (France); Cowan, D.O. [Johns Hopkins Univ., Baltimore, MD (United States). Dept. of Chemistry; Yang, S. [Johns Hopkins Univ., Baltimore, MD (United States). Dept. of Chemistry

1997-02-28

The first example of a metallic charge-transfer salt derived from cis-bis(ethylenethio)-tetrathiafulvalene (BET-TTF) is reported. (BET-TTF){sub 2}SCN and (BET-TTF)SCN salts were obtained by electrocrystallization starting from trans-BET-TTF. X-ray crystal structure of the mixed-valence salt revealed that trans-cis isomerization occurs upon one electron oxidation. In spite of the structural disorder in both BET-TTF and the counterion, 2:1 salt is metallic down to 60 K and then resistance increases slowly down to 4 K. (orig.)

Diversifying selection and functional analysis of interleukin-4 suggests antagonism-driven evolution at receptor-binding interfaces

Directory of Open Access Journals (Sweden)

Brown Scott

2010-07-01

Full Text Available Abstract Background Interleukin-4 (IL4 is a secreted immunoregulatory cytokine critically involved in host protection from parasitic helminths 1. Reasoning that helminths may have evolved mechanisms to antagonize IL4 to maximize their dispersal, we explored mammalian IL4 evolution. Results This analysis revealed evidence of diversifying selection at 15 residues, clustered in epitopes responsible for IL4 binding to its Type I and Type II receptors. Such a striking signature of selective pressure suggested either recurrent episodes of pathogen antagonism or ligand/receptor co-evolution. To test the latter possibility, we performed detailed functional analysis of IL4 allotypes expressed by Mus musculus musculus and Mus musculus castaneus, which happen to differ at 5 residues (including three at positively selected sites in and adjacent to the site 1 epitope that binds the IL4Rα subunit shared by the Type I and Type II IL4 receptors. We show that this intra-species variation affects the ability of IL4 neither to bind IL4 receptor alpha (IL4Rα nor to signal biological responses through its Type I receptor. Conclusions Our results -- reminiscent of clustered positively selected sites revealing functionally important residues at host-virus interaction interfaces -- are consistent with IL4 having evolved to avoid recurrent pathogen antagonism, while maintaining the capacity to bind and signal through its cognate receptor. This work exposes what may be a general feature of evolutionary conflicts fought by pathogen antagonists at host protein-protein interaction interfaces involved in immune signaling: the emergence of receptor-binding ligand epitopes capable of buffering amino acid variation.

Design of the Magnetic Resonance Imaging Evaluation of Mineralocorticoid Receptor Antagonism in Diabetic Atherosclerosis (MAGMA) Trial.

Science.gov (United States)

Rajagopalan, Sanjay; Alaiti, M Amer; Broadwater, Kylene; Goud, Aditya; Gaztanaga, Juan; Connelly, Kim; Fares, Anas; Shirazian, Shayan; Kreatsoulas, Catherine; Farkouh, Michael; Dobre, Mirela; Fink, Jeffrey C; Weir, Matthew R

2017-09-01

Mineralocorticoid receptor (MR) activation plays an essential role in promoting inflammation, fibrosis, and target organ damage. Currently, no studies are investigating MR antagonism in patients with type 2 diabetes mellitus (T2DM) with chronic kidney disease, at high risk for cardiovascular complications, who are otherwise not candidates for MR antagonism by virtue of heart failure. Further, there is limited information on candidate therapies that may demonstrate differential benefit from this therapy. We hypothesized that MR antagonism may provide additional protection from atherosclerosis progression in higher-risk patients who otherwise may not be candidates for such a therapeutic approach. In this double-blind, randomized, placebo-controlled trial, subjects with T2DM with chronic kidney disease (≥ stage 3) will be randomized in a 1:1 manner to placebo or spironolactone (12.5 mg with eventual escalation to 25 mg daily over a 4-week period). The co-primary efficacy endpoint will be percentage change in total atheroma volume in thoracic aorta and left ventricular mass at 52 weeks in patients treated with spironolactone vs placebo. Secondary outcomes include 24-hour mean systolic blood pressure, central aortic blood pressure, and insulin resistance (HOMA-IR) at 6 weeks. A novel measure in the study will be changes in candidate miRNAs that regulate expression of NR3C2 (MR gene) as well as measuring monocyte/macrophage polarization in response to therapy with spironolactone. We envision that our strategy of simultaneously probing the effects of a drug combined with analysis of mechanisms of action and predictive response will likely provide key information with which to design event-based trials. © 2017 Wiley Periodicals, Inc.

Thermal degradation kinetics of all-trans and cis-carotenoids in a light-induced model system.

Science.gov (United States)

Xiao, Ya-Dong; Huang, Wu-Yang; Li, Da-Jing; Song, Jiang-Feng; Liu, Chun-Quan; Wei, Qiu-Yu; Zhang, Min; Yang, Qiu-Ming

2018-01-15

Thermal degradation kinetics of lutein, zeaxanthin, β-cryptoxanthin, β-carotene was studied at 25, 35, and 45°C in a model system. Qualitative and quantitative analyses of all-trans- and cis-carotenoids were conducted using HPLC-DAD-MS technologies. Kinetic and thermodynamic parameters were calculated by non-linear regression. A total of 29 geometrical isomers and four oxidation products were detected, including all-trans-, keto compounds, mono-cis- and di-cis-isomers. Degradations of all-trans-lutein, zeaxanthin, β-cryptoxanthin, and β-carotene were described by a first-order kinetic model, with the order of rate constants as k β -carotene >k β -cryptoxanthin >k lutein >k zeaxanthin . Activation energies of zeaxanthin, lutein, β-cryptoxanthin, and β-carotene were 65.6, 38.9, 33.9, and 8.6kJ/moL, respectively. cis-carotenoids also followed with the first-order kinetic model, but they did not show a defined sequence of degradation rate constants and activation energies at different temperatures. A possible degradation pathway of four carotenoids was identified to better understand the mechanism of carotenoid degradation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Urease from Helicobacter pylori is inactivated by sulforaphane and other isothiocyanates

Science.gov (United States)

Fahey, Jed W.; Stephenson, Katherine K.; Wade, Kristina L.; Talalay, Paul

2013-01-01

Infections by Helicobacter pylori are very common, causing gastroduodenal inflammation including peptic ulcers, and increasing the risk of gastric neoplasia. The isothiocyanate (ITC) sulforaphane [SF; 1-isothiocyanato-4-(methylsulfinyl)butane] derived from edible crucifers such as broccoli is potently bactericidal against Helicobacter, including antibiotic-resistant strains, suggesting a possible dietary therapy. Gastric H. pylori infections express high urease activity which generates ammonia, neutralizes gastric acidity, and promotes inflammation. The finding that SF inhibits (inactivates) urease (jack bean and Helicobacter) raised the issue of whether these properties might be functionally related. The rates of inactivation of urease activity depend on enzyme and SF concentrations and show first order kinetics. Treatment with SF results in time-dependent increases in the ultraviolet absorption of partially purified Helicobacter urease in the 280–340 nm region. This provides direct spectroscopic evidence for the formation of dithiocarbamates between the ITC group of SF and cysteine thiols of urease. The potencies of inactivation of Helicobacter urease by isothiocyanates structurally related to SF were surprisingly variable. Natural isothiocyanates closely related to SF, previously shown to be bactericidal (berteroin, hirsutin, phenethyl isothiocyanate, alyssin, and erucin), did not inactivate urease activity. Furthermore, SF is bactericidal against both urease positive and negative H. pylori strains. In contrast, some isothiocyanates such as benzoyl-ITC, are very potent urease inactivators, but are not bactericidal. The bactericidal effects of SF and other ITC against Helicobacter are therefore not obligatorily linked to urease inactivation, but may reduce the inflammatory component of Helicobacter infections. PMID:23583386

Cooperation, Trust, and Antagonism: How Public Goods Are Promoted.

Science.gov (United States)

Parks, Craig D; Joireman, Jeff; Van Lange, Paul A M

2013-12-01

One of the most continually vexing problems in society is the variability with which citizens support endeavors that are designed to help a great number of people. In this article, we examine the twin roles of cooperative and antagonistic behavior in this variability. We find that each plays an important role, though their contributions are, understandably, at odds. It is this opposition that produces seeming unpredictability in citizen response to collective need. In fact, we suggest that careful consideration of the research allows one to often predict when efforts to provide a collectively beneficial good will succeed and when they will fail. To understand the dynamics of participation in response to collective need, it is necessary to distinguish between the primary types of need situations. A public good is an entity that relies in whole or in part on contributions to be provided. Examples of public goods are charities and public broadcasting. Public goods require that citizens experience a short-term loss (of their contribution) in order to realize a long-term gain (of the good). However, because everyone can use the good once it is provided, there is also an incentive to not contribute, let others give, and then take advantage of their efforts. This state of affairs introduces a conflict between doing what is best for oneself and what is best for the group. In a public goods situation, cooperation and antagonism impact how one resolves this conflict. The other major type of need situation is a common-pool resource problem. Here, a good is fully provided at the outset, and citizens may sample from it. The resource is usually, but not necessarily, partially replenished. Examples of replenished resources are drinking water and trees; examples of resources that are functionally not replenished are oil and minerals. Common-pool resources allow citizens to experience a short-term gain (by getting what they want in the early life of the resource) but also present

Mechanism-based inactivation of benzo[a]pyrene hydroxylase by aryl acetylenes and aryl olefins

International Nuclear Information System (INIS)

Gan, L.S.; Lu, J.Y.L.; Alworth, W.L.

1986-01-01

A series of aryl acetylenes and aryl olefins have been examined as substrates and inhibitors of cytochrome P-450 dependent monooxgenases in liver microsomes from 5,6-benzoflavone or phenobarbital pretreated rats. 1-Ethynylpyrene, 3-ethynylperylene, 2-ethynylfluorene, methyl 1-pyrenyl acetylene, cis- and trans-1-(2-bromovinyl)pyrene, and 1-allylpyrene serve as mechanism-based irreversible inactivators (suicide inhibitors) of benzo[a]pyrene hydroxylase, while 1-vinylpyrene and phenyl 1-pyrenyl acetylene do not cause a detectable suicide inhibition of benzo[a]pyrene hydroxylase. The mechanism-based loss of benzo[a]pyrene hydroxylase caused by the aryl acetylenes is not accompanied by a corresponding loss of the P-450 content of the microsomes (suicide destruction). The suicide inhibition by these aryl acetylenes therefore does not involve covalent binding to the heme moiety of the monooxygenase. Nevertheless, in the presence of NADPH, 3 H-labeled 1-ethynylpyrene becomes covalently attached to the cytochrome P-450 protein; the measured stoichiometry of binding is one 1-ethynylpyrene per P-450 heme unit. The authors conclude that the inhibition of benzo[a]pyrene hydroxylase produced by 1-ethynylpyrene may be related to the mechanism of suicide inhibition of P-450 activity by chloramphenicol rather than the mechanism of suicide destruction of P-450 previously described for acetylene and propyne

Luteinizing hormone-releasing hormone inactivation by purified pituitary plasma membranes: effects of receptor-binding studies.

Science.gov (United States)

Clayton, R N; Shakespear, R A; Duncan, J A; Marshall, J C

1979-05-01

Inactivation of LHRH by purified bovine pituitary plasma membranes was studied in vitro. After incubation of [125I]iodo-LHRH with plasma membranes, the amount of tracer bound to the pellet was measured, and the integrity of the unbound tracer in the supernatant was assessed. Reduction in ability to bind to anti-LHRH serum and to rebind to plasma membranes together with altered electrophoretic mobility on polyacrylamide gels showed that the unbound [125I]iodo-LHRH was inactivated. LHRH inactivation occurred rapidly and was dependent upon membrane concentration and incubation temperature. These results indicate that hormone inactivation must be taken into account in the interpretation of LHRH-receptor interactions. During 37 C incubations, the apparent absence of specific LHRH binding can be explained by inactivation of tracer hormone. Significant LHRH inactivation also occurred at 0 C, which in part explains the insensitivity of LHRH receptor assays. Assessment of LHRH inactivation by different particulate subcellular fractions of pituitary tissue showed that the inactivating enzyme was associated with the plasma membranes; other organelles did not alter LHRH. The enzyme appeared to be an integral part of the plasma membrane structure, since enzymic activity could not be removed by washing without reducing specific LHRH binding. Additionally, reduction of LHRH inactivation by the inhibitors Bacitracin and Trasylol and by magnesium was also accompanied by reduced LHRH binding. Previous studies have shown that the majority of LHRH binding to pituitary plasma membranes is to the low affinity site (approximately 10(-6) M), but the significance of this binding has been uncertain. Our findings indicate that low affinity binding probably represents binding of LHRH to the inactivating enzyme. The LHRH analog, D-Ser6(TBu), des Gly10, ethylamide, has greater biological activity than LHRH and is not inactivated to a significant extent by pituitary plasma membranes. The

Effect of toluene concentration and hydrogen peroxide on Pseudomonas plecoglossicida cometabolizing mixture of cis-DCE and TCE in soil slurry.

Science.gov (United States)

Li, Junhui; Lu, Qihong; de Toledo, Renata Alves; Lu, Ying; Shim, Hojae

2015-12-01

An indigenous Pseudomonas sp., isolated from the regional contaminated soil and identified as P. plecoglossicida, was evaluated for its aerobic cometabolic removal of cis-1,2-dichloroethylene (cis-DCE) and trichloroethylene (TCE) using toluene as growth substrate in a laboratory-scale soil slurry. The aerobic simultaneous bioremoval of the cis-DCE/TCE/toluene mixture was studied under different conditions. Results showed that an increase in toluene concentration level from 300 to 900 mg/kg prolonged the lag phase for the bacterial growth, while the bioremoval extent for cis-DCE, TCE, and toluene declined as the initial toluene concentration increased. In addition, the cometabolic bioremoval of cis-DCE and TCE was inhibited by the presence of hydrogen peroxide as the additional oxygen source, while the bioremoval of toluene (900 mg/kg) was enhanced after 9 days of incubation. The subsequent addition of toluene did not improve the cometabolic bioremoval of cis-DCE and TCE. The obtained results would help to enhance the applicability of bioremediation technology to the mixed waste contaminated sites.

Numerical evaluation of lactoperoxidase inactivation during continuous pulsed electric field processing.

Science.gov (United States)

Buckow, Roman; Semrau, Julius; Sui, Qian; Wan, Jason; Knoerzer, Kai

2012-01-01

A computational fluid dynamics (CFD) model describing the flow, electric field and temperature distribution of a laboratory-scale pulsed electric field (PEF) treatment chamber with co-field electrode configuration was developed. The predicted temperature increase was validated by means of integral temperature studies using thermocouples at the outlet of each flow cell for grape juice and salt solutions. Simulations of PEF treatments revealed intensity peaks of the electric field and laminar flow conditions in the treatment chamber causing local temperature hot spots near the chamber walls. Furthermore, thermal inactivation kinetics of lactoperoxidase (LPO) dissolved in simulated milk ultrafiltrate were determined with a glass capillary method at temperatures ranging from 65 to 80 °C. Temperature dependence of first order inactivation rate constants was accurately described by the Arrhenius equation yielding an activation energy of 597.1 kJ mol(-1). The thermal impact of different PEF processes on LPO activity was estimated by coupling the derived Arrhenius model with the CFD model and the predicted enzyme inactivation was compared to experimental measurements. Results indicated that LPO inactivation during combined PEF/thermal treatments was largely due to thermal effects, but 5-12% enzyme inactivation may be related to other electro-chemical effects occurring during PEF treatments. Copyright © 2012 American Institute of Chemical Engineers (AIChE).

Inactivation of Smad4 in gastric carcinomas.

Science.gov (United States)

Powell, S M; Harper, J C; Hamilton, S R; Robinson, C R; Cummings, O W

1997-10-01

Allelic loss of chromosome 18q has been noted in intestinal type gastric adenocarcinomas. Smad4 is a gene located at 18q that was recently cloned in humans and found to be significantly altered in pancreatic cancers. We sought to determine whether Smad4 genetic alterations played a significant role in gastric tumorigenesis by studying 35 gastric adenocarcinomas of all histopathological types and pathological stages. Microdissected specimens were used for mutational analysis of Smad4 at the nucleotide level, including the entire coding region and intron/exon boundaries. Allelic imbalance was also analyzed at the Smad4 locus using two nearby microsatellite markers. One case of apparent biallelic inactivation of Smad4 was found in our study of 35 gastric carcinomas. A nonsense point mutation at codon 334 was demonstrated, which, similar to other Smad4 mutations, is predicted to truncate the conserved COOH-terminal domain of this protein. This Smad4 C to T transition mutation was proven to be somatically acquired. Allelic loss was also noted on chromosome 18q at a marker near Smad4 in this mutated gastric cancer, apparently producing complete inactivation of Smad4 in this tumor. Significant 18q allelic loss (56% of 34 informative cases) was noted in our gastric carcinomas using microsatellite markers near the Smad4 locus, regardless of histological subtype or pathological stage. Additionally, three cases of microsatellite instability were observed. Thus, Smad4 inactivation was noted in our gastric carcinomas; however, this event was rare. The frequent loss of chromosomal arm 18q observed in gastric cancers suggests the presence of other tumor suppressor genes in this region that are involved in gastric tumorigenesis. Further studies are needed to identify these other targets of inactivation during gastric cancer development.

Female meiotic sex chromosome inactivation in chicken.

Directory of Open Access Journals (Sweden)

Sam Schoenmakers

2009-05-01

Full Text Available During meiotic prophase in male mammals, the heterologous X and Y chromosomes remain largely unsynapsed, and meiotic sex chromosome inactivation (MSCI leads to formation of the transcriptionally silenced XY body. In birds, the heterogametic sex is female, carrying Z and W chromosomes (ZW, whereas males have the homogametic ZZ constitution. During chicken oogenesis, the heterologous ZW pair reaches a state of complete heterologous synapsis, and this might enable maintenance of transcription of Z- and W chromosomal genes during meiotic prophase. Herein, we show that the ZW pair is transiently silenced, from early pachytene to early diplotene using immunocytochemistry and gene expression analyses. We propose that ZW inactivation is most likely achieved via spreading of heterochromatin from the W on the Z chromosome. Also, persistent meiotic DNA double-strand breaks (DSBs may contribute to silencing of Z. Surprisingly, gammaH2AX, a marker of DSBs, and also the earliest histone modification that is associated with XY body formation in mammalian and marsupial spermatocytes, does not cover the ZW during the synapsed stage. However, when the ZW pair starts to desynapse, a second wave of gammaH2AX accumulates on the unsynapsed regions of Z, which also show a reappearance of the DSB repair protein RAD51. This indicates that repair of meiotic DSBs on the heterologous part of Z is postponed until late pachytene/diplotene, possibly to avoid recombination with regions on the heterologously synapsed W chromosome. Two days after entering diplotene, the Z looses gammaH2AX and shows reactivation. This is the first report of meiotic sex chromosome inactivation in a species with female heterogamety, providing evidence that this mechanism is not specific to spermatogenesis. It also indicates the presence of an evolutionary force that drives meiotic sex chromosome inactivation independent of the final achievement of synapsis.

Pathogen inactivation techniques.

Science.gov (United States)

Pelletier, J P R; Transue, S; Snyder, E L

2006-01-01

The desire to rid the blood supply of pathogens of all types has led to the development of many technologies aimed at the same goal--eradication of the pathogen(s) without harming the blood cells or generating toxic chemical agents. This is a very ambitious goal, and one that has yet to be achieved. One approach is to shun the 'one size fits all' concept and to target pathogen-reduction agents at the Individual component types. This permits the development of technologies that might be compatible with, for example, plasma products but that would be cytocidal and thus incompatible with platelet concentrates or red blood cell units. The technologies to be discussed include solvent detergent and methylene blue treatments--designed to inactivate plasma components and derivatives; psoralens (S-59--amotosalen) designed to pathogen-reduce units of platelets; and two products aimed at red blood cells, S-303 (a Frale--frangible anchor-linker effector compound) and Inactine (a binary ethyleneimine). A final pathogen-reduction material that might actually allow one material to inactivate all three blood components--riboflavin (vitamin B2)--is also under development. The sites of action of the amotosalen (S-59), the S-303 Frale, Inactine, and riboflavin are all localized in the nucleic acid part of the pathogen. Solvent detergent materials act by dissolving the plasma envelope, thus compromising the integrity of the pathogen membrane and rendering it non-infectious. By disrupting the pathogen's ability to replicate or survive, its infectivity is removed. The degree to which bacteria and viruses are affected by a particular pathogen-reducing technology relates to its Gram-positive or Gram-negative status, to the sporulation characteristics for bacteria, and the presence of lipid or protein envelopes for viruses. Concerns related to photoproducts and other breakdown products of these technologies remain, and the toxicology of pathogen-reduction treatments is a major ongoing area

Predicting Bacillus coagulans spores inactivation in tomato pulp under nonisothermal heat treatments.

Science.gov (United States)

Zimmermann, Morgana; Longhi, Daniel A; Schaffner, Donald W; Aragão, Gláucia M F

2014-05-01

The knowledge and understanding of Bacillus coagulans inactivation during a thermal treatment in tomato pulp, as well as the influence of temperature variation during thermal processes are essential for design, calculation, and optimization of the process. The aims of this work were to predict B. coagulans spores inactivation in tomato pulp under varying time-temperature profiles with Gompertz-inspired inactivation model and to validate the model's predictions by comparing the predicted values with experimental data. B. coagulans spores in pH 4.3 tomato pulp at 4 °Brix were sealed in capillary glass tubes and heated in thermostatically controlled circulating oil baths. Seven different nonisothermal profiles in the range from 95 to 105 °C were studied. Predicted inactivation kinetics showed similar behavior to experimentally observed inactivation curves when the samples were exposed to temperatures in the upper range of this study (99 to 105 °C). Profiles that resulted in less accurate predictions were those where the range of temperatures analyzed were comparatively lower (inactivation profiles starting at 95 °C). The link between fail prediction and both lower starting temperature and magnitude of the temperature shift suggests some chemical or biological mechanism at work. Statistical analysis showed that overall model predictions were acceptable, with bias factors from 0.781 to 1.012, and accuracy factors from 1.049 to 1.351, and confirm that the models used were adequate to estimate B. coagulans spores inactivation under fluctuating temperature conditions in the range from 95 to 105 °C. How can we estimate Bacillus coagulans inactivation during sudden temperature shifts in heat processing? This article provides a validated model that can be used to predict B. coagulans under changing temperature conditions. B. coagulans is a spore-forming bacillus that spoils acidified food products. The mathematical model developed here can be used to predict the spoilage

Interferon Induction by RNA Viruses and Antagonism by Viral Pathogens

Directory of Open Access Journals (Sweden)

Yuchen Nan

2014-12-01

Full Text Available Interferons are a group of small proteins that play key roles in host antiviral innate immunity. Their induction mainly relies on host pattern recognition receptors (PRR. Host PRR for RNA viruses include Toll-like receptors (TLR and retinoic acid-inducible gene I (RIG-I like receptors (RLR. Activation of both TLR and RLR pathways can eventually lead to the secretion of type I IFNs, which can modulate both innate and adaptive immune responses against viral pathogens. Because of the important roles of interferons, viruses have evolved multiple strategies to evade host TLR and RLR mediated signaling. This review focuses on the mechanisms of interferon induction and antagonism of the antiviral strategy by RNA viruses.

Inactivation of biological substances by local heating

Energy Technology Data Exchange (ETDEWEB)

Saito, Masahiro [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst.

1982-09-01

Mechanism of inactivation of biological substances caused by local heating was investigated. The effect of hot-zone formation by local heating on reaction of radicals was previously evaluated. The thermal increase in a hot zone due to low energy LET x-rays had little effect on reactibility of the radicals, but, in a hot zone caused by high energy LET x-rays, formed radicals seemed immediately react to active biological molecules to inactivate them. Direct thermal effect on biological molecules was analysed. Thermal increase in a hot zone may induce degenaration of biological molecules which seems to occur in a short time judged from the extension of a hot zone and the duration of high temperature.

A saturation screen for cis-acting regulatory DNA in the Hox genes of Ciona intestinalis

Energy Technology Data Exchange (ETDEWEB)

Keys, David N.; Lee, Byung-in; Di Gregorio, Anna; Harafuji, Naoe; Detter, Chris; Wang, Mei; Kahsai, Orsalem; Ahn, Sylvia; Arellano, Andre; Zhang, Quin; Trong, Stephan; Doyle, Sharon A.; Satoh, Noriyuki; Satou, Yutaka; Saiga, Hidetoshi; Christian, Allen; Rokhsar, Dan; Hawkins, Trevor L.; Levine, Mike; Richardson, Paul

2005-01-05

A screen for the systematic identification of cis-regulatory elements within large (>100 kb) genomic domains containing Hox genes was performed by using the basal chordate Ciona intestinalis. Randomly generated DNA fragments from bacterial artificial chromosomes containing two clusters of Hox genes were inserted into a vector upstream of a minimal promoter and lacZ reporter gene. A total of 222 resultant fusion genes were separately electroporated into fertilized eggs, and their regulatory activities were monitored in larvae. In sum, 21 separable cis-regulatory elements were found. These include eight Hox linked domains that drive expression in nested anterior-posterior domains of ectodermally derived tissues. In addition to vertebrate-like CNS regulation, the discovery of cis-regulatory domains that drive epidermal transcription suggests that C. intestinalis has arthropod-like Hox patterning in the epidermis.

Antagonizing Arachidonic Acid-Derived Eicosanoids Reduces Inflammatory Th17 and Th1 Cell-Mediated Inflammation and Colitis Severity

Directory of Open Access Journals (Sweden)

Jennifer M. Monk

2014-01-01

Full Text Available During colitis, activation of two inflammatory T cell subsets, Th17 and Th1 cells, promotes ongoing intestinal inflammatory responses. n-6 polyunsaturated fatty acid- (PUFA- derived eicosanoids, such as prostaglandin E2 (PGE2, promote Th17 cell-mediated inflammation, while n-3 PUFA antagonize both Th17 and Th1 cells and suppress PGE2 levels. We utilized two genetic mouse models, which differentially antagonize PGE2 levels, to examine the effect on Th17 cells and disease outcomes in trinitrobenzene sulfonic acid- (TNBS- induced colitis. Fat-1 mice contain the ω3 desaturase gene from C. elegans and synthesize n-3 PUFA de novo, thereby reducing the biosynthesis of n-6 PUFA-derived eicosanoids. In contrast, Fads1 Null mice contain a disrupted Δ5 desaturase gene and produce lower levels of n-6 PUFA-derived eicosanoids. Compared to Wt littermates, Fat-1 and Fads1 Null mice exhibited a similar colitic phenotype characterized by reduced colonic mucosal inflammatory eicosanoid levels and mRNA expression of Th17 cell markers (IL-17A, RORγτ, and IL-23, decreased percentages of Th17 cells and, improved colon injury scores (P≤0.05. Thus, during colitis, similar outcomes were obtained in two genetically distinct models, both of which antagonize PGE2 levels via different mechanisms. Our data highlight the critical impact of n-6 PUFA-derived eicosanoids in the promotion of Th17 cell-mediated colonic inflammation.

Conformational lock and dissociative thermal inactivation of lentil seedling amine oxidase.

Science.gov (United States)

Moosavi-Nejad, S Zahra; Moosavi-Movahedi, Ali-Akbar; Rezaei-Tavirani, Mostafa; Floris, Giovanni; Medda, Rosaria

2003-03-31

The kinetics of thermal inactivation of copper-containing amine oxidase from lentil seedlings were studied in a 100 mM potassium phosphate buffer, pH 7, using putrescine as the substrate. The temperature range was between 47-60 degrees C. The thermal inactivation curves were not linear at 52 and 57 degrees C; three linear phases were shown. The first phase gave some information about the number of dimeric forms of the enzyme that were induced by the higher temperatures using the "conformational lock" pertaining theory to oligomeric enzyme. The "conformational lock" caused two additional dimeric forms of the enzyme when the temperature increased to 57 degrees C. The second and third phases were interpreted according to a dissociative thermal inactivation model. These phases showed that lentil amine oxidase was reversibly-dissociated before the irreversible thermal inactivation. Although lentil amine oxidase is not a thermostable enzyme, its dimeric structure can form "conformational lock," conferring a structural tolerance to the enzyme against heat stress.

Hydroxylamine technique for in vitro prevention of penicillin inactivation of tobramycin.

Science.gov (United States)

Falkowski, A J; Creger, R J

1984-01-01

Hydroxylamine was evaluated and found to be a highly effective agent for the in vitro prevention of penicillin inactivation of tobramycin. This inactivation reaction resulted in an underestimation of tobramycin concentrations and was dependent on time, temperature, amount and type of penicillin, and amount of tobramycin. Plasma samples containing tobramycin and three clinically relevant concentrations of ticarcillin, carbenicillin, azlocillin, or piperacillin were incubated with and without hydroxylamine, and tobramycin concentrations were monitored at 0, 12, 24, 48, and 72 h. The inactivation reaction was found to be completely inhibited by hydroxylamine (1 mg/ml) compared with a 27 to 50% loss of measured tobramycin concentration in the unprotected tobramycin-penicillin samples. Hydroxylamine did not interfere with the Emit enzyme immunoassay (Syva Co.) at either high or low tobramycin concentrations. Hydroxylamine was effective in inhibiting the tobramycin inactivation at both room and refrigerator temperatures and was 100% effective in protecting tobramycin on a 1:1 molar basis. PMID:6393865

Microbial electrolytic disinfection process for highly efficient Escherichia coli inactivation

DEFF Research Database (Denmark)

Zhou, Shaofeng; Huang, Shaobin; Li, Xiaohu

2018-01-01

extensively studied for recalcitrant organics removal, its application potential towards water disinfection (e.g., inactivation of pathogens) is still unknown. This study investigated the inactivation of Escherichia coli in a microbial electrolysis cell based bio-electro-Fenton system (renamed as microbial......Water quality deterioration caused by a wide variety of recalcitrant organics and pathogenic microorganisms has become a serious concern worldwide. Bio-electro-Fenton systems have been considered as cost-effective and highly efficient water treatment platform technology. While it has been......]OH was identified as one potential mechanism for disinfection. This study successfully demonstrated the feasibility of bio-electro-Fenton process for pathogens inactivation, which offers insight for the future development of sustainable, efficient, and cost-effective biological water treatment technology....

Effect of Coat Layers in Bacillus Subtilis Spores Resistance to Photo-Catalytic Inactivation

Directory of Open Access Journals (Sweden)

Luz del Carmen Huesca-Espitia

2017-10-01

Full Text Available Different water treatment processes (physical and chemical exist to obtain safe water for human or food industry supply. The advanced oxidation technologies are rising as a new alternative to eliminate undesirable chemicals and waterborne diseases. In this work, we analyze the power of the photo-assisted Fenton process using Fe(II/H2O2 and UV radiation (365 nm to inactivate Bacillus subtilis spores, considered among the most resistant biological structures known. Different concentrations of Fe(II, H2O2 and UV radiation (365 nm were used to inactivate wt and some coat spore mutants of B. subtilis. Wt spores of B. subtilis were inactivated after 60 min using this process. In general, all defective coat mutants were more sensitive than the wt spores and, particularly, the double mutant was 10 folds more sensitive than others being inactivated during the first 10 minutes using soft reaction conditions. Presence of Fe(II ions was found essential for spore inactivating process and, for those spores inactivated using the Fe(II/H2O2 under UV radiation process, it is suggested that coat structures are important to their resistance to the treatment process. The photo-assisted Fenton process using Fe(II, H2O2 and UV radiation (365 nm can be used to inactivate any water microorganisms with the same or less resistance that B. subtilis spores to produce safe drinking water in relatively short treatment time.

Kinetic studies on substitution of cis-diaqua-chloro-tris-(dimethyl ...

Indian Academy of Sciences (India)

Abstract. The kinetics of interaction between cis-[RuCl(Me2SO)3(H2O)2]. + ... on interaction of the metal ion with nucleic acid constituents.2–4 ... antiherpes,18 anti-HIV,19 antiamebic,20 anticancer,21–25 antileukemic26 and ... Experimental.

Buffer AVL Alone Does Not Inactivate Ebola Virus in a Representative Clinical Sample Type.

Science.gov (United States)

Smither, Sophie J; Weller, Simon A; Phelps, Amanda; Eastaugh, Lin; Ngugi, Sarah; O'Brien, Lyn M; Steward, Jackie; Lonsdale, Steve G; Lever, Mark S

2015-10-01

Rapid inactivation of Ebola virus (EBOV) is crucial for high-throughput testing of clinical samples in low-resource, outbreak scenarios. The EBOV inactivation efficacy of Buffer AVL (Qiagen) was tested against marmoset serum (EBOV concentration of 1 × 10(8) 50% tissue culture infective dose per milliliter [TCID50 · ml(-1)]) and murine blood (EBOV concentration of 1 × 10(7) TCID50 · ml(-1)) at 4:1 vol/vol buffer/sample ratios. Posttreatment cell culture and enzyme-linked immunosorbent assay (ELISA) analysis indicated that treatment with Buffer AVL did not inactivate EBOV in 67% of samples, indicating that Buffer AVL, which is designed for RNA extraction and not virus inactivation, cannot be guaranteed to inactivate EBOV in diagnostic samples. Murine blood samples treated with ethanol (4:1 [vol/vol] ethanol/sample) or heat (60°C for 15 min) also showed no viral inactivation in 67% or 100% of samples, respectively. However, combined Buffer AVL and ethanol or Buffer AVL and heat treatments showed total viral inactivation in 100% of samples tested. The Buffer AVL plus ethanol and Buffer AVL plus heat treatments were also shown not to affect the extraction of PCR quality RNA from EBOV-spiked murine blood samples. © Crown copyright 2015.

Potential of the Antibody Against cis-Phosphorylated Tau in the Early Diagnosis, Treatment, and Prevention of Alzheimer Disease and Brain Injury.

Science.gov (United States)

Lu, Kun Ping; Kondo, Asami; Albayram, Onder; Herbert, Megan K; Liu, Hekun; Zhou, Xiao Zhen

2016-11-01

Alzheimer disease (AD) and chronic traumatic encephalopathy (CTE) share a common neuropathologic signature-neurofibrillary tangles made of phosphorylated tau-but do not have the same pathogenesis or symptoms. Although whether traumatic brain injury (TBI) could cause AD has not been established, CTE is shown to be associated with TBI. Until recently, whether and how TBI leads to tau-mediated neurodegeneration was unknown. The unique prolyl isomerase Pin1 protects against the development of tau-mediated neurodegeneration in AD by converting the phosphorylated Thr231-Pro motif in tau (ptau) from the pathogenic cis conformation to the physiologic trans conformation, thereby restoring ptau function. The recent development of antibodies able to distinguish and eliminate both conformations specifically has led to the discovery of cis-ptau as a precursor of tau-induced pathologic change and an early driver of neurodegeneration that directly links TBI to CTE and possibly to AD. Within hours of TBI in mice or neuronal stress in vitro, neurons prominently produce cis-ptau, which causes and spreads cis-ptau pathologic changes, termed cistauosis. Cistauosis eventually leads to widespread tau-mediated neurodegeneration and brain atrophy. Cistauosis is effectively blocked by the cis-ptau antibody, which targets intracellular cis-ptau for proteasome-mediated degradation and prevents extracellular cis-ptau from spreading to other neurons. Treating TBI mice with cis-ptau antibody not only blocks early cistauosis but also prevents development and spreading of tau-mediated neurodegeneration and brain atrophy and restores brain histopathologic features and functional outcomes. Thus, cistauosis is a common early disease mechanism for AD, TBI, and CTE, and cis-ptau and its antibody may be useful for early diagnosis, treatment, and prevention of these devastating diseases.

Thallium trinitrate mediated ring contraction of cis-2-decalones

Directory of Open Access Journals (Sweden)

Ferraz Helena M. C.

2001-01-01

Full Text Available The reaction of some cis-2-decalones with TTN in CH2Cl2 at room temperature was investigated. The ring contraction reactions occurred in good yields, however the regio- and diastereoselectivity were low. The effect of the alkyl groups in the regiochemistry of the reaction depends on their position at the decalone ring system.

Cis-Lunar Reusable In-Space Transportation Architecture for the Evolvable Mars Campaign

Science.gov (United States)

McVay, Eric S.; Jones, Christopher A.; Merrill, Raymond G.

2016-01-01

Human exploration missions to Mars or other destinations in the solar system require large quantities of propellant to enable the transportation of required elements from Earth's sphere of influence to Mars. Current and proposed launch vehicles are incapable of launching all of the requisite mass on a single vehicle; hence, multiple launches and in-space aggregation are required to perform a Mars mission. This study examines the potential of reusable chemical propulsion stages based in cis-lunar space to meet the transportation objectives of the Evolvable Mars Campaign and identifies cis-lunar propellant supply requirements. These stages could be supplied with fuel and oxidizer delivered to cis-lunar space, either launched from Earth or other inner solar system sources such as the Moon or near Earth asteroids. The effects of uncertainty in the model parameters are evaluated through sensitivity analysis of key parameters including the liquid propellant combination, inert mass fraction of the vehicle, change in velocity margin, and change in payload masses. The outcomes of this research include a description of the transportation elements, the architecture that they enable, and an option for a campaign that meets the objectives of the Evolvable Mars Campaign. This provides a more complete understanding of the propellant requirements, as a function of time, that must be delivered to cis-lunar space. Over the selected sensitivity ranges for the current payload and schedule requirements of the 2016 point of departure of the Evolvable Mars Campaign destination systems, the resulting propellant delivery quantities are between 34 and 61 tonnes per year of hydrogen and oxygen propellant, or between 53 and 76 tonnes per year of methane and oxygen propellant, or between 74 and 92 tonnes per year of hypergolic propellant. These estimates can guide future propellant manufacture and/or delivery architectural analysis.

Reaction of uridine diphosphate galactose 4-epimerase with a suicide inactivator

International Nuclear Information System (INIS)

Flentke, G.R.; Frey, P.A.

1990-01-01

UDPgalactose 4-epimerase from Escherichia coli is rapidly inactivated by the compounds uridine 5'-diphosphate chloroacetol (UDC) and uridine 5'-diphosphate bromoacetol (UCB). Both UDC and UDB inactivate the enzyme in neutral solution concomitant with the appearance of chromophores absorbing maximally at 325 and 328 nm, respectively. The reaction of UDC with the enzyme follows saturation kinetics characterized by a K D of 0.110 mM and k inact of 0.84 min -1 at pH 8.5 and ionic strength 0.2 M. The inactivation by UDC is competitively inhibited by competitive inhibitors of UDPgalactose 4-epimerase, and it is accompanied by the tight but noncovalent binding of UDC to the enzyme in a stoichiometry of 1 mol of UDC/mol of enzyme dimer, corresponding to 1 mol of UDC/mol of enzyme-bound NAD + . The inactivation of epimerase by uridine 5'-diphosphate [ 2 H 2 ]chloroacetol proceeds with a primary kinetic isotope effect (k H /k D ) of 1.4. The inactivation mechanism is proposed to involve a minimum of three steps: (a) reversible binding of UDC to the active site of UDPgalactose 4-epimerase; (b) enolization of the chloroacetol moiety of enzyme-bound UDC, catalyzed by an enzymic general base at the active site; (c) alkylation of the nicotinamide ring of NAD + at the active site by the chloroacetol enolate. The resulting adduct between UDC and NAD + is proposed to be the chromophore with λ max at 325 nm. The enzymic general base required to facilitate proton transfer in redox catalysis by this enzyme may be the general base that facilitates enolization of the chloroacetol moiety of UDC in the inactivation reaction

Coevolution within a transcriptional network by compensatory trans and cis mutations

KAUST Repository

Kuo, D.; Licon, K.; Bandyopadhyay, S.; Chuang, R.; Luo, C.; Catalana, J.; Ravasi, Timothy; Tan, K.; Ideker, T.

2010-01-01

Transcriptional networks have been shown to evolve very rapidly, prompting questions as to how such changes arise and are tolerated. Recent comparisons of transcriptional networks across species have implicated variations in the cis-acting DNA

Neural network model for thermal inactivation of Salmonella Typhimurium to elimination in ground chicken: Acquisition of data by whole sample enrichment, miniature most-probable-number method

Science.gov (United States)

Predictive models are valuable tools for assessing food safety. Existing thermal inactivation models for Salmonella and ground chicken do not provide predictions above 71 degrees C, which is below the recommended final cooked temperature of 73.9 degrees C. They also do not predict when all Salmone...

Use of cis-[18F] fluoro-proline for assessment of exercise-related collagen synthesis in musculoskeletal connective tissue

DEFF Research Database (Denmark)

Skovgaard, Dorthe; Kjaer, Andreas; Heinemeier, Katja Maria

2011-01-01

Protein turnover in collagen rich tissue is influenced by exercise, but can only with difficulty be studied in vivo due to use of invasive procedure. The present study was done to investigate the possibility of applying the PET-tracer, cis-[(18)F]fluoro-proline (cis-Fpro), for non-invasive assess......Protein turnover in collagen rich tissue is influenced by exercise, but can only with difficulty be studied in vivo due to use of invasive procedure. The present study was done to investigate the possibility of applying the PET-tracer, cis-[(18)F]fluoro-proline (cis-Fpro), for non......-invasive assessment of collagen synthesis in rat musculoskeletal tissues at rest and following short-term (3 days) treadmill running. Musculoskeletal collagen synthesis was studied in rats at rest and 24 h post-exercise. At each session, rats were PET scanned at two time points following injection of cis-FPro: (60...... and 240 min p.i). SUV were calculated for Achilles tendon, calf muscle and tibial bone. The PET-derived results were compared to mRNA expression of collagen type I and III. Tibial bone had the highest SUV that increased significantly (p...

Post-irradiation inactivation, protection, and repair of the sulfhydryl enzyme malate synthase

International Nuclear Information System (INIS)

Durchschlag, H.; Zipper, P.

1985-01-01

Malate synthase from baker's yeast, a trimeric sulfhydryl enzyme with one essential sulfhydryl group per subunit, was inactivated by 2 kGy X-irradiation in air-saturated aqueous solution (enzyme concentration: 0.5 mg/ml). The radiation induced changes of enzymic activity were registered at about 0,30,60 h after irradiation. To elucidate the role of OH - , O 2 , and H 2 O 2 in the X-ray inactivation of the enzyme, experiments were performed in the absence of presence of different concentrations of specific additives (formate, superoxide dismutase, catalase). These additives were added to malate synthase solutions before or after X-irradiation. Moreover, repairs of inactivated malate synthase were initiated at about 0 or 30 h after irradiation by means of the sulfhydryl agent dithiothreitol. Experiments yielded the following results: 1. Irradiation of malate synthase in the absence of additives inactivated the enzyme immediately to a residual activity Asub(r)=3% (corresponding to a D 37 =0.6 kGy), and led to further slow inactivation in the post-irradiation phase. Repairs, initiated at different times after irradiation, restored enzymic activity considerably. The repair initiated at t=0 led to Asub(r)=21%; repairs started later on resulted in somewhat lower activities. The decay of reparability, however, was found to progress more slowly than post-irradiation inactivation itself. After completion of repair the activities of repaired samples did not decrease significantly. 2. The presence of specific additives during irradiation caused significant protective effects against primary inactivation. The protection by formate was very pronounced (e.g., Asub(r)=72% and D 37 =6 kGy for 100 mM formate). The presence of catalytic amounts of superoxide dismutase and/or catalase exhibited only minor effects, depending on the presence and concentration of formate. (orig.)

Inactivation of 1-aminocyclopropane-1-carboxylate oxidase involves oxidative modifications.

Science.gov (United States)

Barlow, J N; Zhang, Z; John, P; Baldwin, J E; Schofield, C J

1997-03-25

1-Aminocyclopropane-1-carboxylate (ACC) oxidase catalyzes the final step in the biosynthesis of the plant signaling molecule ethylene. It is a member of the ferrous iron dependent family of oxidases and dioxygenases and is unusual in that it displays a very short half-life under catalytic conditions, typically less than 20 min, and a requirement for CO2 as an activator. The rates of inactivation of purified, recombinant ACC oxidase from tomato under various combinations of substrates and cofactors were measured. Inactivation was relatively slow in the presence of buffer alone (t1/2 > 1 h), but fast in the presence of ferrous iron and ascorbate (t1/2 approximately 10 min). The rate of iron/ascorbate-mediated inactivation was increased by the addition of ACC, unaffected by the addition of CO2 at saturation (supplied as bicarbonate) but decreased by the addition of catalase or ACC + CO2 at saturation (supplied as bicarbonate). Iron/ascorbate-mediated inactivation was accompanied by partial proteolysis as observed by SDS-PAGE analysis. The fragmentation pattern was altered when ACC was also included, suggesting that ACC can bind to ACC oxidase in the absence of bicarbonate. N-terminal sequencing of fragments resulted in identification of an internal cleavage site which we propose is proximate to active-site bound iron. Thus, ACC oxidase inactivates via relatively slow partial unfolding of the catalytically active conformation, oxidative damage mediated via hydrogen peroxide which is catalase protectable and oxidative damage to the active site which results in partial proteolysis and is not catalase protectable.

An inactivated yellow fever 17DD vaccine cultivated in Vero cell cultures.

Science.gov (United States)

Pereira, Renata C; Silva, Andrea N M R; Souza, Marta Cristina O; Silva, Marlon V; Neves, Patrícia P C C; Silva, Andrea A M V; Matos, Denise D C S; Herrera, Miguel A O; Yamamura, Anna M Y; Freire, Marcos S; Gaspar, Luciane P; Caride, Elena

2015-08-20

Yellow fever is an acute infectious disease caused by prototype virus of the genus Flavivirus. It is endemic in Africa and South America where it represents a serious public health problem causing epidemics of hemorrhagic fever with mortality rates ranging from 20% to 50%. There is no available antiviral therapy and vaccination is the primary method of disease control. Although the attenuated vaccines for yellow fever show safety and efficacy it became necessary to develop a new yellow fever vaccine due to the occurrence of rare serious adverse events, which include visceral and neurotropic diseases. The new inactivated vaccine should be safer and effective as the existing attenuated one. In the present study, the immunogenicity of an inactivated 17DD vaccine in C57BL/6 mice was evaluated. The yellow fever virus was produced by cultivation of Vero cells in bioreactors, inactivated with β-propiolactone, and adsorbed to aluminum hydroxide (alum). Mice were inoculated with inactivated 17DD vaccine containing alum adjuvant and followed by intracerebral challenge with 17DD virus. The results showed that animals receiving 3 doses of the inactivated vaccine (2 μg/dose) with alum adjuvant had neutralizing antibody titers above the cut-off of PRNT50 (Plaque Reduction Neutralization Test). In addition, animals immunized with inactivated vaccine showed survival rate of 100% after the challenge as well as animals immunized with commercial attenuated 17DD vaccine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular chaperone complexes with antagonizing activities regulate stability and activity of the tumor suppressor LKB1.

Science.gov (United States)

Gaude, H; Aznar, N; Delay, A; Bres, A; Buchet-Poyau, K; Caillat, C; Vigouroux, A; Rogon, C; Woods, A; Vanacker, J-M; Höhfeld, J; Perret, C; Meyer, P; Billaud, M; Forcet, C

2012-03-22

LKB1 is a tumor suppressor that is constitutionally mutated in a cancer-prone condition, called Peutz-Jeghers syndrome, as well as somatically inactivated in a sizeable fraction of lung and cervical neoplasms. The LKB1 gene encodes a serine/threonine kinase that associates with the pseudokinase STRAD (STE-20-related pseudokinase) and the scaffolding protein MO25, the formation of this heterotrimeric complex promotes allosteric activation of LKB1. We have previously reported that the molecular chaperone heat shock protein 90 (Hsp90) binds to and stabilizes LKB1. Combining pharmacological studies and RNA interference approaches, we now provide evidence that the co-chaperone Cdc37 participates to the regulation of LKB1 stability. It is known that the Hsp90-Cdc37 complex recognizes a surface within the N-terminal catalytic lobe of client protein kinases. In agreement with this finding, we found that the chaperones Hsp90 and Cdc37 interact with an LKB1 isoform that differs in the C-terminal region, but not with a novel LKB1 variant that lacks a portion of the kinase N-terminal lobe domain. Reconstitution of the two complexes LKB1-STRAD and LKB1-Hsp90-Cdc37 with recombinant proteins revealed that the former is catalytically active whereas the latter is inactive. Furthermore, consistent with a documented repressor function of Hsp90, LKB1 kinase activity was transiently stimulated upon dissociation of Hsp90. Finally, disruption of the LKB1-Hsp90 complex favors the recruitment of both Hsp/Hsc70 and the U-box dependent E3 ubiquitin ligase CHIP (carboxyl terminus of Hsc70-interacting protein) that triggers LKB1 degradation. Taken together, our results establish that the Hsp90-Cdc37 complex controls both the stability and activity of the LKB1 kinase. This study further shows that two chaperone complexes with antagonizing activities, Hsp90-Cdc37 and Hsp/Hsc70-CHIP, finely control the cellular level of LKB1 protein.

Neutral Guest Capture via Lewis Acid/Base Molecular Square Receptors. X-ray Crystal Structure of {Cyclobis[(cis-(dppp)Pt(4-ethynylpyridyl)(2))(cis- (PEt(3))(2)Pt)]Ag(2)}(+6)(phenazine)- ((-)OSO(2)CF(3))(6).

Science.gov (United States)

Whiteford, Jeffery A.; Stang, Peter J.; Huang, Songping D.

1998-10-19

Interaction of {cyclobis[(cis-(dppp)Pt(4-ethynylpyridyl)(2))(cis-(L)M)]Ag(2)}(+6)((-)OSO(2)CF(3))(6), where M = Pt(II) or Pd(II) and L = dppp or 2PEt(3), with pyridine, pyrazine, phenazine, or 4,4'-dipyridyl ketone results in coordination Lewis acid/base host-guest assemblies via the "pi-tweezer effect" and mono or bis neutral guest coordination. All host-guest complexes are air stable microcrystalline solids with decomposition points greater than 170 degrees C. The homometallic Pt(II) receptors are more stable than the heteroaromatic Pt(II)-Pd(II) receptors toward heteratom-containing aromatic guests. The X-ray crystal structure of the host-guest complex {cyclobis[(cis-(dppp)Pt(4-ethynylpyridyl)(2))(cis-(PEt(3))(2)Pt)]Ag(2)}(+6)(phenazine)((-)OSO(2)CF(3))(6) is reported. The crystals with the empirical formula C(62)H(68)AgF(9)N(3)O(9)P(4)Pt(2)S(3) are triclinic P&onemacr; with a = 12.3919(8) Å, b = 17.160(1) Å, c = 18.932(1) Å, alpha = 90.892(1) degrees, beta = 97.127(1) degrees, gamma = 89.969(1) degrees, and Z = 2.

Regulation of Na+ channel inactivation by the DIII and DIV voltage-sensing domains.

Science.gov (United States)

Hsu, Eric J; Zhu, Wandi; Schubert, Angela R; Voelker, Taylor; Varga, Zoltan; Silva, Jonathan R

2017-03-06

Functional eukaryotic voltage-gated Na + (Na V ) channels comprise four domains (DI-DIV), each containing six membrane-spanning segments (S1-S6). Voltage sensing is accomplished by the first four membrane-spanning segments (S1-S4), which together form a voltage-sensing domain (VSD). A critical Na V channel gating process, inactivation, has previously been linked to activation of the VSDs in DIII and DIV. Here, we probe this interaction by using voltage-clamp fluorometry to observe VSD kinetics in the presence of mutations at locations that have been shown to impair Na V channel inactivation. These locations include the DIII-DIV linker, the DIII S4-S5 linker, and the DIV S4-S5 linker. Our results show that, within the 10-ms timeframe of fast inactivation, the DIV-VSD is the primary regulator of inactivation. However, after longer 100-ms pulses, the DIII-DIV linker slows DIII-VSD deactivation, and the rate of DIII deactivation correlates strongly with the rate of recovery from inactivation. Our results imply that, over the course of an action potential, DIV-VSDs regulate the onset of fast inactivation while DIII-VSDs determine its recovery. © 2017 Hsu et al.

Excited State s-cis Rotamers Produced by Extreme Red Edge Excitation of all-trans-1,4-Diphenyl-1,3-butadiene

DEFF Research Database (Denmark)

Wallace-Williams, Stacie E.; Møller, Søren; Goldbeck, Robert A.

1993-01-01

with the wavelength independence observed for the excited singlet-state absorption and fluorescence emission spectra of 1,5-diphenyl-2,3,4,6,7,8- hexahydronaphthalene and for the fluorescence emission spectra of 1,4diphenyl-1,3-cyclopentadiene, s-trans and s-cis structural analogs of DPB, respectively. The spectral...... changes in DPB can be explained in terms of an excitation wavelength-dependent production of s-cis and s-trans rotamer populations in the excited state. The DPB fluorescence emission spectrum was resolved into s-cis and s-trans components. The vibronic structure of the s-cis fluorescence spectrum...... is similar to that of s-trans, but the band origin is red-shifted and there is a slightly larger amplitude on the red edge. The excited-state absorption spectrum of s-cis DPB appears to be red-shifted relative to that of s-trans DPB as well....

Mechanism-based inactivation of cytochrome P-450 dependent benzo[a]pyrene hydroxylase activity by acetylenic and olefinic polycyclic arylhydrocarbons

International Nuclear Information System (INIS)

Gan, L.S.

1986-01-01

A series of aryl acetylenes and aryl olefins have been examined as substrates and inhibitors of cytochrome P-450 dependent monooxygenases in liver microsomes from 5,6-benzoflavone or phenobarbital pretreated rats. 1-Ethynylpyrene (EP), 3-ethynylperylene (EPL), cis- and trans-1-(2-bromo-vinyl)pyrene (c-BVP and t-BVP), and 1-allylpyrene (AP) serve as mechanism-based irreversible inactivators (suicide inhibitors) of benzo(a)pyrene (BP) hydroxylase, while 1-vinyl-pyrene (VP) and phenyl 1-pyrenyl acetylene (PPA) do not cause a detectable suicide inhibition of the BP hydroxylase. The mechanism-based loss of BP hydroxylase activity caused by the aryl acetylenes is not accompanied by a corresponding loss of the P-450 content of the microsomes. In the presence of NADPH, 3 H-labeled EP covalently attached to P-450 isozymes with a measured stoichiometry of one mole of EP per mole of the P-450 heme. The results of the effects of these aryl derivatives in the mammalian cell-mediated mutagenesis assay and toxicity assay show that none of the compounds examined nor any of the their metabolites produced in the incubation system are cytotoxic to V79 cells

Influenza virus inactivated by artificial ribonucleases as a prospective killed virus vaccine.

Science.gov (United States)

Fedorova, Antonina A; Goncharova, Elena P; Kovpak, Mikhail P; Vlassov, Valentin V; Zenkova, Marina A

2012-04-19

The inactivation of viral particles with agents causing minimal damage to the structure of surface epitopes is a well-established approach for the production of killed virus vaccines. Here, we describe new agents for the inactivation of influenza virus, artificial ribonucleases (aRNases), which are chemical compounds capable of cleaving RNA molecules. Several aRNases were identified, exhibiting significant virucidal activity against the influenza A virus and causing a minimal effect on the affinity of monoclonal antibodies for the inactivated virus. Using a murine model of the influenza virus infection, a high protective activity of the aRNase-inactivated virus as a vaccine was demonstrated. The results of the experiments demonstrate the efficacy of novel chemical agents in the preparation of vaccines against influenza and, perhaps, against other infections caused by RNA viruses. Copyright © 2012 Elsevier Ltd. All rights reserved.

Influence of pH, Salt and Temperature on Pressure Inactivation of Hepatitis A virus

Science.gov (United States)

The effects of pH (3-7), NaCl (0-6%), and temperature on pressure inactivation of hepatitis A virus (HAV) were determined. The HAV samples were treated at 400 MPa for 1 min at 5, 20, and 50C. Decreasing solution pH enhanced pressure inactivation of HAV. This enhanced inactivation effect was most e...

Inactivation of human enteric virus surrogates by high-intensity ultrasound.

Science.gov (United States)

Su, Xiaowei; Zivanovic, Svetlana; D'Souza, Doris H

2010-09-01

Foodborne viruses, especially human noroviruses, are recognized as leading causes of nonbacterial gastroenteritis worldwide. Development of effective inactivation methods is of great importance to control their spread. In this study, the effect of high-intensity ultrasound (HIUS) on the infectivity of three foodborne virus surrogates was investigated. The three surrogates, murine norovirus (MNV-1), feline calicivirus (FCV-F9), and MS2 bacteriophage, were diluted in phosphate-buffered saline (PBS) or orange juice to a titer of approximately 6 log(10) PFU/mL or approximately 4 log(10) PFU/mL. The ultrasound treatment was performed in duplicate by immersing the HIUS probe in virus-containing solution that was cooled in ice-water and sonicated at 20 kHz for 2, 5, 10, 15, 20, and 30 min with 30 sec on and 30 sec off. The infectivity of the recovered viruses after each ultrasound treatment was evaluated in duplicate using standardized plaque assays and compared to untreated controls. The results show that HIUS effectiveness depended on the virus type, the initial titer of the viruses, and the virus suspension solution. At titers of approximately 4 log(10) PFU/mL in PBS, feline calicivirus (FCV)-F9, MS2, and murine norovirus (MNV)-1 required 5-, 10-, and 30-min treatment, respectively, for complete inactivation. At initial titers of approximately 4 log(10) PFU/mL in orange juice, FCV-F9 required a 15-min treatment for complete inactivation and only a 1.55 log(10) PFU/mL reduction was achieved for MNV-1 in orange juice after 30-min treatment. Thus, inactivation by HIUS in orange juice was much lower than in PBS. Experiments using titers of approximately 6 log(10) PFU/mL showed decreased effects compared to those using titers of approximately 4 log(10) PFU/mL. These results indicate that HIUS alone is not sufficient to inactivate virus in food. Hurdle technologies that combine HIUS with antimicrobials, heat, or pressure should be explored for viral inactivation.

Evaluation of eco-friendly zwitterionic detergents for enveloped virus inactivation.

Science.gov (United States)

Conley, Lynn; Tao, Yinying; Henry, Alexis; Koepf, Edward; Cecchini, Douglas; Pieracci, John; Ghose, Sanchayita

2017-04-01

Inclusion of a detergent in protein biotherapeutic purification processes is a simple and very robust method for inactivating enveloped viruses. The detergent Triton X-100 has been used for many years and is part of the production process of several commercial therapeutic proteins. However, recent ecological studies have suggested that Triton X-100 and its break-down products can potentially behave as endocrine disrupters in aquatic organisms, raising concerns from an environmental impact perspective. As such, discharge of Triton X-100 into the waste water treatment plants is regulated in some jurisdictions, and alternative detergents for viral inactivation are required. In this work, we report on the identification and evaluation of more eco-friendly detergents as viable replacements for Triton X-100. Five detergent candidates with low to moderate environmental impact were initially identified and evaluated with respect to protein stability, followed by proof-of-concept virus inactivation studies using a model enveloped virus. From the set of candidates lauryldimethylamine N-oxide (LDAO) was identified as the most promising detergent due to its low ecotoxicity, robust anti-viral activity (LRV >4 at validation set-point conditions with X-MuLX), and absence of any negative impact on protein function. This detergent exhibited effective and robust virus inactivation in a broad range of protein concentrations, solution conductivities, pHs, and in several different cell culture fluid matrices. The only process parameter which correlated with reduced virus inactivation potency was LDAO concentration, and then only when the concentration was reduced to below the detergent's critical micelle concentration (CMC). Additionally, this work also demonstrated that LDAO was cleared to below detectable levels after Protein A affinity chromatography, making it suitable for use in a platform process that utilizes this chromatographic mode for protein capture. All these findings

Creating and validating cis-regulatory maps of tissue-specific gene expression regulation

Science.gov (United States)

O'Connor, Timothy R.; Bailey, Timothy L.

2014-01-01

Predicting which genomic regions control the transcription of a given gene is a challenge. We present a novel computational approach for creating and validating maps that associate genomic regions (cis-regulatory modules–CRMs) with genes. The method infers regulatory relationships that explain gene expression observed in a test tissue using widely available genomic data for ‘other’ tissues. To predict the regulatory targets of a CRM, we use cross-tissue correlation between histone modifications present at the CRM and expression at genes within 1 Mbp of it. To validate cis-regulatory maps, we show that they yield more accurate models of gene expression than carefully constructed control maps. These gene expression models predict observed gene expression from transcription factor binding in the CRMs linked to that gene. We show that our maps are able to identify long-range regulatory interactions and improve substantially over maps linking genes and CRMs based on either the control maps or a ‘nearest neighbor’ heuristic. Our results also show that it is essential to include CRMs predicted in multiple tissues during map-building, that H3K27ac is the most informative histone modification, and that CAGE is the most informative measure of gene expression for creating cis-regulatory maps. PMID:25200088

A Cis-Lunar Propellant Infrastructure for Flexible Path Exploration and Space Commerce

Science.gov (United States)

Oeftering, Richard C.

2012-01-01

This paper describes a space infrastructure concept that exploits lunar water for propellant production and delivers it to users in cis-lunar space. The goal is to provide responsive economical space transportation to destinations beyond low Earth orbit (LEO) and enable in-space commerce. This is a game changing concept that could fundamentally affect future space operations, provide greater access to space beyond LEO, and broaden participation in space exploration. The challenge is to minimize infrastructure development cost while achieving a low operational cost. This study discusses the evolutionary development of the infrastructure from a very modest robotic operation to one that is capable of supporting human operations. The cis-lunar infrastructure involves a mix of technologies including cryogenic propellant production, reusable lunar landers, propellant tankers, orbital transfer vehicles, aerobraking technologies, and electric propulsion. This cislunar propellant infrastructure replaces Earth-launched propellants for missions beyond LEO. It enables users to reach destinations with smaller launchers or effectively multiplies the user s existing payload capacity. Users can exploit the expanded capacity to launch logistics material that can then be traded with the infrastructure for propellants. This mutually beneficial trade between the cis-lunar infrastructure and propellant users forms the basis of in-space commerce.

Comparative genome sequencing of drosophila pseudoobscura: Chromosomal, gene and cis-element evolution

Energy Technology Data Exchange (ETDEWEB)

Richards, Stephen; Liu, Yue; Bettencourt, Brian R.; Hradecky, Pavel; Letovsky, Stan; Nielsen, Rasmus; Thornton, Kevin; Todd, Melissa J.; Chen, Rui; Meisel, Richard P.; Couronne, Olivier; Hua, Sujun; Smith, Mark A.; Bussemaker, Harmen J.; van Batenburg, Marinus F.; Howells, Sally L.; Scherer, Steven E.; Sodergren, Erica; Matthews, Beverly B.; Crosby, Madeline A.; Schroeder, Andrew J.; Ortiz-Barrientos, Daniel; Rives, Catherine M.; Metzker, Michael L.; Muzny, Donna M.; Scott, Graham; Steffen, David; Wheeler, David A.; Worley, Kim C.; Havlak, Paul; Durbin, K. James; Egan, Amy; Gill, Rachel; Hume, Jennifer; Morgan, Margaret B.; Miner, George; Hamilton, Cerissa; Huang, Yanmei; Waldron, Lenee; Verduzco, Daniel; Blankenburg, Kerstin P.; Dubchak, Inna; Noor, Mohamed A.F.; Anderson, Wyatt; White, Kevin P.; Clark, Andrew G.; Schaeffer, Stephen W.; Gelbart, William; Weinstock, George M.; Gibbs, Richard A.

2004-04-01

The genome sequence of a second fruit fly, D. pseudoobscura, presents an opportunity for comparative analysis of a primary model organism D. melanogaster. The vast majority of Drosophila genes have remained on the same arm, but within each arm gene order has been extensively reshuffled leading to the identification of approximately 1300 syntenic blocks. A repetitive sequence is found in the D. pseudoobscura genome at many junctions between adjacent syntenic blocks. Analysis of this novel repetitive element family suggests that recombination between offset elements may have given rise to many paracentric inversions, thereby contributing to the shuffling of gene order in the D. pseudoobscura lineage. Based on sequence similarity and synteny, 10,516 putative orthologs have been identified as a core gene set conserved over 35 My since divergence. Genes expressed in the testes had higher amino acid sequence divergence than the genome wide average consistent with the rapid evolution of sex-specific proteins. Cis-regulatory sequences are more conserved than control sequences between the species but the difference is slight, suggesting that the evolution of cis-regulatory elements is flexible. Overall, a picture of repeat mediated chromosomal rearrangement, and high co-adaptation of both male genes and cis-regulatory sequences emerges as important themes of genome divergence between these species of Drosophila.

X-linked gene expression and X-chromosome inactivation: marsupials, mouse, and man compared.

Science.gov (United States)

VandeBerg, J L; Robinson, E S; Samollow, P B; Johnston, P G

1987-01-01

The existence of paternal X inactivation in Australian and American marsupial species suggests that this feature of X-chromosome dosage compensation is not a recent adaptation, but probably predates the evolutionary separation of the Australian and American marsupial lineages. Although it is theoretically possible that the marsupial system is one of random X inactivation with p greater than 0.99 and q less than 0.01 and dependent on parental source, no instance of random X inactivation (p = q or p not equal to q) has ever been verified in any tissue or cell type of any marsupial species. Therefore, we conclude that the most fundamental difference in X inactivation of marsupials and eutherians is whether the inactive X is the paternal one or is determined at random (with p = q in most but not all cases). The only other unequivocal difference between eutherians and marsupials is that both X chromosomes are active in mice and human oocytes, but not in kangaroo oocytes. Apparently, the inactive X is reactivated at a later meiotic stage or during early embryogenesis in kangaroos. X-chromosome inactivation takes place early in embryogenesis of eutherians and marsupials. Extraembryonic membranes of mice exhibit paternal X inactivation, whereas those of humans seem to exhibit random X inactivation with p greater than q (i.e., preferential paternal X inactivation). In general, extraembryonic membranes of marsupial exhibit paternal X inactivation, but the Gpd locus is active on both X chromosomes in at least some cells of kangaroo yolk sac. It is difficult to draw any general conclusion because of major differences in embryogeny of mice, humans, and marsupials, and uncertainties in interpreting the data from humans. Other differences between marsupials and eutherians in patterns of X-linked gene expression and X-chromosome inactivation seem to be quantitative rather than qualitative. Partial expression of some genes on the inactive X is characteristic of marsupials, with

cis-Chlorobenzene Dihydrodiol Dehydrogenase (TcbB) from Pseudomonas sp. Strain P51, Expressed in Escherichia coli DH5α(pTCB149), Catalyzes Enantioselective Dehydrogenase Reactions

OpenAIRE

Raschke, Henning; Fleischmann, Thomas; Van Der Meer, Jan Roelof; Kohler, Hans-Peter E.

1999-01-01

cis-Chlorobenzene dihydrodiol dehydrogenase (CDD) from Pseudomonas sp. strain P51, cloned into Escherichia coli DH5α(pTCB149) was able to oxidize cis-dihydrodihydroxy derivatives (cis-dihydrodiols) of dihydronaphthalene, indene, and four para-substituted toluenes to the corresponding catechols. During the incubation of a nonracemic mixture of cis-1,2-indandiol, only the (+)-cis-(1R,2S) enantiomer was oxidized; the (−)-cis-(S,2R) enantiomer remained unchanged. CDD oxidized both enantiomers of ...

Effect of rising time of rectangular pulse on inactivation of staphylococcus aureus by pulsed electric field

Science.gov (United States)

Zhang, Ruobing; Liang, Dapeng; Zheng, Nanchen; Xiao, Jianfu; Mo, Mengbin; Li, Jing

2013-03-01

Pulsed electric field (PEF) is a novel non-thermal food processing technology that involves the electric discharge of high voltage short pulses through the food product. In PEF study, rectangular pulses are most commonly used for inactivating microorganisms. However, little information is available on the inactivation effect of rising time of rectangular pulse. In this paper, inactivation effects, electric field strength, treatment time and conductivity on staphylococcus aureus inactivation were investigated when the pulse rising time is reduced from 2.5 μs to 200 ns. Experimental results showed that inactivation effect of PEF increased with electric field strength, solution conductivity and treatment time. Rising time of the rectangular pulse had a significant effect on the inactivation of staphylococcus aureus. Rectangular pulses with a rising time of 200 ns had a better inactivation effect than that with 2 μs. In addition, temperature increase of the solution treated by pulses with 200 ns rising time was lower than that with 2 μs. In order to obtain a given inactivation effect, treatment time required for the rectangular pulse with 200 ns rise time was shorter than that with 2 μs.

Effect of rising time of rectangular pulse on inactivation of staphylococcus aureus by pulsed electric field

International Nuclear Information System (INIS)

Zhang, Ruobing; Liang, Dapeng; Xiao, Jianfu; Mo, Mengbin; Li, Jing; Zheng, Nanchen

2013-01-01

Pulsed electric field (PEF) is a novel non-thermal food processing technology that involves the electric discharge of high voltage short pulses through the food product. In PEF study, rectangular pulses are most commonly used for inactivating microorganisms. However, little information is available on the inactivation effect of rising time of rectangular pulse. In this paper, inactivation effects, electric field strength, treatment time and conductivity on staphylococcus aureus inactivation were investigated when the pulse rising time is reduced from 2.5 μs to 200 ns. Experimental results showed that inactivation effect of PEF increased with electric field strength, solution conductivity and treatment time. Rising time of the rectangular pulse had a significant effect on the inactivation of staphylococcus aureus. Rectangular pulses with a rising time of 200 ns had a better inactivation effect than that with 2 μs. In addition, temperature increase of the solution treated by pulses with 200 ns rising time was lower than that with 2 μs. In order to obtain a given inactivation effect, treatment time required for the rectangular pulse with 200 ns rise time was shorter than that with 2 μs.

ASSESSING THE EFFECTIVENESS OF LOW PRESSURE ULTRAVIOLET LIGHT FOR INACTIVATING HELICOBACTER PYLORI

Science.gov (United States)

Three strains of Helicobacter pylori were exposed to ultraviolet (UV) light from a low-pressure source to determine log inactivation versus applied fluence. Results indicate that H. pylori is readily inactivated at UV fluences typically used in water treatment r...

Some factors affecting urokinase inactivation. [Gamma radiation

Energy Technology Data Exchange (ETDEWEB)

Iwata, Hiroo; Iketa, Yoshito

1985-10-01

The enzymatic activity of urokinase adsorbed on various polymer surfaces was measured to study the interaction between protein and polymers. The polymer films on which urokinase was adsorbed were exposed to either a high temperature or ..gamma..-radiation. The thermal inactivation rates were higher on hydrophobic polymers such as poly(ethylene terephthalate), nylon 6, and poly(vinylidene fluoride) than hydrophilic polymers like cellulose and ethylene-vinyl alcohol copolymer, indicating their substantial dependence on the interfacial free energy between the polymer and water. A similar dependence was also seen for the ..gamma..-radiation inactivation. Urokinase adsorbed on the hydrophobic polymers lost more easily its enzymatic activity by exposure to ..gamma..-radiation. The interfacial free energy seems to be one of the driving forces to denaturate proteins on polymers.

Inactivation of Staphylococcus aureus and Enterococcus faecalis by a direct-current, cold atmospheric-pressure air plasma microjet.

Science.gov (United States)

Tian, Ye; Sun, Peng; Wu, Haiyan; Bai, Na; Wang, Ruixue; Zhu, Weidong; Zhang, Jue; Liu, Fuxiang

2010-07-01

A direct-current, cold atmospheric-pressure air plasma microjet (PMJ) was performed to inactivate Staphylococcus aureus (S. aureus) and Enterococcus faecalis (E. faecalis) in air. The process of sterilization and morphology of bacteria was observed. We wish to know the possible inactivation mechanisms of PMJ and explore a potential application in dental and other temperature sensitive treatment. In this study, we employed a direct current, atmospheric pressure, cold air PMJ to inactivate bacterias. Scanning electron microscopy was employed to evaluate the morphology of S. aureus and showed rupture of cell walls after the plasma treatment and Optical emission spectrum (OES) were used to understand the possible inactivation mechanisms of PMJ. The inactivation rates could reach 100% in 5 min. When the distance between the exit nozzle of the PMJ device and Petri dish was extended from 1 cm to 3 cm, effective inactivation was also observed with a similar inactivation curve. The inactivation of bacteria is attributed to the abundant reactive oxygen and nitrogen species, as well as ultroviolet radiation in the plasma. Different life spans and defensibilities of these killing agents may hold the key to understanding the different inactivation curves at different treatment distances.

Investigation of cis-trans isomer dependent dermatotoxicokinetics of UV filter ethylhexyl methoxycinnamate through stratum corneum in vivo.

Science.gov (United States)

Sharma, Anežka; Bányiová, Katarína; Vrana, Branislav; Justan, Ivan; Čupr, Pavel

2017-11-01

2-Ethylhexyl methoxycinnamate (EHMC) is one of the most used ultraviolet filters in personal care products. It undergoes cis/trans isomerization in sunlight, and there is limited toxicological understanding of the effects of the cis-isomer. It is known that two geometric isomers of one compound can have different physico-chemical properties and effects. However, there are no studies focusing on toxicokinetics of EHMC isomerization products to compare their potential difference in dermal exposure to cis-EHMC and trans-EHMC due to the difference in their dermatotoxicokinetics. In this study, dermal absorption of the parental trans-EHMC and its cis isomer was studied. A commercially available sunscreen lotion containing trans-EHMC and spiked with laboratory-prepared cis-EHMC was locally applied on the forearm skin of two volunteers. After 8 h of skin exposure, the stratum corneum (SC) layer was removed by tape stripping. The removed thickness of the SC was determined spectrophotometrically using a total protein assay. The concentration of both isomers in the removed SC was measured by HPLC-DAD. A new diffusion and permeability coefficient of both EHMC isomers in SC were determined by Fick's second law of diffusion in vivo. The difference in dermatotoxicokinetic parameters between the two isomers was not statistically significant. However, separate toxicological studies of isomeric forms and the determination of their dermatotoxicokinetic parameters are crucial for refinement of human risk assessment.

A review of recent analyses of the Canadian Incidence Study of Reported Child Abuse and Neglect (CIS

Directory of Open Access Journals (Sweden)

D. Potter

2015-01-01

Full Text Available Introduction: The objective of this analysis is to identify, assess the quality and summarize the findings of peer-reviewed articles that used data from the Canadian Incidence Study of Reported Child Abuse and Neglect (CIS published since November 2011 and data from provincial oversamples of the CIS as well as to illustrate evolving uses of these datasets. Methods: Articles were identified from the Public Health Agency of Canada's data request records tracking access to CIS data and publications produced from that data. At least two raters independently reviewed and appraised the quality of each article. Results: A total of 32 articles were included. Common strengths of articles included clearly stated research aims, appropriate control variables and analyses, sufficient sample sizes, appropriate conclusions and relevance to practice or policy. Common problem areas of articles included unclear definitions for variables and inclusion criteria of cases. Articles frequently measured the associations between maltreatment, child, caregiver, household and agency/referral characteristics and investigative outcomes such as opening cases for ongoing services and placement. Conclusion: Articles using CIS data were rated positively on most quality indicators. Researchers have recently focussed on inadequately studied categories of maltreatment (exposure to intimate partner violence [IPV], neglect and emotional maltreatment and examined factors specific to First Nations children. Data from the CIS oversamples have been underutilized. The use of multivariate analysis techniques has increased.

cis-Difluoridobis(1,10-phenanthroline)chromium(III) perchlorate monohydrate

DEFF Research Database (Denmark)

Birk, Torben; Bendix, Jesper; Weihe, Högni

2008-01-01

The title complex, [CrF(2)(C(12)H(8)N(2))(2)]ClO(4)·H(2)O, displays a slightly distorted octa-hedral coordination geometry around the central chromium(III) ion. The Cr environment is composed of a cis arrangement of two 1,10-phenanthroline [average Cr(III)-N = 2.0726 (10) Å] and two fluoride [ave...

Electronic structure description of the cis-MoOS unit in models for molybdenum hydroxylases.

Science.gov (United States)

Doonan, Christian J; Rubie, Nick D; Peariso, Katrina; Harris, Hugh H; Knottenbelt, Sushilla Z; George, Graham N; Young, Charles G; Kirk, Martin L

2008-01-09

The molybdenum hydroxylases catalyze the oxidation of numerous aromatic heterocycles and simple organics and, unlike other hydroxylases, utilize water as the source of oxygen incorporated into the product. The electronic structures of the cis-MoOS units in CoCp2[TpiPrMoVOS(OPh)] and TpiPrMoVIOS(OPh) (TpiPr = hydrotris(3-isopropylpyrazol-1-yl)borate), new models for molybdenum hydroxylases, have been studied in detail using S K-edge X-ray absorption spectroscopy, vibrational spectroscopy, and detailed bonding calculations. The results show a highly delocalized Mo=S pi* LUMO redox orbital that is formally Mo(dxy) with approximately 35% sulfido ligand character. Vibrational spectroscopy has been used to quantitate Mo-Ssulfido bond order changes in the cis-MoOS units as a function of redox state. Results support a redox active molecular orbital that has a profound influence on MoOS bonding through changes to the relative electro/nucleophilicity of the terminal sulfido ligand accompanying oxidation state changes. The bonding description for these model cis-MoOS systems supports enzyme mechanisms that are under orbital control and dominantly influenced by the unique electronic structure of the cis-MoOS site. The electronic structure of the oxidized enzyme site is postulated to play a role in polarizing a substrate carbon center for nucleophilic attack by metal activated water and acting as an electron sink in the two-electron oxidation of substrates.

A method for selecting cis-acting regulatory sequences that respond to small molecule effectors

Directory of Open Access Journals (Sweden)

Allas Ülar

2010-08-01

Full Text Available Abstract Background Several cis-acting regulatory sequences functioning at the level of mRNA or nascent peptide and specifically influencing transcription or translation have been described. These regulatory elements often respond to specific chemicals. Results We have developed a method that allows us to select cis-acting regulatory sequences that respond to diverse chemicals. The method is based on the β-lactamase gene containing a random sequence inserted into the beginning of the ORF. Several rounds of selection are used to isolate sequences that suppress β-lactamase expression in response to the compound under study. We have isolated sequences that respond to erythromycin, troleandomycin, chloramphenicol, meta-toluate and homoserine lactone. By introducing synonymous and non-synonymous mutations we have shown that at least in the case of erythromycin the sequences act at the peptide level. We have also tested the cross-activities of the constructs and found that in most cases the sequences respond most strongly to the compound on which they were isolated. Conclusions Several selected peptides showed ligand-specific changes in amino acid frequencies, but no consensus motif could be identified. This is consistent with previous observations on natural cis-acting peptides, showing that it is often impossible to demonstrate a consensus. Applying the currently developed method on a larger scale, by selecting and comparing an extended set of sequences, might allow the sequence rules underlying the activity of cis-acting regulatory peptides to be identified.

Carvacrol suppresses high pressure high temperature inactivation of Bacillus cereus spores.

Science.gov (United States)

Luu-Thi, Hue; Corthouts, Jorinde; Passaris, Ioannis; Grauwet, Tara; Aertsen, Abram; Hendrickx, Marc; Michiels, Chris W

2015-03-16

The inactivation of bacterial spores generally proceeds faster and at lower temperatures when heat treatments are conducted under high pressure, and high pressure high temperature (HPHT) processing is, therefore, receiving an increased interest from food processors. However, the mechanisms of spore inactivation by HPHT treatment are poorly understood, particularly at moderately elevated temperature. In the current work, we studied inactivation of the spores of Bacillus cereus F4430/73 by HPHT treatment for 5 min at 600MPa in the temperature range of 50-100°C, using temperature increments of 5°C. Additionally, we investigated the effect of the natural antimicrobial carvacrol on spore germination and inactivation under these conditions. Spore inactivation by HPHT was less than about 1 log unit at 50 to 70°C, but gradually increased at higher temperatures up to about 5 log units at 100°C. DPA release and loss of spore refractility in the spore population were higher at moderate (≤65°C) than at high (≥70°C) treatment temperatures, and we propose that moderate conditions induced the normal physiological pathway of spore germination resulting in fully hydrated spores, while at higher temperatures this pathway was suppressed and replaced by another mechanism of pressure-induced dipicolinic acid (DPA) release that results only in partial spore rehydration, probably because spore cortex hydrolysis is inhibited. Carvacrol strongly suppressed DPA release and spore rehydration during HPHT treatment at ≤65°C and also partly inhibited DPA release at ≥65°C. Concomitantly, HPHT spore inactivation was reduced by carvacrol at 65-90°C but unaffected at 95-100°C. Copyright © 2014 Elsevier B.V. All rights reserved.

Metabolomic fingerprinting of primed tobacco cells provide the first evidence for the biological origin of cis-chlorogenic acid

CSIR Research Space (South Africa)

Mhlongo, MI

2015-01-01

Full Text Available . Very little, however, is known about the biological significance and origin of cis-isomers. Here we show for the first time the accumulation of cis-5-caffeoylquinic acid in cultured tobacco cells treated with different inducers of plant defence...

Separation behavior of octadecadienoic acid isomers and identification of cis- and trans-isomers using gas chromatography.

Science.gov (United States)

Shibamoto, Shigeaki; Gooley, Andrew; Yamamoto, Kouhei

2015-01-01

Using a strongly polar cyanopropyl capillary column we have investigated the gas chromatography (GC) separation behaviors of 24 octadecadienoic acid methyl ester (18:2ME) isomers compared against saturated methyl stearate (18:0ME) and arachidic acid methyl ester (20:0ME), and the dependency on the GC column temperature. The 24 isomers were obtained by performing cis-to trans-isomerization of six regioisomers: five of the 18:2ME isomers were prepared by the partial reduction of methyl α-linolenate and methyl γ-linolenate C18 trienoic acids with different double bond positions, whereas the sixth isomer, 18:2ME (c5, c9), was obtained from a raw constituent fatty acid methyl ester (FAME) sample extracted from Japanese yew seeds. There are no reference standards commercially available for 18:2ME isomers, and in elucidating the elution order of these isomers this study should help the future identification of cis- and trans-type of 18:2ME. We also report the identification method of cis- and trans-type of FAME using equivalent chain lengths and attempt the identification of cis- and trans-type of 18:2ME isomers from partially hydrogenated canola oil.

Inactivation of Ichthyophonus spores using sodium hypochlorite and polyvinyl pyrrolidone iodine.

Science.gov (United States)

Hershberger, P K; Pacheco, C A; Gregg, J L

2008-11-01

Chlorine and iodine solutions were effective at inactivating Ichthyophonus spores in vitro. Inactivation in sea water increased directly with halogen concentration and exposure duration, with significant differences (P < 0.05) from controls occurring at all chlorine concentrations and exposure durations tested (1.5-13.3 ppm for 1-60 min) and at most iodine concentrations and exposure durations tested (1.2 ppm for 60 min and 5.9-10.7 ppm for 1-60 min). However, 10-fold reductions in spore viability occurred only after exposure to halogen solutions at higher concentrations and/or longer durations (13 ppm total chlorine for 1-60 min, 5.9 ppm total iodine for 60 min, and 10.7 ppm total iodine for 1-60 min). Inactivation efficacy was greater when halogen solutions were prepared in fresh water, presumably because of combined effects of halogen-induced inactivation and general spore instability in fresh water. The results have practical implications for disinfection and biocontainment in research laboratories and other facilities that handle live Ichthyophonus cultures and/or infected fish.

Synthesis, spectroscopic and TD-DFT quantum mechanical study of azo-azomethine dyes. A laser induced trans-cis-trans photoisomerization cycle.

Science.gov (United States)

Georgiev, Anton; Kostadinov, Anton; Ivanov, Deyan; Dimov, Deyan; Stoyanov, Simeon; Nedelchev, Lian; Nazarova, Dimana; Yancheva, Denitsa

2018-03-05

This paper describes the synthesis, spectroscopic characterization and quantum mechanical calculations of three azo-azomethine dyes. The dyes were synthesized via condensation reaction between 4-(dimethylamino)benzaldehyde and three different 4-aminobenzene azo dyes. Quantum chemical calculations on the optimized molecular geometry and electron densities of the trans (E) and cis (Z) isomers and their vibrational frequencies have been computed by using DFT/B3LYP density-functional theory with 6-311++G(d,p) basis set in vacuo. The thermodynamic parameters such as total electronic energy E (RB3LYP), enthalpy H 298 (sum of electronic and thermal enthalpies), free Gibbs energy G 298 (sum of electronic and thermal free Gibbs energies) and dipole moment μ were computed for trans (E) and cis (Z) isomers in order to estimate the ΔE trans→cis , Δμ trans→cis, ΔH trans→cis , ΔG trans→cis and ΔS trans→cis values. After molecular geometry optimization the electronic spectra have been obtained by TD-DFT calculations at same basis set and correlated with the spectra of vapour deposited nanosized films of the dyes. The NBO analysis was performed in order to understand the intramolecular charge transfer and energy of resonance stabilization. Solvatochromism was investigated by UV-VIS spectroscopy in five different organic solvents with increasing polarity. The dynamic photoisomerization experiments have been performed in DMF by pump lasers λ=355nm (mostly E→Z) and λ=491nm (mostly Z→E) in spectral region 300nm - 800nm at equal concentrations and times of illumination in order to investigate the photodynamical trans-cis-trans properties of the CHN and NN chromophore groups of the dyes. Copyright © 2017 Elsevier B.V. All rights reserved.

Ablation of cholesterol biosynthesis in neural stem cells increases their VEGF expression and angiogenesis but causes neuron apoptosis.

Science.gov (United States)

Saito, Kanako; Dubreuil, Veronique; Arai, Yoko; Wilsch-Bräuninger, Michaela; Schwudke, Dominik; Saher, Gesine; Miyata, Takaki; Breier, Georg; Thiele, Christoph; Shevchenko, Andrej; Nave, Klaus-Armin; Huttner, Wieland B

2009-05-19

Although sufficient cholesterol supply is known to be crucial for neurons in the developing mammalian brain, the cholesterol requirement of neural stem and progenitor cells in the embryonic central nervous system has not been addressed. Here we have conditionally ablated the activity of squalene synthase (SQS), a key enzyme for endogenous cholesterol production, in the neural stem and progenitor cells of the ventricular zone (VZ) of the embryonic mouse brain. Mutant embryos exhibited a reduced brain size due to the atrophy of the neuronal layers, and died at birth. Analyses of the E11.5-E15.5 dorsal telencephalon and diencephalon revealed that this atrophy was due to massive apoptosis of newborn neurons, implying that this progeny of the SQS-ablated neural stem and progenitor cells was dependent on endogenous cholesterol biosynthesis for survival. Interestingly, the neural stem and progenitor cells of the VZ, the primary target of SQS inactivation, did not undergo significant apoptosis. Instead, vascular endothelial growth factor (VEGF) expression in these cells was strongly upregulated via a hypoxia-inducible factor-1-independent pathway, and angiogenesis in the VZ was increased. Consistent with an increased supply of lipoproteins to these cells, the level of lipid droplets containing triacylglycerides with unsaturated fatty acyl chains was found to be elevated. Our study establishes a direct link between intracellular cholesterol levels, VEGF expression, and angiogenesis. Moreover, our data reveal a hitherto unknown compensatory process by which the neural stem and progenitor cells of the developing mammalian brain evade the detrimental consequences of impaired endogenous cholesterol biosynthesis.

Preparation and characterization of fluorophenylboronic acid-functionalized affinity monolithic columns for the selective enrichment of cis-diol-containing biomolecules.

Science.gov (United States)

Li, Qianjin; Liu, Zhen

2015-01-01

Boronate affinity monolithic columns have been developed into an important means for the selective recognition and capture of cis-diol-containing biomolecules, such as glycoproteins, nucleosides and saccharides. The ligands of boronic acids are playing an important role in boronate affinity monolithic columns. Although several boronate affinity monoliths with high affinity toward cis-diol-containing biomolecules have been reported, only few publications are focused on their detailed procedures for preparation and characterization. This chapter describes in detail the preparation and characterization of a boronate affinity monolithic column applying 2,4-difluoro-3-formyl-phenylboronic acid (DFFPBA) as a ligand. The DFFPBA-functionalized monolithic column not only exhibited an ultrahigh boronate affinity toward cis-diol-containing biomolecules, but also showed great potential for the selective enrichment of cis-diol-containing biomolecules in real samples.

Thermal and Carbon Dioxide Inactivation of Alkaline Phosphatase in Buffer and Milk

Directory of Open Access Journals (Sweden)

Osman Erkmen

2004-01-01

Full Text Available The effects of temperature and CO2 treatment on the inactivation of alkaline phosphatase (ALP were studied. The thermal stability of ALP was found to be significantly (P< 0.05 different in glycine/NaOH buffer, pasteurized milk and raw milk. ALP was completely inactivated in the buffer at 60, 70 and 80 °C but approximately 12 % of activity was present at 50 °C after 55 min of treatment. The time required for complete inactivation of the enzyme in the buffer was reduced from 50 to 4 min as temperature increased from 60 to 80 °C. Complete inactivation of the enzyme in pasteurized milk was achieved at 70 and 80 °C but 28 and 15 % of ALP activity was still present at 50 and 60 °C after 120 min of treatment. Inactivation time for raw milk was reduced nearly 18-fold by increasing temperature from 50 to 70 °C. ALP in the buffer exposed to CO2 (under atmospheric pressure treatment at different temperatures showed a decrease in enzyme activity. Inactivation was found to be higher as the temperature increased from 20 to 50 °C. At the end of a 30-min treatment, residual ALP activity was found to be 84 and 19 % at 20 and 50 °C, respectively. Faster drop in pH and enzyme activity occurred within 5 min. The change in pH and enzyme activity dependant on CO2 treatment was not observed in raw milk mainly due to strong buffering capacity of milk.

Network University of the CIS as a tool for development of academic mobility within a single (unified educational space of the CIS member states

Directory of Open Access Journals (Sweden)

Гульнара Амангельдиновна Краснова

2010-03-01

Full Text Available The article presents the results of the project «Establishment of a network University of the CIS (2008-2010 years» realization, aimed to establish a joint master's programs in the commonwealth, to strengthen international cooperation in the training of highly qualified specialists, specified tasks to further its implementation in 2010.

Nucleus incertus inactivation impairs spatial learning and memory in rats.

Science.gov (United States)

Nategh, Mohsen; Nikseresht, Sara; Khodagholi, Fariba; Motamedi, Fereshteh

2015-02-01

Nucleus incertus (NI) is a pontine nucleus which releases mainly GABA and relaxin-3 in rats. Its suggested functions include response to stress, arousal, and modulation of hippocampal theta rhythm. Since the role of NI in learning and memory has not been well characterized, therefore the involvement of this nucleus in spatial learning and memory and the aftermath hippocampal levels of c-fos and pCREB were evaluated. NI was targeted by implanting cannula in male rats. For reference memory, NI was inactivated by lidocaine (0.4 μl, 4%) at three stages of acquisition, consolidation and retrieval in Morris water maze paradigm. For working memory, NI was inactivated in acquisition and retrieval phases. Injection of lidocaine prior to the first training session of reference memory significantly increased the distance moved, suggesting that inactivation of NI delays acquisition in this spatial task. Inactivation also interfered with the retrieval phase of spatial reference memory, as the time in target quadrant for lidocaine group was less, and the escape latency was higher compared to the control group. However, no difference was observed in the consolidation phase. In the working memory task, with inter-trial intervals of 75 min, the escape latency was higher when NI was inactivated in the retrieval phase. In addition, c-fos and pCREB/CREB levels decreased in NI-inhibited rats. This study suggests that nucleus incertus might participate in acquisition of spatial reference, and retrieval of both spatial reference and working memory. Further studies should investigate possible roles of NI in the hippocampal plasticity. Copyright © 2014 Elsevier Inc. All rights reserved.

Effective inactivation of a wide range of viruses by pasteurization.

Science.gov (United States)

Gröner, Albrecht; Broumis, Connie; Fang, Randel; Nowak, Thomas; Popp, Birgit; Schäfer, Wolfram; Roth, Nathan J

2018-01-01

Careful selection and testing of plasma reduces the risk of blood-borne viruses in the starting material for plasma-derived products. Furthermore, effective measures such as pasteurization at 60°C for 10 hours have been implemented in the manufacturing process of therapeutic plasma proteins such as human albumin, coagulation factors, immunoglobulins, and enzyme inhibitors to inactivate blood-borne viruses of concern. A comprehensive compilation of the virus reduction capacity of pasteurization is presented including the effect of stabilizers used to protect the therapeutic protein from modifications during heat treatment. The virus inactivation kinetics of pasteurization for a broad range of viruses were evaluated in the relevant intermediates from more than 15 different plasma manufacturing processes. Studies were carried out under the routine manufacturing target variables, such as temperature and product-specific stabilizer composition. Additional studies were also performed under robustness conditions, that is, outside production specifications. The data demonstrate that pasteurization inactivates a wide range of enveloped and nonenveloped viruses of diverse physicochemical characteristics. After a maximum of 6 hours' incubation, no residual infectivity could be detected for the majority of enveloped viruses. Effective inactivation of a range of nonenveloped viruses, with the exception of nonhuman parvoviruses, was documented. Pasteurization is a very robust and reliable virus inactivation method with a broad effectiveness against known blood-borne pathogens and emerging or potentially emerging viruses. Pasteurization has proven itself to be a highly effective step, in combination with other complementary safety measures, toward assuring the virus safety of final product. © 2017 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

SB-224289 Antagonizes the Antifungal Mechanism of the Marine Depsipeptide Papuamide A.

Directory of Open Access Journals (Sweden)

Chelsi D Cassilly

Full Text Available In order to expand the repertoire of antifungal compounds a novel, high-throughput phenotypic drug screen targeting fungal phosphatidylserine (PS synthase (Cho1p was developed based on antagonism of the toxin papuamide A (Pap-A. Pap-A is a cyclic depsipeptide that binds to PS in the membrane of wild-type Candida albicans, and permeabilizes its plasma membrane, ultimately causing cell death. Organisms with a homozygous deletion of the CHO1 gene (cho1ΔΔ do not produce PS and are able to survive in the presence of Pap-A. Using this phenotype (i.e. resistance to Pap-A as an indicator of Cho1p inhibition, we screened over 5,600 small molecules for Pap-A resistance and identified SB-224289 as a positive hit. SB-224289, previously reported as a selective human 5-HT1B receptor antagonist, also confers resistance to the similar toxin theopapuamide (TPap-A, but not to other cytotoxic depsipeptides tested. Structurally similar molecules and truncated variants of SB-224289 do not confer resistance to Pap-A, suggesting that the toxin-blocking ability of SB-224289 is very specific. Further biochemical characterization revealed that SB-224289 does not inhibit Cho1p, indicating that Pap-A resistance is conferred by another undetermined mechanism. Although the mode of resistance is unclear, interaction between SB-224289 and Pap-A or TPap-A suggests this screening assay could be adapted for discovering other compounds which could antagonize the effects of other environmentally- or medically-relevant depsipeptide toxins.

Synthesis of 1-[{sup 13}CD{sub 3}]-9-cis-retinoic acid

Energy Technology Data Exchange (ETDEWEB)

Bennani, Y.L. [Ligand Pharmaceuticals Inc., San Diego, CA (United States). Dept. of Medicinal Chemistry

1995-12-31

1-[{sup 13}CD{sub 3}]-9-cis-Retinoic acid was prepared in 8 steps from 2,6-dimethylcyclohexanone. Alkylation of 2,6-dimethylcyclohexanone under LiHMDS/MnBr{sub 2}/{sup 13}CD{sub 3}I gave the corresponding labeled 2-[{sup 13}CD{sub 3}]-2,2,6-trimethylcyclohexanone 4 in good yield. Further functionalization of 4 to 6-[{sup 13}CD{sub 3}]-{beta}-cyclocitral 6 proceeded through a Shapiro reaction. Aldehyde 6 was condensed with ethyl 3,3-dimethylacrylate to afford the corresponding bicyclic pyranone 7. Reduction of 7 to lactol 8, followed by acid-catalyzed ring opening gave the 9-cis-aldehyde 9. Wittig-Horner olefination and saponification afforded the title compound in good overall yield and in excellent isotopic purity. (Author).

9-cis-retinoic Acid and troglitazone impacts cellular adhesion, proliferation, and integrin expression in K562 cells.

Science.gov (United States)

Hanson, Amanda M; Gambill, Jessica; Phomakay, Venusa; Staten, C Tyler; Kelley, Melissa D

2014-01-01

Retinoids are established pleiotropic regulators of both adaptive and innate immune responses. Recently, troglitazone, a PPAR gamma agonist, has been demonstrated to have anti-inflammatory effects. Separately, retinoids and troglitazone are implicated in immune related processes; however, their combinatory role in cellular adhesion and proliferation has not been well established. In this study, the effect of 9-cis-retinoic acid (9-cis-RA) and troglitazone on K562 cellular adhesion and proliferation was investigated. Troglitazone exposure decreased K562 cellular adhesion to RGD containing extracellular matrix proteins fibronectin, FN-120, and vitronectin in a concentration and time-dependent manner. In the presence of troglitazone, 9-cis-retinoic acid restores cellular adhesion to levels comparable to vehicle treatment alone on fibronectin, FN-120, and vitronectin substrates within 72 hours. Due to the prominent role of integrins in attachment to extracellular matrix proteins, we evaluated the level of integrin α5 subunit expression. Troglitazone treatment results in decrease in α5 subunit expression on the cell surface. In the presence of both agonists, cell surface α5 subunit expression was restored to levels comparable to vehicle treatment alone. Additionally, troglitazone and 9-cis-RA mediated cell adhesion was decreased in the presence of a function blocking integrin alpha 5 inhibitor. Further, through retinoid metabolic profiling and HPLC analysis, our study demonstrates that troglitazone augments retinoid availability in K562 cells. Finally, we demonstrate that troglitazone and 9-cis-retinoic acid synergistically dampen cellular proliferation in K562 cells. Our study is the first to report that the combination of troglitazone and 9-cis-retinoic acid restores cellular adhesion, alters retinoid availability, impacts integrin expression, and dampens cellular proliferation in K562 cells.

Pathogen inactivation of Dengue virus in red blood cells using amustaline and glutathione.

Science.gov (United States)

Aubry, Maite; Laughhunn, Andrew; Santa Maria, Felicia; Lanteri, Marion C; Stassinopoulos, Adonis; Musso, Didier

2017-12-01

Dengue virus (DENV) is an arbovirus primarily transmitted through mosquito bite; however, DENV transfusion-transmitted infections (TTIs) have been reported and asymptomatic DENV RNA-positive blood donors have been identified in endemic countries. DENV is considered a high-risk pathogen for blood safety. One of the mitigation strategies to prevent arbovirus TTIs is pathogen inactivation. In this study we demonstrate that the amustaline and glutathione (S-303/GSH) treatment previously found effective against Zika virus in red blood cells (RBCs) is also effective in inactivating DENV. Red blood cells were spiked with high levels of DENV. Viral RNA loads and infectious titers were measured in the untreated control and before and after pathogen inactivation treatment of RBC samples. DENV infectivity was also assessed over five successive cell culture passages to detect any potential residual replicative virus. The mean ± SD DENV titer in RBCs before inactivation was 6.61 ± 0.19 log 50% tissue culture infectious dose (TCID 50 )/mL and the mean viral RNA load was 8.42 log genome equivalents/mL. No replicative DENV was detected either immediately after completion of treatment using S-303/GSH or after cell culture passages. Treatment using S-303/GSH inactivated high levels of DENV in RBCs to the limit of detection. In combination with previous studies showing the effective inactivation of DENV in plasma and platelets using the licensed amotosalen/UVA system, this study demonstrates that high levels of DENV can be inactivated in all blood components. © 2017 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

Sunlight inactivation of Escherichia coli in waste stabilization microcosms in a sahelian region (Ouagadougou, Burkina Faso).

Science.gov (United States)

Maïga, Ynoussa; Denyigba, Kokou; Wethe, Joseph; Ouattara, Aboubakar Sidiki

2009-02-09

Experiments on sunlight inactivation of Escherichia coli were conducted from November 2006 to June 2007 in eight outdoors microcosms with different depths filled with maturation pond wastewater in order to determine pond depth influence on sunlight inactivation of E. coli. The long-term aim was to maximize sunlight inactivation of waterborne pathogens in waste stabilization ponds (WSPs) in sahelian regions where number of sunny days enable longer exposure of wastewater to sunlight. The inactivation was followed during daylight from 8.00 h to 17.00 h and during the night. Sunlight inactivation rates (K(S)), as a function of cumulative global solar radiation (insolation), were 16 and 24 times higher than the corresponding dark inactivation (K(D)) rates, respectively in cold and warm season. In warm season, E. coli was inactivated far more rapidly. Inactivation of E. coli follows the evolution of radiation during the day. In shallow depth microcosms, E. coli was inactivated far more rapidly than in high depth microcosms. The physical chemical parameters [pH, dissolved oxygen (DO)] of microcosms water were higher in shallow depth microcosms than in high depth microcosms suggesting a synergistic effect of sunlight and these parameters to damage E. coli. To increase the efficiency of the elimination of waterborne bacteria, the use of maturation ponds with intermediate depths (0.4m) would be advisable in view of the high temperatures and thus evaporation recorded in sahelian regions.